@article {pmid40259563,
year = {2025},
author = {Cornish, F and Sabaine, B and Soares, L and Caldas, B and Portela, MC and Bousquat, A and Aveling, EL},
title = {The erasure of infection-associated chronic conditions: Critical interpretive synthesis of literature on healthcare for long COVID and related conditions in Brazil.},
journal = {Global public health},
volume = {20},
number = {1},
pages = {2490720},
doi = {10.1080/17441692.2025.2490720},
pmid = {40259563},
issn = {1744-1706},
mesh = {Humans ; Brazil/epidemiology ; *COVID-19/epidemiology/therapy/complications ; Chronic Disease/epidemiology/therapy ; SARS-CoV-2 ; *Delivery of Health Care ; Post-Acute COVID-19 Syndrome ; },
abstract = {Evidence is emerging that long COVID is at least as prevalent in the Global South as the Global North, but literature on long COVID healthcare in the Global South is in its infancy. Brazil is seeing significant levels of debility due to long COVID but a limited national evidence-base. long COVID shares symptomatology and appropriate care with a wider category of infection-associated chronic conditions (IACCs). This article reviews literature published between 2000 and 2023 addressing healthcare for long COVID and IACCs in Brazil, in the interest of exploring challenges and opportunities for the SUS (Brazil's universal health system) to offer appropriate long COVID healthcare. We find that long COVID and IACCs collectively are subject to erasure from Brazilian healthcare knowledge, through lack of expertise, a resource-limited health system prioritising urgent care, and the concentration of poor health in marginalised populations with limited decision-making power. A nascent intellectual will to address long COVID, and a tradition of social participation in healthcare governance present potential opportunities. We call for ignition of a global step-change in tackling healthcare for long COVID and IACCs. Global equity in long COVID healthcare requires the development and sharing of expertise regarding its universal and context-specific features.},
}

Humans
Brazil/epidemiology
*COVID-19/epidemiology/therapy/complications
Chronic Disease/epidemiology/therapy
SARS-CoV-2
*Delivery of Health Care
Post-Acute COVID-19 Syndrome

@article {pmid40246350,
year = {2025},
author = {Rubio-Casillas, A and Rodríguez-Quintero, CM and Hromić-Jahjefendić, A and Uversky, VN and Redwan, EM and Brogna, C},
title = {The essential role of prebiotics in restoring gut health in long COVID.},
journal = {Progress in molecular biology and translational science},
volume = {213},
number = {},
pages = {385-411},
doi = {10.1016/bs.pmbts.2025.01.004},
pmid = {40246350},
issn = {1878-0814},
mesh = {Humans ; *Prebiotics/administration & dosage ; *COVID-19/microbiology/immunology ; *Gastrointestinal Microbiome/drug effects ; SARS-CoV-2 ; Dysbiosis/microbiology ