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RJR: Recommended Bibliography 19 Feb 2025 at 01:51 Created:
Long Covid: Review Papers
Wikipedia: Long Covid refers to a group of health problems persisting or developing after an initial COVID-19 infection. Symptoms can last weeks, months or years and are often debilitating. Long COVID is characterised by a large number of symptoms, which sometimes disappear and reappear. Commonly reported symptoms of long COVID are fatigue, memory problems, shortness of breath, and sleep disorder. Many other symptoms can also be present, including headaches, loss of smell or taste, muscle weakness, fever, and cognitive dysfunction and problems with mental health. Symptoms often get worse after mental or physical effort, a process called post-exertional malaise. The causes of long COVID are not yet fully understood. Hypotheses include lasting damage to organs and blood vessels, problems with blood clotting, neurological dysfunction, persistent virus or a reactivation of latent viruses and autoimmunity. Diagnosis of long COVID is based on suspected or confirmed COVID-19 infection, symptoms and by excluding alternative diagnoses. Estimates of the prevalence of long COVID vary based on definition, population studied, time period studied, and methodology, generally ranging between 5% and 50%. Prevalence is less after vaccination.
Created with PubMed® Query: ( "long covid" AND review[SB] ) NOT pmcbook NOT ispreviousversion
Citations The Papers (from PubMed®)
RevDate: 2025-02-18
Cognitive reserve moderates the effect of COVID-19 on cognition: A systematic review and meta-analysis of individual participant data.
Neuroscience and biobehavioral reviews pii:S0149-7634(25)00067-3 [Epub ahead of print].
Elucidating the factors that mitigate the effects of COVID-19 on cognitive function offers important insights for public health policy and intervention. This systematic review and individual participant data (IPD) meta-analysis assesses cognitive reserve (CR) as a potential moderator of post-COVID-19 cognitive dysfunction (PCCD). Under PRISMA-IPD guidelines, data searches were conducted via PubMed, PsycINFO, Scopus, and Embase, up to January 2023. Eligible studies included at least one cognitive assessment, CR proxy, and disease severity indicator. Of 5,604 studies, 87 were eligible (10,950 COVID-19 cases; 78,305 controls), and IPD was obtained for 29 datasets (3,919 COVID-19 cases; 8,267 controls). Three-level random-effects meta-analyses indicated that CR had a moderate positive association (rsp =.29), and COVID-19 severity had a small negative association (rsp = -.07) with cognitive outcomes. These effects were moderated by a significant within-study interaction. Cognitive deficits following COVID-19 were 33% smaller among high CR individuals, and 33% greater among low CR individuals, relative to those with average CR. Population-based initiatives promoting reserve-building behaviors may alleviate the PCCD-related public health burden. REVIEW REGISTRATION: PROSPERO registration number: CRD42022360670.
Additional Links: PMID-39965723
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@article {pmid39965723,
year = {2025},
author = {Foreman, L and Child, B and Saywell, I and Collins-Praino, L and Baetu, I},
title = {Cognitive reserve moderates the effect of COVID-19 on cognition: A systematic review and meta-analysis of individual participant data.},
journal = {Neuroscience and biobehavioral reviews},
volume = {},
number = {},
pages = {106067},
doi = {10.1016/j.neubiorev.2025.106067},
pmid = {39965723},
issn = {1873-7528},
abstract = {Elucidating the factors that mitigate the effects of COVID-19 on cognitive function offers important insights for public health policy and intervention. This systematic review and individual participant data (IPD) meta-analysis assesses cognitive reserve (CR) as a potential moderator of post-COVID-19 cognitive dysfunction (PCCD). Under PRISMA-IPD guidelines, data searches were conducted via PubMed, PsycINFO, Scopus, and Embase, up to January 2023. Eligible studies included at least one cognitive assessment, CR proxy, and disease severity indicator. Of 5,604 studies, 87 were eligible (10,950 COVID-19 cases; 78,305 controls), and IPD was obtained for 29 datasets (3,919 COVID-19 cases; 8,267 controls). Three-level random-effects meta-analyses indicated that CR had a moderate positive association (rsp =.29), and COVID-19 severity had a small negative association (rsp = -.07) with cognitive outcomes. These effects were moderated by a significant within-study interaction. Cognitive deficits following COVID-19 were 33% smaller among high CR individuals, and 33% greater among low CR individuals, relative to those with average CR. Population-based initiatives promoting reserve-building behaviors may alleviate the PCCD-related public health burden. REVIEW REGISTRATION: PROSPERO registration number: CRD42022360670.},
}
RevDate: 2025-02-18
CmpDate: 2025-02-18
The Role of SARS-CoV-2 Spike Protein in Long-term Damage of Tissues and Organs, the Underestimated Role of Retrotransposons and Stem Cells, a Working Hypothesis.
Endocrine, metabolic & immune disorders drug targets, 25(2):85-98.
Coronavirus disease-2019 (COVID-19) is a respiratory disease in which Spike protein from SARS-CoV-2 plays a key role in transferring virus genomic code into target cells. Spike protein, which is found on the surface of the SARS-CoV-2 virus, latches onto angiotensin-converting enzyme 2 receptors (ACE2r) on target cells. The RNA genome of coronaviruses, with an average length of 29 kb, is the longest among all RNA viruses and comprises six to ten open reading frames (ORFs) responsible for encoding replicase and structural proteins for the virus. Each component of the viral genome is inserted into a helical nucleocapsid surrounded by a lipid bilayer. The Spike protein is responsible for damage to several organs and tissues, even leading to severe impairments and long-term disabilities. Spike protein could also be the cause of the long-term post-infectious conditions known as Long COVID-19, characterized by a group of unresponsive idiopathic severe neuro- and cardiovascular disorders, including strokes, cardiopathies, neuralgias, fibromyalgia, and Guillaume- Barret's like-disease. In this paper, we suggest a pervasive mechanism whereby the Spike proteins either from SARS-CoV-2 mRNA or mRNA vaccines, tend to enter the mature cells, and progenitor, multipotent, and pluripotent stem cells (SCs), altering the genome integrity. This will eventually lead to the production of newly affected clones and mature cells. The hypothesis presented in this paper proposes that the mRNA integration into DNA occurs through several components of the evolutionarily genetic mechanism such as retrotransposons and retrotransposition, LINE-1 or L1 (long interspersed element-1), and ORF-1 and 2 responsible for the generation of retrogenes. Once the integration phase is concluded, somatic cells, progenitor cells, and SCs employ different silencing mechanisms. DNA methylation, followed by histone modification, begins to generate unlimited lines of affected cells and clones that form affected tissues characterized by abnormal patterns that become targets of systemic immune cells, generating uncontrolled inflammatory conditions, as observed in both Long COVID-19 syndrome and the mRNA vaccine.
Additional Links: PMID-38468535
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@article {pmid38468535,
year = {2025},
author = {Balzanelli, MG and Rastmanesh, R and Distratis, P and Lazzaro, R and Inchingolo, F and Del Prete, R and Pham, VH and Aityan, SK and Cong, TT and Nguyen, KCD and Isacco, CG},
title = {The Role of SARS-CoV-2 Spike Protein in Long-term Damage of Tissues and Organs, the Underestimated Role of Retrotransposons and Stem Cells, a Working Hypothesis.},
journal = {Endocrine, metabolic & immune disorders drug targets},
volume = {25},
number = {2},
pages = {85-98},
pmid = {38468535},
issn = {2212-3873},
mesh = {Humans ; *COVID-19/metabolism/virology/immunology ; *Spike Glycoprotein, Coronavirus/metabolism/genetics ; *SARS-CoV-2/genetics/metabolism ; *Retroelements/genetics ; Stem Cells/metabolism/virology ; Animals ; },
abstract = {Coronavirus disease-2019 (COVID-19) is a respiratory disease in which Spike protein from SARS-CoV-2 plays a key role in transferring virus genomic code into target cells. Spike protein, which is found on the surface of the SARS-CoV-2 virus, latches onto angiotensin-converting enzyme 2 receptors (ACE2r) on target cells. The RNA genome of coronaviruses, with an average length of 29 kb, is the longest among all RNA viruses and comprises six to ten open reading frames (ORFs) responsible for encoding replicase and structural proteins for the virus. Each component of the viral genome is inserted into a helical nucleocapsid surrounded by a lipid bilayer. The Spike protein is responsible for damage to several organs and tissues, even leading to severe impairments and long-term disabilities. Spike protein could also be the cause of the long-term post-infectious conditions known as Long COVID-19, characterized by a group of unresponsive idiopathic severe neuro- and cardiovascular disorders, including strokes, cardiopathies, neuralgias, fibromyalgia, and Guillaume- Barret's like-disease. In this paper, we suggest a pervasive mechanism whereby the Spike proteins either from SARS-CoV-2 mRNA or mRNA vaccines, tend to enter the mature cells, and progenitor, multipotent, and pluripotent stem cells (SCs), altering the genome integrity. This will eventually lead to the production of newly affected clones and mature cells. The hypothesis presented in this paper proposes that the mRNA integration into DNA occurs through several components of the evolutionarily genetic mechanism such as retrotransposons and retrotransposition, LINE-1 or L1 (long interspersed element-1), and ORF-1 and 2 responsible for the generation of retrogenes. Once the integration phase is concluded, somatic cells, progenitor cells, and SCs employ different silencing mechanisms. DNA methylation, followed by histone modification, begins to generate unlimited lines of affected cells and clones that form affected tissues characterized by abnormal patterns that become targets of systemic immune cells, generating uncontrolled inflammatory conditions, as observed in both Long COVID-19 syndrome and the mRNA vaccine.},
}
MeSH Terms:
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Humans
*COVID-19/metabolism/virology/immunology
*Spike Glycoprotein, Coronavirus/metabolism/genetics
*SARS-CoV-2/genetics/metabolism
*Retroelements/genetics
Stem Cells/metabolism/virology
Animals
RevDate: 2025-02-16
Autoimmunity in Long-COVID.
The Journal of allergy and clinical immunology pii:S0091-6749(25)00171-X [Epub ahead of print].
Long-COVID (also termed Post-Acute Sequelae of SARS-CoV-2 or PASC) affects up to 10% of people recovering from SARS-CoV-2 infection. Diagnosis is hampered by diffuse symptomatology, lack of biomarkers, an incomplete understanding of pathogenesis, and the lack of validated treatments. In terms of pathogenesis, hypothesised causes include viral persistence, the legacy of endotheliitis and thrombosis, low-grade tissue-based inflammation and/or scarring, perturbation of the host virome/microbiome, or triggering of autoimmunity. Several studies show pre-existing and/or de novo production of autoantibodies after infection with SARS-CoV-2, but the persistence of these antibodies and their role in causing long-COVID is debated. Here, we review the mechanisms through which autoimmune responses can arise during and after viral infection, focusing on the evidence for B-cell dysregulation and autoantibody production in acute and long-COVID.
Additional Links: PMID-39956285
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@article {pmid39956285,
year = {2025},
author = {Talwar, S and Harker, JA and Openshaw, PJM and Thwaites, RS},
title = {Autoimmunity in Long-COVID.},
journal = {The Journal of allergy and clinical immunology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaci.2025.02.005},
pmid = {39956285},
issn = {1097-6825},
abstract = {Long-COVID (also termed Post-Acute Sequelae of SARS-CoV-2 or PASC) affects up to 10% of people recovering from SARS-CoV-2 infection. Diagnosis is hampered by diffuse symptomatology, lack of biomarkers, an incomplete understanding of pathogenesis, and the lack of validated treatments. In terms of pathogenesis, hypothesised causes include viral persistence, the legacy of endotheliitis and thrombosis, low-grade tissue-based inflammation and/or scarring, perturbation of the host virome/microbiome, or triggering of autoimmunity. Several studies show pre-existing and/or de novo production of autoantibodies after infection with SARS-CoV-2, but the persistence of these antibodies and their role in causing long-COVID is debated. Here, we review the mechanisms through which autoimmune responses can arise during and after viral infection, focusing on the evidence for B-cell dysregulation and autoantibody production in acute and long-COVID.},
}
RevDate: 2025-02-16
Cost-effectiveness models assessing COVID-19 booster vaccines across eight countries: A review of methods and data inputs.
Vaccine, 51:126879 pii:S0264-410X(25)00176-8 [Epub ahead of print].
Coronavirus disease 2019 (COVID-19) continues to cause serious health consequences globally. Policy makers now assess cost effectiveness (CE) when evaluating COVID-19 vaccines. A targeted literature review was performed to examine recent CE evidence for COVID-19 vaccines, as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transitions from pandemic to endemic, to identify best practices. Data were from large EU countries (UK, Spain, Germany, France, and Italy), US, Canada, and Australia. Nine CE studies met the inclusion criteria. Studies evaluated booster vaccination, and mainly considered mRNA vaccines. CE studies reported that COVID-19 vaccines provided health benefits and were cost-effective or showed cost-savings. Benefits were more pronounced in older and high-risk populations based on higher rates of COVID-19 hospitalization and death. CE findings were most sensitive to estimates of incidence of COVID-19, SARS-CoV-2 transmissibility, vaccine effectiveness, waning/duration of vaccine protection, and hospitalization costs. Most data inputs were sourced from real-world evidence (RWE). Lack of inclusion of some parameters, such as transmission modeling, productivity losses, and the impact of long COVID may undervalue COVID-19 vaccines. As SARS-CoV-2 evolves and COVID-19 vaccines are updated, continuous generation of RWE is needed to demonstrate the CE of COVID-19 vaccines in an ongoing manner.
Additional Links: PMID-39956089
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@article {pmid39956089,
year = {2025},
author = {Smith, DS and Postma, M and Fisman, D and Mould-Quevedo, J},
title = {Cost-effectiveness models assessing COVID-19 booster vaccines across eight countries: A review of methods and data inputs.},
journal = {Vaccine},
volume = {51},
number = {},
pages = {126879},
doi = {10.1016/j.vaccine.2025.126879},
pmid = {39956089},
issn = {1873-2518},
abstract = {Coronavirus disease 2019 (COVID-19) continues to cause serious health consequences globally. Policy makers now assess cost effectiveness (CE) when evaluating COVID-19 vaccines. A targeted literature review was performed to examine recent CE evidence for COVID-19 vaccines, as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transitions from pandemic to endemic, to identify best practices. Data were from large EU countries (UK, Spain, Germany, France, and Italy), US, Canada, and Australia. Nine CE studies met the inclusion criteria. Studies evaluated booster vaccination, and mainly considered mRNA vaccines. CE studies reported that COVID-19 vaccines provided health benefits and were cost-effective or showed cost-savings. Benefits were more pronounced in older and high-risk populations based on higher rates of COVID-19 hospitalization and death. CE findings were most sensitive to estimates of incidence of COVID-19, SARS-CoV-2 transmissibility, vaccine effectiveness, waning/duration of vaccine protection, and hospitalization costs. Most data inputs were sourced from real-world evidence (RWE). Lack of inclusion of some parameters, such as transmission modeling, productivity losses, and the impact of long COVID may undervalue COVID-19 vaccines. As SARS-CoV-2 evolves and COVID-19 vaccines are updated, continuous generation of RWE is needed to demonstrate the CE of COVID-19 vaccines in an ongoing manner.},
}
RevDate: 2025-02-15
Understanding neural mechanisms and the use of targeted non-invasive brain stimulation for treatment of post-stroke fatigue: A scoping review.
Journal of the neurological sciences, 470:123399 pii:S0022-510X(25)00016-4 [Epub ahead of print].
BACKGROUND: Post-stroke fatigue (PSF) is one of the most prevalent symptoms that affects quality of life and daily function after stroke. Despite a growing body of research, its pathophysiology is poorly understood. Non-invasive brain stimulation (NIBS), such as the transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), can serve as a non-pharmacological intervention for PSF. In this review, we aim to (1) evaluate PSF neuroimaging studies to deduce potential neural mechanisms, (2) describe NIBS as a tool to probe brain structures to further understand pathophysiology of fatigue, and (3) assess NIBS as a treatment intervention for PSF.
METHODS: A systematic search was conducted for the databases PubMed, Embase, Scopus, CINAHL and Cochrane. Studies were included based on the following inclusion and exclusion criteria: >18 years with PSF, use of neuroimaging and/or NIBS for investigation or as an intervention for PSF, English language, study types including cohort, case control, or randomized controlled trials. Data extracted included participant characteristics, concept, context, study methods, and key findings relevant to the review questions.
RESULTS: A total of 30 studies met criteria. Neuroimaging papers that investigated brain structure (MRI) found conflicting associations between lesion location and PSF. Functional methods (fMRI, TMS) revealed altered resting state functional connectivity (rsFC), cortical excitability, and a disruption in interhemispheric inhibitory balance as potential mechanisms of PSF. There were no studies using TMS as an intervention for PSF. Of the six articles that used tDCS, only two reported statistically significant reductions in the severity of PSF.
CONCLUSION: Structural characteristics of stroke lesions had conflicting findings, while functional neuroimaging studies suggested that altered rsFC, cortical excitability and interhemispheric inhibitory balance contribute to the development of PSF. There were inconsistent results on the effectiveness of tDCS as an intervention for PSF, due to varying methodologies and lack of precise targeting of underlying neural mechanisms. Further investigations are needed to determine if NIBS could be a potential treatment to alleviate the effects of PSF.
Additional Links: PMID-39954574
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@article {pmid39954574,
year = {2025},
author = {Soltsov, M and Jang, DH and Kim, JH and Keenan, A and Pain, K and Jaywant, A and Stilling, J},
title = {Understanding neural mechanisms and the use of targeted non-invasive brain stimulation for treatment of post-stroke fatigue: A scoping review.},
journal = {Journal of the neurological sciences},
volume = {470},
number = {},
pages = {123399},
doi = {10.1016/j.jns.2025.123399},
pmid = {39954574},
issn = {1878-5883},
abstract = {BACKGROUND: Post-stroke fatigue (PSF) is one of the most prevalent symptoms that affects quality of life and daily function after stroke. Despite a growing body of research, its pathophysiology is poorly understood. Non-invasive brain stimulation (NIBS), such as the transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), can serve as a non-pharmacological intervention for PSF. In this review, we aim to (1) evaluate PSF neuroimaging studies to deduce potential neural mechanisms, (2) describe NIBS as a tool to probe brain structures to further understand pathophysiology of fatigue, and (3) assess NIBS as a treatment intervention for PSF.
METHODS: A systematic search was conducted for the databases PubMed, Embase, Scopus, CINAHL and Cochrane. Studies were included based on the following inclusion and exclusion criteria: >18 years with PSF, use of neuroimaging and/or NIBS for investigation or as an intervention for PSF, English language, study types including cohort, case control, or randomized controlled trials. Data extracted included participant characteristics, concept, context, study methods, and key findings relevant to the review questions.
RESULTS: A total of 30 studies met criteria. Neuroimaging papers that investigated brain structure (MRI) found conflicting associations between lesion location and PSF. Functional methods (fMRI, TMS) revealed altered resting state functional connectivity (rsFC), cortical excitability, and a disruption in interhemispheric inhibitory balance as potential mechanisms of PSF. There were no studies using TMS as an intervention for PSF. Of the six articles that used tDCS, only two reported statistically significant reductions in the severity of PSF.
CONCLUSION: Structural characteristics of stroke lesions had conflicting findings, while functional neuroimaging studies suggested that altered rsFC, cortical excitability and interhemispheric inhibitory balance contribute to the development of PSF. There were inconsistent results on the effectiveness of tDCS as an intervention for PSF, due to varying methodologies and lack of precise targeting of underlying neural mechanisms. Further investigations are needed to determine if NIBS could be a potential treatment to alleviate the effects of PSF.},
}
RevDate: 2025-02-14
Psychotherapy in patients with long/post-COVID - A systematic review on the feasibility, acceptability, safety, and efficacy of available and emerging interventions.
Journal of psychosomatic research, 190:112048 pii:S0022-3999(25)00012-1 [Epub ahead of print].
BACKGROUNDS: There is an urgent need for effective treatments for patients with long/post-COVID. Current recommendations for management favor a multimodal approach including psychotherapy and emphasize that interventions should also consider the mental health impact of living with long/post-COVID. This systematic review synthesizes psychotherapeutic interventions that currently target long/post-COVID complaints and summarizes data on the feasibility, acceptability, safety, and efficacy of psychotherapy for patients with long/post-COVID.
METHODS: This systematic review was conducted according to the PRISMA statement. Studies were retrieved from three databases (PubMed, PsycInfo, Web of Science) and independently assessed by two raters. Studies investigating patients of any age suffering from long/post-COVID were included if the intervention involved psychotherapeutic treatment and changes in long/post-COVID symptoms were reported. The review has been pre-registered on PROSPERO.
RESULTS: A total of 12 studies were included in the analysis. Of these, 10 were multimodal approaches with integrated psychotherapeutic interventions, and two were studies on stand-alone psychotherapy. The majority of studies were uncontrolled and demonstrate pre-post improvements in a range of long/post-COVID symptoms. Only one RCT could be identified, which supports the benefit of CBT for COVID-related fatigue. It was not possible to draw general conclusions regarding the efficacy of psychotherapy for long/post-COVID. However, data on feasibility, acceptability, and safety support the potential of psychotherapy as a treatment approach for long/post-COVID.
CONCLUSION: Future studies investigating the potential of psychotherapy approach for long/post-COVID which go beyond the pilot stage are needed to systematically assess feasibility, acceptability, safety, and efficacy in large-scale confirmatory trials.
Additional Links: PMID-39952011
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@article {pmid39952011,
year = {2025},
author = {Schurr, M and Graf, J and Junne, F and Giel, KE},
title = {Psychotherapy in patients with long/post-COVID - A systematic review on the feasibility, acceptability, safety, and efficacy of available and emerging interventions.},
journal = {Journal of psychosomatic research},
volume = {190},
number = {},
pages = {112048},
doi = {10.1016/j.jpsychores.2025.112048},
pmid = {39952011},
issn = {1879-1360},
abstract = {BACKGROUNDS: There is an urgent need for effective treatments for patients with long/post-COVID. Current recommendations for management favor a multimodal approach including psychotherapy and emphasize that interventions should also consider the mental health impact of living with long/post-COVID. This systematic review synthesizes psychotherapeutic interventions that currently target long/post-COVID complaints and summarizes data on the feasibility, acceptability, safety, and efficacy of psychotherapy for patients with long/post-COVID.
METHODS: This systematic review was conducted according to the PRISMA statement. Studies were retrieved from three databases (PubMed, PsycInfo, Web of Science) and independently assessed by two raters. Studies investigating patients of any age suffering from long/post-COVID were included if the intervention involved psychotherapeutic treatment and changes in long/post-COVID symptoms were reported. The review has been pre-registered on PROSPERO.
RESULTS: A total of 12 studies were included in the analysis. Of these, 10 were multimodal approaches with integrated psychotherapeutic interventions, and two were studies on stand-alone psychotherapy. The majority of studies were uncontrolled and demonstrate pre-post improvements in a range of long/post-COVID symptoms. Only one RCT could be identified, which supports the benefit of CBT for COVID-related fatigue. It was not possible to draw general conclusions regarding the efficacy of psychotherapy for long/post-COVID. However, data on feasibility, acceptability, and safety support the potential of psychotherapy as a treatment approach for long/post-COVID.
CONCLUSION: Future studies investigating the potential of psychotherapy approach for long/post-COVID which go beyond the pilot stage are needed to systematically assess feasibility, acceptability, safety, and efficacy in large-scale confirmatory trials.},
}
RevDate: 2025-02-13
Targeting the SARS-CoV-2 reservoir in long COVID.
The Lancet. Infectious diseases pii:S1473-3099(24)00769-2 [Epub ahead of print].
There are no approved treatments for post-COVID-19 condition (also known as long COVID), a debilitating disease state following SARS-CoV-2 infection that is estimated to affect tens of millions of people. A growing body of evidence shows that SARS-CoV-2 can persist for months or years following COVID-19 in a subset of individuals, with this reservoir potentially driving long-COVID symptoms or sequelae. There is, therefore, an urgent need for clinical trials targeting persistent SARS-CoV-2, and several trials of antivirals or monoclonal antibodies for long COVID are underway. However, because mechanisms of SARS-CoV-2 persistence are not yet fully understood, such studies require important considerations related to the mechanism of action of candidate therapeutics, participant selection, duration of treatment, standardisation of reservoir-associated biomarkers and measurables, optimal outcome assessments, and potential combination approaches. In addition, patient subgroups might respond to some interventions or combinations of interventions, making post-hoc analyses crucial. Here, we outline these and other key considerations, with the goal of informing the design, implementation, and interpretation of trials in this rapidly growing field. Our recommendations are informed by knowledge gained from trials targeting the HIV reservoir, hepatitis C, and other RNA viruses, as well as precision oncology, which share many of the same hurdles facing long-COVID trials.
Additional Links: PMID-39947217
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@article {pmid39947217,
year = {2025},
author = {Proal, AD and Aleman, S and Bomsel, M and Brodin, P and Buggert, M and Cherry, S and Chertow, DS and Davies, HE and Dupont, CL and Deeks, SG and Ely, EW and Fasano, A and Freire, M and Geng, LN and Griffin, DE and Henrich, TJ and Hewitt, SM and Iwasaki, A and Krumholz, HM and Locci, M and Marconi, VC and Mehandru, S and Muller-Trutwin, M and Painter, MM and Pretorius, E and Price, DA and Putrino, D and Qian, Y and Roan, NR and Salmon, D and Tan, GS and VanElzakker, MB and Wherry, EJ and Van Weyenbergh, J and Yonker, LM and Peluso, MJ},
title = {Targeting the SARS-CoV-2 reservoir in long COVID.},
journal = {The Lancet. Infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/S1473-3099(24)00769-2},
pmid = {39947217},
issn = {1474-4457},
abstract = {There are no approved treatments for post-COVID-19 condition (also known as long COVID), a debilitating disease state following SARS-CoV-2 infection that is estimated to affect tens of millions of people. A growing body of evidence shows that SARS-CoV-2 can persist for months or years following COVID-19 in a subset of individuals, with this reservoir potentially driving long-COVID symptoms or sequelae. There is, therefore, an urgent need for clinical trials targeting persistent SARS-CoV-2, and several trials of antivirals or monoclonal antibodies for long COVID are underway. However, because mechanisms of SARS-CoV-2 persistence are not yet fully understood, such studies require important considerations related to the mechanism of action of candidate therapeutics, participant selection, duration of treatment, standardisation of reservoir-associated biomarkers and measurables, optimal outcome assessments, and potential combination approaches. In addition, patient subgroups might respond to some interventions or combinations of interventions, making post-hoc analyses crucial. Here, we outline these and other key considerations, with the goal of informing the design, implementation, and interpretation of trials in this rapidly growing field. Our recommendations are informed by knowledge gained from trials targeting the HIV reservoir, hepatitis C, and other RNA viruses, as well as precision oncology, which share many of the same hurdles facing long-COVID trials.},
}
RevDate: 2025-02-13
Cardiovascular outcomes in long COVID-19: a systematic review and meta-analysis.
Frontiers in cardiovascular medicine, 12:1450470.
INTRODUCTION: There is growing evidence that patients with SARS-CoV-2 (The severe acute respiratory syndrome coronavirus 2) may have a variety of cardiovascular complications in the post-acute phase of COVID-19, but these manifestations have not yet been comprehensively characterized.
METHODS: We performed a systematic review and meta-analysis of primary research papers which evaluated individuals at least four weeks after confirmed COVID-19 diagnosis and reported on cardiovascular disease prevalence. Systematic search conducted without language restrictions from December 1, 2019 to June 31, 2022 on PubMed, EMBASE, Web of Science, Cochrane library, ProQuest Coronavirus Research Database, COVID-19 Living Overview of the Evidence (L-OVE) subset of Episteminokos and the World Health Organization (WHO) Covid-19 databases. Study was reported according to MOOSE-lists and the PRISMA guidelines. The risk of bias was identified using the Newcastle-Ottawa Scale (NOS) for observational studies. Random-effects meta-analyses examined the pooled risk difference in the prevalence of each symptom or symptom combination in cases with confirmed SARS-coV-2 infection compared with controls.
RESULTS: Eight cohort studies were eligible, including nearly 10 million people. Long COVID-19 was associated with a higher risk of thromboembolic disorders [HR 3.12 (1.60, 6.08)], coronary heart disease [HR 1.61 (1.13, 2.31)], stroke [HR 1.71 (1.07,2.72)], arrhythmia [HR 1.60 (1.13, 2.26)], cardiomyopathy [HR 1.71 (1.12, 2.61)], myocarditis [HR 6.11 (4.17,8.94)], hypertension [HR 1.70 (1.56, 1.85)], heart failure [HR 1.72 (1.15,2.59)] and cardiogenic shock [HR 2.09 (1.53,2.86)] compared to non-COVID-19 controls. Pooled risk differences in long COVID cases compared to controls were significantly higher for cardiomyopathy [0.15% (0.06, 0.23)], deep vein thrombosis [0.45% (0.06, 0.83)] and hypertension (0.32%, (0.06, 0.58) but not for thromboembolic disorders, coronary disease, stroke, arrhythmia, cardiomyopathy, myocarditis, hypertension, heart failure or cardiogenic shock.
CONCLUSION: The risk of cardiovascular disease increased significantly four weeks or more after recovering from acute COVID-19. Care for survivors after an acute attack of COVID-19 should include paying close attention to cardiovascular health and disease.
PROSPERO [CRD42022353965].
Additional Links: PMID-39944605
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@article {pmid39944605,
year = {2025},
author = {Zhang, T and Li, Z and Mei, Q and Walline, JH and Zhang, Z and Liu, Y and Zhu, H and Du, B},
title = {Cardiovascular outcomes in long COVID-19: a systematic review and meta-analysis.},
journal = {Frontiers in cardiovascular medicine},
volume = {12},
number = {},
pages = {1450470},
pmid = {39944605},
issn = {2297-055X},
abstract = {INTRODUCTION: There is growing evidence that patients with SARS-CoV-2 (The severe acute respiratory syndrome coronavirus 2) may have a variety of cardiovascular complications in the post-acute phase of COVID-19, but these manifestations have not yet been comprehensively characterized.
METHODS: We performed a systematic review and meta-analysis of primary research papers which evaluated individuals at least four weeks after confirmed COVID-19 diagnosis and reported on cardiovascular disease prevalence. Systematic search conducted without language restrictions from December 1, 2019 to June 31, 2022 on PubMed, EMBASE, Web of Science, Cochrane library, ProQuest Coronavirus Research Database, COVID-19 Living Overview of the Evidence (L-OVE) subset of Episteminokos and the World Health Organization (WHO) Covid-19 databases. Study was reported according to MOOSE-lists and the PRISMA guidelines. The risk of bias was identified using the Newcastle-Ottawa Scale (NOS) for observational studies. Random-effects meta-analyses examined the pooled risk difference in the prevalence of each symptom or symptom combination in cases with confirmed SARS-coV-2 infection compared with controls.
RESULTS: Eight cohort studies were eligible, including nearly 10 million people. Long COVID-19 was associated with a higher risk of thromboembolic disorders [HR 3.12 (1.60, 6.08)], coronary heart disease [HR 1.61 (1.13, 2.31)], stroke [HR 1.71 (1.07,2.72)], arrhythmia [HR 1.60 (1.13, 2.26)], cardiomyopathy [HR 1.71 (1.12, 2.61)], myocarditis [HR 6.11 (4.17,8.94)], hypertension [HR 1.70 (1.56, 1.85)], heart failure [HR 1.72 (1.15,2.59)] and cardiogenic shock [HR 2.09 (1.53,2.86)] compared to non-COVID-19 controls. Pooled risk differences in long COVID cases compared to controls were significantly higher for cardiomyopathy [0.15% (0.06, 0.23)], deep vein thrombosis [0.45% (0.06, 0.83)] and hypertension (0.32%, (0.06, 0.58) but not for thromboembolic disorders, coronary disease, stroke, arrhythmia, cardiomyopathy, myocarditis, hypertension, heart failure or cardiogenic shock.
CONCLUSION: The risk of cardiovascular disease increased significantly four weeks or more after recovering from acute COVID-19. Care for survivors after an acute attack of COVID-19 should include paying close attention to cardiovascular health and disease.
PROSPERO [CRD42022353965].},
}
RevDate: 2025-02-13
CmpDate: 2025-02-13
Cardiovascular Symposium on Perspectives in Long COVID.
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis, 31:10760296251319963.
Significant progress has been made in treating Coronavirus disease (COVID) - an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). An ominous turn in the pandemic is the evolving public health crisis emanating from persistent SARS-CoV-2 infection and its associated long-term impact. Long COVID or post-COVID syndrome describes protean symptoms that persist at least 3 months after the onset of acute illness and last for at least 2 months in individuals with a history of confirmed SARS-CoV-2 infection. Long COVID has become a public health concern. Millions of infected individuals are now facing chronic multi-organ failures, including neuropsychiatric, cardiovascular, pulmonary, and kidney complications. In general, the cause of long COVID syndrome is unclear but factors such as prolonged activation of immune responses, and viral persistence triggering transcription dysregulation of genes associated with normal thrombotic disease may play a role in cardiovascular complications. Although inflammatory biomarkers are reported in other disorders, it remains unclear whether similar biomarkers are associated with cardiovascular manifestations following COVID. Medications such as sulodexide directed at glycocalyx and coagulation have demonstrated benefits for long COVID in smaller studies. Here, we describe the outcomes of the symposium on the underlying cardiovascular mechanisms of the long COVID.
Additional Links: PMID-39943820
Publisher:
PubMed:
Citation:
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@article {pmid39943820,
year = {2025},
author = {Dieter, RS and Kempaiah, P and Dieter, EG and Alcazar, A and Tafur, A and Gerotziafas, G and Gonzalez Ochoa, A and Abdesselem, S and Biller, J and Kipshidze, N and Vandreden, P and Guerrini, M and Dieter, RA and Durvasula, R and Singh, M and Fareed, J},
title = {Cardiovascular Symposium on Perspectives in Long COVID.},
journal = {Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis},
volume = {31},
number = {},
pages = {10760296251319963},
doi = {10.1177/10760296251319963},
pmid = {39943820},
issn = {1938-2723},
mesh = {Humans ; *COVID-19/complications ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; *Cardiovascular Diseases/etiology ; Pandemics ; Congresses as Topic ; COVID-19 Drug Treatment ; },
abstract = {Significant progress has been made in treating Coronavirus disease (COVID) - an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). An ominous turn in the pandemic is the evolving public health crisis emanating from persistent SARS-CoV-2 infection and its associated long-term impact. Long COVID or post-COVID syndrome describes protean symptoms that persist at least 3 months after the onset of acute illness and last for at least 2 months in individuals with a history of confirmed SARS-CoV-2 infection. Long COVID has become a public health concern. Millions of infected individuals are now facing chronic multi-organ failures, including neuropsychiatric, cardiovascular, pulmonary, and kidney complications. In general, the cause of long COVID syndrome is unclear but factors such as prolonged activation of immune responses, and viral persistence triggering transcription dysregulation of genes associated with normal thrombotic disease may play a role in cardiovascular complications. Although inflammatory biomarkers are reported in other disorders, it remains unclear whether similar biomarkers are associated with cardiovascular manifestations following COVID. Medications such as sulodexide directed at glycocalyx and coagulation have demonstrated benefits for long COVID in smaller studies. Here, we describe the outcomes of the symposium on the underlying cardiovascular mechanisms of the long COVID.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*COVID-19/complications
*Post-Acute COVID-19 Syndrome
*SARS-CoV-2
*Cardiovascular Diseases/etiology
Pandemics
Congresses as Topic
COVID-19 Drug Treatment
RevDate: 2025-02-13
CmpDate: 2025-02-13
The Proteome Content of Blood Clots Observed Under Different Conditions: Successful Role in Predicting Clot Amyloid(ogenicity).
Molecules (Basel, Switzerland), 30(3): pii:molecules30030668.
A recent analysis compared the proteome of (i) blood clots seen in two diseases-sepsis and long COVID-when blood was known to have clotted into an amyloid microclot form (as judged by staining with the fluorogenic amyloid stain thioflavin T) with (ii) that of those non-amyloid clots considered to have formed normally. Such fibrinaloid microclots are also relatively resistant to fibrinolysis. The proteins that the amyloid microclots contained differed markedly both from the soluble proteome of typical plasma and that of normal clots, and also between the diseases studied (an acute syndrome in the form of sepsis in an ITU and a chronic disease represented by Long COVID). Many proteins in the amyloid microclots were low in concentration in plasma and were effectively accumulated into the fibres, whereas many other abundant plasma proteins were excluded. The proteins found in the microclots associated with the diseases also tended to be themselves amyloidogenic. We here ask effectively the inverse question. This is: can the clot proteome tell us whether the clots associated with a particular disease contained proteins that are observed uniquely (or are highly over-represented) in known amyloid clots relative to normal clots, and thus were in fact amyloid in nature? The answer is in the affirmative in a variety of major coagulopathies, viz., venous thromboembolism, pulmonary embolism, deep vein thrombosis, various cardiac issues, and ischaemic stroke. Galectin-3-binding protein and thrombospondin-1 seem to be especially widely associated with amyloid-type clots, and the latter has indeed been shown to be incorporated into growing fibrin fibres. These may consequently provide useful biomarkers with a mechanistic basis.
Additional Links: PMID-39942772
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PubMed:
Citation:
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@article {pmid39942772,
year = {2025},
author = {Kell, DB and Pretorius, E},
title = {The Proteome Content of Blood Clots Observed Under Different Conditions: Successful Role in Predicting Clot Amyloid(ogenicity).},
journal = {Molecules (Basel, Switzerland)},
volume = {30},
number = {3},
pages = {},
doi = {10.3390/molecules30030668},
pmid = {39942772},
issn = {1420-3049},
mesh = {Humans ; *Proteome/metabolism/analysis ; *Thrombosis/metabolism ; *Amyloid/metabolism ; *Blood Coagulation ; COVID-19/metabolism ; Sepsis/metabolism/blood ; SARS-CoV-2/metabolism ; },
abstract = {A recent analysis compared the proteome of (i) blood clots seen in two diseases-sepsis and long COVID-when blood was known to have clotted into an amyloid microclot form (as judged by staining with the fluorogenic amyloid stain thioflavin T) with (ii) that of those non-amyloid clots considered to have formed normally. Such fibrinaloid microclots are also relatively resistant to fibrinolysis. The proteins that the amyloid microclots contained differed markedly both from the soluble proteome of typical plasma and that of normal clots, and also between the diseases studied (an acute syndrome in the form of sepsis in an ITU and a chronic disease represented by Long COVID). Many proteins in the amyloid microclots were low in concentration in plasma and were effectively accumulated into the fibres, whereas many other abundant plasma proteins were excluded. The proteins found in the microclots associated with the diseases also tended to be themselves amyloidogenic. We here ask effectively the inverse question. This is: can the clot proteome tell us whether the clots associated with a particular disease contained proteins that are observed uniquely (or are highly over-represented) in known amyloid clots relative to normal clots, and thus were in fact amyloid in nature? The answer is in the affirmative in a variety of major coagulopathies, viz., venous thromboembolism, pulmonary embolism, deep vein thrombosis, various cardiac issues, and ischaemic stroke. Galectin-3-binding protein and thrombospondin-1 seem to be especially widely associated with amyloid-type clots, and the latter has indeed been shown to be incorporated into growing fibrin fibres. These may consequently provide useful biomarkers with a mechanistic basis.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Proteome/metabolism/analysis
*Thrombosis/metabolism
*Amyloid/metabolism
*Blood Coagulation
COVID-19/metabolism
Sepsis/metabolism/blood
SARS-CoV-2/metabolism
RevDate: 2025-02-13
Long COVID Research, 2020-2024: A PubMed-Based Bibliometric Analysis.
Healthcare (Basel, Switzerland), 13(3): pii:healthcare13030298.
Long COVID is a SARS-CoV-2 infection-associated chronic condition with great potential to impact health and socioeconomic outcomes. The research efforts to face the challenges related to long COVID have resulted in a substantial amount of publications, which warrants the need for bibliometric profiling. This is a large-scale PubMed-based bibliometric analysis of more than 390,000 COVID-19 publications. The overall aim was to update the profile of long COVID publications in comparison with the rest of the COVID-19 scientific literature through December 2024. The estimated proportion of long COVID publications was relatively low (2.3% of all COVID-19 publications), although the cumulative frequency (n = 8928) continues to pose a challenge for proper information management. Currently, "treatment" and "mechanism" appear to be the most predominant research topics in the long COVID literature. Interestingly, this evaluation revealed a distinctive profile of the long COVID literature, with a clear preponderance of "case report" and "mechanism" research topics when compared with other COVID-19 publications. This evaluation also identified and ranked the most prolific scientific journals in the production of long COVID-related publications. This study may improve the visibility of long COVID research and contribute to the management of the growing scientific knowledge on long COVID.
Additional Links: PMID-39942487
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PubMed:
Citation:
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@article {pmid39942487,
year = {2025},
author = {Honorato-Cia, C and Cacho-Asenjo, E and Martinez-Simon, A and Aquerreta, I and Núñez-Córdoba, JM},
title = {Long COVID Research, 2020-2024: A PubMed-Based Bibliometric Analysis.},
journal = {Healthcare (Basel, Switzerland)},
volume = {13},
number = {3},
pages = {},
doi = {10.3390/healthcare13030298},
pmid = {39942487},
issn = {2227-9032},
support = {0011-3638-2020-000001 and 49-2022//Gobierno de Navarra/ ; },
abstract = {Long COVID is a SARS-CoV-2 infection-associated chronic condition with great potential to impact health and socioeconomic outcomes. The research efforts to face the challenges related to long COVID have resulted in a substantial amount of publications, which warrants the need for bibliometric profiling. This is a large-scale PubMed-based bibliometric analysis of more than 390,000 COVID-19 publications. The overall aim was to update the profile of long COVID publications in comparison with the rest of the COVID-19 scientific literature through December 2024. The estimated proportion of long COVID publications was relatively low (2.3% of all COVID-19 publications), although the cumulative frequency (n = 8928) continues to pose a challenge for proper information management. Currently, "treatment" and "mechanism" appear to be the most predominant research topics in the long COVID literature. Interestingly, this evaluation revealed a distinctive profile of the long COVID literature, with a clear preponderance of "case report" and "mechanism" research topics when compared with other COVID-19 publications. This evaluation also identified and ranked the most prolific scientific journals in the production of long COVID-related publications. This study may improve the visibility of long COVID research and contribute to the management of the growing scientific knowledge on long COVID.},
}
RevDate: 2025-02-13
CmpDate: 2025-02-13
Dietary Supplementation for Fatigue Symptoms in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)-A Systematic Review.
Nutrients, 17(3): pii:nu17030475.
Background/Objectives: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex neuroimmunological disorder with limited treatment options. Despite the widespread use of Dietary Supplements (DSs) among ME/CFS patients to alleviate fatigue and associated symptoms, evidence remains inconclusive. This systematic review aims to provide an updated synthesis of the efficacy of DS interventions and explore possible mechanisms underlying their therapeutic effects. Methods: This systematic review was conducted according to PRISMA guidelines. Several databases (Ebsco Host, PubMed, Scopus, Google Scholar) were used for the systematic search, which was based on the broad search terms ME/CFS and DS with a focus on publications between 1994 and 2024. The primary outcome was fatigue, with additional considerations including psychological well-being, physical activity, and biochemical markers. Two independent researchers screened the studies for eligibility in a multi-stage process and assessed quality and bias using Cochrane's risk of bias tools (RoB-2, ROBINS-I). Results: Fourteen studies (N = 809) of heterogeneous designs were included, showing a high risk of bias, mostly due to missing data and selection bias. While some interventions (L-carnitine and guanidinoacetic acid, oxaloacetate, CoQ10-selenium combination, NADH and NADH-CoQ10 combination) showed significant reductions in fatigue, methodological limitations, like small sample sizes and missing data, prevent firm conclusions. Mixed results were reported for secondary outcomes like cognitive function and inflammatory markers. Six studies noted adverse effects, including nausea and insomnia. Conclusions: Though some DSs showed potential in reducing fatigue in ME/CFS, methodological limitations and inconsistent results hinder definitive conclusions. Future research should improve diagnostic criteria and include more diverse populations.
Additional Links: PMID-39940333
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PubMed:
Citation:
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@article {pmid39940333,
year = {2025},
author = {Dorczok, MC and Mittmann, G and Mossaheb, N and Schrank, B and Bartova, L and Neumann, M and Steiner-Hofbauer, V},
title = {Dietary Supplementation for Fatigue Symptoms in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)-A Systematic Review.},
journal = {Nutrients},
volume = {17},
number = {3},
pages = {},
doi = {10.3390/nu17030475},
pmid = {39940333},
issn = {2072-6643},
mesh = {Humans ; *Fatigue Syndrome, Chronic/diet therapy/therapy ; *Dietary Supplements ; Fatigue ; Female ; Selenium/administration & dosage ; Carnitine/administration & dosage ; Treatment Outcome ; Ubiquinone/analogs & derivatives/administration & dosage ; Adult ; Male ; },
abstract = {Background/Objectives: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex neuroimmunological disorder with limited treatment options. Despite the widespread use of Dietary Supplements (DSs) among ME/CFS patients to alleviate fatigue and associated symptoms, evidence remains inconclusive. This systematic review aims to provide an updated synthesis of the efficacy of DS interventions and explore possible mechanisms underlying their therapeutic effects. Methods: This systematic review was conducted according to PRISMA guidelines. Several databases (Ebsco Host, PubMed, Scopus, Google Scholar) were used for the systematic search, which was based on the broad search terms ME/CFS and DS with a focus on publications between 1994 and 2024. The primary outcome was fatigue, with additional considerations including psychological well-being, physical activity, and biochemical markers. Two independent researchers screened the studies for eligibility in a multi-stage process and assessed quality and bias using Cochrane's risk of bias tools (RoB-2, ROBINS-I). Results: Fourteen studies (N = 809) of heterogeneous designs were included, showing a high risk of bias, mostly due to missing data and selection bias. While some interventions (L-carnitine and guanidinoacetic acid, oxaloacetate, CoQ10-selenium combination, NADH and NADH-CoQ10 combination) showed significant reductions in fatigue, methodological limitations, like small sample sizes and missing data, prevent firm conclusions. Mixed results were reported for secondary outcomes like cognitive function and inflammatory markers. Six studies noted adverse effects, including nausea and insomnia. Conclusions: Though some DSs showed potential in reducing fatigue in ME/CFS, methodological limitations and inconsistent results hinder definitive conclusions. Future research should improve diagnostic criteria and include more diverse populations.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Fatigue Syndrome, Chronic/diet therapy/therapy
*Dietary Supplements
Fatigue
Female
Selenium/administration & dosage
Carnitine/administration & dosage
Treatment Outcome
Ubiquinone/analogs & derivatives/administration & dosage
Adult
Male
RevDate: 2025-02-11
CmpDate: 2025-02-12
Assessment of psychosocial aspects in adults in post-COVID-19 condition: the EURONET-SOMA recommendations on core outcome domains for clinical and research use.
BMC medicine, 23(1):81.
BACKGROUND: Harmonizing core outcome domains allows for pooling data, comparing interventions, and streamlining research evaluation. At the same time clinicians require concise and feasible measures for routine practice. Considering the heterogeneity of post-COVID-19 condition, a biopsychosocial approach requires sufficient coverage of the psychosocial dimension with assessments. Previous recommendations for core outcome sets have serious limitations regarding the psychosocial aspects of post-COVID-19 condition. This paper specifically focuses on psychosocial outcomes for adults with post-COVID-19 condition, providing both a comprehensive set of outcome domains for research and a streamlined clinical core set tailored for routine clinical use.
METHODS: In a structured Consensus Development Approach, the European Network to improve diagnostic, treatment, and healthcare for patients with persistent somatic symptoms (EURONET-SOMA) developed psychosocial core outcome domains and assessments regarding post-COVID-19 condition. The experts identified variables and instruments which should be considered in studies on adults suffering from post-COVID-19 condition, and which are feasible in the clinical setting and relevant for research.
RESULTS: We identified three higher-order dimensions with each encompassing several domains: The first higher-order dimension, "outcomes", encompasses (1) the classification/ diagnostics of post-COVID-19 condition, (2) somatic symptoms (including fatigue), (3) the psychopathological status and mental comorbidities, (4) the physical status and somatic comorbidities, (5) neurocognitive symptoms, and (6) illness consequences. The second higher-order domain "mechanisms" encompasses (7) cognitive components, (8) affective components, (9) behavioral components, (10) social components, and (11) psychobiological bridge markers (e.g., neuroimmunological and psychoneuroendocrinological variables). The third higher-order domain, "risk factors", includes factors such as (12) socioeconomic status and sociocultural factors, (13) pre-existing mental and somatic health issues, (14) personality factors (e.g., neuroticism), (15) adverse childhood experiences, (16) ongoing disability or pension claim, and (17) social media use. For each domain, specific instruments are suggested for research purposes and clinical use.
CONCLUSIONS: The recommended core domains help to increase consistency in a biopsychosocial approach to post-COVID-19 condition across investigations, improve synergies, and facilitate decision-making when comparing different interventional approaches. It allows to better identify relevant subgroups in heterogeneous post-COVID-19 condition populations offering practical tools for routine clinical practice through the clinical core set.
Additional Links: PMID-39934846
PubMed:
Citation:
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@article {pmid39934846,
year = {2025},
author = {Salzmann, S and de Vroege, L and Engelmann, P and Fink, P and Fischer, S and Frisch, S and Gormsen, LK and Hüfner, K and Kop, WJ and Köteles, F and Lehnen, N and Löwe, B and Pieh, C and Pitron, V and Rask, CU and Sainio, M and Schaefert, R and Shedden-Mora, M and Toussaint, A and von Känel, R and Werneke, U and Rief, W and , },
title = {Assessment of psychosocial aspects in adults in post-COVID-19 condition: the EURONET-SOMA recommendations on core outcome domains for clinical and research use.},
journal = {BMC medicine},
volume = {23},
number = {1},
pages = {81},
pmid = {39934846},
issn = {1741-7015},
mesh = {Humans ; *COVID-19/psychology ; Adult ; SARS-CoV-2 ; Outcome Assessment, Health Care ; Europe ; Post-Acute COVID-19 Syndrome ; Consensus ; },
abstract = {BACKGROUND: Harmonizing core outcome domains allows for pooling data, comparing interventions, and streamlining research evaluation. At the same time clinicians require concise and feasible measures for routine practice. Considering the heterogeneity of post-COVID-19 condition, a biopsychosocial approach requires sufficient coverage of the psychosocial dimension with assessments. Previous recommendations for core outcome sets have serious limitations regarding the psychosocial aspects of post-COVID-19 condition. This paper specifically focuses on psychosocial outcomes for adults with post-COVID-19 condition, providing both a comprehensive set of outcome domains for research and a streamlined clinical core set tailored for routine clinical use.
METHODS: In a structured Consensus Development Approach, the European Network to improve diagnostic, treatment, and healthcare for patients with persistent somatic symptoms (EURONET-SOMA) developed psychosocial core outcome domains and assessments regarding post-COVID-19 condition. The experts identified variables and instruments which should be considered in studies on adults suffering from post-COVID-19 condition, and which are feasible in the clinical setting and relevant for research.
RESULTS: We identified three higher-order dimensions with each encompassing several domains: The first higher-order dimension, "outcomes", encompasses (1) the classification/ diagnostics of post-COVID-19 condition, (2) somatic symptoms (including fatigue), (3) the psychopathological status and mental comorbidities, (4) the physical status and somatic comorbidities, (5) neurocognitive symptoms, and (6) illness consequences. The second higher-order domain "mechanisms" encompasses (7) cognitive components, (8) affective components, (9) behavioral components, (10) social components, and (11) psychobiological bridge markers (e.g., neuroimmunological and psychoneuroendocrinological variables). The third higher-order domain, "risk factors", includes factors such as (12) socioeconomic status and sociocultural factors, (13) pre-existing mental and somatic health issues, (14) personality factors (e.g., neuroticism), (15) adverse childhood experiences, (16) ongoing disability or pension claim, and (17) social media use. For each domain, specific instruments are suggested for research purposes and clinical use.
CONCLUSIONS: The recommended core domains help to increase consistency in a biopsychosocial approach to post-COVID-19 condition across investigations, improve synergies, and facilitate decision-making when comparing different interventional approaches. It allows to better identify relevant subgroups in heterogeneous post-COVID-19 condition populations offering practical tools for routine clinical practice through the clinical core set.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*COVID-19/psychology
Adult
SARS-CoV-2
Outcome Assessment, Health Care
Europe
Post-Acute COVID-19 Syndrome
Consensus
RevDate: 2025-02-11
CmpDate: 2025-02-10
The prolonged health sequelae "of the COVID-19 pandemic" in sub-Saharan Africa: a systematic review and meta-analysis.
Frontiers in public health, 13:1415427.
BACKGROUND: Survivors of coronavirus disease 2019 (COVID-19) often face persistent and significant challenges that affect their physical, mental, and financial wellbeing, which can significantly diminish their overall quality of life. The emergence of new symptoms or the persistence of existing ones after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis has given rise to a complex clinical issue known as "long COVID-19" (LC). This situation has placed additional strain on global healthcare systems, underscoring the urgent need for ongoing clinical management of these patients. While numerous studies have been conducted on the long-term effects of COVID-19, our systematic review, and meta-analysis, is the first of its kind in sub-Saharan Africa, providing a comprehensive understanding of the situation in the region and highlighting the necessity for continuous clinical management.
OBJECTIVE: This study aimed to systematically synthesize evidence on the persistent sequelae of COVID-19 and their predictors in sub-Saharan Africa.
METHODS: A thorough search was conducted across multiple databases, including PubMed/MEDLINE, Web of Science, Google/Google Scholar, African online journals, and selected reference lists, from the inception of these databases until January 12, 2024. A meta-analysis of proportions was conducted using the random-effects restricted maximum-likelihood model. The association between various factors was also analyzed to determine the pooled factors that influence long COVID-19 outcomes.
RESULTS: Our comprehensive analysis of 16 research articles, involving a total of 18,104 participants revealed a pooled prevalence of COVID-19 sequelae at 42.1% (95% CI: 29.9-55.4). The long-term health sequelae identified in this review included persistent pulmonary sequelae (27.5%), sleep disturbance (22.5%), brain fog (27.4%), fatigue (17.4%), anxiety (22.3%), and chest pain (13.2%). We also found a significant association was observed between comorbidities and long COVID-19 sequelae [POR = 4.34 (95% CI: 1.28-14.72)], providing a comprehensive understanding of the factors influencing long COVID-19 outcomes.
CONCLUSION: COVID-19 can have long-lasting effects on various organ systems, even after a person has recovered from the infection. These effects can include brain fog, pulmonary symptoms, sleep disturbances, anxiety, fatigue, and other neurological, psychiatric, respiratory, cardiovascular, and general symptoms. It is crucial for individuals who have recovered from COVID-19 to receive careful follow-up care to assess and reduce any potential organ damage and maintain their quality of life.
Clinicaltrial.gov, identifier CRD42024501158.
Additional Links: PMID-39925756
PubMed:
Citation:
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@article {pmid39925756,
year = {2025},
author = {Alie, MS and Tesema, GA and Abebe, GF and Girma, D},
title = {The prolonged health sequelae "of the COVID-19 pandemic" in sub-Saharan Africa: a systematic review and meta-analysis.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1415427},
pmid = {39925756},
issn = {2296-2565},
mesh = {Humans ; *COVID-19/epidemiology ; Africa South of the Sahara/epidemiology ; *Quality of Life ; SARS-CoV-2 ; Survivors/statistics & numerical data ; Pandemics ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: Survivors of coronavirus disease 2019 (COVID-19) often face persistent and significant challenges that affect their physical, mental, and financial wellbeing, which can significantly diminish their overall quality of life. The emergence of new symptoms or the persistence of existing ones after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis has given rise to a complex clinical issue known as "long COVID-19" (LC). This situation has placed additional strain on global healthcare systems, underscoring the urgent need for ongoing clinical management of these patients. While numerous studies have been conducted on the long-term effects of COVID-19, our systematic review, and meta-analysis, is the first of its kind in sub-Saharan Africa, providing a comprehensive understanding of the situation in the region and highlighting the necessity for continuous clinical management.
OBJECTIVE: This study aimed to systematically synthesize evidence on the persistent sequelae of COVID-19 and their predictors in sub-Saharan Africa.
METHODS: A thorough search was conducted across multiple databases, including PubMed/MEDLINE, Web of Science, Google/Google Scholar, African online journals, and selected reference lists, from the inception of these databases until January 12, 2024. A meta-analysis of proportions was conducted using the random-effects restricted maximum-likelihood model. The association between various factors was also analyzed to determine the pooled factors that influence long COVID-19 outcomes.
RESULTS: Our comprehensive analysis of 16 research articles, involving a total of 18,104 participants revealed a pooled prevalence of COVID-19 sequelae at 42.1% (95% CI: 29.9-55.4). The long-term health sequelae identified in this review included persistent pulmonary sequelae (27.5%), sleep disturbance (22.5%), brain fog (27.4%), fatigue (17.4%), anxiety (22.3%), and chest pain (13.2%). We also found a significant association was observed between comorbidities and long COVID-19 sequelae [POR = 4.34 (95% CI: 1.28-14.72)], providing a comprehensive understanding of the factors influencing long COVID-19 outcomes.
CONCLUSION: COVID-19 can have long-lasting effects on various organ systems, even after a person has recovered from the infection. These effects can include brain fog, pulmonary symptoms, sleep disturbances, anxiety, fatigue, and other neurological, psychiatric, respiratory, cardiovascular, and general symptoms. It is crucial for individuals who have recovered from COVID-19 to receive careful follow-up care to assess and reduce any potential organ damage and maintain their quality of life.
Clinicaltrial.gov, identifier CRD42024501158.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*COVID-19/epidemiology
Africa South of the Sahara/epidemiology
*Quality of Life
SARS-CoV-2
Survivors/statistics & numerical data
Pandemics
Post-Acute COVID-19 Syndrome
RevDate: 2025-02-08
Prevalence and Impact of Post-Exertional Malaise on Recovery in Adults with Post COVID-19 Condition. A Systematic Review with Meta-Analysis.
Archives of physical medicine and rehabilitation pii:S0003-9993(25)00501-5 [Epub ahead of print].
OBJECTIVE: To assess the prevalence of PEM in people with PCC; and the change in prevalence of PEM following rehabilitation interventions in people with PCC.
DATA SOURCES: We searched MEDLINE, Embase, Central, CINAHL, PsychINFO and Clinical Trial Registries from inception until January 12[th], 2024.
STUDY SELECTION: We included observational studies that measured the prevalence of PEM in adults with PCC and interventional studies that measured the change in prevalence of PEM following rehabilitation interventions in adults with PCC. Two independent researchers screened titles and abstracts. Any discrepancies underwent full text review. Two independent researchers screened the articles included at the full text level. Any discrepancies were resolved by consensus.
DATA EXTRACTION: Two independent researchers extracted data from eligible studies. We extracted point-prevalence from the cross-sectional studies; and period-prevalence from the longitudinal studies. Two independent reviewers assessed the risk of bias (ROB). Discrepancies were resolved with a senior research team member. For the prevalence studies we used the Cochrane Risk Of Bias In Non-randomized Studies - of Exposure (ROBINS-E) tool. For randomised controlled trials we used the Cochrane Risk of Bias tool II - (RoB2). For non-randomised interventional studies we used the Cochrane Risk Of Bias In Non-Randomized Studies - of Interventions (ROBINS-I)[1] to assess the non-randomised studies. We applied the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach to grade the quality of the evidence DATA SYNTHESIS: We performed a single-arm proportional meta-analysis to synthesize prevalence estimates using logit transformation. We conducted a sensitivity analysis using multilevel-mixed-effects logistic regression. This study is registered with PROSPERO (CRD42024516682).The prevalence of PEM in community-dwelling adults living with PCC was 36% (95% CI: 0.19 to 0.57; 2,263 participants). Two of the included studies (61 patients) found a decrease in the frequency and intensity of PEM episodes in adults with PCC following a tailored rehabilitation program centered on integrating pacing approaches. None of the included studies reported an increase of PEM symptoms' frequency and intensity following an individually tailored rehabilitation program with a therapeutic exercise component (5 studies; 892 patients).
CONCLUSIONS: Our research confirms that there is a large burden of PEM in adults living with PCC, highlighting a critical challenge for healthcare systems and an urgent need for more inclusive and rigorous research, to offer safe and effective therapeutic solutions and meet the variable needs of people with PCC that experience PEM.There is a subgroup of patients with PCC that do not experience PEM; and there is limited evidence that supervised, individually tailored, symptom-titrated rehabilitation interventions with active exercise components may not trigger PEM in this subgroup of people with PCC. Our results are limited by the insufficient reporting of the percentage of PEM in the baseline before enrolling patients in the rehabilitation programs, and the large number of studies using non-validated, unstandardized tools to measure PEM in people with PCC, hence there is an urgent need to strengthen the methods of future trials.
Additional Links: PMID-39921187
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PubMed:
Citation:
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@article {pmid39921187,
year = {2025},
author = {Pouliopoulou, DV and Hawthorne, M and MacDermid, JC and Billias, N and Miller, E and Quinn, K and Décary, S and Razak, FA and Cheung, A and Galiatsatos, P and Pereira, TV and Bobos, P},
title = {Prevalence and Impact of Post-Exertional Malaise on Recovery in Adults with Post COVID-19 Condition. A Systematic Review with Meta-Analysis.},
journal = {Archives of physical medicine and rehabilitation},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.apmr.2025.01.471},
pmid = {39921187},
issn = {1532-821X},
abstract = {OBJECTIVE: To assess the prevalence of PEM in people with PCC; and the change in prevalence of PEM following rehabilitation interventions in people with PCC.
DATA SOURCES: We searched MEDLINE, Embase, Central, CINAHL, PsychINFO and Clinical Trial Registries from inception until January 12[th], 2024.
STUDY SELECTION: We included observational studies that measured the prevalence of PEM in adults with PCC and interventional studies that measured the change in prevalence of PEM following rehabilitation interventions in adults with PCC. Two independent researchers screened titles and abstracts. Any discrepancies underwent full text review. Two independent researchers screened the articles included at the full text level. Any discrepancies were resolved by consensus.
DATA EXTRACTION: Two independent researchers extracted data from eligible studies. We extracted point-prevalence from the cross-sectional studies; and period-prevalence from the longitudinal studies. Two independent reviewers assessed the risk of bias (ROB). Discrepancies were resolved with a senior research team member. For the prevalence studies we used the Cochrane Risk Of Bias In Non-randomized Studies - of Exposure (ROBINS-E) tool. For randomised controlled trials we used the Cochrane Risk of Bias tool II - (RoB2). For non-randomised interventional studies we used the Cochrane Risk Of Bias In Non-Randomized Studies - of Interventions (ROBINS-I)[1] to assess the non-randomised studies. We applied the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach to grade the quality of the evidence DATA SYNTHESIS: We performed a single-arm proportional meta-analysis to synthesize prevalence estimates using logit transformation. We conducted a sensitivity analysis using multilevel-mixed-effects logistic regression. This study is registered with PROSPERO (CRD42024516682).The prevalence of PEM in community-dwelling adults living with PCC was 36% (95% CI: 0.19 to 0.57; 2,263 participants). Two of the included studies (61 patients) found a decrease in the frequency and intensity of PEM episodes in adults with PCC following a tailored rehabilitation program centered on integrating pacing approaches. None of the included studies reported an increase of PEM symptoms' frequency and intensity following an individually tailored rehabilitation program with a therapeutic exercise component (5 studies; 892 patients).
CONCLUSIONS: Our research confirms that there is a large burden of PEM in adults living with PCC, highlighting a critical challenge for healthcare systems and an urgent need for more inclusive and rigorous research, to offer safe and effective therapeutic solutions and meet the variable needs of people with PCC that experience PEM.There is a subgroup of patients with PCC that do not experience PEM; and there is limited evidence that supervised, individually tailored, symptom-titrated rehabilitation interventions with active exercise components may not trigger PEM in this subgroup of people with PCC. Our results are limited by the insufficient reporting of the percentage of PEM in the baseline before enrolling patients in the rehabilitation programs, and the large number of studies using non-validated, unstandardized tools to measure PEM in people with PCC, hence there is an urgent need to strengthen the methods of future trials.},
}
RevDate: 2025-02-08
CmpDate: 2025-02-07
Advancements in the development of antivirals against SARS-Coronavirus.
Frontiers in cellular and infection microbiology, 15:1520811.
Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) caused an outbreak in 2002-2003, spreading to 29 countries with a mortality rate of about 10%. Strict quarantine and infection control methods quickly stopped the spread of the disease. Later research showed that SARS-CoV came from animals (zoonosis) and stressed the possibility of a similar spread from host to human, which was clearly shown by the COVID-19 outbreak. The COVID-19 pandemic, instigated by SARS-CoV-2, has affected 776 million confirmed cases and more than seven million deaths globally as of Sept 15, 2024. The existence of animal reservoirs of coronaviruses continues to pose a risk of re-emergence with improved fitness and virulence. Given the high death rate (up to 70 percent) and the high rate of severe sickness (up to 68.7 percent in long-COVID patients), it is even more critical to identify new therapies as soon as possible. This study combines research on antivirals that target SARS coronaviruses that have been conducted over the course of more than twenty years. It is a beneficial resource that might be useful in directing future studies.
Additional Links: PMID-39917633
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@article {pmid39917633,
year = {2025},
author = {Kumar, M and Baig, MS and Bhardwaj, K},
title = {Advancements in the development of antivirals against SARS-Coronavirus.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1520811},
pmid = {39917633},
issn = {2235-2988},
mesh = {*Antiviral Agents/pharmacology/therapeutic use ; Humans ; *SARS-CoV-2/drug effects ; Animals ; *COVID-19 Drug Treatment ; COVID-19/epidemiology ; Severe acute respiratory syndrome-related coronavirus/drug effects/pathogenicity ; Severe Acute Respiratory Syndrome/drug therapy/virology/epidemiology ; Drug Development ; },
abstract = {Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) caused an outbreak in 2002-2003, spreading to 29 countries with a mortality rate of about 10%. Strict quarantine and infection control methods quickly stopped the spread of the disease. Later research showed that SARS-CoV came from animals (zoonosis) and stressed the possibility of a similar spread from host to human, which was clearly shown by the COVID-19 outbreak. The COVID-19 pandemic, instigated by SARS-CoV-2, has affected 776 million confirmed cases and more than seven million deaths globally as of Sept 15, 2024. The existence of animal reservoirs of coronaviruses continues to pose a risk of re-emergence with improved fitness and virulence. Given the high death rate (up to 70 percent) and the high rate of severe sickness (up to 68.7 percent in long-COVID patients), it is even more critical to identify new therapies as soon as possible. This study combines research on antivirals that target SARS coronaviruses that have been conducted over the course of more than twenty years. It is a beneficial resource that might be useful in directing future studies.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Antiviral Agents/pharmacology/therapeutic use
Humans
*SARS-CoV-2/drug effects
Animals
*COVID-19 Drug Treatment
COVID-19/epidemiology
Severe acute respiratory syndrome-related coronavirus/drug effects/pathogenicity
Severe Acute Respiratory Syndrome/drug therapy/virology/epidemiology
Drug Development
RevDate: 2025-02-08
CmpDate: 2025-02-06
[Cognition and Long COVID: A PRISMA Systematic Review of Longitudinal Studies].
Revista de neurologia, 79(12):37385.
INTRODUCTION: Long COVID is defined by National Institute for Health and Care Excellence (NICE) as the set of signs and symptoms that develop during or after a SARS-CoV-2 infection and continue for more than twelve weeks without any alternative diagnosis. One of the most frequent persistent symptoms reported by patients and verified in neuroimaging studies is cognitive dysfunction, due to a generalized hypoconnectivity and a diffuse axonal lesion in white matter. Therefore, the objectives of the present review are to determine how long cognitive functions remain affected during Long COVID and to explore which cognitive functions are most affected beyond three months of follow-up in patients up to 65 years of age without previous neuropsychological or psychiatric complications.
METHODS: A systematic review was performed using PRISMA criteria and 11 articles were included through a comprehensive search of five different databases: PubMed, Medline, Scopus, WOS and ProQuest. The risk of bias of the articles was assessed using the Newcastle-Ottawa scale.
RESULTS: Cognitive problems in Long COVID persist over time and improve slowly, although studies seem to agree that most areas improved significantly after one year. The cognitive functions that remained impaired the longest were processing speed and attention.
CONCLUSIONS: These cognitive alterations cause a reduction in the quality of life of the patients and a reduction in work capacity and manifest the need for a cognitive intervention.
Additional Links: PMID-39910970
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@article {pmid39910970,
year = {2025},
author = {Tudorache Pantazi, MA and Gadea-Doménech, M and Espert Tortajada, R},
title = {[Cognition and Long COVID: A PRISMA Systematic Review of Longitudinal Studies].},
journal = {Revista de neurologia},
volume = {79},
number = {12},
pages = {37385},
pmid = {39910970},
issn = {1576-6578},
mesh = {Humans ; *COVID-19/complications ; *Post-Acute COVID-19 Syndrome ; Longitudinal Studies ; Cognition ; Cognitive Dysfunction/etiology ; Time Factors ; },
abstract = {INTRODUCTION: Long COVID is defined by National Institute for Health and Care Excellence (NICE) as the set of signs and symptoms that develop during or after a SARS-CoV-2 infection and continue for more than twelve weeks without any alternative diagnosis. One of the most frequent persistent symptoms reported by patients and verified in neuroimaging studies is cognitive dysfunction, due to a generalized hypoconnectivity and a diffuse axonal lesion in white matter. Therefore, the objectives of the present review are to determine how long cognitive functions remain affected during Long COVID and to explore which cognitive functions are most affected beyond three months of follow-up in patients up to 65 years of age without previous neuropsychological or psychiatric complications.
METHODS: A systematic review was performed using PRISMA criteria and 11 articles were included through a comprehensive search of five different databases: PubMed, Medline, Scopus, WOS and ProQuest. The risk of bias of the articles was assessed using the Newcastle-Ottawa scale.
RESULTS: Cognitive problems in Long COVID persist over time and improve slowly, although studies seem to agree that most areas improved significantly after one year. The cognitive functions that remained impaired the longest were processing speed and attention.
CONCLUSIONS: These cognitive alterations cause a reduction in the quality of life of the patients and a reduction in work capacity and manifest the need for a cognitive intervention.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*COVID-19/complications
*Post-Acute COVID-19 Syndrome
Longitudinal Studies
Cognition
Cognitive Dysfunction/etiology
Time Factors
RevDate: 2025-02-06
Serotonergic psychedelics as potential therapeutics for post-COVID-19 syndrome (or Long COVID): A comprehensive review.
Progress in neuro-psychopharmacology & biological psychiatry pii:S0278-5846(25)00033-8 [Epub ahead of print].
RATIONALE: In our ongoing battle against the coronavirus 2019 (COVID-19) pandemic, a major challenge is the enduring symptoms that continue after acute infection. Also known as Long COVID, post-COVID-19 syndrome (PCS) often comes with debilitating symptoms like fatigue, disordered sleep, olfactory dysfunction, and cognitive issues ("brain fog"). Currently, there are no approved treatments for PCS. Recent research has uncovered that the severity of PCS is inversely linked to circulating serotonin levels, highlighting the potential of serotonin-modulating therapeutics for PCS. Therefore, we propose that serotonergic psychedelics, acting mainly via the 5-HT2A serotonin receptor, hold promise for treating PCS.
OBJECTIVES: Our review aims to elucidate potential mechanisms by which serotonergic psychedelics may alleviate the symptoms of PCS.
RESULTS: Potential mechanisms through which serotonergic psychedelics may alleviate PCS symptoms are discussed, with emphasis on their effects on inflammation, neuroplasticity, and gastrointestinal function. Additionally, this review explores the potential of serotonergic psychedelics in mitigating endothelial dysfunction, a pivotal aspect of PCS pathophysiology implicated in organ dysfunction. This review also examines the potential role of serotonergic psychedelics in alleviating specific PCS symptoms, which include olfactory dysfunction, cognitive impairment, sleep disturbances, and mental health challenges.
CONCLUSIONS: Emerging evidence suggests that serotonergic psychedelics may alleviate PCS symptoms. However, further high-quality research is needed to thoroughly assess their safety and efficacy in treating patients with PCS.
Additional Links: PMID-39909170
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PubMed:
Citation:
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@article {pmid39909170,
year = {2025},
author = {Low, ZXB and Yong, SJ and Alrasheed, HA and Al-Subaie, MF and Al Kaabi, NA and Alfaresi, M and Albayat, H and Alotaibi, J and Al Bshabshe, A and Alwashmi, ASS and Sabour, AA and Alshiekheid, MA and Almansour, ZH and Alharthi, H and Al Ali, HA and Almoumen, AA and Alqasimi, NA and AlSaihati, H and Rodriguez-Morales, AJ and Rabaan, AA},
title = {Serotonergic psychedelics as potential therapeutics for post-COVID-19 syndrome (or Long COVID): A comprehensive review.},
journal = {Progress in neuro-psychopharmacology & biological psychiatry},
volume = {},
number = {},
pages = {111279},
doi = {10.1016/j.pnpbp.2025.111279},
pmid = {39909170},
issn = {1878-4216},
abstract = {RATIONALE: In our ongoing battle against the coronavirus 2019 (COVID-19) pandemic, a major challenge is the enduring symptoms that continue after acute infection. Also known as Long COVID, post-COVID-19 syndrome (PCS) often comes with debilitating symptoms like fatigue, disordered sleep, olfactory dysfunction, and cognitive issues ("brain fog"). Currently, there are no approved treatments for PCS. Recent research has uncovered that the severity of PCS is inversely linked to circulating serotonin levels, highlighting the potential of serotonin-modulating therapeutics for PCS. Therefore, we propose that serotonergic psychedelics, acting mainly via the 5-HT2A serotonin receptor, hold promise for treating PCS.
OBJECTIVES: Our review aims to elucidate potential mechanisms by which serotonergic psychedelics may alleviate the symptoms of PCS.
RESULTS: Potential mechanisms through which serotonergic psychedelics may alleviate PCS symptoms are discussed, with emphasis on their effects on inflammation, neuroplasticity, and gastrointestinal function. Additionally, this review explores the potential of serotonergic psychedelics in mitigating endothelial dysfunction, a pivotal aspect of PCS pathophysiology implicated in organ dysfunction. This review also examines the potential role of serotonergic psychedelics in alleviating specific PCS symptoms, which include olfactory dysfunction, cognitive impairment, sleep disturbances, and mental health challenges.
CONCLUSIONS: Emerging evidence suggests that serotonergic psychedelics may alleviate PCS symptoms. However, further high-quality research is needed to thoroughly assess their safety and efficacy in treating patients with PCS.},
}
RevDate: 2025-02-07
CmpDate: 2025-02-05
Autoantibodies as potential prognostic factors for clinical outcomes related to COVID-19: a systematic review of inception prospective cohort studies with GRADE recommendations.
Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas, 58:e13965.
This systematic review of inception prospective cohort studies aimed to investigate whether autoantibodies are potential prognostic factors for short- and long-term clinical outcomes of COVID-19. Searches were conducted in MEDLINE, EMBASE, AMED, GLOBAL HEALTH, and COCHRANE databases from 2019 to 2022. When possible, meta-analysis was conducted, otherwise findings from individual studies were reported using odds ratios (OR) with 95% confidence intervals (CI). Quality of evidence was summarized using the GRADE criteria. We identified 2292 references, 18 inception prospective cohort studies (3178 patients) were included in the systematic review, and 12 studies reached criteria for meta-analysis. Studies achieved, in general, low to moderate risk of bias. Moderate quality of evidence showed that anti-interferon (IFN) was associated with increased risk of severity (OR=7.75; CI=1.79-33.61) and mechanical ventilation (OR=4.19; CI=2.06-8.53), but not with COVID-19 mortality (OR=1.68; CI=0.63-4.44). Antiphospholipids were not associated with COVID-19 mortality (OR=1.42; CI=0.85-2.37; P=0.18; I2=3.21) nor with thrombosis risk (OR=1.41; CI: 0.71-2.8; P=0.33). Antinuclear antibody level was not associated with risk of mortality or severity (risk for mortality: OR=3.8; CI=0.78-18.6; P=0.1; I2: 32.3; severity: OR=1.74; CI=0.96-3.16; P=0.07). Evidence currently available is insufficient for a quantitative analysis of autoantibodies association with long COVID-19. Anti-IFN measurement should be considered in COVID-19 follow-up. In a population-based rational, optimized vaccination strategies should be considered for individuals with anti-IFN antibodies since it could represent a risk for a worse prognosis. High-quality prospective studies for short- and long-term disease effects and autoantibody evaluation are still needed.
Additional Links: PMID-39907423
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Citation:
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@article {pmid39907423,
year = {2025},
author = {Araújo, FC and Amaral, ACD and Silva, HJ and Santos, JNV and Mendonça, VA and Oliveira, VC and Rocha-Vieira, E},
title = {Autoantibodies as potential prognostic factors for clinical outcomes related to COVID-19: a systematic review of inception prospective cohort studies with GRADE recommendations.},
journal = {Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas},
volume = {58},
number = {},
pages = {e13965},
pmid = {39907423},
issn = {1414-431X},
mesh = {Humans ; *COVID-19/immunology/mortality ; *Autoantibodies/blood ; Prognosis ; *SARS-CoV-2/immunology ; Prospective Studies ; },
abstract = {This systematic review of inception prospective cohort studies aimed to investigate whether autoantibodies are potential prognostic factors for short- and long-term clinical outcomes of COVID-19. Searches were conducted in MEDLINE, EMBASE, AMED, GLOBAL HEALTH, and COCHRANE databases from 2019 to 2022. When possible, meta-analysis was conducted, otherwise findings from individual studies were reported using odds ratios (OR) with 95% confidence intervals (CI). Quality of evidence was summarized using the GRADE criteria. We identified 2292 references, 18 inception prospective cohort studies (3178 patients) were included in the systematic review, and 12 studies reached criteria for meta-analysis. Studies achieved, in general, low to moderate risk of bias. Moderate quality of evidence showed that anti-interferon (IFN) was associated with increased risk of severity (OR=7.75; CI=1.79-33.61) and mechanical ventilation (OR=4.19; CI=2.06-8.53), but not with COVID-19 mortality (OR=1.68; CI=0.63-4.44). Antiphospholipids were not associated with COVID-19 mortality (OR=1.42; CI=0.85-2.37; P=0.18; I2=3.21) nor with thrombosis risk (OR=1.41; CI: 0.71-2.8; P=0.33). Antinuclear antibody level was not associated with risk of mortality or severity (risk for mortality: OR=3.8; CI=0.78-18.6; P=0.1; I2: 32.3; severity: OR=1.74; CI=0.96-3.16; P=0.07). Evidence currently available is insufficient for a quantitative analysis of autoantibodies association with long COVID-19. Anti-IFN measurement should be considered in COVID-19 follow-up. In a population-based rational, optimized vaccination strategies should be considered for individuals with anti-IFN antibodies since it could represent a risk for a worse prognosis. High-quality prospective studies for short- and long-term disease effects and autoantibody evaluation are still needed.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*COVID-19/immunology/mortality
*Autoantibodies/blood
Prognosis
*SARS-CoV-2/immunology
Prospective Studies
RevDate: 2025-02-07
CmpDate: 2025-02-05
Prevalent symptoms and characteristics of the Long COVID-19 population: a scoping review.
Revista latino-americana de enfermagem, 33:e4479.
UNLABELLED: to map the scientific literature on the clinical and demographic characteristics of Long COVID-19. this is a scoping review based on the principles recommended by the JBI and the PRISMA guidelines for data extraction, carried out on four databases. The PCC strategy was used for data collection, and the results were described and diagrammed. The studies were selected after removing duplicates, individual and peer review. an analysis of the 13 articles selected showed that Long COVID affects all age groups and people of both sexes, presenting a multiplicity of symptoms, such as fatigue (61.5%), dyspnea (46.1%), changes in smell and/or taste (38.6%), anxiety (15.3%) and cognitive impairment (30.7%). Females were found to be at increased risk of developing Long COVID. identifying the symptoms prevalent in Long COVID contributes to public health strategies for diagnosing and assisting people affected by the disease. Future studies are recommended on the approach to the persistence of symptoms in Long COVID and the relationship between adherence to the vaccination schedule against COVID-19, gender, race/ethnicity, degree of susceptibility in the different age groups, level of education and income, as well as the most recurrent comorbidities in the population.
BACKGROUND: (1) It was found that Long COVID affects all age groups of both sexes. (2) Most common symptoms: fatigue, dyspnea and altered sense of smell and/or taste. (3) Risk factors: female gender, COVID-19 severity and comorbidities.
Additional Links: PMID-39907353
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Citation:
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@article {pmid39907353,
year = {2025},
author = {Prediger, KM and Ribeiro, AC and Uehara, SCDSA},
title = {Prevalent symptoms and characteristics of the Long COVID-19 population: a scoping review.},
journal = {Revista latino-americana de enfermagem},
volume = {33},
number = {},
pages = {e4479},
pmid = {39907353},
issn = {1518-8345},
mesh = {Female ; Humans ; Male ; *COVID-19/epidemiology ; Dyspnea/epidemiology ; Post-Acute COVID-19 Syndrome ; Prevalence ; Risk Factors ; SARS-CoV-2 ; Sex Factors ; },
abstract = {UNLABELLED: to map the scientific literature on the clinical and demographic characteristics of Long COVID-19. this is a scoping review based on the principles recommended by the JBI and the PRISMA guidelines for data extraction, carried out on four databases. The PCC strategy was used for data collection, and the results were described and diagrammed. The studies were selected after removing duplicates, individual and peer review. an analysis of the 13 articles selected showed that Long COVID affects all age groups and people of both sexes, presenting a multiplicity of symptoms, such as fatigue (61.5%), dyspnea (46.1%), changes in smell and/or taste (38.6%), anxiety (15.3%) and cognitive impairment (30.7%). Females were found to be at increased risk of developing Long COVID. identifying the symptoms prevalent in Long COVID contributes to public health strategies for diagnosing and assisting people affected by the disease. Future studies are recommended on the approach to the persistence of symptoms in Long COVID and the relationship between adherence to the vaccination schedule against COVID-19, gender, race/ethnicity, degree of susceptibility in the different age groups, level of education and income, as well as the most recurrent comorbidities in the population.
BACKGROUND: (1) It was found that Long COVID affects all age groups of both sexes. (2) Most common symptoms: fatigue, dyspnea and altered sense of smell and/or taste. (3) Risk factors: female gender, COVID-19 severity and comorbidities.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Female
Humans
Male
*COVID-19/epidemiology
Dyspnea/epidemiology
Post-Acute COVID-19 Syndrome
Prevalence
Risk Factors
SARS-CoV-2
Sex Factors
RevDate: 2025-02-05
Medium- to long-term health condition of patients post-COVID-19, exercise intolerance and potential mechanisms: A narrative review and perspective.
SAGE open medicine, 12:20503121241296701.
BACKGROUND: Patients recovering from COVID-19 often present with impaired health and persisting symptoms such as exercise intolerance ⩾3 months post-infection. Uncertainty remains about long-term recovery. We aimed to review studies examining cardiac function, macro- or microvascular function, blood biomarkers and physical activity in adult patients post-COVID-19 and highlight current knowledge gaps.
RESULTS: Using echocardiography, persistent cardiac involvement of the left ventricle was observed in a fraction of patients both hospitalized and non-hospitalized. Ventricular dysfunction was often subclinical but may partly contribute to exercise intolerance post-COVID-19. Endothelial dysfunction was seen on micro- and macrovascular levels using retinal vessel imaging methods and brachial artery flow-mediated dilation, respectively. Studies reporting blood biomarkers of disease-specific impairment and endothelial dysfunction yielded upregulated inflammation, hypercoagulability, organ and endothelial damage up to several months after infection. Omics' scale lipid profiling studies provide preliminary evidence of alterations in several lipid subspecies, mostly during acute COVID-19, which might contribute to subsequent endothelial and cardiometabolic dysfunction. Yet, more robust evidence is warranted. Physical activity may be reduced up to 6 months post-COVID-19. However, studies measuring physical activity more precisely using accelerometry are sparse. Overall, there is growing evidence for long-term multiple organ dysfunction.
CONCLUSION: Research combining all the above methods in the search for underlying mechanisms of post-COVID-19 symptoms is mostly missing. Moreover, studies with longer follow-ups (i.e. ⩾18 months) and well-matched control groups are lacking. The findings may aid the development of rehabilitation regimes for post-COVID-19 syndrome.
CONDENSED ABSTRACT: This review examined cardiac function, vascular function, blood biomarkers and physical activity in patients post-COVID-19. Evidence suggests long-term dysfunction in multiple organ systems and exercise intolerance due to various factors, including endothelial damage and, in some patients, subclinical ventricular dysfunction. We highlight knowledge gaps for further research to aid post-COVID-19 rehabilitation.
Additional Links: PMID-39902344
PubMed:
Citation:
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@article {pmid39902344,
year = {2024},
author = {Schwendinger, F and Infanger, D and Maurer, DJ and Radtke, T and Carrard, J and Kröpfl, JM and Emmenegger, A and Hanssen, H and Hauser, C and Schwehr, U and Hirsch, HH and Ivanisevic, J and Leuzinger, K and Martinez, AE and Maurer, M and Sigrist, T and Streese, L and von Känel, R and Hinrichs, T and Schmidt-Trucksäss, A},
title = {Medium- to long-term health condition of patients post-COVID-19, exercise intolerance and potential mechanisms: A narrative review and perspective.},
journal = {SAGE open medicine},
volume = {12},
number = {},
pages = {20503121241296701},
pmid = {39902344},
issn = {2050-3121},
abstract = {BACKGROUND: Patients recovering from COVID-19 often present with impaired health and persisting symptoms such as exercise intolerance ⩾3 months post-infection. Uncertainty remains about long-term recovery. We aimed to review studies examining cardiac function, macro- or microvascular function, blood biomarkers and physical activity in adult patients post-COVID-19 and highlight current knowledge gaps.
RESULTS: Using echocardiography, persistent cardiac involvement of the left ventricle was observed in a fraction of patients both hospitalized and non-hospitalized. Ventricular dysfunction was often subclinical but may partly contribute to exercise intolerance post-COVID-19. Endothelial dysfunction was seen on micro- and macrovascular levels using retinal vessel imaging methods and brachial artery flow-mediated dilation, respectively. Studies reporting blood biomarkers of disease-specific impairment and endothelial dysfunction yielded upregulated inflammation, hypercoagulability, organ and endothelial damage up to several months after infection. Omics' scale lipid profiling studies provide preliminary evidence of alterations in several lipid subspecies, mostly during acute COVID-19, which might contribute to subsequent endothelial and cardiometabolic dysfunction. Yet, more robust evidence is warranted. Physical activity may be reduced up to 6 months post-COVID-19. However, studies measuring physical activity more precisely using accelerometry are sparse. Overall, there is growing evidence for long-term multiple organ dysfunction.
CONCLUSION: Research combining all the above methods in the search for underlying mechanisms of post-COVID-19 symptoms is mostly missing. Moreover, studies with longer follow-ups (i.e. ⩾18 months) and well-matched control groups are lacking. The findings may aid the development of rehabilitation regimes for post-COVID-19 syndrome.
CONDENSED ABSTRACT: This review examined cardiac function, vascular function, blood biomarkers and physical activity in patients post-COVID-19. Evidence suggests long-term dysfunction in multiple organ systems and exercise intolerance due to various factors, including endothelial damage and, in some patients, subclinical ventricular dysfunction. We highlight knowledge gaps for further research to aid post-COVID-19 rehabilitation.},
}
RevDate: 2025-02-06
Post infectious fatigue and circadian rhythm disruption in long-COVID and other infections: a need for further research.
EClinicalMedicine, 80:103073.
Chronic fatigue syndrome (CFS) remains a subject of scientific research specifically with regards to its association with infections, including the more recently described Long COVID condition. Chronic fatigue and sleep disturbances in Long COVID are intricately linked to disruptions in circadian rhythms, driven by distinct molecular and cellular mechanisms triggered by SARS-CoV-2 infection. This can be driven by various mechanisms including dysregulation of key clock genes (CLOCK, BMAL1, PER2), mitochondrial dysfunction impairing oxidative phosphorylation, and cytokine-induced neuroinflammation (e.g., interleukin-6, tumor necrosis factor-alpha). Epigenetic changes, including DNA methylation at clock-related loci, particularly in peripheral tissues, further contribute to systemic circadian dysregulation. This work underscores the multifaceted molecular and systemic disruptions to circadian regulation in relation to fatigue and sleep disturbances identified as post-infectious sequelae, focusing on the Long COVID condition.
Additional Links: PMID-39896874
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Citation:
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@article {pmid39896874,
year = {2025},
author = {Livieratos, A and Lockley, SW and Tsiodras, S},
title = {Post infectious fatigue and circadian rhythm disruption in long-COVID and other infections: a need for further research.},
journal = {EClinicalMedicine},
volume = {80},
number = {},
pages = {103073},
pmid = {39896874},
issn = {2589-5370},
abstract = {Chronic fatigue syndrome (CFS) remains a subject of scientific research specifically with regards to its association with infections, including the more recently described Long COVID condition. Chronic fatigue and sleep disturbances in Long COVID are intricately linked to disruptions in circadian rhythms, driven by distinct molecular and cellular mechanisms triggered by SARS-CoV-2 infection. This can be driven by various mechanisms including dysregulation of key clock genes (CLOCK, BMAL1, PER2), mitochondrial dysfunction impairing oxidative phosphorylation, and cytokine-induced neuroinflammation (e.g., interleukin-6, tumor necrosis factor-alpha). Epigenetic changes, including DNA methylation at clock-related loci, particularly in peripheral tissues, further contribute to systemic circadian dysregulation. This work underscores the multifaceted molecular and systemic disruptions to circadian regulation in relation to fatigue and sleep disturbances identified as post-infectious sequelae, focusing on the Long COVID condition.},
}
RevDate: 2025-02-04
CmpDate: 2025-02-04
Cerebral Blood Flow in Orthostatic Intolerance.
Journal of the American Heart Association, 14(3):e036752.
Cerebral blood flow (CBF) is vital for delivering oxygen and nutrients to the brain. Many forms of orthostatic intolerance (OI) involve impaired regulation of CBF in the upright posture, which results in disabling symptoms that decrease quality of life. Because CBF is not easy to measure, rises in heart rate or drops in blood pressure are used as proxies for abnormal CBF. These result in diagnoses such as postural orthostatic tachycardia syndrome and orthostatic hypotension. However, in many other OI syndromes such as myalgic encephalomyelitis/chronic fatigue syndrome and long COVID, heart rate and blood pressure are frequently normal despite significant drops in CBF. This often leads to the incorrect conclusion that there is nothing hemodynamically abnormal in these patients and thus no explanation or treatment is needed. There is a need to measure CBF, as orthostatic hypoperfusion is the shared pathophysiology for all forms of OI. In this review, we examine the literature studying CBF dysfunction in various syndromes with OI and evaluate methods of measuring CBF including transcranial Doppler ultrasound, extracranial cerebral blood flow ultrasound, near infrared spectroscopy, and wearable devices.
Additional Links: PMID-39895557
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@article {pmid39895557,
year = {2025},
author = {Khan, MS and Miller, AJ and Ejaz, A and Molinger, J and Goyal, P and MacLeod, DB and Swavely, A and Wilson, E and Pergola, M and Tandri, H and Mills, CF and Raj, SR and Fudim, M},
title = {Cerebral Blood Flow in Orthostatic Intolerance.},
journal = {Journal of the American Heart Association},
volume = {14},
number = {3},
pages = {e036752},
doi = {10.1161/JAHA.124.036752},
pmid = {39895557},
issn = {2047-9980},
mesh = {Humans ; *Cerebrovascular Circulation/physiology ; *Orthostatic Intolerance/physiopathology/diagnosis ; COVID-19/complications/physiopathology ; Ultrasonography, Doppler, Transcranial ; Spectroscopy, Near-Infrared ; Postural Orthostatic Tachycardia Syndrome/physiopathology/diagnosis ; },
abstract = {Cerebral blood flow (CBF) is vital for delivering oxygen and nutrients to the brain. Many forms of orthostatic intolerance (OI) involve impaired regulation of CBF in the upright posture, which results in disabling symptoms that decrease quality of life. Because CBF is not easy to measure, rises in heart rate or drops in blood pressure are used as proxies for abnormal CBF. These result in diagnoses such as postural orthostatic tachycardia syndrome and orthostatic hypotension. However, in many other OI syndromes such as myalgic encephalomyelitis/chronic fatigue syndrome and long COVID, heart rate and blood pressure are frequently normal despite significant drops in CBF. This often leads to the incorrect conclusion that there is nothing hemodynamically abnormal in these patients and thus no explanation or treatment is needed. There is a need to measure CBF, as orthostatic hypoperfusion is the shared pathophysiology for all forms of OI. In this review, we examine the literature studying CBF dysfunction in various syndromes with OI and evaluate methods of measuring CBF including transcranial Doppler ultrasound, extracranial cerebral blood flow ultrasound, near infrared spectroscopy, and wearable devices.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Cerebrovascular Circulation/physiology
*Orthostatic Intolerance/physiopathology/diagnosis
COVID-19/complications/physiopathology
Ultrasonography, Doppler, Transcranial
Spectroscopy, Near-Infrared
Postural Orthostatic Tachycardia Syndrome/physiopathology/diagnosis
RevDate: 2025-01-31
Transformative approaches in SARS-CoV-2 management: Vaccines, therapeutics and future direction.
Virology, 604:110394 pii:S0042-6822(25)00006-6 [Epub ahead of print].
The global healthcare and economic challenges caused by the pandemic of COVID-19 reinforced the urgent demand for quick and effective therapeutic and preventative interventions. While vaccines served as the frontline of defense, antivirals emerged as adjunctive countermeasures, especially for people who developed infection, were immunocompromised, or were reluctant to be vaccinated. Beyond the serious complications of SARS-CoV-2 infection, the threats of long-COVID and the potential for zoonotic spillover continue to be significant health concerns that cannot be overlooked. Moreover, the incessant viral evolution, clinical safety issues, waning immune responses, and the emergence of drug-resistant variants pinpoint towards more severe viral threats in the future and call for broad-spectrum innovative therapies as a pre-pandemic preparedness measure. The present review provides a comprehensive up-to-date overview of the strategies utilized in the development of classical and next-generation vaccines against SARS-CoV-2, the clinical and experimental data obtained from clinical trials, while addressing safety risks that may arise. Besides vaccines, the review also covers recent breakthroughs in anti-SARS-CoV-2 drug discovery, emphasizing druggable viral and host targets, virus- and host-targeting antivirals, and highlighting mechanistically representative molecules that are either approved or are under clinical investigation. In conclusion, the integration of both vaccines and antiviral therapies, along with swift innovative strategies to address viral evolution and drug resistance is crucial to strengthen our preparedness against future viral outbreaks.
Additional Links: PMID-39889481
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@article {pmid39889481,
year = {2025},
author = {Saha, A and Choudhary, S and Walia, P and Kumar, P and Tomar, S},
title = {Transformative approaches in SARS-CoV-2 management: Vaccines, therapeutics and future direction.},
journal = {Virology},
volume = {604},
number = {},
pages = {110394},
doi = {10.1016/j.virol.2025.110394},
pmid = {39889481},
issn = {1096-0341},
abstract = {The global healthcare and economic challenges caused by the pandemic of COVID-19 reinforced the urgent demand for quick and effective therapeutic and preventative interventions. While vaccines served as the frontline of defense, antivirals emerged as adjunctive countermeasures, especially for people who developed infection, were immunocompromised, or were reluctant to be vaccinated. Beyond the serious complications of SARS-CoV-2 infection, the threats of long-COVID and the potential for zoonotic spillover continue to be significant health concerns that cannot be overlooked. Moreover, the incessant viral evolution, clinical safety issues, waning immune responses, and the emergence of drug-resistant variants pinpoint towards more severe viral threats in the future and call for broad-spectrum innovative therapies as a pre-pandemic preparedness measure. The present review provides a comprehensive up-to-date overview of the strategies utilized in the development of classical and next-generation vaccines against SARS-CoV-2, the clinical and experimental data obtained from clinical trials, while addressing safety risks that may arise. Besides vaccines, the review also covers recent breakthroughs in anti-SARS-CoV-2 drug discovery, emphasizing druggable viral and host targets, virus- and host-targeting antivirals, and highlighting mechanistically representative molecules that are either approved or are under clinical investigation. In conclusion, the integration of both vaccines and antiviral therapies, along with swift innovative strategies to address viral evolution and drug resistance is crucial to strengthen our preparedness against future viral outbreaks.},
}
RevDate: 2025-02-04
Post-pandemic insights on COVID-19 and premature ovarian insufficiency.
Open life sciences, 20(1):20221028.
The COVID-19 pandemic has raised concerns regarding its potential impact on premature ovarian insufficiency (POI). This overview examines the possible interactions between COVID-19 and POI, while also suggesting preventive measures. The viral infection's inflammatory response and immune dysregulation may adversely affect ovarian tissues, leading to inflammation and damage. Additionally, alterations in vascular function could impair ovarian blood flow and hormonal imbalances may disrupt normal ovarian function. Long-term health effects, such as "long COVID," may exacerbate these issues through chronic inflammation and immune dysfunction. Public health measures, such as vaccination and home isolation, may indirectly protect ovarian health by reducing systemic inflammation. Vaccines could mitigate the severity of COVID-19's impact on ovarian function, while isolation may reduce stress and inflammation. However, further research is needed to validate these mechanisms.
Additional Links: PMID-39886482
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@article {pmid39886482,
year = {2025},
author = {Han, Y and Dai, Y and Wang, K and Zhang, X and Shao, Z and Zhu, X},
title = {Post-pandemic insights on COVID-19 and premature ovarian insufficiency.},
journal = {Open life sciences},
volume = {20},
number = {1},
pages = {20221028},
pmid = {39886482},
issn = {2391-5412},
abstract = {The COVID-19 pandemic has raised concerns regarding its potential impact on premature ovarian insufficiency (POI). This overview examines the possible interactions between COVID-19 and POI, while also suggesting preventive measures. The viral infection's inflammatory response and immune dysregulation may adversely affect ovarian tissues, leading to inflammation and damage. Additionally, alterations in vascular function could impair ovarian blood flow and hormonal imbalances may disrupt normal ovarian function. Long-term health effects, such as "long COVID," may exacerbate these issues through chronic inflammation and immune dysfunction. Public health measures, such as vaccination and home isolation, may indirectly protect ovarian health by reducing systemic inflammation. Vaccines could mitigate the severity of COVID-19's impact on ovarian function, while isolation may reduce stress and inflammation. However, further research is needed to validate these mechanisms.},
}
RevDate: 2025-02-04
CmpDate: 2025-01-30
Risk of long covid in patients with pre-existing chronic respiratory diseases: a systematic review and meta-analysis.
BMJ open respiratory research, 12(1):.
BACKGROUND: An estimated 10-30% of people with COVID-19 experience debilitating long-term symptoms or long covid. Underlying health conditions associated with chronic inflammation may increase the risk of long covid.
METHODS: We conducted a systematic review and meta-analysis to examine whether long covid risk was altered by pre-existing asthma or chronic obstructive pulmonary disease (COPD) in adults. We identified studies by searching the PubMed and Embase databases from inception to 13 September 2024. We excluded studies that focused on children or defined long covid only in terms of respiratory symptoms. We used random-effects, restricted maximum likelihood models to analyse data pooled from 51 studies, which included 43 analyses of asthma and 30 analyses of COPD. The risk of bias was assessed using a ROBINS-E table.
RESULTS: We found 41% increased odds of long covid with pre-existing asthma (95% CI 1.29 to 1.54); pre-existing COPD was associated with 32% increased odds (95% CI 1.16 to 1.51). Pre-existing asthma, but not COPD, was associated with increased odds of long covid-associated fatigue. We observed heterogeneity in the results of studies of asthma related to hospitalisation status. Potential confounding and inconsistent measurement of exposure and outcome variables were among the identified limitations.
CONCLUSIONS: Our findings support the hypothesis that pre-existing asthma and COPD increase the risk of long covid, including chronic fatigue outcomes in patients with asthma. Because COVID-19 targets the respiratory tract, these inflammatory conditions of the lower respiratory tract could provide mechanistic clues to a common pathway for the development of long-term sequelae in patients with long covid.
Additional Links: PMID-39884720
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Citation:
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@article {pmid39884720,
year = {2025},
author = {Terry, P and Heidel, RE and Wilson, AQ and Dhand, R},
title = {Risk of long covid in patients with pre-existing chronic respiratory diseases: a systematic review and meta-analysis.},
journal = {BMJ open respiratory research},
volume = {12},
number = {1},
pages = {},
pmid = {39884720},
issn = {2052-4439},
mesh = {Humans ; *COVID-19/complications/epidemiology ; *Asthma/epidemiology/complications ; *Pulmonary Disease, Chronic Obstructive/epidemiology/complications ; *SARS-CoV-2 ; Risk Factors ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: An estimated 10-30% of people with COVID-19 experience debilitating long-term symptoms or long covid. Underlying health conditions associated with chronic inflammation may increase the risk of long covid.
METHODS: We conducted a systematic review and meta-analysis to examine whether long covid risk was altered by pre-existing asthma or chronic obstructive pulmonary disease (COPD) in adults. We identified studies by searching the PubMed and Embase databases from inception to 13 September 2024. We excluded studies that focused on children or defined long covid only in terms of respiratory symptoms. We used random-effects, restricted maximum likelihood models to analyse data pooled from 51 studies, which included 43 analyses of asthma and 30 analyses of COPD. The risk of bias was assessed using a ROBINS-E table.
RESULTS: We found 41% increased odds of long covid with pre-existing asthma (95% CI 1.29 to 1.54); pre-existing COPD was associated with 32% increased odds (95% CI 1.16 to 1.51). Pre-existing asthma, but not COPD, was associated with increased odds of long covid-associated fatigue. We observed heterogeneity in the results of studies of asthma related to hospitalisation status. Potential confounding and inconsistent measurement of exposure and outcome variables were among the identified limitations.
CONCLUSIONS: Our findings support the hypothesis that pre-existing asthma and COPD increase the risk of long covid, including chronic fatigue outcomes in patients with asthma. Because COVID-19 targets the respiratory tract, these inflammatory conditions of the lower respiratory tract could provide mechanistic clues to a common pathway for the development of long-term sequelae in patients with long covid.},
}
MeSH Terms:
show MeSH Terms
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Humans
*COVID-19/complications/epidemiology
*Asthma/epidemiology/complications
*Pulmonary Disease, Chronic Obstructive/epidemiology/complications
*SARS-CoV-2
Risk Factors
Post-Acute COVID-19 Syndrome
RevDate: 2025-01-31
Prevalence and risk factors for long COVID among cancer patients: a systematic review and meta-analysis.
Frontiers in oncology, 14:1506366.
OBJECTIVE: The prevalence of long COVID among cancer patients remains unknown. This study aimed to determine the prevalence of long COVID and explore potential risk factors among cancer patients.
METHODS: A systematic search was performed on PubMed, Web of Science, and Embase from database inception until 21 March 2024, to identify studies that reported long COVID in cancer patients. Two investigators independently screened the studies and extracted all information about long COVID in cancer patients for subsequent analysis. Methodological quality was assessed using the "Joannagen Briggs Institute (JBI) Critical Appraisal Checklist for Studies Reporting Prevalence Data".
RESULTS: A total of 13 studies involving 6,653 patients were included. The pooled prevalence of long COVID was 23.52% [95% confidence interval (CI), 12.14% to 40.64%] among cancer patients reported experiencing long COVID after acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The pooled prevalence of any long COVID in cancer patients was 20.51% (95% CI, 15.91% to 26.03%), 15.79% (95% CI, 11.39% to 21.47%), and 12.54% (95% CI, 6.38% to 23.18%) in 3, 6, and 12 months follow-up duration. Fatigue was the most common symptom, followed by respiratory symptoms, myalgia, and sleep disturbance. Patients with comorbidities had a significantly higher risk of experiencing long COVID [odds ratio (OR) = 1.72; 95% CI, 1.09 to 2.70; p = 0.019]. No statistically significant differences in sex, primary tumor, or tumor stage were detected.
CONCLUSION: Nearly a quarter of cancer patients will experience long COVID after surviving from SARS-CoV-2 infection, and this would even last for 1 year or longer. Fatigue, respiratory symptoms, myalgia, and sleep disturbance need to be more addressed and managed to reduce symptom burden on cancer patients and improve quality of life. Patients with comorbidities are at a high risk of developing long COVID. Further randomized controlled trials with rigorous methodological designs and large sample sizes are needed for future validation.
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023456665.
Additional Links: PMID-39882453
PubMed:
Citation:
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@article {pmid39882453,
year = {2024},
author = {Xu, H and Lu, T and Liu, Y and Yang, J and Ren, S and Han, B and Lai, H and Ge, L and Liu, J},
title = {Prevalence and risk factors for long COVID among cancer patients: a systematic review and meta-analysis.},
journal = {Frontiers in oncology},
volume = {14},
number = {},
pages = {1506366},
pmid = {39882453},
issn = {2234-943X},
abstract = {OBJECTIVE: The prevalence of long COVID among cancer patients remains unknown. This study aimed to determine the prevalence of long COVID and explore potential risk factors among cancer patients.
METHODS: A systematic search was performed on PubMed, Web of Science, and Embase from database inception until 21 March 2024, to identify studies that reported long COVID in cancer patients. Two investigators independently screened the studies and extracted all information about long COVID in cancer patients for subsequent analysis. Methodological quality was assessed using the "Joannagen Briggs Institute (JBI) Critical Appraisal Checklist for Studies Reporting Prevalence Data".
RESULTS: A total of 13 studies involving 6,653 patients were included. The pooled prevalence of long COVID was 23.52% [95% confidence interval (CI), 12.14% to 40.64%] among cancer patients reported experiencing long COVID after acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The pooled prevalence of any long COVID in cancer patients was 20.51% (95% CI, 15.91% to 26.03%), 15.79% (95% CI, 11.39% to 21.47%), and 12.54% (95% CI, 6.38% to 23.18%) in 3, 6, and 12 months follow-up duration. Fatigue was the most common symptom, followed by respiratory symptoms, myalgia, and sleep disturbance. Patients with comorbidities had a significantly higher risk of experiencing long COVID [odds ratio (OR) = 1.72; 95% CI, 1.09 to 2.70; p = 0.019]. No statistically significant differences in sex, primary tumor, or tumor stage were detected.
CONCLUSION: Nearly a quarter of cancer patients will experience long COVID after surviving from SARS-CoV-2 infection, and this would even last for 1 year or longer. Fatigue, respiratory symptoms, myalgia, and sleep disturbance need to be more addressed and managed to reduce symptom burden on cancer patients and improve quality of life. Patients with comorbidities are at a high risk of developing long COVID. Further randomized controlled trials with rigorous methodological designs and large sample sizes are needed for future validation.
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023456665.},
}
RevDate: 2025-01-31
Oral medications for the treatment of postural orthostatic tachycardia syndrome; a systematic review of studies before and during the COVID-19 pandemic.
Frontiers in neurology, 15:1515486.
BACKGROUND: Postural Orthostatic Tachycardia Syndrome (POTS) is a complex form of dysautonomia that presents with abnormal autonomic reflexes upon standing, leading to symptoms such as lightheadedness, tachycardia, fatigue, and cognitive impairment. The COVID-19 pandemic has brought renewed attention to POTS due to its overlap with post-acute sequelae of COVID-19 (PASC). Studies have found that a substantial percentage of COVID-19 survivors exhibit symptoms resembling POTS, elevating POTS diagnoses to previously unseen levels. We systematically reviewed the literature for existing high-quality evidence on potential interventions.
METHODS: A systematic review of the literature was performed to identify studies of oral medications for the management of POTS. We searched for published manuscripts on the medical management of POTS through 6 April 2024 which met pre-specified inclusion criteria. We conducted quality appraisal and assessed risk of bias before extracting the data and performing synthesis to determine the current state of the evidence; particularly in the context of PASC.
RESULTS: The study search and selection process identified 32 studies that met inclusion criteria, comprising randomized controlled trials, observational studies, and systematic reviews. Most included studies were judged to be of moderate to high quality, with largely low risk of bias. The most frequently studied medications were beta-blockers, ivabradine, and midodrine. Ivabradine and midodrine demonstrated the highest rate of symptomatic improvement, while beta-blockers showed the largest reduction in heart rate variability. Limited evidence was available for PASC-associated POTS, but findings suggest that treatments may have similar efficacy in both PASC and non-PASC cases.
CONCLUSION: Ivabradine, midodrine, and beta-blockers currently appear to be reasonable front-line choices in pharmacologic management of POTS (PASC associated and otherwise). Further RCTs that evaluate long term outcomes of medications are needed to further establish evidence based pharmacologic treatment approaches for POTS. Particular areas of inquiry include differential efficacy of recommended therapies based on POTS subtypes, and a need for treatments directly targeting the underlying autonomic nervous system dysfunction.
PROSPERO, identifier CRD42024505967, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=505967.
Additional Links: PMID-39882369
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Citation:
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@article {pmid39882369,
year = {2024},
author = {Pierson, BC and Apilado, K and Franzos, MA and Allard, R and Mancuso, JD and Tribble, D and Saunders, D and Koehlmoos, TP},
title = {Oral medications for the treatment of postural orthostatic tachycardia syndrome; a systematic review of studies before and during the COVID-19 pandemic.},
journal = {Frontiers in neurology},
volume = {15},
number = {},
pages = {1515486},
pmid = {39882369},
issn = {1664-2295},
abstract = {BACKGROUND: Postural Orthostatic Tachycardia Syndrome (POTS) is a complex form of dysautonomia that presents with abnormal autonomic reflexes upon standing, leading to symptoms such as lightheadedness, tachycardia, fatigue, and cognitive impairment. The COVID-19 pandemic has brought renewed attention to POTS due to its overlap with post-acute sequelae of COVID-19 (PASC). Studies have found that a substantial percentage of COVID-19 survivors exhibit symptoms resembling POTS, elevating POTS diagnoses to previously unseen levels. We systematically reviewed the literature for existing high-quality evidence on potential interventions.
METHODS: A systematic review of the literature was performed to identify studies of oral medications for the management of POTS. We searched for published manuscripts on the medical management of POTS through 6 April 2024 which met pre-specified inclusion criteria. We conducted quality appraisal and assessed risk of bias before extracting the data and performing synthesis to determine the current state of the evidence; particularly in the context of PASC.
RESULTS: The study search and selection process identified 32 studies that met inclusion criteria, comprising randomized controlled trials, observational studies, and systematic reviews. Most included studies were judged to be of moderate to high quality, with largely low risk of bias. The most frequently studied medications were beta-blockers, ivabradine, and midodrine. Ivabradine and midodrine demonstrated the highest rate of symptomatic improvement, while beta-blockers showed the largest reduction in heart rate variability. Limited evidence was available for PASC-associated POTS, but findings suggest that treatments may have similar efficacy in both PASC and non-PASC cases.
CONCLUSION: Ivabradine, midodrine, and beta-blockers currently appear to be reasonable front-line choices in pharmacologic management of POTS (PASC associated and otherwise). Further RCTs that evaluate long term outcomes of medications are needed to further establish evidence based pharmacologic treatment approaches for POTS. Particular areas of inquiry include differential efficacy of recommended therapies based on POTS subtypes, and a need for treatments directly targeting the underlying autonomic nervous system dysfunction.
PROSPERO, identifier CRD42024505967, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=505967.},
}
RevDate: 2025-01-30
CmpDate: 2025-01-28
Prevalence of depression, anxiety, stress, and suicide tendency among individual with long-COVID and determinants: A systematic review and meta-analysis.
PloS one, 20(1):e0312351.
BACKGROUND: While mental health alterations during active COVID-19 infection have been documented, the prevalence of long-term mental health consequences remains unclear. This study aimed to determine the prevalence of mental health symptoms-depression, anxiety, stress, and suicidal tendencies-and to identify their trends and associated risk factors in individuals with long-COVID.
METHODS: We conducted a systematic literature search of databases including PubMed, EMBASE, Scopus, CINAHL, Cochrane Library, Web of Science, and PsycINFO up to August 2024, targeting observational studies published in English. Study quality was assessed using structured standard tools. The primary outcome was the pooled prevalence of depression, anxiety, stress, and suicidal tendencies in individuals with long-COVID. Secondary outcomes included trends in these mental health problems over time and identification of associated determinants.
RESULTS: A total of 94 eligible studies were included in the analysis. The pooled prevalence estimates, regardless of follow up times duration, were as follows: depression, 25% (95%CI:22-28%; PI:1-59%); anxiety (adjusted via trim and fill method), 23%(95%CI:21-25%;PI:2-35%); composite outcomes of depression and/or anxiety, 25% (95%CI:23-27%;PI:2-51%); stress, 26%(95%CI:13-39%;PI:1-69%); and suicidality, 19%(95%CI:15-22%;PI:13-25%). The results of meta-regression analyses revealed a statistically significant trend showing a gradual decrease in the prevalence of the composite outcome of anxiety and/or depression over time (RD = -0.004,P = 0.022). Meta-regression results indicated that being female and younger age were significantly associated with a higher prevalence of mental health symptoms. Study design and study setting did not contribute to heterogeneity.
CONCLUSION: One-fourth of individual with long-COVID experience mental health symptoms, including depression, anxiety, and stress, which remain prevalent even two years post-infection despite a slight decreasing trend. Factors such as female gender and younger age were linked to higher rates of anxiety and depression. These findings indicate the need for ongoing mental health screening and early interventions to mitigate long-term psychological distress in long-COVID patients.
Additional Links: PMID-39874315
PubMed:
Citation:
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@article {pmid39874315,
year = {2025},
author = {Bidhendi-Yarandi, R and Biglarian, A and Karlstad, JL and Moe, CF and Bakhshi, E and Khodaei-Ardakani, MR and Behboudi-Gandevani, S},
title = {Prevalence of depression, anxiety, stress, and suicide tendency among individual with long-COVID and determinants: A systematic review and meta-analysis.},
journal = {PloS one},
volume = {20},
number = {1},
pages = {e0312351},
pmid = {39874315},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/epidemiology/psychology ; *Depression/epidemiology ; *Anxiety/epidemiology ; Prevalence ; *Stress, Psychological/epidemiology ; Suicidal Ideation ; Risk Factors ; SARS-CoV-2 ; Suicide/psychology/statistics & numerical data ; Mental Health ; Female ; },
abstract = {BACKGROUND: While mental health alterations during active COVID-19 infection have been documented, the prevalence of long-term mental health consequences remains unclear. This study aimed to determine the prevalence of mental health symptoms-depression, anxiety, stress, and suicidal tendencies-and to identify their trends and associated risk factors in individuals with long-COVID.
METHODS: We conducted a systematic literature search of databases including PubMed, EMBASE, Scopus, CINAHL, Cochrane Library, Web of Science, and PsycINFO up to August 2024, targeting observational studies published in English. Study quality was assessed using structured standard tools. The primary outcome was the pooled prevalence of depression, anxiety, stress, and suicidal tendencies in individuals with long-COVID. Secondary outcomes included trends in these mental health problems over time and identification of associated determinants.
RESULTS: A total of 94 eligible studies were included in the analysis. The pooled prevalence estimates, regardless of follow up times duration, were as follows: depression, 25% (95%CI:22-28%; PI:1-59%); anxiety (adjusted via trim and fill method), 23%(95%CI:21-25%;PI:2-35%); composite outcomes of depression and/or anxiety, 25% (95%CI:23-27%;PI:2-51%); stress, 26%(95%CI:13-39%;PI:1-69%); and suicidality, 19%(95%CI:15-22%;PI:13-25%). The results of meta-regression analyses revealed a statistically significant trend showing a gradual decrease in the prevalence of the composite outcome of anxiety and/or depression over time (RD = -0.004,P = 0.022). Meta-regression results indicated that being female and younger age were significantly associated with a higher prevalence of mental health symptoms. Study design and study setting did not contribute to heterogeneity.
CONCLUSION: One-fourth of individual with long-COVID experience mental health symptoms, including depression, anxiety, and stress, which remain prevalent even two years post-infection despite a slight decreasing trend. Factors such as female gender and younger age were linked to higher rates of anxiety and depression. These findings indicate the need for ongoing mental health screening and early interventions to mitigate long-term psychological distress in long-COVID patients.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*COVID-19/epidemiology/psychology
*Depression/epidemiology
*Anxiety/epidemiology
Prevalence
*Stress, Psychological/epidemiology
Suicidal Ideation
Risk Factors
SARS-CoV-2
Suicide/psychology/statistics & numerical data
Mental Health
Female
RevDate: 2025-02-06
CmpDate: 2025-02-06
Subphenotypes of Long COVID and the clinical applications of probiotics.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 183:117855.
As the number of infections and deaths attributable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to rise, it is now becoming apparent that the health impacts of the Coronavirus disease (COVID-19) may not be limited to infection and the subsequent resolution of symptoms. Reports have shown that patients with SARS-CoV-2 infection may experience multiple symptoms across different organ systems that are associated with adverse health outcomes and develop new cardiac, renal, respiratory, musculoskeletal, and nervous conditions, a condition known as Long COVID or the post-acute sequelae of COVID-19 (PASC). This review provides insights into distinct subphenotypes of Long COVID and identifies microbiota dysbiosis as a common theme and crucial target for future therapies. Another important finding is that Long COVID is associated with prolonged and increased inflammation, potentially attributable to immune system dysfunction. A promising solution lies in the potential of probiotics to mitigate Long COVID symptoms by restoring gut microbiota balance and modulating the immune response. By evaluating the current clinical development landscape of the use of probiotics to treat Long COVID symptoms, this paper provides recommendations for future research by stressing the need to understand the modulation of bacterium strains followed by probiotic therapy to understand the association of microbiota dysbiosis with Long COVID symptoms. This will facilitate the development of effective probiotic formulations that could serve as reliable therapies against Long COVID.
Additional Links: PMID-39862702
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@article {pmid39862702,
year = {2025},
author = {Lim, HX and Khalid, K and Abdullah, ADI and Lee, LH and Raja Ali, RA},
title = {Subphenotypes of Long COVID and the clinical applications of probiotics.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {183},
number = {},
pages = {117855},
doi = {10.1016/j.biopha.2025.117855},
pmid = {39862702},
issn = {1950-6007},
mesh = {Humans ; *Probiotics/therapeutic use ; *COVID-19 ; *Dysbiosis ; *Gastrointestinal Microbiome/drug effects ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Phenotype ; },
abstract = {As the number of infections and deaths attributable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to rise, it is now becoming apparent that the health impacts of the Coronavirus disease (COVID-19) may not be limited to infection and the subsequent resolution of symptoms. Reports have shown that patients with SARS-CoV-2 infection may experience multiple symptoms across different organ systems that are associated with adverse health outcomes and develop new cardiac, renal, respiratory, musculoskeletal, and nervous conditions, a condition known as Long COVID or the post-acute sequelae of COVID-19 (PASC). This review provides insights into distinct subphenotypes of Long COVID and identifies microbiota dysbiosis as a common theme and crucial target for future therapies. Another important finding is that Long COVID is associated with prolonged and increased inflammation, potentially attributable to immune system dysfunction. A promising solution lies in the potential of probiotics to mitigate Long COVID symptoms by restoring gut microbiota balance and modulating the immune response. By evaluating the current clinical development landscape of the use of probiotics to treat Long COVID symptoms, this paper provides recommendations for future research by stressing the need to understand the modulation of bacterium strains followed by probiotic therapy to understand the association of microbiota dysbiosis with Long COVID symptoms. This will facilitate the development of effective probiotic formulations that could serve as reliable therapies against Long COVID.},
}
MeSH Terms:
show MeSH Terms
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Humans
*Probiotics/therapeutic use
*COVID-19
*Dysbiosis
*Gastrointestinal Microbiome/drug effects
*Post-Acute COVID-19 Syndrome
SARS-CoV-2
Phenotype
RevDate: 2025-01-30
CmpDate: 2025-01-25
Animal Models of Non-Respiratory, Post-Acute Sequelae of COVID-19.
Viruses, 17(1):.
Post-acute sequelae of COVID-19 (PASC) are a diverse set of symptoms and syndromes driven by dysfunction of multiple organ systems that can persist for years and negatively impact the quality of life for millions of individuals. We currently lack specific therapeutics for patients with PASC, due in part to an incomplete understanding of its pathogenesis, especially for non-pulmonary sequelae. Here, we discuss three animal models that have been utilized to investigate PASC: non-human primates (NHPs), hamsters, and mice. We focus on neurological, gastrointestinal, and cardiovascular PASC and highlight advances in mechanistic insight that have been made using these animal models, as well as discussing the sequelae that warrant continued and intensive research.
Additional Links: PMID-39861887
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@article {pmid39861887,
year = {2025},
author = {Vanderheiden, A and Diamond, MS},
title = {Animal Models of Non-Respiratory, Post-Acute Sequelae of COVID-19.},
journal = {Viruses},
volume = {17},
number = {1},
pages = {},
pmid = {39861887},
issn = {1999-4915},
support = {R01 AI157155/AI/NIAID NIH HHS/United States ; P01 AI168347/NH/NIH HHS/United States ; R01 AI157155/NH/NIH HHS/United States ; P01 AI168347/AI/NIAID NIH HHS/United States ; F32 NS128065/NH/NIH HHS/United States ; F32 NS128065/NS/NINDS NIH HHS/United States ; },
mesh = {Animals ; *COVID-19/complications/virology ; *Disease Models, Animal ; Mice ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome ; Humans ; Cricetinae ; Primates ; },
abstract = {Post-acute sequelae of COVID-19 (PASC) are a diverse set of symptoms and syndromes driven by dysfunction of multiple organ systems that can persist for years and negatively impact the quality of life for millions of individuals. We currently lack specific therapeutics for patients with PASC, due in part to an incomplete understanding of its pathogenesis, especially for non-pulmonary sequelae. Here, we discuss three animal models that have been utilized to investigate PASC: non-human primates (NHPs), hamsters, and mice. We focus on neurological, gastrointestinal, and cardiovascular PASC and highlight advances in mechanistic insight that have been made using these animal models, as well as discussing the sequelae that warrant continued and intensive research.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Animals
*COVID-19/complications/virology
*Disease Models, Animal
Mice
*SARS-CoV-2
*Post-Acute COVID-19 Syndrome
Humans
Cricetinae
Primates
RevDate: 2025-01-30
Post COVID-19 and Long COVID Symptoms in Otorhinolaryngology-A Narrative Review.
Journal of clinical medicine, 14(2):.
Post/Long COVID (syndrome) is defined as a condition with symptoms persisting for more than 12 weeks after the onset of SARS-CoV-2 infection that cannot be explained otherwise. The prevalence of self-reported otorhinolaryngological Post/Long COVID symptoms is high. The aim of this review was to analyze the current literature regarding the actual prevalence, knowledge of the etiopathology, and evidence-based treatment recommendations of otorhinolaryngology-related Post/Long COVID symptoms. A systematic literature search of articles published since 2019 in PubMed and ScienceDirect was performed and resulted in 108 articles. These were the basis for this review and formed a comprehensive series of consented therapy statements on the most important of otorhinolaryngology-related Post/Long COVID symptoms. Otorhinolaryngological symptoms did not appear isolated but as part of a multi-organ syndrome. Self-reported otorhinolaryngology-related Post/Long COVID symptoms were often not confirmed by objective testing. The confirmed prevalence estimated for anosmia, dysgeusia, cough, facial palsy, hoarseness/dysphonia, acute hearing loss, tinnitus, and vertigo/dizziness was about 4%, 2%, 4-19%, 0%, 17-20%, 8%, 20%, and 5-26%, respectively. There are manifold theoretical concepts of the etiopathology of different symptoms, but there is no clear evidence-based proof. This certainly contributes to the fact that there is no effective specific treatment option for any of the symptoms mentioned. Healthcare pathways must be established so that otorhinolaryngological Post/Long COVID symptoms can be recognized and evaluated and otorhinolaryngologists can provide counseling. This would also help to establish and selectively include patients in clinical trials investigating specific therapeutic concepts.
Additional Links: PMID-39860512
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@article {pmid39860512,
year = {2025},
author = {Guntinas-Lichius, O and Bitter, T and Takes, R and Lee, VHF and Saba, NF and Mäkitie, AA and Kowalski, LP and Nixon, IJ and Ferlito, A},
title = {Post COVID-19 and Long COVID Symptoms in Otorhinolaryngology-A Narrative Review.},
journal = {Journal of clinical medicine},
volume = {14},
number = {2},
pages = {},
pmid = {39860512},
issn = {2077-0383},
abstract = {Post/Long COVID (syndrome) is defined as a condition with symptoms persisting for more than 12 weeks after the onset of SARS-CoV-2 infection that cannot be explained otherwise. The prevalence of self-reported otorhinolaryngological Post/Long COVID symptoms is high. The aim of this review was to analyze the current literature regarding the actual prevalence, knowledge of the etiopathology, and evidence-based treatment recommendations of otorhinolaryngology-related Post/Long COVID symptoms. A systematic literature search of articles published since 2019 in PubMed and ScienceDirect was performed and resulted in 108 articles. These were the basis for this review and formed a comprehensive series of consented therapy statements on the most important of otorhinolaryngology-related Post/Long COVID symptoms. Otorhinolaryngological symptoms did not appear isolated but as part of a multi-organ syndrome. Self-reported otorhinolaryngology-related Post/Long COVID symptoms were often not confirmed by objective testing. The confirmed prevalence estimated for anosmia, dysgeusia, cough, facial palsy, hoarseness/dysphonia, acute hearing loss, tinnitus, and vertigo/dizziness was about 4%, 2%, 4-19%, 0%, 17-20%, 8%, 20%, and 5-26%, respectively. There are manifold theoretical concepts of the etiopathology of different symptoms, but there is no clear evidence-based proof. This certainly contributes to the fact that there is no effective specific treatment option for any of the symptoms mentioned. Healthcare pathways must be established so that otorhinolaryngological Post/Long COVID symptoms can be recognized and evaluated and otorhinolaryngologists can provide counseling. This would also help to establish and selectively include patients in clinical trials investigating specific therapeutic concepts.},
}
RevDate: 2025-01-30
Long COVID in Children and Adolescents: Mechanisms, Symptoms, and Long-Term Impact on Health-A Comprehensive Review.
Journal of clinical medicine, 14(2):.
Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), is increasingly recognized as a condition affecting not only adults but also children and adolescents. While children often experience milder acute COVID-19 symptoms compared to adults, some develop persistent physical, psychological, and neurological symptoms lasting for weeks or months after initial infection. The most commonly reported symptoms include debilitating fatigue, respiratory issues, headaches, muscle pain, gastrointestinal disturbances, and cognitive difficulties, which significantly impact daily activities, schooling, and social interactions. Additionally, many children with long COVID experience psychological symptoms, such as anxiety, depression, mood swings, and irritability, likely exacerbated by prolonged illness and lifestyle disruptions. Risk factors for long COVID in children include pre-existing health conditions such as asthma, obesity, and neurological disorders, with adolescents and females seemingly more affected. Hypothesized mechanisms underlying long COVID include chronic immune dysregulation, persistent viral particles stimulating inflammation, autonomic nervous system dysfunction, and mitochondrial impairment, which may collectively contribute to the variety of observed symptoms. Long-term outcomes remain uncertain; however, long COVID can lead to school absenteeism, social withdrawal, and psychological distress, potentially affecting cognitive development. Severe cases may develop chronic conditions such as postural orthostatic tachycardia syndrome (POTS) and reduced exercise tolerance. This review synthesizes the existing literature on long COVID in children, examining its prevalence, symptomatology, risk factors, and potential mechanisms, with an emphasis on the need for further clinical studies. While existing research largely relies on surveys and self-reported data, clinical assessments are essential to accurately characterize long COVID in pediatric populations and to guide effective management strategies.
Additional Links: PMID-39860384
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@article {pmid39860384,
year = {2025},
author = {Basaca, DG and Jugănaru, I and Belei, O and Nicoară, DM and Asproniu, R and Stoicescu, ER and Mărginean, O},
title = {Long COVID in Children and Adolescents: Mechanisms, Symptoms, and Long-Term Impact on Health-A Comprehensive Review.},
journal = {Journal of clinical medicine},
volume = {14},
number = {2},
pages = {},
pmid = {39860384},
issn = {2077-0383},
abstract = {Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), is increasingly recognized as a condition affecting not only adults but also children and adolescents. While children often experience milder acute COVID-19 symptoms compared to adults, some develop persistent physical, psychological, and neurological symptoms lasting for weeks or months after initial infection. The most commonly reported symptoms include debilitating fatigue, respiratory issues, headaches, muscle pain, gastrointestinal disturbances, and cognitive difficulties, which significantly impact daily activities, schooling, and social interactions. Additionally, many children with long COVID experience psychological symptoms, such as anxiety, depression, mood swings, and irritability, likely exacerbated by prolonged illness and lifestyle disruptions. Risk factors for long COVID in children include pre-existing health conditions such as asthma, obesity, and neurological disorders, with adolescents and females seemingly more affected. Hypothesized mechanisms underlying long COVID include chronic immune dysregulation, persistent viral particles stimulating inflammation, autonomic nervous system dysfunction, and mitochondrial impairment, which may collectively contribute to the variety of observed symptoms. Long-term outcomes remain uncertain; however, long COVID can lead to school absenteeism, social withdrawal, and psychological distress, potentially affecting cognitive development. Severe cases may develop chronic conditions such as postural orthostatic tachycardia syndrome (POTS) and reduced exercise tolerance. This review synthesizes the existing literature on long COVID in children, examining its prevalence, symptomatology, risk factors, and potential mechanisms, with an emphasis on the need for further clinical studies. While existing research largely relies on surveys and self-reported data, clinical assessments are essential to accurately characterize long COVID in pediatric populations and to guide effective management strategies.},
}
RevDate: 2025-01-30
Emerging Evidence on Balneotherapy and Thermal Interventions in Post-COVID-19 Syndrome: A Systematic Review.
Healthcare (Basel, Switzerland), 13(2):.
BACKGROUND: Post-COVID-19 syndrome affects 10-60% of SARS-CoV-2 survivors. While conventional treatments show limited efficacy, emerging evidence suggests the potential benefits of balneotherapy in managing persistent symptoms. We aimed to systematically evaluate the efficacy and safety of balneotherapy and thermal treatment interventions in treating post-COVID-19 syndrome.
METHODS: We conducted a systematic review following PRISMA guidelines, searching major databases through 31 January 2024. Eligible studies included randomized controlled trials, observational studies, and pilot studies investigating thermal spa treatments for adult post-COVID-19 patients.
RESULTS: Analysis of six eligible studies (n = 617) demonstrated significant therapeutic benefits. The largest cohort (n = 159) showed 47% reduction in fatigue and 48% reduction in muscle pain (p < 0.01). Comprehensive spa therapy achieved complete symptom resolution in one-third of the participants. Combined spa-ubiquinol therapy improved metabolic function (p < 0.05). All interventions demonstrated favorable safety profiles.
CONCLUSIONS: Preliminary evidence suggests balneotherapy effectively ameliorates multiple post-COVID-19 symptoms, particularly fatigue, muscle pain, and exercise intolerance. While safety profiles appear favorable, larger randomized controlled trials with standardized protocols are needed to establish definitive therapeutic recommendations.
Additional Links: PMID-39857123
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Citation:
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@article {pmid39857123,
year = {2025},
author = {Ferrara, E and Scaramuzzino, M and Murmura, G and D'Addazio, G and Sinjari, B},
title = {Emerging Evidence on Balneotherapy and Thermal Interventions in Post-COVID-19 Syndrome: A Systematic Review.},
journal = {Healthcare (Basel, Switzerland)},
volume = {13},
number = {2},
pages = {},
pmid = {39857123},
issn = {2227-9032},
abstract = {BACKGROUND: Post-COVID-19 syndrome affects 10-60% of SARS-CoV-2 survivors. While conventional treatments show limited efficacy, emerging evidence suggests the potential benefits of balneotherapy in managing persistent symptoms. We aimed to systematically evaluate the efficacy and safety of balneotherapy and thermal treatment interventions in treating post-COVID-19 syndrome.
METHODS: We conducted a systematic review following PRISMA guidelines, searching major databases through 31 January 2024. Eligible studies included randomized controlled trials, observational studies, and pilot studies investigating thermal spa treatments for adult post-COVID-19 patients.
RESULTS: Analysis of six eligible studies (n = 617) demonstrated significant therapeutic benefits. The largest cohort (n = 159) showed 47% reduction in fatigue and 48% reduction in muscle pain (p < 0.01). Comprehensive spa therapy achieved complete symptom resolution in one-third of the participants. Combined spa-ubiquinol therapy improved metabolic function (p < 0.05). All interventions demonstrated favorable safety profiles.
CONCLUSIONS: Preliminary evidence suggests balneotherapy effectively ameliorates multiple post-COVID-19 symptoms, particularly fatigue, muscle pain, and exercise intolerance. While safety profiles appear favorable, larger randomized controlled trials with standardized protocols are needed to establish definitive therapeutic recommendations.},
}
RevDate: 2025-01-30
Unlocking the Potential of RNA Sequencing in COVID-19: Toward Accurate Diagnosis and Personalized Medicine.
Diagnostics (Basel, Switzerland), 15(2):.
COVID-19 has caused widespread morbidity and mortality, with its effects extending to multiple organ systems. Despite known risk factors for severe disease, including advanced age and underlying comorbidities, patient outcomes can vary significantly. This variability complicates efforts to predict disease progression and tailor treatment strategies. While diagnostic and therapeutic approaches are still under debate, RNA sequencing (RNAseq) has emerged as a promising tool to provide deeper insights into the pathophysiology of COVID-19 and guide personalized treatment. A comprehensive literature review was conducted using PubMed, Scopus, Web of Science, and Google Scholar. We employed Medical Subject Headings (MeSH) terms and relevant keywords to identify studies that explored the role of RNAseq in COVID-19 diagnostics, prognostics, and therapeutics. RNAseq has proven instrumental in identifying molecular biomarkers associated with disease severity in patients with COVID-19. It allows for the differentiation between asymptomatic and symptomatic individuals and sheds light on the immune response mechanisms that contribute to disease progression. In critically ill patients, RNAseq has been crucial for identifying key genes that may predict patient outcomes, guiding therapeutic decisions, and assessing the long-term effects of the virus. Additionally, RNAseq has helped in understanding the persistence of viral RNA after recovery, offering new insights into the management of post-acute sequelae, including long COVID. RNA sequencing significantly improves COVID-19 management, particularly for critically ill patients, by enhancing diagnostic accuracy, personalizing treatment, and predicting therapeutic responses. It refines patient stratification, improving outcomes, and holds promise for targeted interventions in both acute and long COVID.
Additional Links: PMID-39857114
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Citation:
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@article {pmid39857114,
year = {2025},
author = {Eldien, HMS and Almaeen, AH and El Fath, AA and Taha, AE and Ahmed, R and Elfadil, H and Hetta, HF},
title = {Unlocking the Potential of RNA Sequencing in COVID-19: Toward Accurate Diagnosis and Personalized Medicine.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {15},
number = {2},
pages = {},
pmid = {39857114},
issn = {2075-4418},
support = {(DSR 2020-04-2621)//Deanship of Scientific Research at Jouf University through research/ ; },
abstract = {COVID-19 has caused widespread morbidity and mortality, with its effects extending to multiple organ systems. Despite known risk factors for severe disease, including advanced age and underlying comorbidities, patient outcomes can vary significantly. This variability complicates efforts to predict disease progression and tailor treatment strategies. While diagnostic and therapeutic approaches are still under debate, RNA sequencing (RNAseq) has emerged as a promising tool to provide deeper insights into the pathophysiology of COVID-19 and guide personalized treatment. A comprehensive literature review was conducted using PubMed, Scopus, Web of Science, and Google Scholar. We employed Medical Subject Headings (MeSH) terms and relevant keywords to identify studies that explored the role of RNAseq in COVID-19 diagnostics, prognostics, and therapeutics. RNAseq has proven instrumental in identifying molecular biomarkers associated with disease severity in patients with COVID-19. It allows for the differentiation between asymptomatic and symptomatic individuals and sheds light on the immune response mechanisms that contribute to disease progression. In critically ill patients, RNAseq has been crucial for identifying key genes that may predict patient outcomes, guiding therapeutic decisions, and assessing the long-term effects of the virus. Additionally, RNAseq has helped in understanding the persistence of viral RNA after recovery, offering new insights into the management of post-acute sequelae, including long COVID. RNA sequencing significantly improves COVID-19 management, particularly for critically ill patients, by enhancing diagnostic accuracy, personalizing treatment, and predicting therapeutic responses. It refines patient stratification, improving outcomes, and holds promise for targeted interventions in both acute and long COVID.},
}
RevDate: 2025-01-31
CmpDate: 2025-01-24
Long COVID and gut microbiome: insights into pathogenesis and therapeutics.
Gut microbes, 17(1):2457495.
Post-acute coronavirus disease 2019 syndrome (PACS), following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 (COVID-19), is typically characterized by long-term debilitating symptoms affecting multiple organs and systems. Unfortunately, there is currently a lack of effective treatment strategies. Altered gut microbiome has been proposed as one of the plausible mechanisms involved in the pathogenesis of PACS; extensive studies have emerged to bridge the gap between the persistent symptoms and the dysbiosis of gut microbiome. Recent clinical trials have indicated that gut microbiome modulation using probiotics, prebiotics, and fecal microbiota transplantation (FMT) led to improvements in multiple symptoms related to PACS, including fatigue, memory loss, difficulty in concentration, gastrointestinal upset, and disturbances in sleep and mood. In this review, we highlight the latest evidence on the key microbial alterations observed in PACS, as well as the use of microbiome-based therapeutics in managing PACS symptoms. These novel findings altogether shed light on the treatment of PACS and other chronic conditions.
Additional Links: PMID-39854158
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@article {pmid39854158,
year = {2025},
author = {Lau, RI and Su, Q and Ng, SC},
title = {Long COVID and gut microbiome: insights into pathogenesis and therapeutics.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2457495},
pmid = {39854158},
issn = {1949-0984},
mesh = {*Gastrointestinal Microbiome ; Humans ; *Fecal Microbiota Transplantation ; *COVID-19/therapy/microbiology ; *Probiotics/therapeutic use ; *Dysbiosis/therapy/microbiology ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome ; Prebiotics/administration & dosage ; },
abstract = {Post-acute coronavirus disease 2019 syndrome (PACS), following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 (COVID-19), is typically characterized by long-term debilitating symptoms affecting multiple organs and systems. Unfortunately, there is currently a lack of effective treatment strategies. Altered gut microbiome has been proposed as one of the plausible mechanisms involved in the pathogenesis of PACS; extensive studies have emerged to bridge the gap between the persistent symptoms and the dysbiosis of gut microbiome. Recent clinical trials have indicated that gut microbiome modulation using probiotics, prebiotics, and fecal microbiota transplantation (FMT) led to improvements in multiple symptoms related to PACS, including fatigue, memory loss, difficulty in concentration, gastrointestinal upset, and disturbances in sleep and mood. In this review, we highlight the latest evidence on the key microbial alterations observed in PACS, as well as the use of microbiome-based therapeutics in managing PACS symptoms. These novel findings altogether shed light on the treatment of PACS and other chronic conditions.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Gastrointestinal Microbiome
Humans
*Fecal Microbiota Transplantation
*COVID-19/therapy/microbiology
*Probiotics/therapeutic use
*Dysbiosis/therapy/microbiology
*SARS-CoV-2
*Post-Acute COVID-19 Syndrome
Prebiotics/administration & dosage
RevDate: 2025-01-29
Current update on the neurological manifestations of long COVID: more questions than answers.
EXCLI journal, 23:1463-1486.
Since the outbreak of the COVID-19 pandemic, there has been a global surge in patients presenting with prolonged or late-onset debilitating sequelae of SARS-CoV-2 infection, colloquially termed long COVID. This narrative review provides an updated synthesis of the latest evidence on the neurological manifestations of long COVID, discussing its clinical phenotypes, underlying pathophysiology, while also presenting the current state of diagnostic and therapeutic approaches. Approximately one-third of COVID-19 survivors experience prolonged neurological sequelae that persist for at least 12-months post-infection, adversely affecting patients' quality of life. Core neurological manifestations comprise fatigue, post-exertional malaise, cognitive impairment, headache, lightheadedness ('brain fog'), sleep disturbances, taste or smell disorders, dysautonomia, anxiety, and depression. Some of these features overlap substantially with those reported in post-intensive-care syndrome, myalgic encephalomyelitis/chronic fatigue syndrome, fibromyalgia, and postural-orthostatic-tachycardia syndrome. Advances in data-driven research utilizing electronic-health-records combined with machine learning and artificial intelligence have propelled the identification of long COVID sub-phenotypes. Furthermore, the evolving definitions reflect the dynamic conceptualization of long COVID in both research and clinical contexts. Although the underlying pathophysiology remains incompletely elucidated, neuroinflammatory responses, endotheliopathy, and metabolic imbalances, rather than direct viral neuroinvasion, are implicated in neurological sequelae. Genetic susceptibility has also emerged as a potential risk factor. While major limitations remain with existing definitions, collaborative strategies to standardize diagnostic approaches are needed. Current therapeutic paradigms advocate for multimodal approaches, integrating pharmacological and non-pharmacological interventions along with comprehensive rehabilitation programs. Although preliminary evidence of therapeutic efficacy has been provided by a number of clinical trials, methodological constraints limit the generalizability of this evidence. Preventive measures, notably vaccination, have proven integral for reducing the global burden of long COVID. Considering the healthcare and socioeconomic repercussions incurred by long COVID worldwide, international collaborative initiatives are warranted to address the remaining challenges in diagnosing and managing patients presenting with neurological sequelae. See also the graphical abstract(Fig. 1).
Additional Links: PMID-39850323
PubMed:
Citation:
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@article {pmid39850323,
year = {2024},
author = {Stefanou, MI and Panagiotopoulos, E and Palaiodimou, L and Bakola, E and Smyrnis, N and Papadopoulou, M and Moschovos, C and Paraskevas, GP and Rizos, E and Boutati, E and Tzavellas, E and Gatzonis, S and Mengel, A and Giannopoulos, S and Tsiodras, S and Kimiskidis, VK and Tsivgoulis, G},
title = {Current update on the neurological manifestations of long COVID: more questions than answers.},
journal = {EXCLI journal},
volume = {23},
number = {},
pages = {1463-1486},
pmid = {39850323},
issn = {1611-2156},
abstract = {Since the outbreak of the COVID-19 pandemic, there has been a global surge in patients presenting with prolonged or late-onset debilitating sequelae of SARS-CoV-2 infection, colloquially termed long COVID. This narrative review provides an updated synthesis of the latest evidence on the neurological manifestations of long COVID, discussing its clinical phenotypes, underlying pathophysiology, while also presenting the current state of diagnostic and therapeutic approaches. Approximately one-third of COVID-19 survivors experience prolonged neurological sequelae that persist for at least 12-months post-infection, adversely affecting patients' quality of life. Core neurological manifestations comprise fatigue, post-exertional malaise, cognitive impairment, headache, lightheadedness ('brain fog'), sleep disturbances, taste or smell disorders, dysautonomia, anxiety, and depression. Some of these features overlap substantially with those reported in post-intensive-care syndrome, myalgic encephalomyelitis/chronic fatigue syndrome, fibromyalgia, and postural-orthostatic-tachycardia syndrome. Advances in data-driven research utilizing electronic-health-records combined with machine learning and artificial intelligence have propelled the identification of long COVID sub-phenotypes. Furthermore, the evolving definitions reflect the dynamic conceptualization of long COVID in both research and clinical contexts. Although the underlying pathophysiology remains incompletely elucidated, neuroinflammatory responses, endotheliopathy, and metabolic imbalances, rather than direct viral neuroinvasion, are implicated in neurological sequelae. Genetic susceptibility has also emerged as a potential risk factor. While major limitations remain with existing definitions, collaborative strategies to standardize diagnostic approaches are needed. Current therapeutic paradigms advocate for multimodal approaches, integrating pharmacological and non-pharmacological interventions along with comprehensive rehabilitation programs. Although preliminary evidence of therapeutic efficacy has been provided by a number of clinical trials, methodological constraints limit the generalizability of this evidence. Preventive measures, notably vaccination, have proven integral for reducing the global burden of long COVID. Considering the healthcare and socioeconomic repercussions incurred by long COVID worldwide, international collaborative initiatives are warranted to address the remaining challenges in diagnosing and managing patients presenting with neurological sequelae. See also the graphical abstract(Fig. 1).},
}
RevDate: 2025-01-30
CmpDate: 2025-01-24
Chronic inflammation in post-acute sequelae of COVID-19 modulates gut microbiome: a review of literature on COVID-19 sequelae and gut dysbiosis.
Molecular medicine (Cambridge, Mass.), 31(1):22.
BACKGROUND: Long COVID or Post-acute sequelae of COVID-19 is an emerging syndrome, recognized in COVID-19 patients who suffer from mild to severe illness and do not recover completely. Most studies define Long COVID, through symptoms like fatigue, brain fog, joint pain, and headache prevailing four or more weeks post-initial infection. Global variations in Long COVID presentation and symptoms make it challenging to standardize features of Long COVID. Long COVID appears to be accompanied by an auto-immune multi-faceted syndrome where the virus or viral antigen persistence causes continuous stimulation of the immune response, resulting in multi-organ immune dysregulation.
MAIN TEXT: This review is focused on understanding the risk factors of Long COVID with a special emphasis on the dysregulation of the gut-brain axis. Two proposed mechanisms are discussed here. The first mechanism is related to the dysfunction of angiotensin-converting enzyme 2 receptor due to Severe Acute Respiratory Syndrome Corona Virus 2 infection, leading to impaired mTOR pathway activation, reduced AMP secretion, and causing dysbiotic changes in the gut. Secondly, gut-brain axis dysregulation accompanied by decreased production of short-chain fatty acids, impaired enteroendocrine cell function, and increased leakiness of the gut, which favors translocation of pathogens or lipopolysaccharide in circulation causing the release of pro-inflammatory cytokines. The altered Hypothalamic-Pituitary-Adrenal axis is accompanied by the reduced level of neurotransmitter, and decreased stimulation of the vagus nerve, which may cause neuroinflammation and dysregulation of serum cortisol levels. The dysbiotic microbiome in Long COVID patients is characterized by a decrease in beneficial short chain fatty acid-producing bacteria (Faecalibacterium, Ruminococcus, Dorea, and Bifidobacterium) and an increase in opportunistic bacteria (Corynebacterium, Streptococcus, Enterococcus). This dysbiosis is transient and may be impacted by interventions including probiotics, and dietary supplements.
CONCLUSIONS: Further studies are required to understand the geographic variation, racial and ethnic differences in phenotypes of Long COVID, the influence of viral strains on existing and emerging phenotypes, to explore long-term effects of gut dysbiosis, and gut-brain axis dysregulation, as well as the potential role of diet and probiotics in alleviating those symptoms.
Additional Links: PMID-39849406
PubMed:
Citation:
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@article {pmid39849406,
year = {2025},
author = {Iqbal, NT and Khan, H and Khalid, A and Mahmood, SF and Nasir, N and Khanum, I and de Siqueira, I and Van Voorhis, W},
title = {Chronic inflammation in post-acute sequelae of COVID-19 modulates gut microbiome: a review of literature on COVID-19 sequelae and gut dysbiosis.},
journal = {Molecular medicine (Cambridge, Mass.)},
volume = {31},
number = {1},
pages = {22},
pmid = {39849406},
issn = {1528-3658},
support = {U01 AI151698/AI/NIAID NIH HHS/United States ; 3U01AI151698//Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases/ ; },
mesh = {Humans ; *COVID-19/immunology/complications ; *Dysbiosis ; *Gastrointestinal Microbiome ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2/physiology ; *Brain-Gut Axis ; Inflammation ; },
abstract = {BACKGROUND: Long COVID or Post-acute sequelae of COVID-19 is an emerging syndrome, recognized in COVID-19 patients who suffer from mild to severe illness and do not recover completely. Most studies define Long COVID, through symptoms like fatigue, brain fog, joint pain, and headache prevailing four or more weeks post-initial infection. Global variations in Long COVID presentation and symptoms make it challenging to standardize features of Long COVID. Long COVID appears to be accompanied by an auto-immune multi-faceted syndrome where the virus or viral antigen persistence causes continuous stimulation of the immune response, resulting in multi-organ immune dysregulation.
MAIN TEXT: This review is focused on understanding the risk factors of Long COVID with a special emphasis on the dysregulation of the gut-brain axis. Two proposed mechanisms are discussed here. The first mechanism is related to the dysfunction of angiotensin-converting enzyme 2 receptor due to Severe Acute Respiratory Syndrome Corona Virus 2 infection, leading to impaired mTOR pathway activation, reduced AMP secretion, and causing dysbiotic changes in the gut. Secondly, gut-brain axis dysregulation accompanied by decreased production of short-chain fatty acids, impaired enteroendocrine cell function, and increased leakiness of the gut, which favors translocation of pathogens or lipopolysaccharide in circulation causing the release of pro-inflammatory cytokines. The altered Hypothalamic-Pituitary-Adrenal axis is accompanied by the reduced level of neurotransmitter, and decreased stimulation of the vagus nerve, which may cause neuroinflammation and dysregulation of serum cortisol levels. The dysbiotic microbiome in Long COVID patients is characterized by a decrease in beneficial short chain fatty acid-producing bacteria (Faecalibacterium, Ruminococcus, Dorea, and Bifidobacterium) and an increase in opportunistic bacteria (Corynebacterium, Streptococcus, Enterococcus). This dysbiosis is transient and may be impacted by interventions including probiotics, and dietary supplements.
CONCLUSIONS: Further studies are required to understand the geographic variation, racial and ethnic differences in phenotypes of Long COVID, the influence of viral strains on existing and emerging phenotypes, to explore long-term effects of gut dysbiosis, and gut-brain axis dysregulation, as well as the potential role of diet and probiotics in alleviating those symptoms.},
}
MeSH Terms:
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Humans
*COVID-19/immunology/complications
*Dysbiosis
*Gastrointestinal Microbiome
*Post-Acute COVID-19 Syndrome
*SARS-CoV-2/physiology
*Brain-Gut Axis
Inflammation
RevDate: 2025-01-21
Strategic Inhibition of CHRM Autoantibodies: Molecular Insights and Therapeutic Potentials in Long COVID.
Journal of medicinal chemistry [Epub ahead of print].
In addition to the conventional symptoms reported for COVID-19, it is becoming increasingly clear that patients with long COVID are exhibiting new symptoms due to the emergence of autoantibodies against G-protein-coupled receptors, among which human muscarinic cholinergic receptors (CHRMs) have been prominently reported. With a chronic condition such as long COVID, additional symptoms caused by anti-CHRM autoantibodies (AAbs) have proven to be an added burden on these patients. The origins of these AAbs, their interactions with, and effects on the function of neural and non-neural cells within the nervous system have remained unknown. Furthermore, the specific symptom complex to which they contribute has not been clearly understood. In this context, we address these issues here and suggest methods to combat the autoantibodies that contribute to neurological symptoms in long COVID.
Additional Links: PMID-39836023
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PubMed:
Citation:
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@article {pmid39836023,
year = {2025},
author = {Baig, AM and Rosko, S and Jaeger, B and Gerlach, J},
title = {Strategic Inhibition of CHRM Autoantibodies: Molecular Insights and Therapeutic Potentials in Long COVID.},
journal = {Journal of medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jmedchem.4c00691},
pmid = {39836023},
issn = {1520-4804},
abstract = {In addition to the conventional symptoms reported for COVID-19, it is becoming increasingly clear that patients with long COVID are exhibiting new symptoms due to the emergence of autoantibodies against G-protein-coupled receptors, among which human muscarinic cholinergic receptors (CHRMs) have been prominently reported. With a chronic condition such as long COVID, additional symptoms caused by anti-CHRM autoantibodies (AAbs) have proven to be an added burden on these patients. The origins of these AAbs, their interactions with, and effects on the function of neural and non-neural cells within the nervous system have remained unknown. Furthermore, the specific symptom complex to which they contribute has not been clearly understood. In this context, we address these issues here and suggest methods to combat the autoantibodies that contribute to neurological symptoms in long COVID.},
}
RevDate: 2025-01-29
CmpDate: 2025-01-21
Autoantibodies in COVID-19: implications for disease severity and clinical outcomes.
Frontiers in immunology, 15:1509289.
Few pathogens have historically been subjected to as intense scientific and clinical scrutiny as SARS-CoV-2. The genetic, immunological, and environmental factors influencing disease severity and post-infection clinical outcomes, known as correlates of immunity, remain largely undefined. Clinical outcomes of SARS-CoV-2 infection vary widely, ranging from asymptomatic cases to those with life-threatening COVID-19 symptoms. While most infected individuals return to their former health and fitness within a few weeks, some develop debilitating chronic symptoms, referred to as long-COVID. Autoimmune responses have been proposed as one of the factors influencing long-COVID and the severity of SARS-CoV-2 infection. The association between viral infections and autoimmune pathologies is not new. Viruses such as Epstein-Barr virus and cytomegalovirus, among others, have been shown to induce the production of autoantibodies and the onset of autoimmune conditions. Given the extensive literature on SARS-CoV-2, here we review current evidence on SARS-CoV-2-induced autoimmune pathologies, with a focus on autoantibodies. We closely examine mechanisms driving autoantibody production, particularly their connection with disease severity and long-COVID.
Additional Links: PMID-39835117
PubMed:
Citation:
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@article {pmid39835117,
year = {2024},
author = {Galipeau, Y and Cooper, C and Langlois, MA},
title = {Autoantibodies in COVID-19: implications for disease severity and clinical outcomes.},
journal = {Frontiers in immunology},
volume = {15},
number = {},
pages = {1509289},
pmid = {39835117},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology ; *Autoantibodies/immunology ; *SARS-CoV-2/immunology ; *Severity of Illness Index ; Autoimmunity ; Autoimmune Diseases/immunology ; },
abstract = {Few pathogens have historically been subjected to as intense scientific and clinical scrutiny as SARS-CoV-2. The genetic, immunological, and environmental factors influencing disease severity and post-infection clinical outcomes, known as correlates of immunity, remain largely undefined. Clinical outcomes of SARS-CoV-2 infection vary widely, ranging from asymptomatic cases to those with life-threatening COVID-19 symptoms. While most infected individuals return to their former health and fitness within a few weeks, some develop debilitating chronic symptoms, referred to as long-COVID. Autoimmune responses have been proposed as one of the factors influencing long-COVID and the severity of SARS-CoV-2 infection. The association between viral infections and autoimmune pathologies is not new. Viruses such as Epstein-Barr virus and cytomegalovirus, among others, have been shown to induce the production of autoantibodies and the onset of autoimmune conditions. Given the extensive literature on SARS-CoV-2, here we review current evidence on SARS-CoV-2-induced autoimmune pathologies, with a focus on autoantibodies. We closely examine mechanisms driving autoantibody production, particularly their connection with disease severity and long-COVID.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*COVID-19/immunology
*Autoantibodies/immunology
*SARS-CoV-2/immunology
*Severity of Illness Index
Autoimmunity
Autoimmune Diseases/immunology
RevDate: 2025-02-10
CmpDate: 2025-02-10
Productivity Losses due to Health Problems Arising from COVID-19 Pandemic: A Systematic Review of Population-Level Studies Worldwide.
Applied health economics and health policy, 23(2):231-251.
AIM: To systematically review the evidence on productivity losses due to health problems arising from the COVID-19 pandemic based on evidence from population-level studies.
METHODS: Following PRISMA statement, we conducted a systematic review using Medline, Embase, Scopus, Web of Science, EconLit, WHO COVID-19 Research and EuropePMC databases and a grey literature search. We included population-level studies using secondary data and qualitatively assessed eligible studies. For a quantitative cross-study comparison, we calculated losses in 2020 international dollars and as a share of gross domestic product. PROSPERO registration number: CRD42023478059.
RESULTS: Thirty-eight studies were eligible for review, most of which reported losses in high-income countries and the European region. COVID-19 was a focus of 33 studies while 3 studies investigated losses from both long COVID and excess mortality. The Human Capital Approach dominated (30 studies) and no study used the Friction Cost Approach. Most studies (84%) reported on premature mortality losses and a quarter provided estimates of losses due to absenteeism. Of the 33 studies eligible for quantitative comparison, we found that the productivity losses ranged from 0 to 2.1% of gross domestic product; the greatest losses were in the high-income countries and for those aged 40-59 years; and losses among men contributed to around 3/4 of the total burden.
CONCLUSION: The available evidence on the topic is limited, particularly considering the methodological approaches used. Thus, more research is needed to reach a more comprehensive understanding of economy-level productivity losses resulting from the recent COVID-19 pandemic.
Additional Links: PMID-39832090
PubMed:
Citation:
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@article {pmid39832090,
year = {2025},
author = {Niewiadomski, P and Ortega-Ortega, M and Łyszczarz, B},
title = {Productivity Losses due to Health Problems Arising from COVID-19 Pandemic: A Systematic Review of Population-Level Studies Worldwide.},
journal = {Applied health economics and health policy},
volume = {23},
number = {2},
pages = {231-251},
pmid = {39832090},
issn = {1179-1896},
support = {2022/47/B/HS4/00081//Narodowe Centrum Nauki/ ; },
mesh = {Humans ; *COVID-19/epidemiology/economics/mortality ; *SARS-CoV-2 ; Efficiency ; Pandemics/economics ; Absenteeism ; Global Health/economics ; Cost of Illness ; },
abstract = {AIM: To systematically review the evidence on productivity losses due to health problems arising from the COVID-19 pandemic based on evidence from population-level studies.
METHODS: Following PRISMA statement, we conducted a systematic review using Medline, Embase, Scopus, Web of Science, EconLit, WHO COVID-19 Research and EuropePMC databases and a grey literature search. We included population-level studies using secondary data and qualitatively assessed eligible studies. For a quantitative cross-study comparison, we calculated losses in 2020 international dollars and as a share of gross domestic product. PROSPERO registration number: CRD42023478059.
RESULTS: Thirty-eight studies were eligible for review, most of which reported losses in high-income countries and the European region. COVID-19 was a focus of 33 studies while 3 studies investigated losses from both long COVID and excess mortality. The Human Capital Approach dominated (30 studies) and no study used the Friction Cost Approach. Most studies (84%) reported on premature mortality losses and a quarter provided estimates of losses due to absenteeism. Of the 33 studies eligible for quantitative comparison, we found that the productivity losses ranged from 0 to 2.1% of gross domestic product; the greatest losses were in the high-income countries and for those aged 40-59 years; and losses among men contributed to around 3/4 of the total burden.
CONCLUSION: The available evidence on the topic is limited, particularly considering the methodological approaches used. Thus, more research is needed to reach a more comprehensive understanding of economy-level productivity losses resulting from the recent COVID-19 pandemic.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*COVID-19/epidemiology/economics/mortality
*SARS-CoV-2
Efficiency
Pandemics/economics
Absenteeism
Global Health/economics
Cost of Illness
RevDate: 2025-02-12
CmpDate: 2025-02-05
Association between physical activity practice and sleep quality of older people in social isolation during the COVID-19 pandemic and Health Guidelines and future studies for the post-COVID period: a systematic review.
Aging, 17(1):51-66.
PURPOSE: Physical activity (PA) is considered an alternative to mitigate the negative impacts of the COVID-19 pandemic on the sleep of older adults. The objective was to verify the association between physical activity and the sleep quality of older people in social isolation during the COVID-19 pandemic, to analyze the Health Guidelines, and suggest future studies for the post-COVID period.
METHODS: This systematic review followed PRISMA recommendations, and the protocol was registered in PROSPERO (CRD 42023406471). The search for articles occurred in April 2024 in the databases PubMed, Web of Science, SCOPUS, and gray literature. Data were extracted and checked in a Microsoft Excel[®] spreadsheet. The quality assessment was performed using tools from the National Institutes of Health.
RESULTS: In total, 1582 studies were found in the databases, of which nine were included in the analyses. Four studies reported a negative association of reduced levels of PA during the pandemic with sleep quality, while one study showed a positive association of PA with sleep quality. Four studies demonstrated no association.
CONCLUSIONS: PA was associated with the sleep quality of older adults during the COVID-19 pandemic and reduced levels of PA during this period demonstrated a negative association with sleep quality. Practice of PA is recommended for this post-COVID scenario, as a measure to reduce social isolation and its negative effects and improve the quality of sleep in older adults.
Additional Links: PMID-39820003
PubMed:
Citation:
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@article {pmid39820003,
year = {2025},
author = {Andrade, A and Bastos, ACRF and D'Oliveira, A and Vilarino, GT},
title = {Association between physical activity practice and sleep quality of older people in social isolation during the COVID-19 pandemic and Health Guidelines and future studies for the post-COVID period: a systematic review.},
journal = {Aging},
volume = {17},
number = {1},
pages = {51-66},
pmid = {39820003},
issn = {1945-4589},
mesh = {Humans ; *COVID-19/epidemiology/psychology/prevention & control ; *Social Isolation/psychology ; *Exercise ; Aged ; *Sleep Quality ; SARS-CoV-2 ; },
abstract = {PURPOSE: Physical activity (PA) is considered an alternative to mitigate the negative impacts of the COVID-19 pandemic on the sleep of older adults. The objective was to verify the association between physical activity and the sleep quality of older people in social isolation during the COVID-19 pandemic, to analyze the Health Guidelines, and suggest future studies for the post-COVID period.
METHODS: This systematic review followed PRISMA recommendations, and the protocol was registered in PROSPERO (CRD 42023406471). The search for articles occurred in April 2024 in the databases PubMed, Web of Science, SCOPUS, and gray literature. Data were extracted and checked in a Microsoft Excel[®] spreadsheet. The quality assessment was performed using tools from the National Institutes of Health.
RESULTS: In total, 1582 studies were found in the databases, of which nine were included in the analyses. Four studies reported a negative association of reduced levels of PA during the pandemic with sleep quality, while one study showed a positive association of PA with sleep quality. Four studies demonstrated no association.
CONCLUSIONS: PA was associated with the sleep quality of older adults during the COVID-19 pandemic and reduced levels of PA during this period demonstrated a negative association with sleep quality. Practice of PA is recommended for this post-COVID scenario, as a measure to reduce social isolation and its negative effects and improve the quality of sleep in older adults.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*COVID-19/epidemiology/psychology/prevention & control
*Social Isolation/psychology
*Exercise
Aged
*Sleep Quality
SARS-CoV-2
RevDate: 2025-01-16
CmpDate: 2025-01-16
A systematic analysis of the literature on the post-COVID-19 condition in Latin America focusing on epidemiology, clinical characteristics, and risk of bias.
Medwave, 25(1):e3014.
This analysis article aimed to identify and analyze all articles published on the post-COVID-19 condition in Latin America and the Caribbean, focusing on epidemiology, clinical characteristics, and risk of bias. We did a systematic survey of the literature with broad inclusion criteria. The only exclusion criteria were articles referring to post-acute COVID-19 sequelae after an intensive care unit stay, which we distinguish from the post-COVID-19 condition. We searched MEDLINE/PubMed, LILACS, SciELO, Scopus, Web of Science, and Epistemonikos. We included 55 records, of which 48 were original articles (44 were observational research, 29 of which had a comparison group; and four reviews). Various definitions for long COVID were reported, or none, and few used the World Health Organization criteria. None of the included studies reported prevalence rates for the region. We extracted the reported signs and symptoms of long COVID for our region. Using the Johanna Briggs Institute critical appraisal tools for observational analytic research, we found that most included studies were prone to limitations and biases. We conclude that more research should be done on the post-COVID-19 condition in Latin America and the Caribbean, using rigorous study designs to inform public health strategies.
Additional Links: PMID-39817917
Publisher:
PubMed:
Citation:
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@article {pmid39817917,
year = {2025},
author = {Bachelet, VC and Carroza, B and Morgado, B and Silva-Ayarza, I},
title = {A systematic analysis of the literature on the post-COVID-19 condition in Latin America focusing on epidemiology, clinical characteristics, and risk of bias.},
journal = {Medwave},
volume = {25},
number = {1},
pages = {e3014},
doi = {10.5867/medwave.2025.01.3014},
pmid = {39817917},
issn = {0717-6384},
mesh = {Humans ; *COVID-19/epidemiology ; Latin America/epidemiology ; *Bias ; Caribbean Region/epidemiology ; Post-Acute COVID-19 Syndrome ; Prevalence ; Intensive Care Units/statistics & numerical data ; },
abstract = {This analysis article aimed to identify and analyze all articles published on the post-COVID-19 condition in Latin America and the Caribbean, focusing on epidemiology, clinical characteristics, and risk of bias. We did a systematic survey of the literature with broad inclusion criteria. The only exclusion criteria were articles referring to post-acute COVID-19 sequelae after an intensive care unit stay, which we distinguish from the post-COVID-19 condition. We searched MEDLINE/PubMed, LILACS, SciELO, Scopus, Web of Science, and Epistemonikos. We included 55 records, of which 48 were original articles (44 were observational research, 29 of which had a comparison group; and four reviews). Various definitions for long COVID were reported, or none, and few used the World Health Organization criteria. None of the included studies reported prevalence rates for the region. We extracted the reported signs and symptoms of long COVID for our region. Using the Johanna Briggs Institute critical appraisal tools for observational analytic research, we found that most included studies were prone to limitations and biases. We conclude that more research should be done on the post-COVID-19 condition in Latin America and the Caribbean, using rigorous study designs to inform public health strategies.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*COVID-19/epidemiology
Latin America/epidemiology
*Bias
Caribbean Region/epidemiology
Post-Acute COVID-19 Syndrome
Prevalence
Intensive Care Units/statistics & numerical data
RevDate: 2025-01-15
Dysphonia and COVID-19: A Review.
Journal of voice : official journal of the Voice Foundation pii:S0892-1997(24)00419-3 [Epub ahead of print].
INTRODUCTION: Vocal symptoms are frequent in patients with coronavirus disease 2019 (COVID-19) and may occur during or after infection.
OBJECTIVE: To conduct a descriptive review on the topic "dysphonia and COVID-19" in order to alert specialists to these symptoms associated with the virus and sequelae.
METHODOLOGY: A literature review was carried out in the main databases: Web of Science, PubMed, Google Scholar, and Scopus, between April 2020 and April 2024 using descriptors that related COVID-19 or severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) to voice disorders.
RESULTS: In total, 41 studies, 13 case reports, 6 retrospective, and 22 prospective, 5139 patients (2131 M, 2991 F), mean age of 51 years. The prevalence of dysphonia ranged from 0.39% to 79%. The most prevalent vocal symptoms were hoarseness, cough, dry throat, sore throat, reflux, aphonia, phonasthenia, stridor, and hypersecretion. Videolaryngoscopic findings: unilateral paralysis (145), bilateral paralysis (16), erythema (84), benign lesions (56), muscle tension dysphonia (54), granulomas (33), edema (31), stenosis (22), atrophy (19), incomplete glottal closure (12), and ventricular hypertrophy (6). Auditory-perceptual analyses identified mild/moderate vocal impairment in infected patients and persistence of changes in the long-COVID period. Acoustic analyses indicated significant changes in Jitter, Shimmer, harmonic-to-noise ratio (NHR), and maximum phonation time in patients with COVID-19.
CONCLUSION: Dysphonia caused by COVID-19 infection is common, both in the acute and chronic phases of the disease. The main causes include vocal fold paralysis, inflammatory laryngitis, and muscle tension dysphonia. All patients who present vocal symptoms after COVID-19 infection should undergo videolaryngoscopy and subjective and acoustic vocal analyses to identify sequelae of the disease.
Additional Links: PMID-39814621
Publisher:
PubMed:
Citation:
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@article {pmid39814621,
year = {2025},
author = {Martins, RHG and de Azevedo, ES and Müller, JVC and Loli, A},
title = {Dysphonia and COVID-19: A Review.},
journal = {Journal of voice : official journal of the Voice Foundation},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jvoice.2024.11.034},
pmid = {39814621},
issn = {1873-4588},
abstract = {INTRODUCTION: Vocal symptoms are frequent in patients with coronavirus disease 2019 (COVID-19) and may occur during or after infection.
OBJECTIVE: To conduct a descriptive review on the topic "dysphonia and COVID-19" in order to alert specialists to these symptoms associated with the virus and sequelae.
METHODOLOGY: A literature review was carried out in the main databases: Web of Science, PubMed, Google Scholar, and Scopus, between April 2020 and April 2024 using descriptors that related COVID-19 or severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) to voice disorders.
RESULTS: In total, 41 studies, 13 case reports, 6 retrospective, and 22 prospective, 5139 patients (2131 M, 2991 F), mean age of 51 years. The prevalence of dysphonia ranged from 0.39% to 79%. The most prevalent vocal symptoms were hoarseness, cough, dry throat, sore throat, reflux, aphonia, phonasthenia, stridor, and hypersecretion. Videolaryngoscopic findings: unilateral paralysis (145), bilateral paralysis (16), erythema (84), benign lesions (56), muscle tension dysphonia (54), granulomas (33), edema (31), stenosis (22), atrophy (19), incomplete glottal closure (12), and ventricular hypertrophy (6). Auditory-perceptual analyses identified mild/moderate vocal impairment in infected patients and persistence of changes in the long-COVID period. Acoustic analyses indicated significant changes in Jitter, Shimmer, harmonic-to-noise ratio (NHR), and maximum phonation time in patients with COVID-19.
CONCLUSION: Dysphonia caused by COVID-19 infection is common, both in the acute and chronic phases of the disease. The main causes include vocal fold paralysis, inflammatory laryngitis, and muscle tension dysphonia. All patients who present vocal symptoms after COVID-19 infection should undergo videolaryngoscopy and subjective and acoustic vocal analyses to identify sequelae of the disease.},
}
RevDate: 2025-01-29
A Comparative Review of the Terms Epipharyngitis and Nasopharyngitis in Medical Literature.
Cureus, 16(12):e75738.
This review explores the usage of the term "epipharyngitis" in medical literature, particularly in non-English-speaking contexts. The term, although rarely used in contemporary English-language medical literature, may lead to confusion due to its overlap with more commonly used terms like "nasopharyngitis." This review aims to trace the origins of the term, analyze its usage across different languages, and discuss the implications of term differences in clinical practice and medical education.
Additional Links: PMID-39811236
PubMed:
Citation:
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@article {pmid39811236,
year = {2024},
author = {Razzak, AN and Kaizu, Y and Starkey, J},
title = {A Comparative Review of the Terms Epipharyngitis and Nasopharyngitis in Medical Literature.},
journal = {Cureus},
volume = {16},
number = {12},
pages = {e75738},
pmid = {39811236},
issn = {2168-8184},
abstract = {This review explores the usage of the term "epipharyngitis" in medical literature, particularly in non-English-speaking contexts. The term, although rarely used in contemporary English-language medical literature, may lead to confusion due to its overlap with more commonly used terms like "nasopharyngitis." This review aims to trace the origins of the term, analyze its usage across different languages, and discuss the implications of term differences in clinical practice and medical education.},
}
RevDate: 2025-01-16
CmpDate: 2025-01-14
Risk impact of SARS-CoV-2 coronavirus and spike protein on cardiac tissue: a comprehensive review.
Physiological research, 73(S3):S655-S669.
The global COVID-19 pandemic, caused by SARS-CoV-2, has led to significant morbidity and mortality, with a profound impact on cardiovascular health. This review investigates the mechanisms of SARS-CoV-2's interaction with cardiac tissue, particularly emphasizing the role of the Spike protein and ACE2 receptor in facilitating viral entry and subsequent cardiac complications. We dissect the structural features of the virus, its interactions with host cell receptors, and the resulting pathophysiological changes in the heart. Highlighting SARS-CoV-2's broad organ tropism, especially its effects on cardiomyocytes via ACE2 and TMPRSS2, the review addresses how these interactions exacerbate cardiovascular issues in patients with pre-existing conditions such as diabetes and hypertension. Additionally, we assess both direct and indirect mechanisms of virus-induced cardiac damage, including myocarditis, arrhythmias, and long-term complications such as 'long COVID'. This review underscores the complexity of SARS-CoV-2's impact on the heart, emphasizing the need for ongoing research to fully understand its long-term effects on cardiovascular health. Key words: COVID-19, Heart, ACE2, Spike protein, Cardiomyocytes, Myocarditis, Long COVID.
Additional Links: PMID-39808169
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PubMed:
Citation:
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@article {pmid39808169,
year = {2024},
author = {Šerý, O and Dziedzinska, R},
title = {Risk impact of SARS-CoV-2 coronavirus and spike protein on cardiac tissue: a comprehensive review.},
journal = {Physiological research},
volume = {73},
number = {S3},
pages = {S655-S669},
doi = {10.33549/physiolres.935476},
pmid = {39808169},
issn = {1802-9973},
mesh = {Humans ; *Spike Glycoprotein, Coronavirus/metabolism ; *COVID-19/metabolism ; *SARS-CoV-2/pathogenicity ; *Angiotensin-Converting Enzyme 2/metabolism ; Animals ; Myocytes, Cardiac/metabolism/virology/pathology ; Virus Internalization ; Myocardium/metabolism/pathology ; },
abstract = {The global COVID-19 pandemic, caused by SARS-CoV-2, has led to significant morbidity and mortality, with a profound impact on cardiovascular health. This review investigates the mechanisms of SARS-CoV-2's interaction with cardiac tissue, particularly emphasizing the role of the Spike protein and ACE2 receptor in facilitating viral entry and subsequent cardiac complications. We dissect the structural features of the virus, its interactions with host cell receptors, and the resulting pathophysiological changes in the heart. Highlighting SARS-CoV-2's broad organ tropism, especially its effects on cardiomyocytes via ACE2 and TMPRSS2, the review addresses how these interactions exacerbate cardiovascular issues in patients with pre-existing conditions such as diabetes and hypertension. Additionally, we assess both direct and indirect mechanisms of virus-induced cardiac damage, including myocarditis, arrhythmias, and long-term complications such as 'long COVID'. This review underscores the complexity of SARS-CoV-2's impact on the heart, emphasizing the need for ongoing research to fully understand its long-term effects on cardiovascular health. Key words: COVID-19, Heart, ACE2, Spike protein, Cardiomyocytes, Myocarditis, Long COVID.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Spike Glycoprotein, Coronavirus/metabolism
*COVID-19/metabolism
*SARS-CoV-2/pathogenicity
*Angiotensin-Converting Enzyme 2/metabolism
Animals
Myocytes, Cardiac/metabolism/virology/pathology
Virus Internalization
Myocardium/metabolism/pathology
RevDate: 2025-01-16
CmpDate: 2025-01-14
Patient-reported outcome measures for post-COVID-19 condition: a systematic review of instruments and measurement properties.
BMJ open, 14(12):e084202.
OBJECTIVES: Post-COVID-19 condition (PCC), also referred to as Long COVID, has become an emerging public health issue requiring adequate prevention, treatment and management strategies. Evaluating these strategies from the patients' perspective using patient-reported outcome measures (PROMs) is critical. In this systematic review, we aimed to critically appraise and summarise the quality of existing PROMs for PCC, and to identify PROMs that can be recommended for use in future research.
DESIGN: Systematic review using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology.
DATA SOURCES: PubMed and Web of Science were searched on 16 January 2023 and again on 23 July 2024.
ELIGIBILITY CRITERIA: We included studies reporting on the development and/or validation of any disease-specific PROMs for PCC.
DATA EXTRACTION AND SYNTHESIS: Two independent reviewers screened the results for eligibility. The methodological quality of each included study was assessed using the COSMIN Risk of Bias Checklist. We further evaluated the quality of measurement properties per PROM and study according to the criteria for good measurement properties as outlined in the COSMIN manual, and graded the evidence of the synthesised results. Based on the overall evidence, we derived recommendations for the use of the identified instruments.
RESULTS: We identified 23 studies reporting on 11 PROMs measuring functional status (COVID-19 Yorkshire Rehabilitation Scale, C19-YRS; Modified COVID-19 Yorkshire Rehabilitation Scale, C19-YRSm; Functional Impairment Checklist, FIC; Post-COVID-19 Functional Status Scale, PCFS), symptom burden and impact (Long COVID Symptom and Severity Score, LC-SSS; Long COVID Symptom Tool, LCST; Long COVID Impact Tool, LCIT; Symptom Burden Questionnaire Long COVID, SBQ-LC), quality of life (Post-acute COVID-19 Quality of Life instrument, PAC-19QoL) and stigma (Long COVID Stigma Scale, LCSS; Post-COVID-19 Condition Stigma Questionnaire, PCCSQ). Sample sizes of the included studies ranged from 29 to 1969 participants. Overall, 95 single studies on measurement properties were evaluated. Among the identified instruments, the Long Covid Stigma Scale (LCSS) showed sufficient content validity and internal consistency and can be recommended for use according to COSMIN criteria. Our assessment of measurement properties revealed significant evidence gaps for all PROMs, indicating the need for further validation studies to make an adequate decision on the recommendation for their use. Content validity is a major shortcoming of all included instruments.
CONCLUSION: The LCSS measuring stigma can be recommended for use in future research. For the assessment of PCC symptoms and impact, no instrument with sufficient measurement properties is currently available. Further validation of all identified PROMs is indicated, in particular comprehensive assessments of content validity involving experts and patients.
PROSPERO REGISTRATION NUMBER: CRD42023391238.
Additional Links: PMID-39806627
PubMed:
Citation:
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@article {pmid39806627,
year = {2024},
author = {Baalmann, AK and Blome, C and Stoletzki, N and Donhauser, T and Apfelbacher, C and Piontek, K},
title = {Patient-reported outcome measures for post-COVID-19 condition: a systematic review of instruments and measurement properties.},
journal = {BMJ open},
volume = {14},
number = {12},
pages = {e084202},
pmid = {39806627},
issn = {2044-6055},
mesh = {Humans ; *Patient Reported Outcome Measures ; *COVID-19 ; *Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {OBJECTIVES: Post-COVID-19 condition (PCC), also referred to as Long COVID, has become an emerging public health issue requiring adequate prevention, treatment and management strategies. Evaluating these strategies from the patients' perspective using patient-reported outcome measures (PROMs) is critical. In this systematic review, we aimed to critically appraise and summarise the quality of existing PROMs for PCC, and to identify PROMs that can be recommended for use in future research.
DESIGN: Systematic review using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology.
DATA SOURCES: PubMed and Web of Science were searched on 16 January 2023 and again on 23 July 2024.
ELIGIBILITY CRITERIA: We included studies reporting on the development and/or validation of any disease-specific PROMs for PCC.
DATA EXTRACTION AND SYNTHESIS: Two independent reviewers screened the results for eligibility. The methodological quality of each included study was assessed using the COSMIN Risk of Bias Checklist. We further evaluated the quality of measurement properties per PROM and study according to the criteria for good measurement properties as outlined in the COSMIN manual, and graded the evidence of the synthesised results. Based on the overall evidence, we derived recommendations for the use of the identified instruments.
RESULTS: We identified 23 studies reporting on 11 PROMs measuring functional status (COVID-19 Yorkshire Rehabilitation Scale, C19-YRS; Modified COVID-19 Yorkshire Rehabilitation Scale, C19-YRSm; Functional Impairment Checklist, FIC; Post-COVID-19 Functional Status Scale, PCFS), symptom burden and impact (Long COVID Symptom and Severity Score, LC-SSS; Long COVID Symptom Tool, LCST; Long COVID Impact Tool, LCIT; Symptom Burden Questionnaire Long COVID, SBQ-LC), quality of life (Post-acute COVID-19 Quality of Life instrument, PAC-19QoL) and stigma (Long COVID Stigma Scale, LCSS; Post-COVID-19 Condition Stigma Questionnaire, PCCSQ). Sample sizes of the included studies ranged from 29 to 1969 participants. Overall, 95 single studies on measurement properties were evaluated. Among the identified instruments, the Long Covid Stigma Scale (LCSS) showed sufficient content validity and internal consistency and can be recommended for use according to COSMIN criteria. Our assessment of measurement properties revealed significant evidence gaps for all PROMs, indicating the need for further validation studies to make an adequate decision on the recommendation for their use. Content validity is a major shortcoming of all included instruments.
CONCLUSION: The LCSS measuring stigma can be recommended for use in future research. For the assessment of PCC symptoms and impact, no instrument with sufficient measurement properties is currently available. Further validation of all identified PROMs is indicated, in particular comprehensive assessments of content validity involving experts and patients.
PROSPERO REGISTRATION NUMBER: CRD42023391238.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Patient Reported Outcome Measures
*COVID-19
*Quality of Life
SARS-CoV-2
Post-Acute COVID-19 Syndrome
RevDate: 2025-01-13
CmpDate: 2025-01-11
Mitochondria and the Repurposing of Diabetes Drugs for Off-Label Health Benefits.
International journal of molecular sciences, 26(1):.
This review describes our current understanding of the role of the mitochondria in the repurposing of the anti-diabetes drugs metformin, gliclazide, GLP-1 receptor agonists, and SGLT2 inhibitors for additional clinical benefits regarding unhealthy aging, long COVID, mental neurogenerative disorders, and obesity. Metformin, the most prominent of these diabetes drugs, has been called the "Drug of Miracles and Wonders," as clinical trials have found it to be beneficial for human patients suffering from these maladies. To promote viral replication in all infected human cells, SARS-CoV-2 stimulates the infected liver cells to produce glucose and to export it into the blood stream, which can cause diabetes in long COVID patients, and metformin, which reduces the levels of glucose in the blood, was shown to cut the incidence rate of long COVID in half for all patients recovering from SARS-CoV-2. Metformin leads to the phosphorylation of the AMP-activated protein kinase AMPK, which accelerates the import of glucose into cells via the glucose transporter GLUT4 and switches the cells to the starvation mode, counteracting the virus. Diabetes drugs also stimulate the unfolded protein response and thus mitophagy, which is beneficial for healthy aging and mental health. Diabetes drugs were also found to mimic exercise and help to reduce body weight.
Additional Links: PMID-39796218
PubMed:
Citation:
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@article {pmid39796218,
year = {2025},
author = {Yip, JMX and Chiang, GSH and Lee, ICJ and Lehming-Teo, R and Dai, K and Dongol, L and Wang, LY and Teo, D and Seah, GT and Lehming, N},
title = {Mitochondria and the Repurposing of Diabetes Drugs for Off-Label Health Benefits.},
journal = {International journal of molecular sciences},
volume = {26},
number = {1},
pages = {},
pmid = {39796218},
issn = {1422-0067},
support = {A-8000724-00-00//Ministry of Education/ ; },
mesh = {Humans ; *Drug Repositioning/methods ; *Mitochondria/metabolism/drug effects ; *Hypoglycemic Agents/therapeutic use/pharmacology ; *COVID-19 Drug Treatment ; Metformin/therapeutic use/pharmacology ; SARS-CoV-2/drug effects ; COVID-19/metabolism/virology ; Off-Label Use ; Diabetes Mellitus/drug therapy/metabolism ; Animals ; },
abstract = {This review describes our current understanding of the role of the mitochondria in the repurposing of the anti-diabetes drugs metformin, gliclazide, GLP-1 receptor agonists, and SGLT2 inhibitors for additional clinical benefits regarding unhealthy aging, long COVID, mental neurogenerative disorders, and obesity. Metformin, the most prominent of these diabetes drugs, has been called the "Drug of Miracles and Wonders," as clinical trials have found it to be beneficial for human patients suffering from these maladies. To promote viral replication in all infected human cells, SARS-CoV-2 stimulates the infected liver cells to produce glucose and to export it into the blood stream, which can cause diabetes in long COVID patients, and metformin, which reduces the levels of glucose in the blood, was shown to cut the incidence rate of long COVID in half for all patients recovering from SARS-CoV-2. Metformin leads to the phosphorylation of the AMP-activated protein kinase AMPK, which accelerates the import of glucose into cells via the glucose transporter GLUT4 and switches the cells to the starvation mode, counteracting the virus. Diabetes drugs also stimulate the unfolded protein response and thus mitophagy, which is beneficial for healthy aging and mental health. Diabetes drugs were also found to mimic exercise and help to reduce body weight.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Drug Repositioning/methods
*Mitochondria/metabolism/drug effects
*Hypoglycemic Agents/therapeutic use/pharmacology
*COVID-19 Drug Treatment
Metformin/therapeutic use/pharmacology
SARS-CoV-2/drug effects
COVID-19/metabolism/virology
Off-Label Use
Diabetes Mellitus/drug therapy/metabolism
Animals
RevDate: 2025-01-13
CmpDate: 2025-01-11
Complex Pattern of Platelet Activation/Reactivity After SARS-CoV-2 Infection.
International journal of molecular sciences, 26(1):.
COVID-19 and post-COVID (long COVID) are associated with thromboembolic complications; however, it is still not clear whether platelets play a leading role in this phenomenon. The platelet hyperreactivity could result from the direct interaction between platelets and viral elements or the response to inflammatory and prothrombotic factors released from blood and vessel cells following infection. The existing literature does not provide clear-cut answers, as the results determining platelet status vary according to methodology. Elevated levels of soluble markers of platelet activation (P selectin, PF4), increased platelet aggregates, and platelet-derived microparticles suggest the activation of platelets circulating in the bloodstream of COVID-19 patients. Similarly, platelets isolated from COVID-19 patients demonstrate increased reactivity in response to collagen, thrombin, and ADP. By contrast, an analysis of whole blood from COVID-19 patients indicates the reduced activation of the fibrinogen receptor. Similarly, some in vitro studies report potential targets for SARS-CoV-2 in platelets, whereas others do not indicate any direct effect of the virus on platelets. The aim of this work is to review and evaluate the reliability of the methodology for testing platelet function after contact with SARS-CoV-2. Despite the diversity of methods yielding varying results and the influence of plasma components or blood cells, it can be concluded that platelets play an important role in the development of thrombotic complications after exposure to SARS-CoV-2.
Additional Links: PMID-39795908
PubMed:
Citation:
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@article {pmid39795908,
year = {2024},
author = {Luzak, B and Golanski, J and Rozalski, M},
title = {Complex Pattern of Platelet Activation/Reactivity After SARS-CoV-2 Infection.},
journal = {International journal of molecular sciences},
volume = {26},
number = {1},
pages = {},
pmid = {39795908},
issn = {1422-0067},
support = {503/6-020-01/503-61-001//Medical University of Lodz, Poland/ ; },
mesh = {Humans ; *COVID-19/blood/virology/immunology ; *Platelet Activation ; *SARS-CoV-2 ; *Blood Platelets/metabolism ; Platelet Aggregation ; Platelet Function Tests ; },
abstract = {COVID-19 and post-COVID (long COVID) are associated with thromboembolic complications; however, it is still not clear whether platelets play a leading role in this phenomenon. The platelet hyperreactivity could result from the direct interaction between platelets and viral elements or the response to inflammatory and prothrombotic factors released from blood and vessel cells following infection. The existing literature does not provide clear-cut answers, as the results determining platelet status vary according to methodology. Elevated levels of soluble markers of platelet activation (P selectin, PF4), increased platelet aggregates, and platelet-derived microparticles suggest the activation of platelets circulating in the bloodstream of COVID-19 patients. Similarly, platelets isolated from COVID-19 patients demonstrate increased reactivity in response to collagen, thrombin, and ADP. By contrast, an analysis of whole blood from COVID-19 patients indicates the reduced activation of the fibrinogen receptor. Similarly, some in vitro studies report potential targets for SARS-CoV-2 in platelets, whereas others do not indicate any direct effect of the virus on platelets. The aim of this work is to review and evaluate the reliability of the methodology for testing platelet function after contact with SARS-CoV-2. Despite the diversity of methods yielding varying results and the influence of plasma components or blood cells, it can be concluded that platelets play an important role in the development of thrombotic complications after exposure to SARS-CoV-2.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*COVID-19/blood/virology/immunology
*Platelet Activation
*SARS-CoV-2
*Blood Platelets/metabolism
Platelet Aggregation
Platelet Function Tests
RevDate: 2025-01-10
CmpDate: 2025-01-09
Comparison of the role of vitamin D in normal organs and those affected by COVID-19.
International journal of medical sciences, 22(2):240-251.
The outbreak of COVID-19 has opened up new avenues for exploring the importance of vitamin D in immunity, in addition to its role in calcium absorption. Recently, vitamin D supplementation has been found to enhance T regulatory lymphocytes, which are reduced in individuals with COVID-19. Increased risk of pneumonia and increases in inflammatory cytokines have been reported to be major threats associated with vitamin-D deficiency. Although vaccination reduces the threat of COVID-19 to a certain extent, herd immunity is the long-term solution to overcoming such diseases. Co-administration of vitamin D with certain inactivated vaccines has been reported to enhance the systemic immune response through stimulation of the production of antigen-specific mucosal immunity. COVID-19 was found to induce multiple organ damage, and vitamin D has a beneficial role in various organs, such as the intestines, pancreas, prostate, kidneys, liver, heart, brain, and immune cells. The consequences that occur after COVID-19 infection known as long COVID-19 are also a concern as they accumulate and target multiple organs, leading to immune dysregulation. The present review covers the overall role and impact of vitamin D and its deficiency for various organs in normal conditions and after COVID-19 infection, which is still a serious issue.
Additional Links: PMID-39781525
PubMed:
Citation:
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@article {pmid39781525,
year = {2025},
author = {Peramaiyan, R and Anthony, J and Varalakshmi, S and Sekar, AK and Ali, EM and A, AHS and Abdallah, BM},
title = {Comparison of the role of vitamin D in normal organs and those affected by COVID-19.},
journal = {International journal of medical sciences},
volume = {22},
number = {2},
pages = {240-251},
pmid = {39781525},
issn = {1449-1907},
mesh = {Humans ; *COVID-19/immunology ; *Vitamin D ; *Vitamin D Deficiency/immunology/complications ; *SARS-CoV-2/immunology ; Dietary Supplements ; },
abstract = {The outbreak of COVID-19 has opened up new avenues for exploring the importance of vitamin D in immunity, in addition to its role in calcium absorption. Recently, vitamin D supplementation has been found to enhance T regulatory lymphocytes, which are reduced in individuals with COVID-19. Increased risk of pneumonia and increases in inflammatory cytokines have been reported to be major threats associated with vitamin-D deficiency. Although vaccination reduces the threat of COVID-19 to a certain extent, herd immunity is the long-term solution to overcoming such diseases. Co-administration of vitamin D with certain inactivated vaccines has been reported to enhance the systemic immune response through stimulation of the production of antigen-specific mucosal immunity. COVID-19 was found to induce multiple organ damage, and vitamin D has a beneficial role in various organs, such as the intestines, pancreas, prostate, kidneys, liver, heart, brain, and immune cells. The consequences that occur after COVID-19 infection known as long COVID-19 are also a concern as they accumulate and target multiple organs, leading to immune dysregulation. The present review covers the overall role and impact of vitamin D and its deficiency for various organs in normal conditions and after COVID-19 infection, which is still a serious issue.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*COVID-19/immunology
*Vitamin D
*Vitamin D Deficiency/immunology/complications
*SARS-CoV-2/immunology
Dietary Supplements
RevDate: 2025-01-08
Cerebromicrovascular mechanisms contributing to long COVID: implications for neurocognitive health.
GeroScience [Epub ahead of print].
Long COVID (also known as post-acute sequelae of SARS-CoV-2 infection [PASC] or post-COVID syndrome) is characterized by persistent symptoms that extend beyond the acute phase of SARS-CoV-2 infection, affecting approximately 10% to over 30% of those infected. It presents a significant clinical challenge, notably due to pronounced neurocognitive symptoms such as brain fog. The mechanisms underlying these effects are multifactorial, with mounting evidence pointing to a central role of cerebromicrovascular dysfunction. This review investigates key pathophysiological mechanisms contributing to cerebrovascular dysfunction in long COVID and their impacts on brain health. We discuss how endothelial tropism of SARS-CoV-2 and direct vascular infection trigger endothelial dysfunction, impaired neurovascular coupling, and blood-brain barrier disruption, resulting in compromised cerebral perfusion. Furthermore, the infection appears to induce mitochondrial dysfunction, enhancing oxidative stress and inflammation within cerebral endothelial cells. Autoantibody formation following infection also potentially exacerbates neurovascular injury, contributing to chronic vascular inflammation and ongoing blood-brain barrier compromise. These factors collectively contribute to the emergence of white matter hyperintensities, promote amyloid pathology, and may accelerate neurodegenerative processes, including Alzheimer's disease. This review also emphasizes the critical role of advanced imaging techniques in assessing cerebromicrovascular health and the need for targeted interventions to address these cerebrovascular complications. A deeper understanding of the cerebrovascular mechanisms of long COVID is essential to advance targeted treatments and mitigate its long-term neurocognitive consequences.
Additional Links: PMID-39777702
PubMed:
Citation:
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@article {pmid39777702,
year = {2025},
author = {Fekete, M and Lehoczki, A and Szappanos, Á and Toth, A and Mahdi, M and Sótonyi, P and Benyó, Z and Yabluchanskiy, A and Tarantini, S and Ungvari, Z},
title = {Cerebromicrovascular mechanisms contributing to long COVID: implications for neurocognitive health.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {39777702},
issn = {2509-2723},
support = {RRF-2.3.1-21-2022-00003//Nemzeti Kutatási, Fejlesztési és Innovaciós Alap/ ; TKP2021-NKTA-47//Nemzeti Kutatási Fejlesztési és Innovációs Hivatal/ ; },
abstract = {Long COVID (also known as post-acute sequelae of SARS-CoV-2 infection [PASC] or post-COVID syndrome) is characterized by persistent symptoms that extend beyond the acute phase of SARS-CoV-2 infection, affecting approximately 10% to over 30% of those infected. It presents a significant clinical challenge, notably due to pronounced neurocognitive symptoms such as brain fog. The mechanisms underlying these effects are multifactorial, with mounting evidence pointing to a central role of cerebromicrovascular dysfunction. This review investigates key pathophysiological mechanisms contributing to cerebrovascular dysfunction in long COVID and their impacts on brain health. We discuss how endothelial tropism of SARS-CoV-2 and direct vascular infection trigger endothelial dysfunction, impaired neurovascular coupling, and blood-brain barrier disruption, resulting in compromised cerebral perfusion. Furthermore, the infection appears to induce mitochondrial dysfunction, enhancing oxidative stress and inflammation within cerebral endothelial cells. Autoantibody formation following infection also potentially exacerbates neurovascular injury, contributing to chronic vascular inflammation and ongoing blood-brain barrier compromise. These factors collectively contribute to the emergence of white matter hyperintensities, promote amyloid pathology, and may accelerate neurodegenerative processes, including Alzheimer's disease. This review also emphasizes the critical role of advanced imaging techniques in assessing cerebromicrovascular health and the need for targeted interventions to address these cerebrovascular complications. A deeper understanding of the cerebrovascular mechanisms of long COVID is essential to advance targeted treatments and mitigate its long-term neurocognitive consequences.},
}
RevDate: 2025-01-13
CmpDate: 2025-01-08
Neuropsychiatric Burden of SARS-CoV-2: A Review of Its Physiopathology, Underlying Mechanisms, and Management Strategies.
Viruses, 16(12):.
The COVID-19 outbreak, caused by the SARS-CoV-2 virus, was linked to significant neurological and psychiatric manifestations. This review examines the physiopathological mechanisms underlying these neuropsychiatric outcomes and discusses current management strategies. Primarily a respiratory disease, COVID-19 frequently leads to neurological issues, including cephalalgia and migraines, loss of sensory perception, cerebrovascular accidents, and neurological impairment such as encephalopathy. Lasting neuropsychological effects have also been recorded in individuals following SARS-CoV-2 infection. These include anxiety, depression, and cognitive dysfunction, suggesting a lasting impact on mental health. The neuroinvasive potential of the virus, inflammatory responses, and the role of angiotensin-converting enzyme 2 (ACE2) in neuroinflammation are critical factors in neuropsychiatric COVID-19 manifestations. In addition, the review highlights the importance of monitoring biomarkers to assess Central Nervous System (CNS) involvement. Management strategies for these neuropsychiatric conditions include supportive therapy, antiepileptic drugs, antithrombotic therapy, and psychotropic drugs, emphasizing the need for a multidisciplinary approach. Understanding the long-term neuropsychiatric implications of COVID-19 is essential for developing effective treatment protocols and improving patient outcomes.
Additional Links: PMID-39772122
PubMed:
Citation:
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@article {pmid39772122,
year = {2024},
author = {Pacnejer, AM and Butuca, A and Dobrea, CM and Arseniu, AM and Frum, A and Gligor, FG and Arseniu, R and Vonica, RC and Vonica-Tincu, AL and Oancea, C and Mogosan, C and Popa Ilie, IR and Morgovan, C and Dehelean, CA},
title = {Neuropsychiatric Burden of SARS-CoV-2: A Review of Its Physiopathology, Underlying Mechanisms, and Management Strategies.},
journal = {Viruses},
volume = {16},
number = {12},
pages = {},
pmid = {39772122},
issn = {1999-4915},
support = {LBUS-IRG-2023/No. 3523, 24 July 2023//Lucian Blaga University of Sibiu/ ; },
mesh = {Humans ; *COVID-19/physiopathology/psychology/virology ; *SARS-CoV-2 ; Mental Disorders/therapy/etiology ; Nervous System Diseases/virology/physiopathology ; Angiotensin-Converting Enzyme 2/metabolism ; },
abstract = {The COVID-19 outbreak, caused by the SARS-CoV-2 virus, was linked to significant neurological and psychiatric manifestations. This review examines the physiopathological mechanisms underlying these neuropsychiatric outcomes and discusses current management strategies. Primarily a respiratory disease, COVID-19 frequently leads to neurological issues, including cephalalgia and migraines, loss of sensory perception, cerebrovascular accidents, and neurological impairment such as encephalopathy. Lasting neuropsychological effects have also been recorded in individuals following SARS-CoV-2 infection. These include anxiety, depression, and cognitive dysfunction, suggesting a lasting impact on mental health. The neuroinvasive potential of the virus, inflammatory responses, and the role of angiotensin-converting enzyme 2 (ACE2) in neuroinflammation are critical factors in neuropsychiatric COVID-19 manifestations. In addition, the review highlights the importance of monitoring biomarkers to assess Central Nervous System (CNS) involvement. Management strategies for these neuropsychiatric conditions include supportive therapy, antiepileptic drugs, antithrombotic therapy, and psychotropic drugs, emphasizing the need for a multidisciplinary approach. Understanding the long-term neuropsychiatric implications of COVID-19 is essential for developing effective treatment protocols and improving patient outcomes.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*COVID-19/physiopathology/psychology/virology
*SARS-CoV-2
Mental Disorders/therapy/etiology
Nervous System Diseases/virology/physiopathology
Angiotensin-Converting Enzyme 2/metabolism
RevDate: 2025-01-15
CmpDate: 2025-01-08
Detrimental Effects of Anti-Nucleocapsid Antibodies in SARS-CoV-2 Infection, Reinfection, and the Post-Acute Sequelae of COVID-19.
Pathogens (Basel, Switzerland), 13(12):.
Antibody-dependent enhancement (ADE) is a phenomenon in which antibodies enhance subsequent viral infections rather than preventing them. Sub-optimal levels of neutralizing antibodies in individuals infected with dengue virus are known to be associated with severe disease upon reinfection with a different dengue virus serotype. For Severe Acute Respiratory Syndrome Coronavirus type-2 infection, three types of ADE have been proposed: (1) Fc receptor-dependent ADE of infection in cells expressing Fc receptors, such as macrophages by anti-spike antibodies, (2) Fc receptor-independent ADE of infection in epithelial cells by anti-spike antibodies, and (3) Fc receptor-dependent ADE of cytokine production in cells expressing Fc receptors, such as macrophages by anti-nucleocapsid antibodies. This review focuses on the Fc receptor-dependent ADE of cytokine production induced by anti-nucleocapsid antibodies, examining its potential role in severe COVID-19 during reinfection and its contribution to the post-acute sequelae of COVID-19, i.e., prolonged symptoms lasting at least three months after the acute phase of the disease. We also discuss the protective effects of recently identified anti-spike antibodies that neutralize Omicron variants.
Additional Links: PMID-39770368
PubMed:
Citation:
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@article {pmid39770368,
year = {2024},
author = {Nakayama, EE and Shioda, T},
title = {Detrimental Effects of Anti-Nucleocapsid Antibodies in SARS-CoV-2 Infection, Reinfection, and the Post-Acute Sequelae of COVID-19.},
journal = {Pathogens (Basel, Switzerland)},
volume = {13},
number = {12},
pages = {},
pmid = {39770368},
issn = {2076-0817},
support = {JM00000160//Center for Infectious Disease Education and Research, CiDER/ ; },
mesh = {Humans ; *COVID-19/immunology/complications ; *SARS-CoV-2/immunology ; *Antibodies, Viral/immunology ; *Reinfection/immunology/virology ; *Antibodies, Neutralizing/immunology ; *Antibody-Dependent Enhancement/immunology ; Cytokines/immunology/metabolism ; Receptors, Fc/immunology ; Nucleocapsid/immunology ; Post-Acute COVID-19 Syndrome ; },
abstract = {Antibody-dependent enhancement (ADE) is a phenomenon in which antibodies enhance subsequent viral infections rather than preventing them. Sub-optimal levels of neutralizing antibodies in individuals infected with dengue virus are known to be associated with severe disease upon reinfection with a different dengue virus serotype. For Severe Acute Respiratory Syndrome Coronavirus type-2 infection, three types of ADE have been proposed: (1) Fc receptor-dependent ADE of infection in cells expressing Fc receptors, such as macrophages by anti-spike antibodies, (2) Fc receptor-independent ADE of infection in epithelial cells by anti-spike antibodies, and (3) Fc receptor-dependent ADE of cytokine production in cells expressing Fc receptors, such as macrophages by anti-nucleocapsid antibodies. This review focuses on the Fc receptor-dependent ADE of cytokine production induced by anti-nucleocapsid antibodies, examining its potential role in severe COVID-19 during reinfection and its contribution to the post-acute sequelae of COVID-19, i.e., prolonged symptoms lasting at least three months after the acute phase of the disease. We also discuss the protective effects of recently identified anti-spike antibodies that neutralize Omicron variants.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*COVID-19/immunology/complications
*SARS-CoV-2/immunology
*Antibodies, Viral/immunology
*Reinfection/immunology/virology
*Antibodies, Neutralizing/immunology
*Antibody-Dependent Enhancement/immunology
Cytokines/immunology/metabolism
Receptors, Fc/immunology
Nucleocapsid/immunology
Post-Acute COVID-19 Syndrome
RevDate: 2025-01-08
Pathophysiological, Neuropsychological, and Psychosocial Influences on Neurological and Neuropsychiatric Symptoms of Post-Acute COVID-19 Syndrome: Impacts on Recovery and Symptom Persistence.
Biomedicines, 12(12):.
Although the impact of post-acute COVID-19 syndrome (PACS) on patients and public health is undeniably significant, its etiology remains largely unclear. Much research has been conducted on the pathophysiology, shedding light on various aspects; however, due to the multitude of symptoms and clinical conditions that directly or indirectly define PACS, it is challenging to establish definitive causations. In this exploration, through systematically reviewing the latest pathophysiological findings related to the neurological symptoms of the syndrome, we aim to examine how psychosocial and neuropsychological symptoms may overlap with neurological ones, and how they may not only serve as risk factors but also contribute to the persistence of some primary symptoms of the disorder. Findings from our synthesis suggest that psychological and psychosocial factors, such as anxiety, depression, and loneliness, may interact with neurological symptoms in a self-reinforcing feedback loop. This cycle seems to be affecting both physical and psychological distress, potentially increasing the persistence and severity of PACS symptoms. By pointing out this interaction, in this review study, we attempt to offer a new perspective on the interconnected nature of psychological, psychosocial, and neurological factors, emphasizing the importance of integrated treatment approaches to disrupt this cycle and improve outcomes when possible.
Additional Links: PMID-39767737
PubMed:
Citation:
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@article {pmid39767737,
year = {2024},
author = {Malioukis, A and Snead, RS and Marczika, J and Ambalavanan, R},
title = {Pathophysiological, Neuropsychological, and Psychosocial Influences on Neurological and Neuropsychiatric Symptoms of Post-Acute COVID-19 Syndrome: Impacts on Recovery and Symptom Persistence.},
journal = {Biomedicines},
volume = {12},
number = {12},
pages = {},
pmid = {39767737},
issn = {2227-9059},
abstract = {Although the impact of post-acute COVID-19 syndrome (PACS) on patients and public health is undeniably significant, its etiology remains largely unclear. Much research has been conducted on the pathophysiology, shedding light on various aspects; however, due to the multitude of symptoms and clinical conditions that directly or indirectly define PACS, it is challenging to establish definitive causations. In this exploration, through systematically reviewing the latest pathophysiological findings related to the neurological symptoms of the syndrome, we aim to examine how psychosocial and neuropsychological symptoms may overlap with neurological ones, and how they may not only serve as risk factors but also contribute to the persistence of some primary symptoms of the disorder. Findings from our synthesis suggest that psychological and psychosocial factors, such as anxiety, depression, and loneliness, may interact with neurological symptoms in a self-reinforcing feedback loop. This cycle seems to be affecting both physical and psychological distress, potentially increasing the persistence and severity of PACS symptoms. By pointing out this interaction, in this review study, we attempt to offer a new perspective on the interconnected nature of psychological, psychosocial, and neurological factors, emphasizing the importance of integrated treatment approaches to disrupt this cycle and improve outcomes when possible.},
}
RevDate: 2025-01-17
CmpDate: 2025-01-17
Navigating neurologic post-COVID-19 conditions in adults: Management strategies for cognitive dysfunction, headaches and neuropathies.
Life sciences, 362:123374.
This review aims to describe the neurologic post-COVID-19 conditions (PCC, also known as "long COVID"), a complex array of diagnoses that can occur following recovery from acute COVID-19. The review also includes clinical considerations for the recognition, diagnosis and management of neurologic manifestations of PCC. Cognitive impairment ("Brain Fog"), headaches, and neuropathies are specifically reviewed.
Additional Links: PMID-39765324
Publisher:
PubMed:
Citation:
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@article {pmid39765324,
year = {2025},
author = {Chopra, A and Franko, N and Chow, EJ},
title = {Navigating neurologic post-COVID-19 conditions in adults: Management strategies for cognitive dysfunction, headaches and neuropathies.},
journal = {Life sciences},
volume = {362},
number = {},
pages = {123374},
doi = {10.1016/j.lfs.2025.123374},
pmid = {39765324},
issn = {1879-0631},
mesh = {Humans ; *COVID-19/complications ; *Cognitive Dysfunction/therapy/etiology ; *Headache/therapy/etiology ; *SARS-CoV-2 ; Nervous System Diseases/therapy/etiology/complications ; Adult ; Post-Acute COVID-19 Syndrome ; },
abstract = {This review aims to describe the neurologic post-COVID-19 conditions (PCC, also known as "long COVID"), a complex array of diagnoses that can occur following recovery from acute COVID-19. The review also includes clinical considerations for the recognition, diagnosis and management of neurologic manifestations of PCC. Cognitive impairment ("Brain Fog"), headaches, and neuropathies are specifically reviewed.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*COVID-19/complications
*Cognitive Dysfunction/therapy/etiology
*Headache/therapy/etiology
*SARS-CoV-2
Nervous System Diseases/therapy/etiology/complications
Adult
Post-Acute COVID-19 Syndrome
RevDate: 2025-01-06
CmpDate: 2025-01-06
The Triad of COVID-19 in Children: Acute COVID-19, Multisystem Inflammatory Syndrome, and Long COVID-Part II.
Pediatric annals, 54(1):e40-e44.
Coronavirus disease 2019 (COVID-19), which is now known to be caused by severe acute respiratory syndrome coronavirus 2, has been a public health threat since early 2020 and has affected millions of people worldwide. Many studies have now shown that this virus exhibits a milder infection in children compared to adults. Acute COVID-19 infection, multisystem inflammatory syndrome in children (MIS-C), and long COVID have been recently well-established in the pediatric population with a myriad of systemic manifestations. This section of the review will focus on the following systems-neurology, psychiatry, endocrinology, hematology, and oncology-under three broad lenses, such as acute COVID-19, MIS-C, and long COVID. [Pediatr Ann. 2025;54(1):e40-e44.].
Additional Links: PMID-39760348
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PubMed:
Citation:
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@article {pmid39760348,
year = {2025},
author = {Gupte, A and Sriram, S and Gunasekaran, V and Chaudhari, K and Kamat, D},
title = {The Triad of COVID-19 in Children: Acute COVID-19, Multisystem Inflammatory Syndrome, and Long COVID-Part II.},
journal = {Pediatric annals},
volume = {54},
number = {1},
pages = {e40-e44},
doi = {10.3928/19382359-20241106-01},
pmid = {39760348},
issn = {1938-2359},
mesh = {Humans ; *COVID-19/complications ; *Systemic Inflammatory Response Syndrome/diagnosis/physiopathology ; Child ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; },
abstract = {Coronavirus disease 2019 (COVID-19), which is now known to be caused by severe acute respiratory syndrome coronavirus 2, has been a public health threat since early 2020 and has affected millions of people worldwide. Many studies have now shown that this virus exhibits a milder infection in children compared to adults. Acute COVID-19 infection, multisystem inflammatory syndrome in children (MIS-C), and long COVID have been recently well-established in the pediatric population with a myriad of systemic manifestations. This section of the review will focus on the following systems-neurology, psychiatry, endocrinology, hematology, and oncology-under three broad lenses, such as acute COVID-19, MIS-C, and long COVID. [Pediatr Ann. 2025;54(1):e40-e44.].},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*COVID-19/complications
*Systemic Inflammatory Response Syndrome/diagnosis/physiopathology
Child
Post-Acute COVID-19 Syndrome
SARS-CoV-2
RevDate: 2025-01-13
CmpDate: 2025-01-06
Neurobiology of COVID-19-Associated Psychosis/Schizophrenia: Implication of Epidermal Growth Factor Receptor Signaling.
Neuropsychopharmacology reports, 45(1):e12520.
COVID-19 exhibits not only respiratory symptoms but also neurological/psychiatric symptoms rarely including delirium/psychosis. Pathological studies on COVID-19 provide evidence that the cytokine storm, in particular (epidermal growth factor) EGF receptor (EGFR, ErbB1, Her1) activation, plays a central role in the progression of viral replication and lung fibrosis. Of note, SARS-CoV-2 virus (specifically, S1 spike domain) mimics EGF and directly transactivates EGFR, preceding the inflammatory process. In agreement, the anticancer drugs targeting EGFR such as Nimotuzumab and tyrosine kinase inhibitors are markedly effective on COVID-19. However, these data might raise a provisional caution regarding implication of psychiatric disorder such as schizophrenia. The author's group has been investigating the etiologic and neuropathologic associations of EGFR signaling with schizophrenia. There are significant molecular associations between schizophrenia and EGFR ligand levels in blood as well as in the brain. In addition, perinatal challenges of EGFR ligands and intraventricular administration of EGF to rodents and monkeys both resulted in severe behavioral and/or electroencephalographic endophenotypes relevant to this disorder. These animal models also display postpubertal abnormality in soliloquy-like self-vocalization as well as in intercortical functional connectivity. Here, we discuss neuropsychiatric implication of coronavirus infection and its interaction with the EGFR system, by searching related literatures in PubMed database as of the end of 2023.
Additional Links: PMID-39754403
PubMed:
Citation:
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@article {pmid39754403,
year = {2025},
author = {Nawa, H and Murakami, M},
title = {Neurobiology of COVID-19-Associated Psychosis/Schizophrenia: Implication of Epidermal Growth Factor Receptor Signaling.},
journal = {Neuropsychopharmacology reports},
volume = {45},
number = {1},
pages = {e12520},
pmid = {39754403},
issn = {2574-173X},
support = {//Grant for Joint Research Program of the Institute for Genetic Medicine, Hokkaido University/ ; 21K18242//Grant-in-Aid for Challenging Exploratory Research/ ; 22H02728//Grant-in-Aid for Scientific Research (B)/ ; JP20fk0108471//AMED/ ; JP21fk0108489//AMED/ ; JP22ek0510030h0003//AMED/ ; JP223fa627005h0001//AMED/ ; JP20ek0510030h0001//AMED/ ; JP19ek0210125h0001//AMED/ ; JP21zf0127004h0001//AMED/ ; JP20H00502//Scientific Research (A)/ ; JP21K19364//Challenging Exploratory Research/ ; JPMXS0120330644//MEXT Quantum LEAP Flagship Program/ ; JP20fk010847h0001//Research Program on Emerging and Re-emerging Infectious Diseases/ ; JP21fk0108489h0001//Research Program on Emerging and Re-emerging Infectious Diseases/ ; },
mesh = {Humans ; *COVID-19/complications/metabolism ; *ErbB Receptors/metabolism ; *Schizophrenia/metabolism/physiopathology/drug therapy ; Animals ; *Signal Transduction ; *Psychotic Disorders/metabolism/physiopathology/etiology/drug therapy ; SARS-CoV-2 ; Brain/metabolism/virology ; },
abstract = {COVID-19 exhibits not only respiratory symptoms but also neurological/psychiatric symptoms rarely including delirium/psychosis. Pathological studies on COVID-19 provide evidence that the cytokine storm, in particular (epidermal growth factor) EGF receptor (EGFR, ErbB1, Her1) activation, plays a central role in the progression of viral replication and lung fibrosis. Of note, SARS-CoV-2 virus (specifically, S1 spike domain) mimics EGF and directly transactivates EGFR, preceding the inflammatory process. In agreement, the anticancer drugs targeting EGFR such as Nimotuzumab and tyrosine kinase inhibitors are markedly effective on COVID-19. However, these data might raise a provisional caution regarding implication of psychiatric disorder such as schizophrenia. The author's group has been investigating the etiologic and neuropathologic associations of EGFR signaling with schizophrenia. There are significant molecular associations between schizophrenia and EGFR ligand levels in blood as well as in the brain. In addition, perinatal challenges of EGFR ligands and intraventricular administration of EGF to rodents and monkeys both resulted in severe behavioral and/or electroencephalographic endophenotypes relevant to this disorder. These animal models also display postpubertal abnormality in soliloquy-like self-vocalization as well as in intercortical functional connectivity. Here, we discuss neuropsychiatric implication of coronavirus infection and its interaction with the EGFR system, by searching related literatures in PubMed database as of the end of 2023.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*COVID-19/complications/metabolism
*ErbB Receptors/metabolism
*Schizophrenia/metabolism/physiopathology/drug therapy
Animals
*Signal Transduction
*Psychotic Disorders/metabolism/physiopathology/etiology/drug therapy
SARS-CoV-2
Brain/metabolism/virology
RevDate: 2025-01-04
CmpDate: 2024-12-30
Connecting dots of long COVID-19 pathogenesis: a vagus nerve- hypothalamic-pituitary- adrenal-mitochondrial axis dysfunction.
Frontiers in cellular and infection microbiology, 14:1501949.
The pathogenesis of long COVID (LC) still presents many areas of uncertainty. This leads to difficulties in finding an effective specific therapy. We hypothesize that the key to LC pathogenesis lies in the presence of chronic functional damage to the main anti-inflammatory mechanisms of our body: the three reflexes mediated by the vagus nerve, the hypothalamic-pituitary-adrenal (HPA) hormonal axis, and the mitochondrial redox status. We will illustrate that this neuro-endocrine-metabolic axis is closely interconnected and how the SARS-CoV-2 can damage it at all stages through direct, immune-inflammatory, epigenetic damage mechanisms, as well as through the reactivation of neurotropic viruses. According to our theory, the direct mitochondrial damage carried out by the virus, which replicates within these organelles, and the cellular oxidative imbalance, cannot be countered in patients who develop LC. This is because their anti-inflammatory mechanisms are inconsistent due to reduced vagal tone and direct damage to the endocrine glands of the HPA axis. We will illustrate how acetylcholine (ACh) and cortisol, with its cytoplasmatic and cellular receptors respectively, are fundamental players in the LC process. Both Ach and cortisol play multifaceted and synergistic roles in reducing inflammation. They achieve this by modulating the activity of innate and cell-mediated immunity, attenuating endothelial and platelet activation, and modulating mitochondrial function, which is crucial for cellular energy production and anti-inflammatory mechanisms. In our opinion, it is essential to study the sensitivity of the glucocorticoids receptor in people who develop LC and whether SARS-CoV-2 can cause long-term epigenetic variations in its expression and function.
Additional Links: PMID-39735263
PubMed:
Citation:
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@article {pmid39735263,
year = {2024},
author = {Camici, M and Del Duca, G and Brita, AC and Antinori, A},
title = {Connecting dots of long COVID-19 pathogenesis: a vagus nerve- hypothalamic-pituitary- adrenal-mitochondrial axis dysfunction.},
journal = {Frontiers in cellular and infection microbiology},
volume = {14},
number = {},
pages = {1501949},
pmid = {39735263},
issn = {2235-2988},
mesh = {Humans ; *Mitochondria/metabolism ; *Hypothalamo-Hypophyseal System/metabolism/virology ; *COVID-19/immunology/physiopathology/virology ; *Vagus Nerve/physiopathology ; *SARS-CoV-2 ; *Pituitary-Adrenal System/virology ; Post-Acute COVID-19 Syndrome ; Hydrocortisone/metabolism ; Acetylcholine/metabolism ; },
abstract = {The pathogenesis of long COVID (LC) still presents many areas of uncertainty. This leads to difficulties in finding an effective specific therapy. We hypothesize that the key to LC pathogenesis lies in the presence of chronic functional damage to the main anti-inflammatory mechanisms of our body: the three reflexes mediated by the vagus nerve, the hypothalamic-pituitary-adrenal (HPA) hormonal axis, and the mitochondrial redox status. We will illustrate that this neuro-endocrine-metabolic axis is closely interconnected and how the SARS-CoV-2 can damage it at all stages through direct, immune-inflammatory, epigenetic damage mechanisms, as well as through the reactivation of neurotropic viruses. According to our theory, the direct mitochondrial damage carried out by the virus, which replicates within these organelles, and the cellular oxidative imbalance, cannot be countered in patients who develop LC. This is because their anti-inflammatory mechanisms are inconsistent due to reduced vagal tone and direct damage to the endocrine glands of the HPA axis. We will illustrate how acetylcholine (ACh) and cortisol, with its cytoplasmatic and cellular receptors respectively, are fundamental players in the LC process. Both Ach and cortisol play multifaceted and synergistic roles in reducing inflammation. They achieve this by modulating the activity of innate and cell-mediated immunity, attenuating endothelial and platelet activation, and modulating mitochondrial function, which is crucial for cellular energy production and anti-inflammatory mechanisms. In our opinion, it is essential to study the sensitivity of the glucocorticoids receptor in people who develop LC and whether SARS-CoV-2 can cause long-term epigenetic variations in its expression and function.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Mitochondria/metabolism
*Hypothalamo-Hypophyseal System/metabolism/virology
*COVID-19/immunology/physiopathology/virology
*Vagus Nerve/physiopathology
*SARS-CoV-2
*Pituitary-Adrenal System/virology
Post-Acute COVID-19 Syndrome
Hydrocortisone/metabolism
Acetylcholine/metabolism
RevDate: 2025-01-05
CmpDate: 2024-12-27
Key Pathophysiological Role of Skeletal Muscle Disturbance in Post COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Accumulated Evidence.
Journal of cachexia, sarcopenia and muscle, 16(1):e13669.
BACKGROUND: Recent studies provide strong evidence for a key role of skeletal muscle pathophysiology in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In a 2021 review article on the pathophysiology of ME/CFS, we postulated that hypoperfusion and ischemia can result in excessive sodium and calcium overload in skeletal muscles of ME/CFS patients to cause mitochondrial damage. Since then, experimental evidence has been provided that supports this concept.
METHODS: We collect, summarize and discuss the current state of knowledge for the key role of skeletal muscle pathophysiology. We try to explain which risk factors and mechanisms are responsible for a subgroup of patients with post COVID syndrome (PCS) to develop ME/CFS (PC-ME/CFS).
RESULTS: Mitochondrial dysfunction is a long-held assumption to explain cardinal symptoms of ME/CFS. However, mitochondrial dysfunction could not be convincingly shown in leukocytes. By contrast, recent studies provide strong evidence for mitochondrial dysfunction in skeletal muscle tissue in ME/CFS. An electron microscopy study could directly show damage of mitochondria in skeletal muscle of ME/CFS patients with a preferential subsarcolemmal localization but not in PCS. Another study shows signs of skeletal muscle damage and regeneration in biopsies taken one day after exercise in PC-ME/CFS. The simultaneous presence of necroses and signs of regeneration supports the concept of repeated damage. Other studies correlated diminished hand grip strength (HGS) with symptom severity and prognosis. A MRI study showed that intracellular sodium in muscles of ME/CFS patients is elevated and that levels correlate inversely with HGS. This finding corroborates our concept of sodium and consecutive calcium overload as cause of muscular and mitochondrial damage caused by enhanced proton-sodium exchange due to anaerobic metabolism and diminished activity of the sodium-potassium-ATPase. The histological investigations in ME/CFS exclude ischemia by microvascular obstruction, viral presence or immune myositis. The only known exercise-induced mechanism of damage left is sodium induced calcium overload. If ionic disturbance and mitochondrial dysfunction is severe enough the patient may be captured in a vicious circle. This energy deficit is the most likely cause of exertional intolerance and post exertional malaise and is further aggravated by exertion.
CONCLUSION: Based on this pathomechanism, future treatment approaches should focus on normalizing the cause of ionic disbalance. Current treatment strategies targeting hypoperfusion have the potential to improve the dysfunction of ion transporters.
Additional Links: PMID-39727052
PubMed:
Citation:
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@article {pmid39727052,
year = {2025},
author = {Scheibenbogen, C and Wirth, KJ},
title = {Key Pathophysiological Role of Skeletal Muscle Disturbance in Post COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Accumulated Evidence.},
journal = {Journal of cachexia, sarcopenia and muscle},
volume = {16},
number = {1},
pages = {e13669},
pmid = {39727052},
issn = {2190-6009},
support = {//Weidenhammer Zoebele Foundation/ ; //Lost Voices Foundation/ ; //MECFS Research Foundation/ ; //Fatigatio e.V./ ; //German Research Foundation/ ; //German Ministry of Education and Science/ ; //German Ministry of Health (BMG)/ ; },
mesh = {Humans ; *Fatigue Syndrome, Chronic/diagnosis/physiopathology/virology ; Mitochondria/metabolism ; *Muscle, Skeletal/cytology/physiopathology ; *Post-Acute COVID-19 Syndrome/physiopathology/virology ; SARS-CoV-2/pathogenicity ; },
abstract = {BACKGROUND: Recent studies provide strong evidence for a key role of skeletal muscle pathophysiology in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In a 2021 review article on the pathophysiology of ME/CFS, we postulated that hypoperfusion and ischemia can result in excessive sodium and calcium overload in skeletal muscles of ME/CFS patients to cause mitochondrial damage. Since then, experimental evidence has been provided that supports this concept.
METHODS: We collect, summarize and discuss the current state of knowledge for the key role of skeletal muscle pathophysiology. We try to explain which risk factors and mechanisms are responsible for a subgroup of patients with post COVID syndrome (PCS) to develop ME/CFS (PC-ME/CFS).
RESULTS: Mitochondrial dysfunction is a long-held assumption to explain cardinal symptoms of ME/CFS. However, mitochondrial dysfunction could not be convincingly shown in leukocytes. By contrast, recent studies provide strong evidence for mitochondrial dysfunction in skeletal muscle tissue in ME/CFS. An electron microscopy study could directly show damage of mitochondria in skeletal muscle of ME/CFS patients with a preferential subsarcolemmal localization but not in PCS. Another study shows signs of skeletal muscle damage and regeneration in biopsies taken one day after exercise in PC-ME/CFS. The simultaneous presence of necroses and signs of regeneration supports the concept of repeated damage. Other studies correlated diminished hand grip strength (HGS) with symptom severity and prognosis. A MRI study showed that intracellular sodium in muscles of ME/CFS patients is elevated and that levels correlate inversely with HGS. This finding corroborates our concept of sodium and consecutive calcium overload as cause of muscular and mitochondrial damage caused by enhanced proton-sodium exchange due to anaerobic metabolism and diminished activity of the sodium-potassium-ATPase. The histological investigations in ME/CFS exclude ischemia by microvascular obstruction, viral presence or immune myositis. The only known exercise-induced mechanism of damage left is sodium induced calcium overload. If ionic disturbance and mitochondrial dysfunction is severe enough the patient may be captured in a vicious circle. This energy deficit is the most likely cause of exertional intolerance and post exertional malaise and is further aggravated by exertion.
CONCLUSION: Based on this pathomechanism, future treatment approaches should focus on normalizing the cause of ionic disbalance. Current treatment strategies targeting hypoperfusion have the potential to improve the dysfunction of ion transporters.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Fatigue Syndrome, Chronic/diagnosis/physiopathology/virology
Mitochondria/metabolism
*Muscle, Skeletal/cytology/physiopathology
*Post-Acute COVID-19 Syndrome/physiopathology/virology
SARS-CoV-2/pathogenicity
RevDate: 2025-01-11
Long COVID: Pathophysiology, current concepts, and future directions.
The Journal of allergy and clinical immunology pii:S0091-6749(24)02406-0 [Epub ahead of print].
Long COVID, an umbrella term referring to a variety of symptoms and clinical presentations that emerges in a subset of patients after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has a significant effect on quality of life and places a substantial burden on health care systems worldwide, straining financial and human resources. The pathophysiology of long COVID remains incompletely understood, though several hypotheses have been proposed to explain different aspects of this complex condition. SARS-CoV-2 persistence, direct organ damage, innate and adaptive immune system perturbation, autoimmunity, latent virus reactivation, endothelial dysfunction, and microbiome disturbances are among the most relevant avenues for elucidating the evolution, complexity, and mechanisms of long COVID. Active investigation regarding potential biomarkers for long COVID and its associated disease endotypes highlights the role of inflammatory mediators, immunophenotyping, and multiomics approaches. Further advances in understanding long COVID are needed to inform current and future therapeutics.
Additional Links: PMID-39724975
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PubMed:
Citation:
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@article {pmid39724975,
year = {2024},
author = {Skevaki, C and Moschopoulos, CD and Fragkou, PC and Grote, K and Schieffer, E and Schieffer, B},
title = {Long COVID: Pathophysiology, current concepts, and future directions.},
journal = {The Journal of allergy and clinical immunology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaci.2024.12.1074},
pmid = {39724975},
issn = {1097-6825},
abstract = {Long COVID, an umbrella term referring to a variety of symptoms and clinical presentations that emerges in a subset of patients after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has a significant effect on quality of life and places a substantial burden on health care systems worldwide, straining financial and human resources. The pathophysiology of long COVID remains incompletely understood, though several hypotheses have been proposed to explain different aspects of this complex condition. SARS-CoV-2 persistence, direct organ damage, innate and adaptive immune system perturbation, autoimmunity, latent virus reactivation, endothelial dysfunction, and microbiome disturbances are among the most relevant avenues for elucidating the evolution, complexity, and mechanisms of long COVID. Active investigation regarding potential biomarkers for long COVID and its associated disease endotypes highlights the role of inflammatory mediators, immunophenotyping, and multiomics approaches. Further advances in understanding long COVID are needed to inform current and future therapeutics.},
}
RevDate: 2025-01-04
The impact of COVID-19 on accelerating of immunosenescence and brain aging.
Frontiers in cellular neuroscience, 18:1471192.
The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has profoundly impacted global health, affecting not only the immediate morbidity and mortality rates but also long-term health outcomes across various populations. Although the acute effects of COVID-19 on the respiratory system have initially been the primary focus, it is increasingly evident that the virus can have significant impacts on multiple physiological systems, including the nervous and immune systems. The pandemic has highlighted the complex interplay between viral infection, immune aging, and brain health, that can potentially accelerate neuroimmune aging and contribute to the persistence of long COVID conditions. By inducing chronic inflammation, immunosenescence, and neuroinflammation, COVID-19 may exacerbate the processes of neuroimmune aging, leading to increased risks of cognitive decline, neurodegenerative diseases, and impaired immune function. Key factors include chronic immune dysregulation, oxidative stress, neuroinflammation, and the disruption of cellular processes. These overlapping mechanisms between aging and COVID-19 illustrate how the virus can induce and accelerate aging-related processes, leading to an increased risk of neurodegenerative diseases and other age-related conditions. This mini-review examines key features and possible mechanisms of COVID-19-induced neuroimmune aging that may contribute to the persistence and severity of long COVID. Understanding these interactions is crucial for developing effective interventions. Anti-inflammatory therapies, neuroprotective agents, immunomodulatory treatments, and lifestyle interventions all hold potential for mitigating the long-term effects of the virus. By addressing these challenges, we can improve health outcomes and quality of life for millions affected by the pandemic.
Additional Links: PMID-39720706
PubMed:
Citation:
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@article {pmid39720706,
year = {2024},
author = {Müller, L and Di Benedetto, S},
title = {The impact of COVID-19 on accelerating of immunosenescence and brain aging.},
journal = {Frontiers in cellular neuroscience},
volume = {18},
number = {},
pages = {1471192},
pmid = {39720706},
issn = {1662-5102},
abstract = {The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has profoundly impacted global health, affecting not only the immediate morbidity and mortality rates but also long-term health outcomes across various populations. Although the acute effects of COVID-19 on the respiratory system have initially been the primary focus, it is increasingly evident that the virus can have significant impacts on multiple physiological systems, including the nervous and immune systems. The pandemic has highlighted the complex interplay between viral infection, immune aging, and brain health, that can potentially accelerate neuroimmune aging and contribute to the persistence of long COVID conditions. By inducing chronic inflammation, immunosenescence, and neuroinflammation, COVID-19 may exacerbate the processes of neuroimmune aging, leading to increased risks of cognitive decline, neurodegenerative diseases, and impaired immune function. Key factors include chronic immune dysregulation, oxidative stress, neuroinflammation, and the disruption of cellular processes. These overlapping mechanisms between aging and COVID-19 illustrate how the virus can induce and accelerate aging-related processes, leading to an increased risk of neurodegenerative diseases and other age-related conditions. This mini-review examines key features and possible mechanisms of COVID-19-induced neuroimmune aging that may contribute to the persistence and severity of long COVID. Understanding these interactions is crucial for developing effective interventions. Anti-inflammatory therapies, neuroprotective agents, immunomodulatory treatments, and lifestyle interventions all hold potential for mitigating the long-term effects of the virus. By addressing these challenges, we can improve health outcomes and quality of life for millions affected by the pandemic.},
}
RevDate: 2025-01-02
CmpDate: 2024-12-31
Tackling persistent neurological symptoms in patients following acute COVID-19 infection: an update of the literature.
Expert review of neurotherapeutics, 25(1):67-83.
INTRODUCTION: The COVID-19 pandemic has taught myriad lessons and left several questions we are yet to comprehend. Initially, the scientific community was concerned with the management of acute disease and immunization. Once the peak of the pandemic receded, it became clear that a proportion of patients were far from fully recovered. Researchers started to recognize those persisting symptoms as a new entity termed 'Long COVID,' where neurological symptoms are evident and have a major impact on quality of life.
AREAS COVERED: The main purpose of this narrative review is to analyze and synthesize the current literature regarding Long COVID, its relation to the nervous system, and to explore the evidence on treatments for persistent neurological symptoms. The most common reported and observed neurologic manifestations include fatigue, cognitive impairment, pain, polyneuropathy, and neuropsychiatric disorders. A variety of pharmacologic and non-pharmacologic therapies have been evaluated and yielded mixed results. Many of them focused on immunomodulation and none currently have U.S. FDA approval.
EXPERT OPINION: Challenges remain in terms of clinical characterization and prognosis of Long COVID, besides understanding its pathophysiology. Standardization of biomarkers and diagnostic criteria will allow the use of common nomenclature and data elements in the design of future clinical studies.
Additional Links: PMID-39715694
Publisher:
PubMed:
Citation:
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@article {pmid39715694,
year = {2025},
author = {Cáceres, E and Divani, AA and Viñan-Garces, AE and Olivella-Gomez, J and Quintero-Altare, A and Pérez, S and Reyes, LF and Sasso, N and Biller, J},
title = {Tackling persistent neurological symptoms in patients following acute COVID-19 infection: an update of the literature.},
journal = {Expert review of neurotherapeutics},
volume = {25},
number = {1},
pages = {67-83},
doi = {10.1080/14737175.2024.2440543},
pmid = {39715694},
issn = {1744-8360},
mesh = {Humans ; *COVID-19/complications/therapy ; *Nervous System Diseases/therapy ; Post-Acute COVID-19 Syndrome ; Quality of Life ; },
abstract = {INTRODUCTION: The COVID-19 pandemic has taught myriad lessons and left several questions we are yet to comprehend. Initially, the scientific community was concerned with the management of acute disease and immunization. Once the peak of the pandemic receded, it became clear that a proportion of patients were far from fully recovered. Researchers started to recognize those persisting symptoms as a new entity termed 'Long COVID,' where neurological symptoms are evident and have a major impact on quality of life.
AREAS COVERED: The main purpose of this narrative review is to analyze and synthesize the current literature regarding Long COVID, its relation to the nervous system, and to explore the evidence on treatments for persistent neurological symptoms. The most common reported and observed neurologic manifestations include fatigue, cognitive impairment, pain, polyneuropathy, and neuropsychiatric disorders. A variety of pharmacologic and non-pharmacologic therapies have been evaluated and yielded mixed results. Many of them focused on immunomodulation and none currently have U.S. FDA approval.
EXPERT OPINION: Challenges remain in terms of clinical characterization and prognosis of Long COVID, besides understanding its pathophysiology. Standardization of biomarkers and diagnostic criteria will allow the use of common nomenclature and data elements in the design of future clinical studies.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*COVID-19/complications/therapy
*Nervous System Diseases/therapy
Post-Acute COVID-19 Syndrome
Quality of Life
RevDate: 2025-01-04
CmpDate: 2024-12-20
Post-Acute Sequelae of SARS-CoV-2 Infections: Exercise Limitation and Rehabilitation.
The Yale journal of biology and medicine, 97(4):463-472.
Patients with prior SARS-CoV-2 infections can develop chronic symptoms; this clinical presentation has been called post-acute sequelae of SARS-CoV-2 infection, post-COVID condition, and long COVID. It can develop in both outpatient cases and in hospital cases; the frequency depends on the severity of infection and comorbidity. Many of these patients have exercise limitation when tested using cardiopulmonary exercise tests. The potential explanations for reduced exercise capacity include cardiac limitations, respiratory limitations, skeletal muscle weakness, deconditioning, and limiting symptoms out of proportion to any measured physiological limitation, and many patients have more than one explanation for the exercise limitation. Since these patients may have required prolonged hospitalization, deconditioning has been considered a potential explanation for their post-hospitalization limitations. Patients with deconditioning have a low oxygen uptake per minute (VO2) maximum with no obvious cardiac or respiratory limitation, but some do have measurable muscle weakness. One complex study reported that these patients had a high proportion of high-fatigable glycolytic fibers, reduced mitochondrial function, atrophic fibers, and focal necrosis in skeletal muscle. Some post-COVID patients have chronic fatigue and post-exertional malaise and meet the clinical criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Most patients with post-COVID syndrome do improve with conventional cardiopulmonary rehabilitation. However, patients with post-exertional malaise need special attention to their exercise programs and careful monitoring for adverse effects. In summary, patients with long COVID can have complex presentations with a broad range of symptoms and several possible exercise limitations. Their rehabilitation program should be based on their physical capacity and their symptom profile.
Additional Links: PMID-39703612
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Citation:
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@article {pmid39703612,
year = {2024},
author = {Mathew, J and Nugent, K},
title = {Post-Acute Sequelae of SARS-CoV-2 Infections: Exercise Limitation and Rehabilitation.},
journal = {The Yale journal of biology and medicine},
volume = {97},
number = {4},
pages = {463-472},
pmid = {39703612},
issn = {1551-4056},
mesh = {Humans ; *COVID-19/complications/physiopathology ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; Exercise/physiology ; Exercise Tolerance/physiology ; Exercise Therapy/methods ; },
abstract = {Patients with prior SARS-CoV-2 infections can develop chronic symptoms; this clinical presentation has been called post-acute sequelae of SARS-CoV-2 infection, post-COVID condition, and long COVID. It can develop in both outpatient cases and in hospital cases; the frequency depends on the severity of infection and comorbidity. Many of these patients have exercise limitation when tested using cardiopulmonary exercise tests. The potential explanations for reduced exercise capacity include cardiac limitations, respiratory limitations, skeletal muscle weakness, deconditioning, and limiting symptoms out of proportion to any measured physiological limitation, and many patients have more than one explanation for the exercise limitation. Since these patients may have required prolonged hospitalization, deconditioning has been considered a potential explanation for their post-hospitalization limitations. Patients with deconditioning have a low oxygen uptake per minute (VO2) maximum with no obvious cardiac or respiratory limitation, but some do have measurable muscle weakness. One complex study reported that these patients had a high proportion of high-fatigable glycolytic fibers, reduced mitochondrial function, atrophic fibers, and focal necrosis in skeletal muscle. Some post-COVID patients have chronic fatigue and post-exertional malaise and meet the clinical criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Most patients with post-COVID syndrome do improve with conventional cardiopulmonary rehabilitation. However, patients with post-exertional malaise need special attention to their exercise programs and careful monitoring for adverse effects. In summary, patients with long COVID can have complex presentations with a broad range of symptoms and several possible exercise limitations. Their rehabilitation program should be based on their physical capacity and their symptom profile.},
}
MeSH Terms:
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Humans
*COVID-19/complications/physiopathology
*Post-Acute COVID-19 Syndrome
*SARS-CoV-2
Exercise/physiology
Exercise Tolerance/physiology
Exercise Therapy/methods
RevDate: 2025-01-04
CmpDate: 2024-12-20
The Intestine in Acute and Long COVID: Pathophysiological Insights and Key Lessons.
The Yale journal of biology and medicine, 97(4):447-462.
Post-Acute Sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID, represents a significant and complex health challenge with a wide range of symptoms affecting multiple organ systems. This review examines the emerging evidence suggesting a critical role of the gut and gut-brain axis in the pathophysiology of Long COVID. It explores how changes in the gut microbiome, disruption of gut barrier integrity, and the persistence of SARS-CoV-2 antigens within the gastrointestinal tract may contribute to the prolonged and varied symptoms seen in Long COVID, including chronic inflammation and neuropsychiatric disturbances. The review also summarizes key insights gained about Long COVID, highlighting its multifactorial nature, which involves immune dysregulation, microvascular damage, and autonomic nervous system dysfunction, with the gut playing a central role in these processes. While progress has been made in understanding these mechanisms, current evidence remains inconclusive. The challenges of establishing causality, standardizing research methodologies, and addressing individual variations in the microbiome are discussed, emphasizing the need for further longitudinal studies and more comprehensive approaches to enhance our understanding of these complex interactions. This review underscores the importance of personalized approaches in developing effective diagnostic and therapeutic strategies for Long COVID, while also acknowledging the significant gaps in our current understanding. Future research should aim to further unravel the complex interplay between the gut and Long COVID, ultimately improving outcomes for those affected by this condition.
Additional Links: PMID-39703608
PubMed:
Citation:
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@article {pmid39703608,
year = {2024},
author = {Zollner, A and Meyer, M and Jukic, A and Adolph, T and Tilg, H},
title = {The Intestine in Acute and Long COVID: Pathophysiological Insights and Key Lessons.},
journal = {The Yale journal of biology and medicine},
volume = {97},
number = {4},
pages = {447-462},
pmid = {39703608},
issn = {1551-4056},
mesh = {Humans ; *COVID-19/physiopathology/virology/immunology ; *Gastrointestinal Microbiome/physiology ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; Brain-Gut Axis/physiology ; Intestines/virology/physiopathology/microbiology ; },
abstract = {Post-Acute Sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID, represents a significant and complex health challenge with a wide range of symptoms affecting multiple organ systems. This review examines the emerging evidence suggesting a critical role of the gut and gut-brain axis in the pathophysiology of Long COVID. It explores how changes in the gut microbiome, disruption of gut barrier integrity, and the persistence of SARS-CoV-2 antigens within the gastrointestinal tract may contribute to the prolonged and varied symptoms seen in Long COVID, including chronic inflammation and neuropsychiatric disturbances. The review also summarizes key insights gained about Long COVID, highlighting its multifactorial nature, which involves immune dysregulation, microvascular damage, and autonomic nervous system dysfunction, with the gut playing a central role in these processes. While progress has been made in understanding these mechanisms, current evidence remains inconclusive. The challenges of establishing causality, standardizing research methodologies, and addressing individual variations in the microbiome are discussed, emphasizing the need for further longitudinal studies and more comprehensive approaches to enhance our understanding of these complex interactions. This review underscores the importance of personalized approaches in developing effective diagnostic and therapeutic strategies for Long COVID, while also acknowledging the significant gaps in our current understanding. Future research should aim to further unravel the complex interplay between the gut and Long COVID, ultimately improving outcomes for those affected by this condition.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*COVID-19/physiopathology/virology/immunology
*Gastrointestinal Microbiome/physiology
*Post-Acute COVID-19 Syndrome
*SARS-CoV-2
Brain-Gut Axis/physiology
Intestines/virology/physiopathology/microbiology
RevDate: 2025-01-18
CmpDate: 2024-12-26
Tackling algorithmic bias and promoting transparency in health datasets: the STANDING Together consensus recommendations.
The Lancet. Digital health, 7(1):e64-e88.
Without careful dissection of the ways in which biases can be encoded into artificial intelligence (AI) health technologies, there is a risk of perpetuating existing health inequalities at scale. One major source of bias is the data that underpins such technologies. The STANDING Together recommendations aim to encourage transparency regarding limitations of health datasets and proactive evaluation of their effect across population groups. Draft recommendation items were informed by a systematic review and stakeholder survey. The recommendations were developed using a Delphi approach, supplemented by a public consultation and international interview study. Overall, more than 350 representatives from 58 countries provided input into this initiative. 194 Delphi participants from 25 countries voted and provided comments on 32 candidate items across three electronic survey rounds and one in-person consensus meeting. The 29 STANDING Together consensus recommendations are presented here in two parts. Recommendations for Documentation of Health Datasets provide guidance for dataset curators to enable transparency around data composition and limitations. Recommendations for Use of Health Datasets aim to enable identification and mitigation of algorithmic biases that might exacerbate health inequalities. These recommendations are intended to prompt proactive inquiry rather than acting as a checklist. We hope to raise awareness that no dataset is free of limitations, so transparent communication of data limitations should be perceived as valuable, and absence of this information as a limitation. We hope that adoption of the STANDING Together recommendations by stakeholders across the AI health technology lifecycle will enable everyone in society to benefit from technologies which are safe and effective.
Additional Links: PMID-39701919
PubMed:
Citation:
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@article {pmid39701919,
year = {2025},
author = {Alderman, JE and Palmer, J and Laws, E and McCradden, MD and Ordish, J and Ghassemi, M and Pfohl, SR and Rostamzadeh, N and Cole-Lewis, H and Glocker, B and Calvert, M and Pollard, TJ and Gill, J and Gath, J and Adebajo, A and Beng, J and Leung, CH and Kuku, S and Farmer, LA and Matin, RN and Mateen, BA and McKay, F and Heller, K and Karthikesalingam, A and Treanor, D and Mackintosh, M and Oakden-Rayner, L and Pearson, R and Manrai, AK and Myles, P and Kumuthini, J and Kapacee, Z and Sebire, NJ and Nazer, LH and Seah, J and Akbari, A and Berman, L and Gichoya, JW and Righetto, L and Samuel, D and Wasswa, W and Charalambides, M and Arora, A and Pujari, S and Summers, C and Sapey, E and Wilkinson, S and Thakker, V and Denniston, A and Liu, X},
title = {Tackling algorithmic bias and promoting transparency in health datasets: the STANDING Together consensus recommendations.},
journal = {The Lancet. Digital health},
volume = {7},
number = {1},
pages = {e64-e88},
pmid = {39701919},
issn = {2589-7500},
support = {001/WHO_/World Health Organization/International ; },
mesh = {Humans ; Algorithms ; Artificial Intelligence ; Bias ; *Consensus ; Datasets as Topic ; *Delphi Technique ; },
abstract = {Without careful dissection of the ways in which biases can be encoded into artificial intelligence (AI) health technologies, there is a risk of perpetuating existing health inequalities at scale. One major source of bias is the data that underpins such technologies. The STANDING Together recommendations aim to encourage transparency regarding limitations of health datasets and proactive evaluation of their effect across population groups. Draft recommendation items were informed by a systematic review and stakeholder survey. The recommendations were developed using a Delphi approach, supplemented by a public consultation and international interview study. Overall, more than 350 representatives from 58 countries provided input into this initiative. 194 Delphi participants from 25 countries voted and provided comments on 32 candidate items across three electronic survey rounds and one in-person consensus meeting. The 29 STANDING Together consensus recommendations are presented here in two parts. Recommendations for Documentation of Health Datasets provide guidance for dataset curators to enable transparency around data composition and limitations. Recommendations for Use of Health Datasets aim to enable identification and mitigation of algorithmic biases that might exacerbate health inequalities. These recommendations are intended to prompt proactive inquiry rather than acting as a checklist. We hope to raise awareness that no dataset is free of limitations, so transparent communication of data limitations should be perceived as valuable, and absence of this information as a limitation. We hope that adoption of the STANDING Together recommendations by stakeholders across the AI health technology lifecycle will enable everyone in society to benefit from technologies which are safe and effective.},
}
MeSH Terms:
show MeSH Terms
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Humans
Algorithms
Artificial Intelligence
Bias
*Consensus
Datasets as Topic
*Delphi Technique
RevDate: 2025-01-04
Flow cytometry for extracellular vesicle characterization in COVID-19 and post-acute sequelae of SARS-CoV-2 infection.
Extracellular vesicles and circulating nucleic acids, 5(3):417-437.
Infection with SARS-CoV-2, the virus responsible for COVID-19 diseases, can impact different tissues and induce significant cellular alterations. The production of extracellular vesicles (EVs), which are physiologically involved in cell communication, is also altered during COVID-19, along with the dysfunction of cytoplasmic organelles. Since circulating EVs reflect the state of their cells of origin, they represent valuable tools for monitoring pathological conditions. Despite challenges in detecting EVs due to their size and specific cellular compartment origin using different methodologies, flow cytometry has proven to be an effective method for assessing the role of EVs in COVID-19. This review summarizes the involvement of plasmatic EVs in COVID-19 patients and individuals with Long COVID (LC) affected by post-acute sequelae of SARS-CoV-2 infection (PASC), highlighting their dual role in exerting both pro- and antiviral effects. We also emphasize how flow cytometry, with its multiparametric approach, can be employed to characterize circulating EVs, particularly in infectious diseases such as COVID-19, and suggest their potential role in chronic impairments during post-infection.
Additional Links: PMID-39697632
PubMed:
Citation:
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@article {pmid39697632,
year = {2024},
author = {Fanelli, M and Petrone, V and Chirico, R and Radu, CM and Minutolo, A and Matteucci, C},
title = {Flow cytometry for extracellular vesicle characterization in COVID-19 and post-acute sequelae of SARS-CoV-2 infection.},
journal = {Extracellular vesicles and circulating nucleic acids},
volume = {5},
number = {3},
pages = {417-437},
pmid = {39697632},
issn = {2767-6641},
abstract = {Infection with SARS-CoV-2, the virus responsible for COVID-19 diseases, can impact different tissues and induce significant cellular alterations. The production of extracellular vesicles (EVs), which are physiologically involved in cell communication, is also altered during COVID-19, along with the dysfunction of cytoplasmic organelles. Since circulating EVs reflect the state of their cells of origin, they represent valuable tools for monitoring pathological conditions. Despite challenges in detecting EVs due to their size and specific cellular compartment origin using different methodologies, flow cytometry has proven to be an effective method for assessing the role of EVs in COVID-19. This review summarizes the involvement of plasmatic EVs in COVID-19 patients and individuals with Long COVID (LC) affected by post-acute sequelae of SARS-CoV-2 infection (PASC), highlighting their dual role in exerting both pro- and antiviral effects. We also emphasize how flow cytometry, with its multiparametric approach, can be employed to characterize circulating EVs, particularly in infectious diseases such as COVID-19, and suggest their potential role in chronic impairments during post-infection.},
}
RevDate: 2024-12-18
Skeletal muscle adaptations and post-exertional malaise in long COVID.
Trends in endocrinology and metabolism: TEM pii:S1043-2760(24)00298-4 [Epub ahead of print].
When acute SARS-CoV-2 infections cause symptoms that persist longer than 3 months, this condition is termed long COVID. Symptoms experienced by patients often include myalgia, fatigue, brain fog, cognitive impairments, and post-exertional malaise (PEM), which is the worsening of symptoms following mental or physical exertion. There is little consensus on the pathophysiology of exercise-induced PEM and skeletal-muscle-related symptoms. In this opinion article we highlight intrinsic mitochondrial dysfunction, endothelial abnormalities, and a muscle fiber type shift towards a more glycolytic phenotype as main contributors to the reduced exercise capacity in long COVID. The mechanistic trigger for physical exercise to induce PEM is unknown, but rapid skeletal muscle tissue damage and intramuscular infiltration of immune cells contribute to PEM-related symptoms.
Additional Links: PMID-39694730
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PubMed:
Citation:
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@article {pmid39694730,
year = {2024},
author = {Charlton, BT and Goulding, RP and Jaspers, RT and Appelman, B and van Vugt, M and Wüst, RCI},
title = {Skeletal muscle adaptations and post-exertional malaise in long COVID.},
journal = {Trends in endocrinology and metabolism: TEM},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tem.2024.11.008},
pmid = {39694730},
issn = {1879-3061},
abstract = {When acute SARS-CoV-2 infections cause symptoms that persist longer than 3 months, this condition is termed long COVID. Symptoms experienced by patients often include myalgia, fatigue, brain fog, cognitive impairments, and post-exertional malaise (PEM), which is the worsening of symptoms following mental or physical exertion. There is little consensus on the pathophysiology of exercise-induced PEM and skeletal-muscle-related symptoms. In this opinion article we highlight intrinsic mitochondrial dysfunction, endothelial abnormalities, and a muscle fiber type shift towards a more glycolytic phenotype as main contributors to the reduced exercise capacity in long COVID. The mechanistic trigger for physical exercise to induce PEM is unknown, but rapid skeletal muscle tissue damage and intramuscular infiltration of immune cells contribute to PEM-related symptoms.},
}
RevDate: 2025-01-17
CmpDate: 2024-12-18
Reemerging Infectious Diseases and Neuroimmunologic Complications.
Neurology(R) neuroimmunology & neuroinflammation, 12(1):e200356.
During the past decade (and beyond), neurologists have become aware of the emergence, persistence, and consequences of some familiar and new infections affecting the nervous system. Even among the familiar CNS infections, such as herpes virus, polyoma virus/JC, influenza, arbovirus, and hepatitis, challenges remain in developing effective antiviral treatments and treatments of postinfection sequelae. With the changing environment and increased global travel, arthropod vectors that mediate zoonotic disease transmission have spread unfamiliar viruses such as West Nile virus, dengue, chikungunya, equine encephalitis, and Zika, among others. Although the global health impact of these diseases has not risen to that of COVID-19 and HIV, it is likely to dramatically increase with continued spread of transmission vectors and the emergence of new zoonotic animal-to-human diseases mediated by those transmission vectors. Furthermore, specific virus-targeting treatments or effective vaccines for arboviral infections are not yet available, and this represents a major challenge in limiting the morbidity of these infections. By contrast, HIV-1, a disease that originated by direct transmission from nonhuman primates to humans (as early as the 1930s), after many years of intense study, is now targeted by highly specific and effective antiviral drugs that can limit the spread of infection and extend human life and health in all populations. Even with these dramatic therapeutic effects of suppressing HIV replication, neurologic dysfunction (primarily cognitive impairment) affects significant numbers of persons living with HIV. This emphasizes not only the importance of treating the underlying infection but also developing treatments for legacy effects of the initial infection even after antiviral therapy. Notably, the rapid emergence of SARS-CoV-2 infection was met with rapid implementation of highly effective and specific antiviral therapies. This resulted in early and dramatic lowering of the morbidity and mortality of SARS-CoV-2 infection. Nonetheless, the postinfectious complications of SARS-CoV-2 infection (long COVID) are now among the more costly consequences of emerging zoonotic infections worldwide. Developing new antiviral therapies that can penetrate the CNS, vaccines, and therapies that target host immune responses and metabolic dysfunction will be necessary for management of infectious and postinfectious complications of established and emerging infections.
Additional Links: PMID-39693583
PubMed:
Citation:
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@article {pmid39693583,
year = {2025},
author = {Nath, A and Kolson, DL},
title = {Reemerging Infectious Diseases and Neuroimmunologic Complications.},
journal = {Neurology(R) neuroimmunology & neuroinflammation},
volume = {12},
number = {1},
pages = {e200356},
pmid = {39693583},
issn = {2332-7812},
support = {R01 NS122570/NS/NINDS NIH HHS/United States ; },
mesh = {Animals ; Humans ; *Communicable Diseases, Emerging/complications ; COVID-19/complications ; HIV Infections/complications ; },
abstract = {During the past decade (and beyond), neurologists have become aware of the emergence, persistence, and consequences of some familiar and new infections affecting the nervous system. Even among the familiar CNS infections, such as herpes virus, polyoma virus/JC, influenza, arbovirus, and hepatitis, challenges remain in developing effective antiviral treatments and treatments of postinfection sequelae. With the changing environment and increased global travel, arthropod vectors that mediate zoonotic disease transmission have spread unfamiliar viruses such as West Nile virus, dengue, chikungunya, equine encephalitis, and Zika, among others. Although the global health impact of these diseases has not risen to that of COVID-19 and HIV, it is likely to dramatically increase with continued spread of transmission vectors and the emergence of new zoonotic animal-to-human diseases mediated by those transmission vectors. Furthermore, specific virus-targeting treatments or effective vaccines for arboviral infections are not yet available, and this represents a major challenge in limiting the morbidity of these infections. By contrast, HIV-1, a disease that originated by direct transmission from nonhuman primates to humans (as early as the 1930s), after many years of intense study, is now targeted by highly specific and effective antiviral drugs that can limit the spread of infection and extend human life and health in all populations. Even with these dramatic therapeutic effects of suppressing HIV replication, neurologic dysfunction (primarily cognitive impairment) affects significant numbers of persons living with HIV. This emphasizes not only the importance of treating the underlying infection but also developing treatments for legacy effects of the initial infection even after antiviral therapy. Notably, the rapid emergence of SARS-CoV-2 infection was met with rapid implementation of highly effective and specific antiviral therapies. This resulted in early and dramatic lowering of the morbidity and mortality of SARS-CoV-2 infection. Nonetheless, the postinfectious complications of SARS-CoV-2 infection (long COVID) are now among the more costly consequences of emerging zoonotic infections worldwide. Developing new antiviral therapies that can penetrate the CNS, vaccines, and therapies that target host immune responses and metabolic dysfunction will be necessary for management of infectious and postinfectious complications of established and emerging infections.},
}
MeSH Terms:
show MeSH Terms
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Animals
Humans
*Communicable Diseases, Emerging/complications
COVID-19/complications
HIV Infections/complications
RevDate: 2025-01-04
Lights and Shadows of Long COVID: Are Latent Infections the Real Hidden Enemy?.
Journal of clinical medicine, 13(23):.
Long COVID-19 (LC) is a poorly understood, multifactorial condition that persists for at least three months following SARS-CoV-2 infection. The underlying pathophysiological mechanisms responsible for the wide range of associated symptoms-including fatigue, brain fog, and respiratory issues-remain unclear. However, emerging evidence suggests that the reactivation of latent viral infections, such as Epstein-Barr virus, cytomegalovirus, and varicella-zoster virus, may significantly contribute to the complexity of LC. These latent viruses can be reactivated by SARS-CoV-2, contributing to a chronic inflammatory state that prolongs symptomatology. This review confirms the potential involvement of latent viral infections in LC and examines whether these infections play an independent role or act synergistically with other factors. In addition, recent studies have highlighted viral persistence and immune dysregulation as key elements in LC. Our findings suggest that preventative strategies, including vaccination and antiviral treatments during the acute phase of COVID-19, show potential in reducing LC risk by preventing viral reactivation. However, tailored diagnostic and therapeutic strategies targeting these latent infections are urgently needed. Identifying biomarkers of viral reactivation, particularly for high-risk populations, could be considered another effective strategy to mitigate LC severity. Further research is crucial to better understand the interactions between SARS-CoV-2 and latent infections, and to improve the prevention and treatment of LC.
Additional Links: PMID-39685583
PubMed:
Citation:
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@article {pmid39685583,
year = {2024},
author = {Serapide, F and Talarico, M and Rotundo, S and Pascale, V and Serraino, R and Trecarichi, EM and Russo, A},
title = {Lights and Shadows of Long COVID: Are Latent Infections the Real Hidden Enemy?.},
journal = {Journal of clinical medicine},
volume = {13},
number = {23},
pages = {},
pmid = {39685583},
issn = {2077-0383},
abstract = {Long COVID-19 (LC) is a poorly understood, multifactorial condition that persists for at least three months following SARS-CoV-2 infection. The underlying pathophysiological mechanisms responsible for the wide range of associated symptoms-including fatigue, brain fog, and respiratory issues-remain unclear. However, emerging evidence suggests that the reactivation of latent viral infections, such as Epstein-Barr virus, cytomegalovirus, and varicella-zoster virus, may significantly contribute to the complexity of LC. These latent viruses can be reactivated by SARS-CoV-2, contributing to a chronic inflammatory state that prolongs symptomatology. This review confirms the potential involvement of latent viral infections in LC and examines whether these infections play an independent role or act synergistically with other factors. In addition, recent studies have highlighted viral persistence and immune dysregulation as key elements in LC. Our findings suggest that preventative strategies, including vaccination and antiviral treatments during the acute phase of COVID-19, show potential in reducing LC risk by preventing viral reactivation. However, tailored diagnostic and therapeutic strategies targeting these latent infections are urgently needed. Identifying biomarkers of viral reactivation, particularly for high-risk populations, could be considered another effective strategy to mitigate LC severity. Further research is crucial to better understand the interactions between SARS-CoV-2 and latent infections, and to improve the prevention and treatment of LC.},
}
RevDate: 2024-12-16
A Review on Long COVID Screening: Challenges and Perspectives Focusing on Exhaled Breath Gas Sensing.
ACS sensors [Epub ahead of print].
Long COVID (LC) is a great global health concern, affecting individuals recovering from SARS-CoV-2 infection. The persistent and varied symptoms across multiple organs complicate diagnosis and management, and an incomplete understanding of the condition hinders advancements in therapeutics. Current diagnostic methods face challenges related to standardization and completeness. To overcome this, new technologies such as sensor-based electronic noses are being explored for LC assessment, offering a noninvasive screening approach via volatile organic compounds (VOC) sensing in exhaled breath. Although specific LC-associated VOCs have not been fully characterized, insights from COVID-19 research suggest their potential as biomarkers. Additionally, AI-driven chemometrics are promising in identifying and predicting outcomes; despite challenges, AI-driven technologies hold the potential to enhance LC evaluation, providing rapid and accurate diagnostics for improved patient care and outcomes. This review underscores the importance of emerging and sensing technologies and comprehensive diagnostic strategies to address screening and treatment challenges in the face of LC.
Additional Links: PMID-39680873
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Citation:
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@article {pmid39680873,
year = {2024},
author = {Díaz de León-Martínez, L and Flores-Rangel, G and Alcántara-Quintana, LE and Mizaikoff, B},
title = {A Review on Long COVID Screening: Challenges and Perspectives Focusing on Exhaled Breath Gas Sensing.},
journal = {ACS sensors},
volume = {},
number = {},
pages = {},
doi = {10.1021/acssensors.4c02280},
pmid = {39680873},
issn = {2379-3694},
abstract = {Long COVID (LC) is a great global health concern, affecting individuals recovering from SARS-CoV-2 infection. The persistent and varied symptoms across multiple organs complicate diagnosis and management, and an incomplete understanding of the condition hinders advancements in therapeutics. Current diagnostic methods face challenges related to standardization and completeness. To overcome this, new technologies such as sensor-based electronic noses are being explored for LC assessment, offering a noninvasive screening approach via volatile organic compounds (VOC) sensing in exhaled breath. Although specific LC-associated VOCs have not been fully characterized, insights from COVID-19 research suggest their potential as biomarkers. Additionally, AI-driven chemometrics are promising in identifying and predicting outcomes; despite challenges, AI-driven technologies hold the potential to enhance LC evaluation, providing rapid and accurate diagnostics for improved patient care and outcomes. This review underscores the importance of emerging and sensing technologies and comprehensive diagnostic strategies to address screening and treatment challenges in the face of LC.},
}
RevDate: 2025-01-04
Vagal nerve stimulation for the management of long COVID symptoms.
Infectious medicine, 3(4):100149.
This review investigates the therapeutic potential of vagal nerve stimulation (VNS) in managing long COVID, a condition marked by persistent symptoms following acute SARS-CoV-2 infection. Long COVID manifests as ongoing fatigue, cognitive impairment, and autonomic dysfunction, hypothesized to arise from sustained inflammatory and neurological dysregulation. The vagus nerve, central to modulating systemic inflammation and autonomic homeostasis, represents a promising therapeutic target for symptom alleviation through VNS. A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science to identify studies evaluating VNS in the context of long COVID. Preliminary evidence from small-scale pilot studies suggests VNS may attenuate systemic inflammation through activation of the cholinergic anti-inflammatory pathway (CAP), thus restoring autonomic balance and ameliorating symptoms such as fatigue, cognitive dysfunction, and anxiety. In targeting the inflammatory cascade that underlies both acute COVID-19 pathophysiology and its prolonged sequelae, VNS holds potential as an innovative intervention for persistent post-viral symptoms. While these initial findings indicate promise, current data remain limited in scope and robustness, underscoring the need for larger, controlled trials to validate the efficacy and mechanisms of VNS in long COVID management. Establishing a clearer understanding of VNS's impact on inflammation and autonomic regulation in this context is crucial to inform clinical guidelines and therapeutic strategies for long COVID, potentially offering a targeted approach for mitigating this disabling condition.
Additional Links: PMID-39678231
PubMed:
Citation:
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@article {pmid39678231,
year = {2024},
author = {Khan, MWZ and Ahmad, M and Qudrat, S and Afridi, F and Khan, NA and Afridi, Z and Fahad, and Azeem, T and Ikram, J},
title = {Vagal nerve stimulation for the management of long COVID symptoms.},
journal = {Infectious medicine},
volume = {3},
number = {4},
pages = {100149},
pmid = {39678231},
issn = {2772-431X},
abstract = {This review investigates the therapeutic potential of vagal nerve stimulation (VNS) in managing long COVID, a condition marked by persistent symptoms following acute SARS-CoV-2 infection. Long COVID manifests as ongoing fatigue, cognitive impairment, and autonomic dysfunction, hypothesized to arise from sustained inflammatory and neurological dysregulation. The vagus nerve, central to modulating systemic inflammation and autonomic homeostasis, represents a promising therapeutic target for symptom alleviation through VNS. A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science to identify studies evaluating VNS in the context of long COVID. Preliminary evidence from small-scale pilot studies suggests VNS may attenuate systemic inflammation through activation of the cholinergic anti-inflammatory pathway (CAP), thus restoring autonomic balance and ameliorating symptoms such as fatigue, cognitive dysfunction, and anxiety. In targeting the inflammatory cascade that underlies both acute COVID-19 pathophysiology and its prolonged sequelae, VNS holds potential as an innovative intervention for persistent post-viral symptoms. While these initial findings indicate promise, current data remain limited in scope and robustness, underscoring the need for larger, controlled trials to validate the efficacy and mechanisms of VNS in long COVID management. Establishing a clearer understanding of VNS's impact on inflammation and autonomic regulation in this context is crucial to inform clinical guidelines and therapeutic strategies for long COVID, potentially offering a targeted approach for mitigating this disabling condition.},
}
RevDate: 2025-01-08
CmpDate: 2025-01-06
Effectiveness of physiotherapy modalities on persisting dyspnoea in long COVID: A systematic review and meta-analysis.
Respiratory medicine, 236:107909.
BACKGROUND: Dyspnoea is often found months and years later in the "long-covid" syndrome, impairing quality of life and further perpetuating anxiety and post-traumatic stress disorders. Physiotherapy was recommended as a treatment in long-covid, but there is still insufficient evidence on its effectiveness.
METHODS: We conducted a systematic literature search on MEDLINE, PEDro, WOS, Scopus, VHL and the Cochrane Library until July 2023 (PROSPERO registration number: CRD42023427464). We selected comparative trials including adults with persistent breathlessness following COVID-19, regardless of the initial severity, for whom physiotherapy was implemented as a treatment for dyspnoea. We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and assessed the study quality using the PEDro Scale.
RESULTS: 19 studies that included 1292 adults fulfilled the inclusion criteria, of which 15 were randomised controlled trials and 4 non-randomised controlled trials. As for the rehabilitation modalities, 6 studies used respiratory muscle training, 6 studies used low to moderate intensity rehabilitation, 6 used high intensity rehabilitation and one used passive rehabilitation. The methods used between and within each group differed greatly, leading to an expected high heterogeneity of results. Nethertheless the random-effects model found a significant difference favouring physiotherapy (SMD -0.63, 95 CI [-1.03; -0.24], p < 0.001, I[2] = 88 %). Subgroup analysis showed a significant effect in the high intensity rehabilitation group alone, with null heterogeneity.
CONCLUSION: In people suffering from dyspnoea following a SARS-CoV-2 infection, physiotherapy and especially pulmonary rehabilitation may help alleviate respiratory symptoms. Future studies will need to provide more consistent rehabilitation methods and better descriptions of them so as to reveal clear effects and avoid the confusion caused by using too many rehabilitation modalities.
Additional Links: PMID-39667587
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Citation:
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@article {pmid39667587,
year = {2025},
author = {Romanet, C and Wormser, J and Cachanado, M and Santiago, MG and Chatellier, G and Valenza, MC and Philippart, F},
title = {Effectiveness of physiotherapy modalities on persisting dyspnoea in long COVID: A systematic review and meta-analysis.},
journal = {Respiratory medicine},
volume = {236},
number = {},
pages = {107909},
doi = {10.1016/j.rmed.2024.107909},
pmid = {39667587},
issn = {1532-3064},
mesh = {Adult ; Humans ; *Dyspnea/etiology/psychology/therapy ; *Physical Therapy Modalities ; *Post-Acute COVID-19 Syndrome/complications/psychology/therapy ; Quality of Life ; Randomized Controlled Trials as Topic ; SARS-CoV-2 ; Treatment Outcome ; },
abstract = {BACKGROUND: Dyspnoea is often found months and years later in the "long-covid" syndrome, impairing quality of life and further perpetuating anxiety and post-traumatic stress disorders. Physiotherapy was recommended as a treatment in long-covid, but there is still insufficient evidence on its effectiveness.
METHODS: We conducted a systematic literature search on MEDLINE, PEDro, WOS, Scopus, VHL and the Cochrane Library until July 2023 (PROSPERO registration number: CRD42023427464). We selected comparative trials including adults with persistent breathlessness following COVID-19, regardless of the initial severity, for whom physiotherapy was implemented as a treatment for dyspnoea. We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and assessed the study quality using the PEDro Scale.
RESULTS: 19 studies that included 1292 adults fulfilled the inclusion criteria, of which 15 were randomised controlled trials and 4 non-randomised controlled trials. As for the rehabilitation modalities, 6 studies used respiratory muscle training, 6 studies used low to moderate intensity rehabilitation, 6 used high intensity rehabilitation and one used passive rehabilitation. The methods used between and within each group differed greatly, leading to an expected high heterogeneity of results. Nethertheless the random-effects model found a significant difference favouring physiotherapy (SMD -0.63, 95 CI [-1.03; -0.24], p < 0.001, I[2] = 88 %). Subgroup analysis showed a significant effect in the high intensity rehabilitation group alone, with null heterogeneity.
CONCLUSION: In people suffering from dyspnoea following a SARS-CoV-2 infection, physiotherapy and especially pulmonary rehabilitation may help alleviate respiratory symptoms. Future studies will need to provide more consistent rehabilitation methods and better descriptions of them so as to reveal clear effects and avoid the confusion caused by using too many rehabilitation modalities.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Adult
Humans
*Dyspnea/etiology/psychology/therapy
*Physical Therapy Modalities
*Post-Acute COVID-19 Syndrome/complications/psychology/therapy
Quality of Life
Randomized Controlled Trials as Topic
SARS-CoV-2
Treatment Outcome
RevDate: 2025-01-18
CmpDate: 2025-01-18
From Viral Infection to Skin Affliction: Unveiling Mechanisms of Cutaneous Manifestations in COVID-19 and Post-COVID Conditions.
The Journal of investigative dermatology, 145(2):257-265.
COVID-19 skin manifestations are multifaceted, ranging from urticaria, morbilliform or papulovesicular rash, livedoid purpuric lesions, and to pseudochilblains (also called COVID toes). Recent insights into the mechanism of these manifestations have highlighted that morbilliform, papulovesicular, and livedoid/purpuric rashes are related to virus-induced endothelial cell damage and linked to moderate-to-severe disease, whereas pseudochilblains are related to an exaggerated IFN-1 production by plasmacytoid dendritic cells in protected individuals. In this paper, we will review the clinical and physiopathological features of cutaneous COVID-19 manifestations in relation to the direct viral cytopathic effects and dysregulated IFN-1 responses. We will also review the emerging insights into post-COVID conditions (also termed long COVID) and how they may be implicated in the persistence of COVID-19-associated skin diseases.
Additional Links: PMID-39665720
Publisher:
PubMed:
Citation:
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@article {pmid39665720,
year = {2025},
author = {Brahimi, N and Croitoru, D and Saidoune, F and Zabihi, H and Gilliet, M and Piguet, V},
title = {From Viral Infection to Skin Affliction: Unveiling Mechanisms of Cutaneous Manifestations in COVID-19 and Post-COVID Conditions.},
journal = {The Journal of investigative dermatology},
volume = {145},
number = {2},
pages = {257-265},
doi = {10.1016/j.jid.2024.03.047},
pmid = {39665720},
issn = {1523-1747},
mesh = {Humans ; *COVID-19/complications/immunology/virology ; *SARS-CoV-2 ; Skin Diseases/virology/immunology ; Skin/pathology/virology/immunology ; Post-Acute COVID-19 Syndrome ; Urticaria/virology/pathology/immunology ; Interferon Type I/metabolism/immunology ; },
abstract = {COVID-19 skin manifestations are multifaceted, ranging from urticaria, morbilliform or papulovesicular rash, livedoid purpuric lesions, and to pseudochilblains (also called COVID toes). Recent insights into the mechanism of these manifestations have highlighted that morbilliform, papulovesicular, and livedoid/purpuric rashes are related to virus-induced endothelial cell damage and linked to moderate-to-severe disease, whereas pseudochilblains are related to an exaggerated IFN-1 production by plasmacytoid dendritic cells in protected individuals. In this paper, we will review the clinical and physiopathological features of cutaneous COVID-19 manifestations in relation to the direct viral cytopathic effects and dysregulated IFN-1 responses. We will also review the emerging insights into post-COVID conditions (also termed long COVID) and how they may be implicated in the persistence of COVID-19-associated skin diseases.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*COVID-19/complications/immunology/virology
*SARS-CoV-2
Skin Diseases/virology/immunology
Skin/pathology/virology/immunology
Post-Acute COVID-19 Syndrome
Urticaria/virology/pathology/immunology
Interferon Type I/metabolism/immunology
RevDate: 2025-02-08
CmpDate: 2024-12-11
Defining and measuring long COVID fatigue: a scoping review.
BMJ open, 14(12):e088530.
OBJECTIVE: Long COVID encompasses a range of symptoms in which fatigue is one of the most prevalents. It is clear from other conditions that the definition and measurement of fatigue can be complex, but it is not clear how fatigue is defined and measured in long COVID. To advance our understanding, this review summarises the definitions and measures of long COVID fatigue being used by researchers.
DESIGN: Scoping review following JBI methodology and reports using the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews.
DATA SOURCES: Medline, Scopus, CINAHL, PsycINFO, EMCARE, Web of Science, Epistemonikos, Cochrane Central Register of Controlled Trials, Dimensions, Overton and ProQuest Dissertation & Theses Database were searched from January 2020 to May 2023.
ELIGIBILITY CRITERIA: This review included quantitative and qualitative studies that included any definition of long COVID and/or measurement tool that purported to quantify either the impact, severity or symptoms of long COVID fatigue.
DATA EXTRACTION AND SYNTHESIS: Two independent reviewers screened the title, abstracts and full texts of the selected studies based on the inclusion criteria. Data extraction was performed by two independent reviewers. The data were summarised in tabular format and a narrative summary.
RESULTS: The search retrieved 9839 studies, of which 57 met the inclusion criteria. Only 21 (37%) provided a definition of fatigue. Definitions ranged across physical, mental, cognitive, emotional, psychosocial, central, peripheral, postexertional symptom exacerbation and general dimensions of fatigue. Fifty-five (96%) used a measurement or assessment of fatigue. Twenty-six measures of fatigue were identified: 21 self-report measures (eg, Fatigue Assessment Scale) and five fatigability measures that purport to reflect changes in physiological processes that contribute to or reflect fatigue (eg, change in force generating capacity of a muscle).
CONCLUSIONS: The definitions identified demonstrate considerable diversity, each highlighting different dimensions of long COVID fatigue. Long COVID fatigue was predominantly measured through self-report methods, which were problematic. There is an urgent need to better understand long COVID fatigue and to identify the different mechanisms involved. In order to do this, we need consistency with the language around fatigue and its measurement within research and across disciplines.
REVIEW REGISTRATION: The protocol has been registered on open science framework (https://doi.org/10.17605/OSF.IO/HNF8Z).
Additional Links: PMID-39663173
PubMed:
Citation:
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@article {pmid39663173,
year = {2024},
author = {Thomas, B and Pattinson, R and Edwards, D and Dale, C and Jenkins, B and Lande, H and Bundy, C and Davies, J},
title = {Defining and measuring long COVID fatigue: a scoping review.},
journal = {BMJ open},
volume = {14},
number = {12},
pages = {e088530},
pmid = {39663173},
issn = {2044-6055},
mesh = {Humans ; *COVID-19/complications ; *Fatigue/etiology/diagnosis ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {OBJECTIVE: Long COVID encompasses a range of symptoms in which fatigue is one of the most prevalents. It is clear from other conditions that the definition and measurement of fatigue can be complex, but it is not clear how fatigue is defined and measured in long COVID. To advance our understanding, this review summarises the definitions and measures of long COVID fatigue being used by researchers.
DESIGN: Scoping review following JBI methodology and reports using the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews.
DATA SOURCES: Medline, Scopus, CINAHL, PsycINFO, EMCARE, Web of Science, Epistemonikos, Cochrane Central Register of Controlled Trials, Dimensions, Overton and ProQuest Dissertation & Theses Database were searched from January 2020 to May 2023.
ELIGIBILITY CRITERIA: This review included quantitative and qualitative studies that included any definition of long COVID and/or measurement tool that purported to quantify either the impact, severity or symptoms of long COVID fatigue.
DATA EXTRACTION AND SYNTHESIS: Two independent reviewers screened the title, abstracts and full texts of the selected studies based on the inclusion criteria. Data extraction was performed by two independent reviewers. The data were summarised in tabular format and a narrative summary.
RESULTS: The search retrieved 9839 studies, of which 57 met the inclusion criteria. Only 21 (37%) provided a definition of fatigue. Definitions ranged across physical, mental, cognitive, emotional, psychosocial, central, peripheral, postexertional symptom exacerbation and general dimensions of fatigue. Fifty-five (96%) used a measurement or assessment of fatigue. Twenty-six measures of fatigue were identified: 21 self-report measures (eg, Fatigue Assessment Scale) and five fatigability measures that purport to reflect changes in physiological processes that contribute to or reflect fatigue (eg, change in force generating capacity of a muscle).
CONCLUSIONS: The definitions identified demonstrate considerable diversity, each highlighting different dimensions of long COVID fatigue. Long COVID fatigue was predominantly measured through self-report methods, which were problematic. There is an urgent need to better understand long COVID fatigue and to identify the different mechanisms involved. In order to do this, we need consistency with the language around fatigue and its measurement within research and across disciplines.
REVIEW REGISTRATION: The protocol has been registered on open science framework (https://doi.org/10.17605/OSF.IO/HNF8Z).},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*COVID-19/complications
*Fatigue/etiology/diagnosis
SARS-CoV-2
Post-Acute COVID-19 Syndrome
RevDate: 2024-12-12
The overlooked burden of persistent physical symptoms: a call for action in European healthcare.
The Lancet regional health. Europe, 48:101140.
Regardless of their cause, persistent physical symptoms are distressing somatic complaints that occur on most days for at least several months. They are common in patients with somatic diseases, functional somatic disorders, mental disorders, and undiagnosed medical conditions and are often associated with significant impairment and medical costs. Despite their prevalence and impact, persistent physical symptoms are often overlooked in medical care. This Personal View stresses the importance of recognising persistent physical symptoms as a European health issue. It advocates improvements in research, clinical management, public health, and policy. Efforts should prioritise integrating models of symptom perception and biopsychosocial perspectives into medical care and education, fostering interdisciplinary collaboration, and developing standardised guidelines to enhance patient care, reduce stigma, and improve clinical outcomes. Increased research funding can accelerate progress in understanding and effectively managing persistent physical symptoms. Addressing these priorities will support patients and healthcare professionals, ensuring adequate care and a higher quality of life for affected individuals.
Additional Links: PMID-39660101
PubMed:
Citation:
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@article {pmid39660101,
year = {2025},
author = {Toussaint, A and Weigel, A and Löwe, B and , },
title = {The overlooked burden of persistent physical symptoms: a call for action in European healthcare.},
journal = {The Lancet regional health. Europe},
volume = {48},
number = {},
pages = {101140},
pmid = {39660101},
issn = {2666-7762},
abstract = {Regardless of their cause, persistent physical symptoms are distressing somatic complaints that occur on most days for at least several months. They are common in patients with somatic diseases, functional somatic disorders, mental disorders, and undiagnosed medical conditions and are often associated with significant impairment and medical costs. Despite their prevalence and impact, persistent physical symptoms are often overlooked in medical care. This Personal View stresses the importance of recognising persistent physical symptoms as a European health issue. It advocates improvements in research, clinical management, public health, and policy. Efforts should prioritise integrating models of symptom perception and biopsychosocial perspectives into medical care and education, fostering interdisciplinary collaboration, and developing standardised guidelines to enhance patient care, reduce stigma, and improve clinical outcomes. Increased research funding can accelerate progress in understanding and effectively managing persistent physical symptoms. Addressing these priorities will support patients and healthcare professionals, ensuring adequate care and a higher quality of life for affected individuals.},
}
RevDate: 2024-12-10
Treatments for Long COVID autonomic dysfunction: a scoping review.
Clinical autonomic research : official journal of the Clinical Autonomic Research Society [Epub ahead of print].
PURPOSE: For Long COVID autonomic dysfunction, we have summarized published evidence on treatment effectiveness, clinical practice guidelines, and unpublished/ongoing studies.
METHODS: We first interviewed 11 stakeholders (clinicians, clinician/researchers, payors, patient advocates) to gain clinical insights and identify key areas of focus. We searched Embase, CINAHL, Medline, PsycINFO, and PubMed databases for relevant English-language articles published between 1 January 2020 and 30 April 2024. We also searched several other resources for additional relevant guidelines (e.g., UpToDate) and unpublished/ongoing studies (e.g., the International Clinical Trials Registry Platform). All information was summarized narratively.
RESULTS: We included 11 effectiveness studies that investigated numerous treatment regimens (fexofenadine + famotidine, maraviroc + pravastatin, selective serotonin reuptake inhibitors, nutraceutical formulations, multicomponent treatments, heart rate variability biofeedback, inspiratory muscle training, or stellate ganglion block). One randomized trial reported benefits of a nutraceutical (SIM01) on fatigue and gastrointestinal upset. The 11 guidelines and position statements addressed numerous aspects of treatment, but primarily exercise/rehabilitation, fluid/salt intake, and the use of compression garments. The 15 unpublished/ongoing studies are testing nine different interventions, most prominently ivabradine and intravenous immunoglobulin.
CONCLUSION: Existing studies on the treatment of Long COVID autonomic dysfunction are often small and uncontrolled, making it unclear whether the observed pre-post changes were due solely to the administered treatments. Guidelines display some overlap, and we identified no direct contradictions. Unpublished/ongoing studies may shed light on this critical area of patient management.
Additional Links: PMID-39658729
PubMed:
Citation:
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@article {pmid39658729,
year = {2024},
author = {Treadwell, JR and Wagner, J and Reston, JT and Phillips, T and Hedden-Gross, A and Tipton, KN},
title = {Treatments for Long COVID autonomic dysfunction: a scoping review.},
journal = {Clinical autonomic research : official journal of the Clinical Autonomic Research Society},
volume = {},
number = {},
pages = {},
pmid = {39658729},
issn = {1619-1560},
support = {MSA-SOW#06-ECRI-ENG-10-02-2023/PCORI/Patient-Centered Outcomes Research Institute/United States ; },
abstract = {PURPOSE: For Long COVID autonomic dysfunction, we have summarized published evidence on treatment effectiveness, clinical practice guidelines, and unpublished/ongoing studies.
METHODS: We first interviewed 11 stakeholders (clinicians, clinician/researchers, payors, patient advocates) to gain clinical insights and identify key areas of focus. We searched Embase, CINAHL, Medline, PsycINFO, and PubMed databases for relevant English-language articles published between 1 January 2020 and 30 April 2024. We also searched several other resources for additional relevant guidelines (e.g., UpToDate) and unpublished/ongoing studies (e.g., the International Clinical Trials Registry Platform). All information was summarized narratively.
RESULTS: We included 11 effectiveness studies that investigated numerous treatment regimens (fexofenadine + famotidine, maraviroc + pravastatin, selective serotonin reuptake inhibitors, nutraceutical formulations, multicomponent treatments, heart rate variability biofeedback, inspiratory muscle training, or stellate ganglion block). One randomized trial reported benefits of a nutraceutical (SIM01) on fatigue and gastrointestinal upset. The 11 guidelines and position statements addressed numerous aspects of treatment, but primarily exercise/rehabilitation, fluid/salt intake, and the use of compression garments. The 15 unpublished/ongoing studies are testing nine different interventions, most prominently ivabradine and intravenous immunoglobulin.
CONCLUSION: Existing studies on the treatment of Long COVID autonomic dysfunction are often small and uncontrolled, making it unclear whether the observed pre-post changes were due solely to the administered treatments. Guidelines display some overlap, and we identified no direct contradictions. Unpublished/ongoing studies may shed light on this critical area of patient management.},
}
RevDate: 2024-12-10
[Association between obesity and Long-Covid: A narrative review].
Semergen, 51(3):102390 pii:S1138-3593(24)00200-4 [Epub ahead of print].
To analyze the evidence in the scientific literature that relates Long-Covid and obesity, a narrative review of articles published in English and Spanish in Medline and Embase in the last 5years has been carried out. Infection with the SARS-CoV-2 virus causes a systemic inflammatory state increasing nutritional demand that favors sarcopenia in Long-Covid syndrome. It also causes endothelial dysfunction and a prothrombotic state that favors the formation of microthrombi and tissue hypoxia. A healthy and balanced diet is essential to treat obesity in addition to modifying the microbiota in Long-Covid and promoting physical and mental well-being. Obesity is an independent risk factor that increases the need for hospitalization, cardiovascular risk and mortality, as well as susceptibility to Long-Covid. Adipose tissue is a good reservoir of the virus, enhancing the comorbidities associated with obesity (high blood pressure, diabetes mellitus, dyslipidemia or fatty liver). There is insufficient evidence to recommend nutritional supplements to improve Long-Covid symptoms.
Additional Links: PMID-39657574
Publisher:
PubMed:
Citation:
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@article {pmid39657574,
year = {2024},
author = {Fernández-García, JM and Romero-Secin, A and Rubín-García, M},
title = {[Association between obesity and Long-Covid: A narrative review].},
journal = {Semergen},
volume = {51},
number = {3},
pages = {102390},
doi = {10.1016/j.semerg.2024.102390},
pmid = {39657574},
issn = {1578-8865},
abstract = {To analyze the evidence in the scientific literature that relates Long-Covid and obesity, a narrative review of articles published in English and Spanish in Medline and Embase in the last 5years has been carried out. Infection with the SARS-CoV-2 virus causes a systemic inflammatory state increasing nutritional demand that favors sarcopenia in Long-Covid syndrome. It also causes endothelial dysfunction and a prothrombotic state that favors the formation of microthrombi and tissue hypoxia. A healthy and balanced diet is essential to treat obesity in addition to modifying the microbiota in Long-Covid and promoting physical and mental well-being. Obesity is an independent risk factor that increases the need for hospitalization, cardiovascular risk and mortality, as well as susceptibility to Long-Covid. Adipose tissue is a good reservoir of the virus, enhancing the comorbidities associated with obesity (high blood pressure, diabetes mellitus, dyslipidemia or fatty liver). There is insufficient evidence to recommend nutritional supplements to improve Long-Covid symptoms.},
}
RevDate: 2024-12-11
The involvement of the dysfunctional insulin receptor signaling system in long COVID patients with diabetes and chronic pain and its implications for the clinical management using taVNS.
Frontiers in pain research (Lausanne, Switzerland), 5:1486851.
In clinical terms, chronic pain is the most prevalent sequela resulting from COVID-19, which is induced by the novel coronavirus (SARS-CoV-2), while type 2 diabetes mellitus (T2D) is the most common comorbidity. This triangular relationship can be attributed to the dysfunction of the insulin receptor signaling system (IRSS) in both central and peripheral systems. Patients with T2D are essentially more susceptible to SARS-CoV-2 infection due to the widespread expression of angiotensin converting enzyme 2 (ACE2) in their pancreatic beta cells, which serves as the cellular port for the SARS-CoV-2 to infect and enter the cell. This infection can exacerbate chronic pain and insulin resistance for various reasons. Peripherally, once infected, the virus can cause damage to peripheral nerves and pancreatic β-cells, further exacerbating pain and glucose metabolism conditions. Additionally, in the central nervous system, dysfunctional IRSS is closely linked to chronic pain. Over the past few years of the COVID-19 pandemic, an increasing body of evidence suggests that insulin and other medications currently used in clinical practice for hyperglycemia control may not be safe for treating these patients. Therefore, we need a proper approach for the treatment of chronic pain in long COVID patients, especially patients with T2D. This review presents evidence that transcutaneous auricular vagal nerve stimulation (taVNS) may provide a viable treatment option for chronic pain and metabolic dysfunction by improving the function of IRSS in both the central nervous system and peripheral tissues.
Additional Links: PMID-39654800
PubMed:
Citation:
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@article {pmid39654800,
year = {2024},
author = {Li, R and Liu, W and Liu, D and Jin, X and Wang, S},
title = {The involvement of the dysfunctional insulin receptor signaling system in long COVID patients with diabetes and chronic pain and its implications for the clinical management using taVNS.},
journal = {Frontiers in pain research (Lausanne, Switzerland)},
volume = {5},
number = {},
pages = {1486851},
pmid = {39654800},
issn = {2673-561X},
abstract = {In clinical terms, chronic pain is the most prevalent sequela resulting from COVID-19, which is induced by the novel coronavirus (SARS-CoV-2), while type 2 diabetes mellitus (T2D) is the most common comorbidity. This triangular relationship can be attributed to the dysfunction of the insulin receptor signaling system (IRSS) in both central and peripheral systems. Patients with T2D are essentially more susceptible to SARS-CoV-2 infection due to the widespread expression of angiotensin converting enzyme 2 (ACE2) in their pancreatic beta cells, which serves as the cellular port for the SARS-CoV-2 to infect and enter the cell. This infection can exacerbate chronic pain and insulin resistance for various reasons. Peripherally, once infected, the virus can cause damage to peripheral nerves and pancreatic β-cells, further exacerbating pain and glucose metabolism conditions. Additionally, in the central nervous system, dysfunctional IRSS is closely linked to chronic pain. Over the past few years of the COVID-19 pandemic, an increasing body of evidence suggests that insulin and other medications currently used in clinical practice for hyperglycemia control may not be safe for treating these patients. Therefore, we need a proper approach for the treatment of chronic pain in long COVID patients, especially patients with T2D. This review presents evidence that transcutaneous auricular vagal nerve stimulation (taVNS) may provide a viable treatment option for chronic pain and metabolic dysfunction by improving the function of IRSS in both the central nervous system and peripheral tissues.},
}
RevDate: 2024-12-09
CmpDate: 2024-12-09
The Triad of COVID-19 in Children: Acute COVID-19, Multisystem Inflammatory Syndrome, and Long COVID-Part I.
Pediatric annals, 53(12):e473-e477.
The coronavirus disease 2019 (COVID-19) originated in Wuhan, China, in late 2019. Within a span of a few months, it was deemed a global pandemic by the World Health Organization. It was first thought to affect the adult population, but soon after, cases of COVID-19 in children started emerging. As more and more pediatric cases started unveiling, an entity called multisystem inflammatory syndrome in children (MIS-C) that replicated Kawasaki disease was established. More recently, it has been noted that children have persistent symptoms for weeks or months after acute COVID-19 infection, and the term coined for these symptoms is "long COVID." This section of the review will summarize the respiratory, cardiovascular, dermatological, and gastroenterological manifestations noted in infants in three broad categories: acute COVID, MIS-C, and long COVID. [Pediatr Ann. 2024;53(12):e473-e477.].
Additional Links: PMID-39653343
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PubMed:
Citation:
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@article {pmid39653343,
year = {2024},
author = {Gupte, A and Sriram, S and Gunasekaran, V and Chaudhari, K and Kamat, D},
title = {The Triad of COVID-19 in Children: Acute COVID-19, Multisystem Inflammatory Syndrome, and Long COVID-Part I.},
journal = {Pediatric annals},
volume = {53},
number = {12},
pages = {e473-e477},
doi = {10.3928/19382359-20241003-03},
pmid = {39653343},
issn = {1938-2359},
mesh = {Humans ; *COVID-19/complications/epidemiology ; *Systemic Inflammatory Response Syndrome/diagnosis/physiopathology ; Child ; Infant ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Mucocutaneous Lymph Node Syndrome/diagnosis ; },
abstract = {The coronavirus disease 2019 (COVID-19) originated in Wuhan, China, in late 2019. Within a span of a few months, it was deemed a global pandemic by the World Health Organization. It was first thought to affect the adult population, but soon after, cases of COVID-19 in children started emerging. As more and more pediatric cases started unveiling, an entity called multisystem inflammatory syndrome in children (MIS-C) that replicated Kawasaki disease was established. More recently, it has been noted that children have persistent symptoms for weeks or months after acute COVID-19 infection, and the term coined for these symptoms is "long COVID." This section of the review will summarize the respiratory, cardiovascular, dermatological, and gastroenterological manifestations noted in infants in three broad categories: acute COVID, MIS-C, and long COVID. [Pediatr Ann. 2024;53(12):e473-e477.].},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*COVID-19/complications/epidemiology
*Systemic Inflammatory Response Syndrome/diagnosis/physiopathology
Child
Infant
Post-Acute COVID-19 Syndrome
SARS-CoV-2
Mucocutaneous Lymph Node Syndrome/diagnosis
RevDate: 2024-12-16
Inflammaging and Immunosenescence in the Post-COVID Era: Small Molecules, Big Challenges.
ChemMedChem [Epub ahead of print].
Aging naturally involves a decline in biological functions, often triggering a disequilibrium of physiological processes. A common outcome is the altered response exerted by the immune system to counteract infections, known as immunosenescence, which has been recognized as a primary cause, among others, of the so-called long-COVID syndrome. Moreover, the uncontrolled immunoreaction leads to a state of subacute, chronic inflammatory state known as inflammaging, responsible in turn for the chronicization of concomitant pathologies in a self-sustaining process. Anti-inflammatory and immunosuppressant drugs are the current choice for the therapy of inflammaging in post-COVID complications, with contrasting results. The increasing knowledge of the biochemical pathways of inflammaging led to disclose new small molecules-based therapies directed toward different biological targets involved in inflammation, immunological response, and oxidative stress. Herein, paying particular attention to recent clinical data and preclinical literature, we focus on the role of endocannabinoid system in inflammaging, and the promising therapeutic option represented by the CB2R agonists, the role of novel ligands of the formyl peptide receptor 2 and ultimately the potential of newly discovered monoamine oxidase (MAO) inhibitors with neuroprotective activity in the treatment of immunosenescence.
Additional Links: PMID-39651728
Publisher:
PubMed:
Citation:
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@article {pmid39651728,
year = {2024},
author = {Francavilla, F and Intranuovo, F and La Spada, G and Lacivita, E and Catto, M and Graps, EA and Altomare, CD},
title = {Inflammaging and Immunosenescence in the Post-COVID Era: Small Molecules, Big Challenges.},
journal = {ChemMedChem},
volume = {},
number = {},
pages = {e202400672},
doi = {10.1002/cmdc.202400672},
pmid = {39651728},
issn = {1860-7187},
abstract = {Aging naturally involves a decline in biological functions, often triggering a disequilibrium of physiological processes. A common outcome is the altered response exerted by the immune system to counteract infections, known as immunosenescence, which has been recognized as a primary cause, among others, of the so-called long-COVID syndrome. Moreover, the uncontrolled immunoreaction leads to a state of subacute, chronic inflammatory state known as inflammaging, responsible in turn for the chronicization of concomitant pathologies in a self-sustaining process. Anti-inflammatory and immunosuppressant drugs are the current choice for the therapy of inflammaging in post-COVID complications, with contrasting results. The increasing knowledge of the biochemical pathways of inflammaging led to disclose new small molecules-based therapies directed toward different biological targets involved in inflammation, immunological response, and oxidative stress. Herein, paying particular attention to recent clinical data and preclinical literature, we focus on the role of endocannabinoid system in inflammaging, and the promising therapeutic option represented by the CB2R agonists, the role of novel ligands of the formyl peptide receptor 2 and ultimately the potential of newly discovered monoamine oxidase (MAO) inhibitors with neuroprotective activity in the treatment of immunosenescence.},
}
RevDate: 2025-01-30
Postacute Sequelae of COVID-19 in Pediatric Patients Within the United States: A Scoping Review.
American journal of medicine open, 12:100078.
A subset of children and adolescents experience recurrent or persistent symptoms following SARS-CoV-2 infection, known as postacute sequelae of COVID-19 (PASC), however, the clinical epidemiology within the United States (US) is not yet well understood. This scoping review aims to synthesize the clinical epidemiology of pediatric PASC in the US. A comprehensive literature search was conducted and databases were queried from inception until January 29, 2024. Studies including US children and adolescents <21 years old were considered. From 1028 studies identified, 29 met the inclusion criteria. Prevalence of PASC ranged from less than 1%-27%. Risk factors included older age, female sex, asthma, obesity, and severe initial infection. Common symptoms were dyspnea, fatigue, headaches, and chest pain. A multidisciplinary approach for diagnosis and management was common across studies. Most studies had a high risk of bias and were limited by a lack of standardized definitions and short follow-up duration. This review establishes a foundation for understanding pediatric PASC and highlights the critical need for continued research to optimize prevention and treatment strategies.
Additional Links: PMID-39639960
PubMed:
Citation:
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@article {pmid39639960,
year = {2024},
author = {Miller, CM and Borre, C and Green, A and Funaro, M and Oliveira, CR and Iwasaki, A},
title = {Postacute Sequelae of COVID-19 in Pediatric Patients Within the United States: A Scoping Review.},
journal = {American journal of medicine open},
volume = {12},
number = {},
pages = {100078},
pmid = {39639960},
issn = {2667-0364},
abstract = {A subset of children and adolescents experience recurrent or persistent symptoms following SARS-CoV-2 infection, known as postacute sequelae of COVID-19 (PASC), however, the clinical epidemiology within the United States (US) is not yet well understood. This scoping review aims to synthesize the clinical epidemiology of pediatric PASC in the US. A comprehensive literature search was conducted and databases were queried from inception until January 29, 2024. Studies including US children and adolescents <21 years old were considered. From 1028 studies identified, 29 met the inclusion criteria. Prevalence of PASC ranged from less than 1%-27%. Risk factors included older age, female sex, asthma, obesity, and severe initial infection. Common symptoms were dyspnea, fatigue, headaches, and chest pain. A multidisciplinary approach for diagnosis and management was common across studies. Most studies had a high risk of bias and were limited by a lack of standardized definitions and short follow-up duration. This review establishes a foundation for understanding pediatric PASC and highlights the critical need for continued research to optimize prevention and treatment strategies.},
}
RevDate: 2025-01-16
CmpDate: 2025-01-16
Intrinsic Factors Behind the Long-COVID: V. Immunometabolic Disorders.
Journal of cellular biochemistry, 126(1):e30683.
The complex link between COVID-19 and immunometabolic diseases demonstrates the important interaction between metabolic dysfunction and immunological response during viral infections. Severe COVID-19, defined by a hyperinflammatory state, is greatly impacted by underlying chronic illnesses aggravating the cytokine storm caused by increased levels of Pro-inflammatory cytokines. Metabolic reprogramming, including increased glycolysis and altered mitochondrial function, promotes viral replication and stimulates inflammatory cytokine production, contributing to illness severity. Mitochondrial metabolism abnormalities, strongly linked to various systemic illnesses, worsen metabolic dysfunction during and after the pandemic, increasing cardiovascular consequences. Long COVID-19, defined by chronic inflammation and immune dysregulation, poses continuous problems, highlighting the need for comprehensive therapy solutions that address both immunological and metabolic aspects. Understanding these relationships shows promise for effectively managing COVID-19 and its long-term repercussions, which is the focus of this review paper.
Additional Links: PMID-39639607
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PubMed:
Citation:
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@article {pmid39639607,
year = {2025},
author = {Adilović, M and Hromić-Jahjefendić, A and Mahmutović, L and Šutković, J and Rubio-Casillas, A and Redwan, EM and Uversky, VN},
title = {Intrinsic Factors Behind the Long-COVID: V. Immunometabolic Disorders.},
journal = {Journal of cellular biochemistry},
volume = {126},
number = {1},
pages = {e30683},
doi = {10.1002/jcb.30683},
pmid = {39639607},
issn = {1097-4644},
mesh = {Humans ; *COVID-19/immunology/virology/metabolism/complications ; *SARS-CoV-2 ; Cytokine Release Syndrome ; Cytokines/metabolism ; Post-Acute COVID-19 Syndrome ; Mitochondria/metabolism ; Inflammation/metabolism ; Glycolysis ; },
abstract = {The complex link between COVID-19 and immunometabolic diseases demonstrates the important interaction between metabolic dysfunction and immunological response during viral infections. Severe COVID-19, defined by a hyperinflammatory state, is greatly impacted by underlying chronic illnesses aggravating the cytokine storm caused by increased levels of Pro-inflammatory cytokines. Metabolic reprogramming, including increased glycolysis and altered mitochondrial function, promotes viral replication and stimulates inflammatory cytokine production, contributing to illness severity. Mitochondrial metabolism abnormalities, strongly linked to various systemic illnesses, worsen metabolic dysfunction during and after the pandemic, increasing cardiovascular consequences. Long COVID-19, defined by chronic inflammation and immune dysregulation, poses continuous problems, highlighting the need for comprehensive therapy solutions that address both immunological and metabolic aspects. Understanding these relationships shows promise for effectively managing COVID-19 and its long-term repercussions, which is the focus of this review paper.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*COVID-19/immunology/virology/metabolism/complications
*SARS-CoV-2
Cytokine Release Syndrome
Cytokines/metabolism
Post-Acute COVID-19 Syndrome
Mitochondria/metabolism
Inflammation/metabolism
Glycolysis
RevDate: 2025-01-21
CmpDate: 2024-12-05
[Long COVID - neurological or somatoform disease?].
Ideggyogyaszati szemle, 77(11-12):397-405.
BACKGROUND AND PURPOSE: Post-COVID condition (also known as long COVID) is a syndrome characterized by persistent symptoms following a suspected or confirmed SARS-CoV-2 infection, lasting for at least two months and are not attributable to other conditions. The most common symptoms include fatigue, diffuse pain, post-exertional malaise and “brain fog” (impairment of memory and concentration). The pathomechanism of long COVID is the subject of ongoing, intensive research. Our purpose was to review the literature on the pathomechanism of long COVID.
METHODS: We reviewed original and review articles in Hungarian and English on the pathomechanism of long COVID, published between January 2019 and June 2024, in the PubMed and Google Scholar databases.
RESULTS: Potential underlying causes of the symptoms are outlined in three main theories. 1) The concept of “long COVID as a distinct neurological disease” suggests that direct viral neuroinvasion, apoptosis, and demyelination processes are responsible for the symptoms. 2) The theory of “long COVID as a systemic disease with neurological symptoms” is based on the virus induced, prolonged cytokine and chemokine release, as well as the reactivation of latent viral infections. 3) According to the concept of “long COVID as a somatoform disorder”, the disease results from abnormal activation of the proinflammatory cytokine network leading to central nervous system sensitization, a well-known psychoneuroimmunological mechanism. Our study highlighted significant overlaps between long COVID and conditions such as chronic fatigue syndrome/myalgic encephalomyelitis, a group of symptoms not defined as a distinct mental disorder in DSM-5, but commonly referred to as Gulf War syndrome, chronic Lyme disease and somatic symptom disorder.
CONCLUSION: The pathomechanism of long COVID, which presents with a wide range of nonspecific symptoms, remains unknown, and no reproducible disease-specific biomarker has been identified to date. Clarifying the etiology of the disease is crucial for determining adequate and effective therapeutic methods.
Additional Links: PMID-39635815
Publisher:
PubMed:
Citation:
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@article {pmid39635815,
year = {2024},
author = {Tényi, D and Tényi, T and Janszky, J},
title = {[Long COVID - neurological or somatoform disease?].},
journal = {Ideggyogyaszati szemle},
volume = {77},
number = {11-12},
pages = {397-405},
doi = {10.18071/isz.77.0397},
pmid = {39635815},
issn = {0019-1442},
mesh = {Humans ; *COVID-19/complications/psychology ; *Somatoform Disorders/psychology ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Nervous System Diseases/virology ; },
abstract = {BACKGROUND AND PURPOSE: Post-COVID condition (also known as long COVID) is a syndrome characterized by persistent symptoms following a suspected or confirmed SARS-CoV-2 infection, lasting for at least two months and are not attributable to other conditions. The most common symptoms include fatigue, diffuse pain, post-exertional malaise and “brain fog” (impairment of memory and concentration). The pathomechanism of long COVID is the subject of ongoing, intensive research. Our purpose was to review the literature on the pathomechanism of long COVID.
METHODS: We reviewed original and review articles in Hungarian and English on the pathomechanism of long COVID, published between January 2019 and June 2024, in the PubMed and Google Scholar databases.
RESULTS: Potential underlying causes of the symptoms are outlined in three main theories. 1) The concept of “long COVID as a distinct neurological disease” suggests that direct viral neuroinvasion, apoptosis, and demyelination processes are responsible for the symptoms. 2) The theory of “long COVID as a systemic disease with neurological symptoms” is based on the virus induced, prolonged cytokine and chemokine release, as well as the reactivation of latent viral infections. 3) According to the concept of “long COVID as a somatoform disorder”, the disease results from abnormal activation of the proinflammatory cytokine network leading to central nervous system sensitization, a well-known psychoneuroimmunological mechanism. Our study highlighted significant overlaps between long COVID and conditions such as chronic fatigue syndrome/myalgic encephalomyelitis, a group of symptoms not defined as a distinct mental disorder in DSM-5, but commonly referred to as Gulf War syndrome, chronic Lyme disease and somatic symptom disorder.
CONCLUSION: The pathomechanism of long COVID, which presents with a wide range of nonspecific symptoms, remains unknown, and no reproducible disease-specific biomarker has been identified to date. Clarifying the etiology of the disease is crucial for determining adequate and effective therapeutic methods.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*COVID-19/complications/psychology
*Somatoform Disorders/psychology
*Post-Acute COVID-19 Syndrome
SARS-CoV-2
Nervous System Diseases/virology
RevDate: 2024-12-05
A deeper look at long-term effects of COVID-19 on myocardial function in survivors with no prior heart diseases: a GRADE approach systematic review and meta-analysis.
Frontiers in cardiovascular medicine, 11:1458389.
OBJECTIVES: The COVID-19 pandemic has challenged global health systems since December 2019, with the novel virus SARS-CoV-2 causing multi-systemic disease, including heart complications. While acute cardiac effects are well-known, long-term implications are understudied. This review hopes to fill a gap in the literature and provide valuable insights into the long-term cardiac consequences of the virus, which can inform future public health policies and clinical practices.
METHODS: This systematic review was prepared using PRISMA reporting guidelines. The databases searched were PubMed, Scopus, Web of Science, and Cochrane. Risk of Bias was assessed using ROBINS-I. The GRADE approach was employed to evaluate the level of certainty in the evidence for each outcome. A meta-analysis was conducted using the Comprehensive Meta-Analysis (CMA) software. In order to identify the underlying cause of high heterogeneity, a subgroup analysis was conducted. Sensitivity analysis was checked.
RESULTS: Sixty-six studies were included in this review. Thirty-two of them enrolled in meta-analysis and the rest in qualitative synthesis. Most outcomes showed a moderate certainty of evidence according to the GRADE framework. Post-COVID individuals with no prior heart diseases showed significant changes in left ventricular (LV) and right ventricular (RV) echocardiographic indices compared to controls. These significant findings were seen in both post-acute and long-COVID survivors regardless of the severity of initial infection.
CONCLUSION: This review implies that individuals recovering from post-acute and long-term effects of COVID-19 may experience changes in myocardial function as a result of the novel coronavirus. These changes, along with cardiac symptoms, have been observed in patients without prior heart diseases or comorbidities.
PROSPERO, identifier (CRD42024481337).
Additional Links: PMID-39628552
PubMed:
Citation:
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@article {pmid39628552,
year = {2024},
author = {Dehghan, M and Mirzohreh, ST and Kaviani, R and Yousefi, S and Pourmehran, Y},
title = {A deeper look at long-term effects of COVID-19 on myocardial function in survivors with no prior heart diseases: a GRADE approach systematic review and meta-analysis.},
journal = {Frontiers in cardiovascular medicine},
volume = {11},
number = {},
pages = {1458389},
pmid = {39628552},
issn = {2297-055X},
abstract = {OBJECTIVES: The COVID-19 pandemic has challenged global health systems since December 2019, with the novel virus SARS-CoV-2 causing multi-systemic disease, including heart complications. While acute cardiac effects are well-known, long-term implications are understudied. This review hopes to fill a gap in the literature and provide valuable insights into the long-term cardiac consequences of the virus, which can inform future public health policies and clinical practices.
METHODS: This systematic review was prepared using PRISMA reporting guidelines. The databases searched were PubMed, Scopus, Web of Science, and Cochrane. Risk of Bias was assessed using ROBINS-I. The GRADE approach was employed to evaluate the level of certainty in the evidence for each outcome. A meta-analysis was conducted using the Comprehensive Meta-Analysis (CMA) software. In order to identify the underlying cause of high heterogeneity, a subgroup analysis was conducted. Sensitivity analysis was checked.
RESULTS: Sixty-six studies were included in this review. Thirty-two of them enrolled in meta-analysis and the rest in qualitative synthesis. Most outcomes showed a moderate certainty of evidence according to the GRADE framework. Post-COVID individuals with no prior heart diseases showed significant changes in left ventricular (LV) and right ventricular (RV) echocardiographic indices compared to controls. These significant findings were seen in both post-acute and long-COVID survivors regardless of the severity of initial infection.
CONCLUSION: This review implies that individuals recovering from post-acute and long-term effects of COVID-19 may experience changes in myocardial function as a result of the novel coronavirus. These changes, along with cardiac symptoms, have been observed in patients without prior heart diseases or comorbidities.
PROSPERO, identifier (CRD42024481337).},
}
RevDate: 2025-01-01
CmpDate: 2024-12-31
Tackling pulmonary fibrosis risks in post-COVID-19: cutting-edge treatments.
Expert opinion on pharmacotherapy, 26(1):75-84.
INTRODUCTION: Pulmonary fibrosis (PF) post-COVID-19 has been identified as an important complication of Long-COVID, especially in patients with severe respiratory symptoms. High-resolution computed tomography (HRCT) is the main tool for detecting fibrotic lesions in patients with PF post-COVID-19.
AREAS COVERED: We conducted a systematic review with the following objectives: (1) to summarize the incidence and disease burden of post‑COVID‑19 pulmonary fibrosis, (2) to provide information on available therapies and drugs for its management, (3) to comprehensively evaluate the initial treatment efficacy of these drugs, and (4) to identify the limitations and challenges associated with current treatment approaches.
EXPERT OPINION: Cutting-edge treatments for PF post-COVID-19 are focused on the complex and multifactorial nature of the disease progreession during Long COVID, which involves chronic inflammation, fibroblast activation, and excessive extracellular matrix deposition leading to stiffening and fibrosis of lung tissue. While traditional antifibrotic drugs with nintedanid and pirfenidone are being used, novel therapies with anti-interleukines, mesenchymal stem cells, and Rho-kinase inhibitors promise the new treatment approaches for patients with PF post-COVID-19. Further research and clinical trials are needed to determine the most effective strategies for managing this complex condition, with the goal of improving patient outcomes and quality of life.
Additional Links: PMID-39628270
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PubMed:
Citation:
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@article {pmid39628270,
year = {2025},
author = {Duong-Quy, S and Nguyen Hai, C and Huynh-Anh, T and Nguyen-Nhu, V},
title = {Tackling pulmonary fibrosis risks in post-COVID-19: cutting-edge treatments.},
journal = {Expert opinion on pharmacotherapy},
volume = {26},
number = {1},
pages = {75-84},
doi = {10.1080/14656566.2024.2438322},
pmid = {39628270},
issn = {1744-7666},
mesh = {Humans ; *Pulmonary Fibrosis/etiology/drug therapy ; *COVID-19/complications ; Antifibrotic Agents/therapeutic use ; Tomography, X-Ray Computed ; },
abstract = {INTRODUCTION: Pulmonary fibrosis (PF) post-COVID-19 has been identified as an important complication of Long-COVID, especially in patients with severe respiratory symptoms. High-resolution computed tomography (HRCT) is the main tool for detecting fibrotic lesions in patients with PF post-COVID-19.
AREAS COVERED: We conducted a systematic review with the following objectives: (1) to summarize the incidence and disease burden of post‑COVID‑19 pulmonary fibrosis, (2) to provide information on available therapies and drugs for its management, (3) to comprehensively evaluate the initial treatment efficacy of these drugs, and (4) to identify the limitations and challenges associated with current treatment approaches.
EXPERT OPINION: Cutting-edge treatments for PF post-COVID-19 are focused on the complex and multifactorial nature of the disease progreession during Long COVID, which involves chronic inflammation, fibroblast activation, and excessive extracellular matrix deposition leading to stiffening and fibrosis of lung tissue. While traditional antifibrotic drugs with nintedanid and pirfenidone are being used, novel therapies with anti-interleukines, mesenchymal stem cells, and Rho-kinase inhibitors promise the new treatment approaches for patients with PF post-COVID-19. Further research and clinical trials are needed to determine the most effective strategies for managing this complex condition, with the goal of improving patient outcomes and quality of life.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Pulmonary Fibrosis/etiology/drug therapy
*COVID-19/complications
Antifibrotic Agents/therapeutic use
Tomography, X-Ray Computed
RevDate: 2025-01-09
CmpDate: 2025-01-09
Long COVID: a consequence of chronic post-infectious inflammation!.
Expert review of respiratory medicine, 18(12):939-945.
INTRODUCTION: Long COVID defines persistence of symptoms in patients that recovered from acute COVID-19 infections. This manuscript is a brief update on current thinking on long COVID and potential causes and consequences.
AREAS COVERED: The extent of long COVID varies between patients with some 200 symptoms described and of different severities. Persistent inflammatory or persistent viral infections or both may be the cause of long COVID but sorting this out will take years.
EXPERT OPINION: Long COVID is an unfortunate consequence of COVID-19 infection and it remains uncertain why some people are afflicted and others not and as with other infectious diseases, it may be both a function of the virus strain, the host or both. Direct organ damage during acute infection versus inflammatory mediated damage over time are important questions to address. The disease outcome and chronic sequelae are likely related to the strains of infectious agent and/or host immunity and genetic predisposition.
Additional Links: PMID-39625700
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PubMed:
Citation:
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@article {pmid39625700,
year = {2024},
author = {Blondeau, JM},
title = {Long COVID: a consequence of chronic post-infectious inflammation!.},
journal = {Expert review of respiratory medicine},
volume = {18},
number = {12},
pages = {939-945},
doi = {10.1080/17476348.2024.2438104},
pmid = {39625700},
issn = {1747-6356},
mesh = {Humans ; *COVID-19/immunology/complications ; *Inflammation/immunology/virology ; Chronic Disease ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2/immunology ; },
abstract = {INTRODUCTION: Long COVID defines persistence of symptoms in patients that recovered from acute COVID-19 infections. This manuscript is a brief update on current thinking on long COVID and potential causes and consequences.
AREAS COVERED: The extent of long COVID varies between patients with some 200 symptoms described and of different severities. Persistent inflammatory or persistent viral infections or both may be the cause of long COVID but sorting this out will take years.
EXPERT OPINION: Long COVID is an unfortunate consequence of COVID-19 infection and it remains uncertain why some people are afflicted and others not and as with other infectious diseases, it may be both a function of the virus strain, the host or both. Direct organ damage during acute infection versus inflammatory mediated damage over time are important questions to address. The disease outcome and chronic sequelae are likely related to the strains of infectious agent and/or host immunity and genetic predisposition.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*COVID-19/immunology/complications
*Inflammation/immunology/virology
Chronic Disease
Post-Acute COVID-19 Syndrome
SARS-CoV-2/immunology
RevDate: 2024-11-30
CmpDate: 2024-11-27
Interventions for the management of long covid (post-covid condition): living systematic review.
BMJ (Clinical research ed.), 387:e081318.
OBJECTIVE: To compare the effectiveness of interventions for the management of long covid (post-covid condition).
DESIGN: Living systematic review.
DATA SOURCES: Medline, Embase, CINAHL, PsycInfo, Allied and Complementary Medicine Database, and Cochrane Central Register of Controlled Trials from inception to December 2023.
ELIGIBILITY CRITERIA: Trials that randomised adults (≥18 years) with long covid to drug or non-drug interventions, placebo or sham, or usual care.
RESULTS: 24 trials with 3695 patients were eligible. Four trials (n=708 patients) investigated drug interventions, eight (n=985) physical activity or rehabilitation, three (n=314) behavioural, four (n=794) dietary, four (n=309) medical devices and technologies, and one (n=585) a combination of physical exercise and mental health rehabilitation. Moderate certainty evidence suggested that, compared with usual care, an online programme of cognitive behavioural therapy (CBT) probably reduces fatigue (mean difference -8.4, 95% confidence interval (CI) -13.11 to -3.69; Checklist for Individual Strength fatigue subscale; range 8-56, higher scores indicate greater impairment) and probably improves concentration (mean difference -5.2, -7.97 to -2.43; Checklist for Individual Strength concentration problems subscale; range 4-28; higher scores indicate greater impairment). Moderate certainty evidence suggested that, compared with usual care, an online, supervised, combined physical and mental health rehabilitation programme probably leads to improvement in overall health, with an estimated 161 more patients per 1000 (95% CI 61 more to 292 more) experiencing meaningful improvement or recovery, probably reduces symptoms of depression (mean difference -1.50, -2.41 to -0.59; Hospital Anxiety and Depression Scale depression subscale; range 0-21; higher scores indicate greater impairment), and probably improves quality of life (0.04, 95% CI 0.00 to 0.08; Patient-Reported Outcomes Measurement Information System 29+2 Profile; range -0.022-1; higher scores indicate less impairment). Moderate certainty evidence suggested that intermittent aerobic exercise 3-5 times weekly for 4-6 weeks probably improves physical function compared with continuous exercise (mean difference 3.8, 1.12 to 6.48; SF-36 physical component summary score; range 0-100; higher scores indicate less impairment). No compelling evidence was found to support the effectiveness of other interventions, including, among others, vortioxetine, leronlimab, combined probiotics-prebiotics, coenzyme Q10, amygdala and insula retraining, combined L-arginine and vitamin C, inspiratory muscle training, transcranial direct current stimulation, hyperbaric oxygen, a mobile application providing education on long covid.
CONCLUSION: Moderate certainty evidence suggests that CBT and physical and mental health rehabilitation probably improve symptoms of long covid.
Open Science Framework https://osf.io/9h7zm/.
READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.
Additional Links: PMID-39603702
PubMed:
Citation:
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@article {pmid39603702,
year = {2024},
author = {Zeraatkar, D and Ling, M and Kirsh, S and Jassal, T and Shahab, M and Movahed, H and Talukdar, JR and Walch, A and Chakraborty, S and Turner, T and Turkstra, L and McIntyre, RS and Izcovich, A and Mbuagbaw, L and Agoritsas, T and Flottorp, SA and Garner, P and Pitre, T and Couban, RJ and Busse, JW},
title = {Interventions for the management of long covid (post-covid condition): living systematic review.},
journal = {BMJ (Clinical research ed.)},
volume = {387},
number = {},
pages = {e081318},
pmid = {39603702},
issn = {1756-1833},
mesh = {Humans ; *COVID-19/rehabilitation/therapy/complications ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Cognitive Behavioral Therapy/methods ; Randomized Controlled Trials as Topic ; Exercise ; },
abstract = {OBJECTIVE: To compare the effectiveness of interventions for the management of long covid (post-covid condition).
DESIGN: Living systematic review.
DATA SOURCES: Medline, Embase, CINAHL, PsycInfo, Allied and Complementary Medicine Database, and Cochrane Central Register of Controlled Trials from inception to December 2023.
ELIGIBILITY CRITERIA: Trials that randomised adults (≥18 years) with long covid to drug or non-drug interventions, placebo or sham, or usual care.
RESULTS: 24 trials with 3695 patients were eligible. Four trials (n=708 patients) investigated drug interventions, eight (n=985) physical activity or rehabilitation, three (n=314) behavioural, four (n=794) dietary, four (n=309) medical devices and technologies, and one (n=585) a combination of physical exercise and mental health rehabilitation. Moderate certainty evidence suggested that, compared with usual care, an online programme of cognitive behavioural therapy (CBT) probably reduces fatigue (mean difference -8.4, 95% confidence interval (CI) -13.11 to -3.69; Checklist for Individual Strength fatigue subscale; range 8-56, higher scores indicate greater impairment) and probably improves concentration (mean difference -5.2, -7.97 to -2.43; Checklist for Individual Strength concentration problems subscale; range 4-28; higher scores indicate greater impairment). Moderate certainty evidence suggested that, compared with usual care, an online, supervised, combined physical and mental health rehabilitation programme probably leads to improvement in overall health, with an estimated 161 more patients per 1000 (95% CI 61 more to 292 more) experiencing meaningful improvement or recovery, probably reduces symptoms of depression (mean difference -1.50, -2.41 to -0.59; Hospital Anxiety and Depression Scale depression subscale; range 0-21; higher scores indicate greater impairment), and probably improves quality of life (0.04, 95% CI 0.00 to 0.08; Patient-Reported Outcomes Measurement Information System 29+2 Profile; range -0.022-1; higher scores indicate less impairment). Moderate certainty evidence suggested that intermittent aerobic exercise 3-5 times weekly for 4-6 weeks probably improves physical function compared with continuous exercise (mean difference 3.8, 1.12 to 6.48; SF-36 physical component summary score; range 0-100; higher scores indicate less impairment). No compelling evidence was found to support the effectiveness of other interventions, including, among others, vortioxetine, leronlimab, combined probiotics-prebiotics, coenzyme Q10, amygdala and insula retraining, combined L-arginine and vitamin C, inspiratory muscle training, transcranial direct current stimulation, hyperbaric oxygen, a mobile application providing education on long covid.
CONCLUSION: Moderate certainty evidence suggests that CBT and physical and mental health rehabilitation probably improve symptoms of long covid.
Open Science Framework https://osf.io/9h7zm/.
READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*COVID-19/rehabilitation/therapy/complications
*SARS-CoV-2
Post-Acute COVID-19 Syndrome
Cognitive Behavioral Therapy/methods
Randomized Controlled Trials as Topic
Exercise
RevDate: 2025-01-30
CmpDate: 2024-11-27
Reporting of pre-existing multiple long-term conditions in physical rehabilitation for long COVID: a scoping review.
European respiratory review : an official journal of the European Respiratory Society, 33(174):.
BACKGROUND: Physical rehabilitation may improve health and wellbeing outcomes for some adults living with long COVID. However, individuals living with pre-existing multiple long-term conditions (MLTCs) and long COVID may have additional rehabilitation challenges. This scoping review aims to identify the available evidence describing physical rehabilitation interventions for adults living with long COVID, to systematically map the reporting of pre-existing MLTCs, and to describe the characteristics of physical rehabilitation interventions used in adults with both pre-existing long-term conditions (LTCs) and long COVID.
METHODS: MEDLINE, CINAHL, Scopus, APA PsycInfo, medRxiv, OpenGrey and MedNar were searched from January 2020 to July 2023. Eligibility criteria included adults with long COVID, rehabilitation interventions including a physical component in any setting and any study design investigating interventions or intervention content except case series/reports.
RESULTS: Of 5326 unique records, 50 articles met the inclusion criteria, of which 25 (50%) made reference to pre-existing LTCs. These articles included four protocols and one consensus statement. Four of the remaining 20 studies (20%) reported the number of pre-existing LTCs, enabling the differentiation of individuals with MLTCs. One study reported outcomes of individuals with MLTCs separately to those without. The interventions described (k=24) typically consisted of combined aerobic and strength exercises (k=17 (71%)) in an outpatient setting (k=13 (54%)).
CONCLUSIONS: There is limited and inconsistent reporting of the presence of MLTCs in studies of physical rehabilitation for adults with long COVID. Clarity and consistency of reporting of MLTCs is required to enable evaluation and adaptation of interventions to improve health and wellbeing for this population.
Additional Links: PMID-39603665
PubMed:
Citation:
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@article {pmid39603665,
year = {2024},
author = {Gardiner, L and Young, HML and Drover, H and Morgan-Selvaratnam, E and Natt, M and Smith, N and Daynes, E and Orme, MW and Taylor, RS and Singh, SJ and Evans, RA},
title = {Reporting of pre-existing multiple long-term conditions in physical rehabilitation for long COVID: a scoping review.},
journal = {European respiratory review : an official journal of the European Respiratory Society},
volume = {33},
number = {174},
pages = {},
pmid = {39603665},
issn = {1600-0617},
support = {/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; *COVID-19/rehabilitation/epidemiology ; Physical Therapy Modalities ; SARS-CoV-2 ; Time Factors ; Chronic Disease ; Treatment Outcome ; },
abstract = {BACKGROUND: Physical rehabilitation may improve health and wellbeing outcomes for some adults living with long COVID. However, individuals living with pre-existing multiple long-term conditions (MLTCs) and long COVID may have additional rehabilitation challenges. This scoping review aims to identify the available evidence describing physical rehabilitation interventions for adults living with long COVID, to systematically map the reporting of pre-existing MLTCs, and to describe the characteristics of physical rehabilitation interventions used in adults with both pre-existing long-term conditions (LTCs) and long COVID.
METHODS: MEDLINE, CINAHL, Scopus, APA PsycInfo, medRxiv, OpenGrey and MedNar were searched from January 2020 to July 2023. Eligibility criteria included adults with long COVID, rehabilitation interventions including a physical component in any setting and any study design investigating interventions or intervention content except case series/reports.
RESULTS: Of 5326 unique records, 50 articles met the inclusion criteria, of which 25 (50%) made reference to pre-existing LTCs. These articles included four protocols and one consensus statement. Four of the remaining 20 studies (20%) reported the number of pre-existing LTCs, enabling the differentiation of individuals with MLTCs. One study reported outcomes of individuals with MLTCs separately to those without. The interventions described (k=24) typically consisted of combined aerobic and strength exercises (k=17 (71%)) in an outpatient setting (k=13 (54%)).
CONCLUSIONS: There is limited and inconsistent reporting of the presence of MLTCs in studies of physical rehabilitation for adults with long COVID. Clarity and consistency of reporting of MLTCs is required to enable evaluation and adaptation of interventions to improve health and wellbeing for this population.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*COVID-19/rehabilitation/epidemiology
Physical Therapy Modalities
SARS-CoV-2
Time Factors
Chronic Disease
Treatment Outcome
RevDate: 2024-12-04
CmpDate: 2024-11-27
Beyond Antivirals: Alternative Therapies for Long COVID.
Viruses, 16(11):.
Long COVID or Post-Acute Sequelae of SARS-CoV-2 infection (PASC) is a condition characterized by numerous lingering symptoms that persist for weeks to months following the viral illness. While treatment for PASC is still evolving, several therapeutic approaches beyond traditional antiviral therapies are being investigated, such as immune-modulating agents, anti-inflammatory drugs, and various supportive interventions focusing at alleviating symptoms and enhancing recovery. We aimed to summarize the breadth of available evidence, identify knowledge gaps, and highlight promising non-antiviral therapies for Long COVID/PASC. We followed the framework of a scoping methodology by mapping existing evidence from a range of studies, including randomized clinical trials, observational research, and case series. Treatments evaluated include metformin, low-dose naltrexone (LDN), dexamethasone, statins, omega-3 fatty acids, L-arginine, and emerging therapies like intravenous immunoglobulin (IVIg) and therapeutic apheresis. Early findings suggest that metformin has the strongest clinical evidence, particularly from large phase 3 trials, while LDN and dexamethasone show potential based on observational studies. However, many treatments lack robust, large-scale trials. This review emphasizes the need for further research to confirm the efficacy of these treatments and guide clinical practice for Long COVID management.
Additional Links: PMID-39599909
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@article {pmid39599909,
year = {2024},
author = {Livieratos, A and Gogos, C and Akinosoglou, K},
title = {Beyond Antivirals: Alternative Therapies for Long COVID.},
journal = {Viruses},
volume = {16},
number = {11},
pages = {},
pmid = {39599909},
issn = {1999-4915},
mesh = {Humans ; *COVID-19/therapy ; *SARS-CoV-2/drug effects ; *Antiviral Agents/therapeutic use ; Post-Acute COVID-19 Syndrome ; Metformin/therapeutic use ; COVID-19 Drug Treatment ; Anti-Inflammatory Agents/therapeutic use ; Immunoglobulins, Intravenous/therapeutic use ; Fatty Acids, Omega-3/therapeutic use ; Dexamethasone/therapeutic use ; Naltrexone/therapeutic use ; },
abstract = {Long COVID or Post-Acute Sequelae of SARS-CoV-2 infection (PASC) is a condition characterized by numerous lingering symptoms that persist for weeks to months following the viral illness. While treatment for PASC is still evolving, several therapeutic approaches beyond traditional antiviral therapies are being investigated, such as immune-modulating agents, anti-inflammatory drugs, and various supportive interventions focusing at alleviating symptoms and enhancing recovery. We aimed to summarize the breadth of available evidence, identify knowledge gaps, and highlight promising non-antiviral therapies for Long COVID/PASC. We followed the framework of a scoping methodology by mapping existing evidence from a range of studies, including randomized clinical trials, observational research, and case series. Treatments evaluated include metformin, low-dose naltrexone (LDN), dexamethasone, statins, omega-3 fatty acids, L-arginine, and emerging therapies like intravenous immunoglobulin (IVIg) and therapeutic apheresis. Early findings suggest that metformin has the strongest clinical evidence, particularly from large phase 3 trials, while LDN and dexamethasone show potential based on observational studies. However, many treatments lack robust, large-scale trials. This review emphasizes the need for further research to confirm the efficacy of these treatments and guide clinical practice for Long COVID management.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*COVID-19/therapy
*SARS-CoV-2/drug effects
*Antiviral Agents/therapeutic use
Post-Acute COVID-19 Syndrome
Metformin/therapeutic use
COVID-19 Drug Treatment
Anti-Inflammatory Agents/therapeutic use
Immunoglobulins, Intravenous/therapeutic use
Fatty Acids, Omega-3/therapeutic use
Dexamethasone/therapeutic use
Naltrexone/therapeutic use
RevDate: 2024-11-30
CmpDate: 2024-11-27
Bone Mineral Density, Bone Biomarkers, and Joints in Acute, Post, and Long COVID-19: A Systematic Review.
Viruses, 16(11):.
SARS-CoV-2 is highly transmissible and affects the respiratory system. People with COVID-19 are at higher risk of physical and mental health conditions, which could impact bone health. The aim of this review was to explore the effects of COVID-19 on BMD, BTMs, and joints. An electronic search of the PubMed, Web of Science, Scopus, and Ovid Medline databases considered studies published between 1 January 2020 and 1 November 2023. The search was limited to English, original studies in adult humans. The title and abstract of the identified papers were screened, followed by a full-text review using inclusion and exclusion criteria. The data extracted included the study and participant characteristics, BTMs, BMD, and joint abnormalities. The Newcastle-Ottawa scale quality assessment tool was used to assess the risk of bias. Five studies involving 305 out of 495 infected individuals observed a reduced BMD after COVID-19, with the most significant reduction occurring a year later. Both bone resorption and bone formation markers decreased, while regulatory markers showed higher levels in infected patients. COVID-19 may harm bone health by increasing bone regulatory markers and reducing bone formation and absorption, leading to a lower BMD. Elderly, frail, and osteopenic or osteoporotic individuals are at higher risk and should be regularly monitored for bone loss if they have long COVID.
Additional Links: PMID-39599809
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@article {pmid39599809,
year = {2024},
author = {Alghamdi, F and Mokbel, K and Meertens, R and Obotiba, AD and Alharbi, M and Knapp, KM and Strain, WD},
title = {Bone Mineral Density, Bone Biomarkers, and Joints in Acute, Post, and Long COVID-19: A Systematic Review.},
journal = {Viruses},
volume = {16},
number = {11},
pages = {},
pmid = {39599809},
issn = {1999-4915},
mesh = {Humans ; *COVID-19 ; *Bone Density ; *Biomarkers ; *SARS-CoV-2 ; Joints/virology ; Osteoporosis/metabolism ; Bone and Bones/metabolism/virology ; Post-Acute COVID-19 Syndrome ; },
abstract = {SARS-CoV-2 is highly transmissible and affects the respiratory system. People with COVID-19 are at higher risk of physical and mental health conditions, which could impact bone health. The aim of this review was to explore the effects of COVID-19 on BMD, BTMs, and joints. An electronic search of the PubMed, Web of Science, Scopus, and Ovid Medline databases considered studies published between 1 January 2020 and 1 November 2023. The search was limited to English, original studies in adult humans. The title and abstract of the identified papers were screened, followed by a full-text review using inclusion and exclusion criteria. The data extracted included the study and participant characteristics, BTMs, BMD, and joint abnormalities. The Newcastle-Ottawa scale quality assessment tool was used to assess the risk of bias. Five studies involving 305 out of 495 infected individuals observed a reduced BMD after COVID-19, with the most significant reduction occurring a year later. Both bone resorption and bone formation markers decreased, while regulatory markers showed higher levels in infected patients. COVID-19 may harm bone health by increasing bone regulatory markers and reducing bone formation and absorption, leading to a lower BMD. Elderly, frail, and osteopenic or osteoporotic individuals are at higher risk and should be regularly monitored for bone loss if they have long COVID.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*COVID-19
*Bone Density
*Biomarkers
*SARS-CoV-2
Joints/virology
Osteoporosis/metabolism
Bone and Bones/metabolism/virology
Post-Acute COVID-19 Syndrome
RevDate: 2024-11-30
Exercise in Postural Orthostatic Tachycardia Syndrome: Focus on Individualized Exercise Approach.
Journal of clinical medicine, 13(22):.
Exercise is a vital component of health and is commonly utilized as a non-pharmacologic therapy for many disorders, including postural orthostatic tachycardia syndrome (POTS). However, exercise intolerance is a key feature of POTS and other autonomic disorders and, therefore, presents a major barrier for many patients. Despite exercise being uniformly recommended as a therapeutic intervention, a majority of patients with POTS, especially those with severe orthostatic intolerance and fatigue, are unable to complete or sustain rigorous exercise programs or successfully integrate them into their daily routine. In this narrative review, we discuss the current literature on exercise and POTS and our clinical experience with a home-based exercise approach developed at the Dysautonomia Clinic. We conclude that individualized exercise programs that are delivered remotely by a certified physical therapist may be convenient, easily accessible, and safe for patients with POTS, especially those with severe symptoms who may be home- or bedbound. Future randomized controlled studies are needed to quantify and characterize the benefits of home-based exercise programs delivered remotely compared to standard therapy.
Additional Links: PMID-39597891
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@article {pmid39597891,
year = {2024},
author = {Trimble, KZ and Switzer, JN and Blitshteyn, S},
title = {Exercise in Postural Orthostatic Tachycardia Syndrome: Focus on Individualized Exercise Approach.},
journal = {Journal of clinical medicine},
volume = {13},
number = {22},
pages = {},
pmid = {39597891},
issn = {2077-0383},
abstract = {Exercise is a vital component of health and is commonly utilized as a non-pharmacologic therapy for many disorders, including postural orthostatic tachycardia syndrome (POTS). However, exercise intolerance is a key feature of POTS and other autonomic disorders and, therefore, presents a major barrier for many patients. Despite exercise being uniformly recommended as a therapeutic intervention, a majority of patients with POTS, especially those with severe orthostatic intolerance and fatigue, are unable to complete or sustain rigorous exercise programs or successfully integrate them into their daily routine. In this narrative review, we discuss the current literature on exercise and POTS and our clinical experience with a home-based exercise approach developed at the Dysautonomia Clinic. We conclude that individualized exercise programs that are delivered remotely by a certified physical therapist may be convenient, easily accessible, and safe for patients with POTS, especially those with severe symptoms who may be home- or bedbound. Future randomized controlled studies are needed to quantify and characterize the benefits of home-based exercise programs delivered remotely compared to standard therapy.},
}
RevDate: 2024-12-01
Nerve Growth Factor and Brain-Derived Neurotrophic Factor in COVID-19.
Biology, 13(11):.
Neurotrophins (NTs) constitute a family of small protein messengers that play a fundamental role in both the central and peripheral nervous systems. In particular, the nerve growth factor (NGF) and the brain-derived neurotrophic factor (BDNF) play a subtle role in the survival, differentiation, and functioning of neuronal populations, as well as in the fine regulation of immune functions. The SARS-CoV-2 infection was characterized by a sequela of symptoms (serious respiratory pathology, inflammatory storm, neurological discomfort, up to the less serious flu-like symptoms), which caused, at the end of 2023, more than 7 million deaths worldwide. Despite the official end of the pandemic, the physical and psychological consequences are currently the object of scientific research, both acute and chronic/long-lasting (Long-COVID-19). Given the multifactorial nature of the outcomes of SARS-CoV-2 infection in adults and children, several studies have investigated the potential involvement of the NGF and BDNF systems in the pathology. This narrative review aims to summarize the most recent evidence on this crucial topic.
Additional Links: PMID-39596862
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Citation:
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@article {pmid39596862,
year = {2024},
author = {Petrella, C and Ferraguti, G and Tarani, L and Tarani, F and Messina, MP and Fiore, M},
title = {Nerve Growth Factor and Brain-Derived Neurotrophic Factor in COVID-19.},
journal = {Biology},
volume = {13},
number = {11},
pages = {},
pmid = {39596862},
issn = {2079-7737},
abstract = {Neurotrophins (NTs) constitute a family of small protein messengers that play a fundamental role in both the central and peripheral nervous systems. In particular, the nerve growth factor (NGF) and the brain-derived neurotrophic factor (BDNF) play a subtle role in the survival, differentiation, and functioning of neuronal populations, as well as in the fine regulation of immune functions. The SARS-CoV-2 infection was characterized by a sequela of symptoms (serious respiratory pathology, inflammatory storm, neurological discomfort, up to the less serious flu-like symptoms), which caused, at the end of 2023, more than 7 million deaths worldwide. Despite the official end of the pandemic, the physical and psychological consequences are currently the object of scientific research, both acute and chronic/long-lasting (Long-COVID-19). Given the multifactorial nature of the outcomes of SARS-CoV-2 infection in adults and children, several studies have investigated the potential involvement of the NGF and BDNF systems in the pathology. This narrative review aims to summarize the most recent evidence on this crucial topic.},
}
RevDate: 2024-12-24
CmpDate: 2024-12-19
Intravenous immunoglobulin as a therapy for autoimmune conditions.
Autoimmunity reviews, 24(1):103710.
Intravenous immunoglobulin (IVIg) is a medical preparation used as replacement therapy for patients with immunodeficiencies. Over time, IVIg's anti-inflammatory and immunomodulatory effects have been recognized, which have led to the approval of this therapy in the treatment of various pathologies, such as Kawasaki disease, immune thrombocytopenia, and Guillain-Barré syndrome. There are numerous studies in the literature regarding the off-label use of IVIg in the treatment of autoimmune diseases (e.g. myositis and vasculitis), and hematological disorders. Since the role of immunoglobulins in fields other than replacement therapy is now consolidated, in this study we carried out a review of the literature to evaluate the main uses of IVIg therapy. We have focused our attention on the treatment of autoimmune, neurological, hematological, dermatological and pediatric diseases. Furthermore, our analysis of the literature also extended to the potential use of IVIg as an adjuvant treatment of long COVID-19. From our analysis, we found consistent data about IVIg's effectiveness in treating numerous clinical conditions. Treatment with IVIg represents a second-line approach or a valid adjuvant to standard therapies capable of positively influencing the clinical course of many pathologies and reducing or avoiding side effects of standard therapies, with a good safety profile.
Additional Links: PMID-39592027
Publisher:
PubMed:
Citation:
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@article {pmid39592027,
year = {2025},
author = {Danieli, MG and Antonelli, E and Gammeri, L and Longhi, E and Cozzi, MF and Palmeri, D and Gangemi, S and Shoenfeld, Y},
title = {Intravenous immunoglobulin as a therapy for autoimmune conditions.},
journal = {Autoimmunity reviews},
volume = {24},
number = {1},
pages = {103710},
doi = {10.1016/j.autrev.2024.103710},
pmid = {39592027},
issn = {1873-0183},
mesh = {Humans ; *Autoimmune Diseases/immunology/therapy ; COVID-19/immunology/therapy ; *Immunoglobulins, Intravenous/therapeutic use ; },
abstract = {Intravenous immunoglobulin (IVIg) is a medical preparation used as replacement therapy for patients with immunodeficiencies. Over time, IVIg's anti-inflammatory and immunomodulatory effects have been recognized, which have led to the approval of this therapy in the treatment of various pathologies, such as Kawasaki disease, immune thrombocytopenia, and Guillain-Barré syndrome. There are numerous studies in the literature regarding the off-label use of IVIg in the treatment of autoimmune diseases (e.g. myositis and vasculitis), and hematological disorders. Since the role of immunoglobulins in fields other than replacement therapy is now consolidated, in this study we carried out a review of the literature to evaluate the main uses of IVIg therapy. We have focused our attention on the treatment of autoimmune, neurological, hematological, dermatological and pediatric diseases. Furthermore, our analysis of the literature also extended to the potential use of IVIg as an adjuvant treatment of long COVID-19. From our analysis, we found consistent data about IVIg's effectiveness in treating numerous clinical conditions. Treatment with IVIg represents a second-line approach or a valid adjuvant to standard therapies capable of positively influencing the clinical course of many pathologies and reducing or avoiding side effects of standard therapies, with a good safety profile.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Autoimmune Diseases/immunology/therapy
COVID-19/immunology/therapy
*Immunoglobulins, Intravenous/therapeutic use
RevDate: 2024-11-28
Identifying Factors That Might Affect Outcomes of Exercise-Based Therapies in Long-COVID.
Diseases (Basel, Switzerland), 12(11):.
BACKGROUND: Long-COVID, which might develop after a SARS-CoV-2 infection, is a rather new disease without standardized treatment strategies. A large number of approaches that integrate physical activity have been described in the literature, and this systematic review aims to examine changes in symptom severity, physical fitness, respiratory symptoms and quality of life during training and identify factors that might influence the respective outcomes.
METHODS: A literature search was conducted using the databases Pubmed, PEDro, BioMed Central, EBSCOhost, ProQuest and the ZBSport from 13 February 2024 to 27 February 2024, and 39 studies fulfilled the search criteria.
RESULTS: The analyzed study designs varied regarding the type of intervention (isolated vs. multidisciplinary), duration and intensity of training sessions and overall length of the program. Individualized holistic concepts of physical activity paralleled by additional approaches demonstrated high effectiveness. However, many of the participants continue to suffer from Long-COVID after the intervention.
CONCLUSIONS: Long-COVID treatment should be individualized, multifactorial and not limited in time and should consider each patient's pre-existing conditions and individual course of the disease to provide the best possible support and care.
Additional Links: PMID-39589967
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Citation:
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@article {pmid39589967,
year = {2024},
author = {Krüger, AL and Haiduk, B and Grau, M},
title = {Identifying Factors That Might Affect Outcomes of Exercise-Based Therapies in Long-COVID.},
journal = {Diseases (Basel, Switzerland)},
volume = {12},
number = {11},
pages = {},
pmid = {39589967},
issn = {2079-9721},
abstract = {BACKGROUND: Long-COVID, which might develop after a SARS-CoV-2 infection, is a rather new disease without standardized treatment strategies. A large number of approaches that integrate physical activity have been described in the literature, and this systematic review aims to examine changes in symptom severity, physical fitness, respiratory symptoms and quality of life during training and identify factors that might influence the respective outcomes.
METHODS: A literature search was conducted using the databases Pubmed, PEDro, BioMed Central, EBSCOhost, ProQuest and the ZBSport from 13 February 2024 to 27 February 2024, and 39 studies fulfilled the search criteria.
RESULTS: The analyzed study designs varied regarding the type of intervention (isolated vs. multidisciplinary), duration and intensity of training sessions and overall length of the program. Individualized holistic concepts of physical activity paralleled by additional approaches demonstrated high effectiveness. However, many of the participants continue to suffer from Long-COVID after the intervention.
CONCLUSIONS: Long-COVID treatment should be individualized, multifactorial and not limited in time and should consider each patient's pre-existing conditions and individual course of the disease to provide the best possible support and care.},
}
RevDate: 2024-11-26
The consequences of SARS-CoV-2 within-host persistence.
Nature reviews. Microbiology [Epub ahead of print].
SARS-CoV-2 causes an acute respiratory tract infection that resolves in most people in less than a month. Yet some people with severely weakened immune systems fail to clear the virus, leading to persistent infections with high viral titres in the respiratory tract. In a subset of cases, persistent SARS-CoV-2 replication results in an accelerated accumulation of adaptive mutations that confer escape from neutralizing antibodies and enhance cellular infection. This may lead to the evolution of extensively mutated SARS-CoV-2 variants and introduce an element of chance into the timing of variant evolution, as variant formation may depend on evolution in a single person. Whether long COVID is also caused by persistence of replicating SARS-CoV-2 is controversial. One line of evidence is detection of SARS-CoV-2 RNA and proteins in different body compartments long after SARS-CoV-2 infection has cleared from the upper respiratory tract. However, thus far, no replication competent virus has been cultured from individuals with long COVID who are immunocompetent. In this Review, we consider mechanisms of viral persistence, intra-host evolution in persistent infections, the connection of persistent infections with SARS-CoV-2 variants and the possible role of SARS-CoV-2 persistence in long COVID. Understanding persistent infections may therefore resolve much of what is still unclear in COVID-19 pathophysiology, with possible implications for other emerging viruses.
Additional Links: PMID-39587352
PubMed:
Citation:
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@article {pmid39587352,
year = {2024},
author = {Sigal, A and Neher, RA and Lessells, RJ},
title = {The consequences of SARS-CoV-2 within-host persistence.},
journal = {Nature reviews. Microbiology},
volume = {},
number = {},
pages = {},
pmid = {39587352},
issn = {1740-1534},
abstract = {SARS-CoV-2 causes an acute respiratory tract infection that resolves in most people in less than a month. Yet some people with severely weakened immune systems fail to clear the virus, leading to persistent infections with high viral titres in the respiratory tract. In a subset of cases, persistent SARS-CoV-2 replication results in an accelerated accumulation of adaptive mutations that confer escape from neutralizing antibodies and enhance cellular infection. This may lead to the evolution of extensively mutated SARS-CoV-2 variants and introduce an element of chance into the timing of variant evolution, as variant formation may depend on evolution in a single person. Whether long COVID is also caused by persistence of replicating SARS-CoV-2 is controversial. One line of evidence is detection of SARS-CoV-2 RNA and proteins in different body compartments long after SARS-CoV-2 infection has cleared from the upper respiratory tract. However, thus far, no replication competent virus has been cultured from individuals with long COVID who are immunocompetent. In this Review, we consider mechanisms of viral persistence, intra-host evolution in persistent infections, the connection of persistent infections with SARS-CoV-2 variants and the possible role of SARS-CoV-2 persistence in long COVID. Understanding persistent infections may therefore resolve much of what is still unclear in COVID-19 pathophysiology, with possible implications for other emerging viruses.},
}
RevDate: 2024-12-15
CmpDate: 2024-12-08
The effect of pre-COVID and post-COVID vaccination on long COVID: A systematic review and meta-analysis.
The Journal of infection, 89(6):106358.
BACKGROUND: Long COVID affects millions of people and results in a substantial decrease in quality of life. Previous primary studies and reviews attempted to study the effect of vaccination against long COVID, but these studies varied in the cut-off time of long COVID. We adhered to the WHO's definition of long COVID and conducted a systematic review and meta-analysis on the effect of pre-COVID and post-COVID vaccination on long COVID.
METHODS: We obtained data from 13 databases up to 18 February 2024, including peer reviewed and preprint studies. Our inclusion criteria were: (1) long COVID definition as 3 months or beyond, (2) comparing long COVID symptoms between vaccinated and unvaccinated groups, (3) subjects received vaccinations either before or after infected with COVID, (4) the number of doses received by participants was specified. We extracted study characteristics and data and computed the summary odds ratio (OR) with the DerSimonian and Laird random effects model. We then performed subgroup analyses based on the main vaccine brand and long COVID assessment method. ROBINS-I framework was used for assessment of risk of bias and the GRADE approach was used for evaluating the certainty of evidence.
FINDINGS: We included data from 25 observational studies (n = 14,128,260) with no randomised controlled trials. One-dose pre-COVID vaccination did not have an effect on long COVID (number of studies = 10, summary OR = 1.01, 95% CI = 0.88-1.15, p-value = 0.896). Two-dose pre-COVID vaccination was associated with a 24% reduced odds of long COVID (number of studies = 15, summary OR = 0.76, 95% CI = 0.65-0.89, p-value = 0.001) and 4 symptoms (fatigue, headache, loss of smell, muscle pain) out of 10 symptoms analysed. The OR of three-dose pre-COVID vaccination against overall long COVID was statistically insignificant but was far away from 1 (number of studies = 3, summary OR = 0.31, 95% CI = 0.05-1.84, p-value = 0.198). One-dose post-COVID vaccination was associated with a 15% reduced odds of long COVID (number of studies = 5, summary OR = 0.85, 95% CI = 0.73-0.98, p-value = 0.024). The OR of two-dose post-COVID vaccination against long COVID was statistically insignificant but was far away from 1 (number of studies = 3, summary OR = 0.63, 95% CI = 0.38-1.03, p-value = 0.066).
INTERPRETATION: Our study suggests that 2-dose pre-COVID vaccination and 1-dose post-COVID vaccination are associated with a lower risk of long COVID. Since long COVID reduces quality of life substantially, vaccination could be a possible measure to maintain quality of life by partially protecting against long COVID.
Additional Links: PMID-39580033
Publisher:
PubMed:
Citation:
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@article {pmid39580033,
year = {2024},
author = {Chow, NKN and Tsang, CYW and Chan, YH and Telaga, SA and Ng, LYA and Chung, CM and Yip, YM and Cheung, PP},
title = {The effect of pre-COVID and post-COVID vaccination on long COVID: A systematic review and meta-analysis.},
journal = {The Journal of infection},
volume = {89},
number = {6},
pages = {106358},
doi = {10.1016/j.jinf.2024.106358},
pmid = {39580033},
issn = {1532-2742},
mesh = {Humans ; *COVID-19/complications/immunology/prevention & control ; *COVID-19 Vaccines/administration & dosage ; *Post-Acute COVID-19 Syndrome/epidemiology/immunology/prevention & control/virology ; Quality of Life ; SARS-CoV-2/immunology ; *Vaccination/statistics & numerical data ; },
abstract = {BACKGROUND: Long COVID affects millions of people and results in a substantial decrease in quality of life. Previous primary studies and reviews attempted to study the effect of vaccination against long COVID, but these studies varied in the cut-off time of long COVID. We adhered to the WHO's definition of long COVID and conducted a systematic review and meta-analysis on the effect of pre-COVID and post-COVID vaccination on long COVID.
METHODS: We obtained data from 13 databases up to 18 February 2024, including peer reviewed and preprint studies. Our inclusion criteria were: (1) long COVID definition as 3 months or beyond, (2) comparing long COVID symptoms between vaccinated and unvaccinated groups, (3) subjects received vaccinations either before or after infected with COVID, (4) the number of doses received by participants was specified. We extracted study characteristics and data and computed the summary odds ratio (OR) with the DerSimonian and Laird random effects model. We then performed subgroup analyses based on the main vaccine brand and long COVID assessment method. ROBINS-I framework was used for assessment of risk of bias and the GRADE approach was used for evaluating the certainty of evidence.
FINDINGS: We included data from 25 observational studies (n = 14,128,260) with no randomised controlled trials. One-dose pre-COVID vaccination did not have an effect on long COVID (number of studies = 10, summary OR = 1.01, 95% CI = 0.88-1.15, p-value = 0.896). Two-dose pre-COVID vaccination was associated with a 24% reduced odds of long COVID (number of studies = 15, summary OR = 0.76, 95% CI = 0.65-0.89, p-value = 0.001) and 4 symptoms (fatigue, headache, loss of smell, muscle pain) out of 10 symptoms analysed. The OR of three-dose pre-COVID vaccination against overall long COVID was statistically insignificant but was far away from 1 (number of studies = 3, summary OR = 0.31, 95% CI = 0.05-1.84, p-value = 0.198). One-dose post-COVID vaccination was associated with a 15% reduced odds of long COVID (number of studies = 5, summary OR = 0.85, 95% CI = 0.73-0.98, p-value = 0.024). The OR of two-dose post-COVID vaccination against long COVID was statistically insignificant but was far away from 1 (number of studies = 3, summary OR = 0.63, 95% CI = 0.38-1.03, p-value = 0.066).
INTERPRETATION: Our study suggests that 2-dose pre-COVID vaccination and 1-dose post-COVID vaccination are associated with a lower risk of long COVID. Since long COVID reduces quality of life substantially, vaccination could be a possible measure to maintain quality of life by partially protecting against long COVID.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*COVID-19/complications/immunology/prevention & control
*COVID-19 Vaccines/administration & dosage
*Post-Acute COVID-19 Syndrome/epidemiology/immunology/prevention & control/virology
Quality of Life
SARS-CoV-2/immunology
*Vaccination/statistics & numerical data
RevDate: 2024-11-22
'It's that camaraderie': Experiences of a Long-COVID peer support group for staff working in health, social care and emergency services.
Journal of health psychology [Epub ahead of print].
Health, social care and emergency services staff, continue to feel the impact of Long-COVID. Using quantitative and qualitative methods, this study aims to evaluate the experience of UK health and social care staff who participated in a virtual Long-COVID peer support group between May 2021 and May 2023. The outcome measures (SWEMWBS and PHQ9) show an improvement in post-group scores, suggesting participation in the peer support group is linked to improved wellbeing. Thematic analysis identified five key themes: finding connectedness, reciprocity, effective facilitation, filling the gaps and virtual format. This evaluation shows how peer support groups provided space for reciprocity and the positive outcomes associated with this. This evaluation highlights the importance of co-produced, needs-based services providing Long-COVID peer support.
Additional Links: PMID-39575994
Publisher:
PubMed:
Citation:
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@article {pmid39575994,
year = {2024},
author = {Somerton, A and Jeffrey, H},
title = {'It's that camaraderie': Experiences of a Long-COVID peer support group for staff working in health, social care and emergency services.},
journal = {Journal of health psychology},
volume = {},
number = {},
pages = {13591053241296184},
doi = {10.1177/13591053241296184},
pmid = {39575994},
issn = {1461-7277},
abstract = {Health, social care and emergency services staff, continue to feel the impact of Long-COVID. Using quantitative and qualitative methods, this study aims to evaluate the experience of UK health and social care staff who participated in a virtual Long-COVID peer support group between May 2021 and May 2023. The outcome measures (SWEMWBS and PHQ9) show an improvement in post-group scores, suggesting participation in the peer support group is linked to improved wellbeing. Thematic analysis identified five key themes: finding connectedness, reciprocity, effective facilitation, filling the gaps and virtual format. This evaluation shows how peer support groups provided space for reciprocity and the positive outcomes associated with this. This evaluation highlights the importance of co-produced, needs-based services providing Long-COVID peer support.},
}
RevDate: 2024-11-23
Promoting Awareness of Data Confidentiality and Security During the COVID-19 Pandemic in a Low-Income Country-Sierra Leone.
Public health reviews, 45:1607540.
OBJECTIVES: World Health Organization issued Joint Statement on Data Protection and Privacy in the COVID-19 Response stating that collection of vast amounts of personal data may potentially lead to the infringement of fundamental human rights and freedoms. The Organization for Economic Cooperation and Development called on national governments to adhere to the international principles for data security and confidentiality. This paper describes the methods used to assist the Ministry of Health in bringing awareness of the data ownership, confidentiality and security principles to COVID-19 responders.
METHODS: The Sierra Leone Epidemiological Data (SLED) Team data managers conducted training for groups of COVID-19 responders. Training included presentations on data confidentiality, information disclosure, physical and electronic data security, and cyber-security; and interactive discussion of real-life scenarios. A game of Jeopardy was created to test the participant's knowledge.
RESULTS: This paper describes the methods used by the SLED Team to bring awareness of the DOCS principles to more than 2,500 COVID-19 responders.
CONCLUSION: Similar efforts may benefit other countries where the knowledge, resources, and governing rules for protection of personal data are limited.
Additional Links: PMID-39574837
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid39574837,
year = {2024},
author = {Kanu, JS and Vandi, MA and Bangura, B and Draper, K and Gorina, Y and Foster, MA and Harding, JD and Ikoona, EN and Jambai, A and Kamara, MAM and Kaitibi, D and Moffett, DB and Singh, T and Redd, JT},
title = {Promoting Awareness of Data Confidentiality and Security During the COVID-19 Pandemic in a Low-Income Country-Sierra Leone.},
journal = {Public health reviews},
volume = {45},
number = {},
pages = {1607540},
pmid = {39574837},
issn = {0301-0422},
abstract = {OBJECTIVES: World Health Organization issued Joint Statement on Data Protection and Privacy in the COVID-19 Response stating that collection of vast amounts of personal data may potentially lead to the infringement of fundamental human rights and freedoms. The Organization for Economic Cooperation and Development called on national governments to adhere to the international principles for data security and confidentiality. This paper describes the methods used to assist the Ministry of Health in bringing awareness of the data ownership, confidentiality and security principles to COVID-19 responders.
METHODS: The Sierra Leone Epidemiological Data (SLED) Team data managers conducted training for groups of COVID-19 responders. Training included presentations on data confidentiality, information disclosure, physical and electronic data security, and cyber-security; and interactive discussion of real-life scenarios. A game of Jeopardy was created to test the participant's knowledge.
RESULTS: This paper describes the methods used by the SLED Team to bring awareness of the DOCS principles to more than 2,500 COVID-19 responders.
CONCLUSION: Similar efforts may benefit other countries where the knowledge, resources, and governing rules for protection of personal data are limited.},
}
RevDate: 2025-01-13
CmpDate: 2024-12-10
Hypopituitarism and COVID-19.
Pituitary, 27(6):925-934.
PURPOSE: This review aims to collect and examine recent research findings regarding hypopituitarism and COVID-19, focusing on the virus's impact on the pituitary gland and the outcomes for infected patients with hormonal deficiencies.
METHODS: Literature review using PubMed (pubmed.ncbi.nlm.nih.gov). The search included the following terms: "COVID19" in combination with "Pituitary" and "Hypopituitarism".
RESULTS: Many studies have aimed to evaluate the function of the pituitary gland in infected patients, revealing variable degrees of deficiencies. The results are very heterogenous mostly because many different tests and hormonal cut-off have been adopted. It is unclear whether primary virus damage or the inflammatory response is responsible for these hormonal alterations. Interestingly, pituitary defects may persist long after the initial infection, possibly contributing to the "Long COVID syndrome". However, data on the recovery of pituitary function and long-term follow-up are not yet available. On the other hand, although findings are not consistent, patients with hypopituitarism may be at a higher risk for COVID-19 infection rate, complications, and mortality.
CONCLUSION: The COVID-19 pandemic presented challenges for endocrinologists. The endocrine system appears to be involved in both the acute phase of infection and the recovery period. Hypopituitarism can be a consequence of SARS-COV-2 infection, and patients with existing hypopituitarism may face higher risks of complications. It is advisable to educate these patients on how to adjust their replacement therapies. Long-term follow-up data on pituitary function after recovery from COVID-19 are needed.
Additional Links: PMID-39560821
PubMed:
Citation:
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@article {pmid39560821,
year = {2024},
author = {Carosi, G and Cremaschi, A and Giavoli, C and Ferrante, E and Mantovani, G},
title = {Hypopituitarism and COVID-19.},
journal = {Pituitary},
volume = {27},
number = {6},
pages = {925-934},
pmid = {39560821},
issn = {1573-7403},
mesh = {Humans ; *COVID-19/epidemiology/complications ; *Hypopituitarism/etiology ; Pandemics ; Pituitary Gland ; SARS-CoV-2/physiology ; },
abstract = {PURPOSE: This review aims to collect and examine recent research findings regarding hypopituitarism and COVID-19, focusing on the virus's impact on the pituitary gland and the outcomes for infected patients with hormonal deficiencies.
METHODS: Literature review using PubMed (pubmed.ncbi.nlm.nih.gov). The search included the following terms: "COVID19" in combination with "Pituitary" and "Hypopituitarism".
RESULTS: Many studies have aimed to evaluate the function of the pituitary gland in infected patients, revealing variable degrees of deficiencies. The results are very heterogenous mostly because many different tests and hormonal cut-off have been adopted. It is unclear whether primary virus damage or the inflammatory response is responsible for these hormonal alterations. Interestingly, pituitary defects may persist long after the initial infection, possibly contributing to the "Long COVID syndrome". However, data on the recovery of pituitary function and long-term follow-up are not yet available. On the other hand, although findings are not consistent, patients with hypopituitarism may be at a higher risk for COVID-19 infection rate, complications, and mortality.
CONCLUSION: The COVID-19 pandemic presented challenges for endocrinologists. The endocrine system appears to be involved in both the acute phase of infection and the recovery period. Hypopituitarism can be a consequence of SARS-COV-2 infection, and patients with existing hypopituitarism may face higher risks of complications. It is advisable to educate these patients on how to adjust their replacement therapies. Long-term follow-up data on pituitary function after recovery from COVID-19 are needed.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*COVID-19/epidemiology/complications
*Hypopituitarism/etiology
Pandemics
Pituitary Gland
SARS-CoV-2/physiology
RevDate: 2024-11-20
A Narrative Review of Impact of Incentive Spirometer Respiratory Training in Long COVID.
International journal of general medicine, 17:5233-5246.
Long COVID refers to symptoms that appear 3 months after initial infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus of Coronavirus disease 2019 (COVID-19), and last for at least 2 months, not attributable to other diagnoses. This health issue significantly burdens patients' quality of life, the economy, and society. Improving the af-termath of COVID-19 is a crucial global health issue in the post-pandemic era. According to current results, it is evident that developing a simple, low-cost respiratory training method that can be easily used at home by themselves with long Coronavirus disease 2019 symptoms (long COVID) is an important and urgent issue. The incentive spirometer is widely used in physical, speech, and respiratory therapy, as well as in preventing postoperative pulmonary infections and improving sputum clearance. However, to date, the role of incentive spirometer respiratory training in long COVID symptoms is still limited. In this literature review is presented to explore the effectiveness of incentive spirometer respiratory training in alleviating symptoms among individuals recovering from long COVID. We also compile non-invasive assessment methods, with the aim to enable individuals to undergo training and assessments conveniently at home or in the community. In this review, a literature review approach was utilized to explore the effectiveness of incentive spirometer intervention in alleviating long-term COVID symptoms. This study is to synthesize the findings of articles published during January 2019 and December 2023 retrieved from PubMed/CINAHL/MEDLINE/ Google Scholar without re-strictions on study type. We ultimately identified seven articles and have summarized similar past studies. This review could contribute to improving symptoms related to long COVID by incentive spirometer respiratory training and serve as practical reference material for clinical medical staff and provide insights for healthcare policymakers in de-veloping guidelines for future research directions, clinical guidance, and educational strategies in the context of nursing care.
Additional Links: PMID-39559556
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid39559556,
year = {2024},
author = {Chen, YH and Hsieh, YS},
title = {A Narrative Review of Impact of Incentive Spirometer Respiratory Training in Long COVID.},
journal = {International journal of general medicine},
volume = {17},
number = {},
pages = {5233-5246},
pmid = {39559556},
issn = {1178-7074},
abstract = {Long COVID refers to symptoms that appear 3 months after initial infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus of Coronavirus disease 2019 (COVID-19), and last for at least 2 months, not attributable to other diagnoses. This health issue significantly burdens patients' quality of life, the economy, and society. Improving the af-termath of COVID-19 is a crucial global health issue in the post-pandemic era. According to current results, it is evident that developing a simple, low-cost respiratory training method that can be easily used at home by themselves with long Coronavirus disease 2019 symptoms (long COVID) is an important and urgent issue. The incentive spirometer is widely used in physical, speech, and respiratory therapy, as well as in preventing postoperative pulmonary infections and improving sputum clearance. However, to date, the role of incentive spirometer respiratory training in long COVID symptoms is still limited. In this literature review is presented to explore the effectiveness of incentive spirometer respiratory training in alleviating symptoms among individuals recovering from long COVID. We also compile non-invasive assessment methods, with the aim to enable individuals to undergo training and assessments conveniently at home or in the community. In this review, a literature review approach was utilized to explore the effectiveness of incentive spirometer intervention in alleviating long-term COVID symptoms. This study is to synthesize the findings of articles published during January 2019 and December 2023 retrieved from PubMed/CINAHL/MEDLINE/ Google Scholar without re-strictions on study type. We ultimately identified seven articles and have summarized similar past studies. This review could contribute to improving symptoms related to long COVID by incentive spirometer respiratory training and serve as practical reference material for clinical medical staff and provide insights for healthcare policymakers in de-veloping guidelines for future research directions, clinical guidance, and educational strategies in the context of nursing care.},
}
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RJR Experience and Expertise
Researcher
Robbins holds BS, MS, and PhD degrees in the life sciences. He served as a tenured faculty member in the Zoology and Biological Science departments at Michigan State University. He is currently exploring the intersection between genomics, microbial ecology, and biodiversity — an area that promises to transform our understanding of the biosphere.
Educator
Robbins has extensive experience in college-level education: At MSU he taught introductory biology, genetics, and population genetics. At JHU, he was an instructor for a special course on biological database design. At FHCRC, he team-taught a graduate-level course on the history of genetics. At Bellevue College he taught medical informatics.
Administrator
Robbins has been involved in science administration at both the federal and the institutional levels. At NSF he was a program officer for database activities in the life sciences, at DOE he was a program officer for information infrastructure in the human genome project. At the Fred Hutchinson Cancer Research Center, he served as a vice president for fifteen years.
Technologist
Robbins has been involved with information technology since writing his first Fortran program as a college student. At NSF he was the first program officer for database activities in the life sciences. At JHU he held an appointment in the CS department and served as director of the informatics core for the Genome Data Base. At the FHCRC he was VP for Information Technology.
Publisher
While still at Michigan State, Robbins started his first publishing venture, founding a small company that addressed the short-run publishing needs of instructors in very large undergraduate classes. For more than 20 years, Robbins has been operating The Electronic Scholarly Publishing Project, a web site dedicated to the digital publishing of critical works in science, especially classical genetics.
Speaker
Robbins is well-known for his speaking abilities and is often called upon to provide keynote or plenary addresses at international meetings. For example, in July, 2012, he gave a well-received keynote address at the Global Biodiversity Informatics Congress, sponsored by GBIF and held in Copenhagen. The slides from that talk can be seen HERE.
Facilitator
Robbins is a skilled meeting facilitator. He prefers a participatory approach, with part of the meeting involving dynamic breakout groups, created by the participants in real time: (1) individuals propose breakout groups; (2) everyone signs up for one (or more) groups; (3) the groups with the most interested parties then meet, with reports from each group presented and discussed in a subsequent plenary session.
Designer
Robbins has been engaged with photography and design since the 1960s, when he worked for a professional photography laboratory. He now prefers digital photography and tools for their precision and reproducibility. He designed his first web site more than 20 years ago and he personally designed and implemented this web site. He engages in graphic design as a hobby.
RJR Picks from Around the Web (updated 11 MAY 2018 )
Old Science
Weird Science
Treating Disease with Fecal Transplantation
Fossils of miniature humans (hobbits) discovered in Indonesia
Paleontology
Dinosaur tail, complete with feathers, found preserved in amber.
Astronomy
Mysterious fast radio burst (FRB) detected in the distant universe.
Big Data & Informatics
Big Data: Buzzword or Big Deal?
Hacking the genome: Identifying anonymized human subjects using publicly available data.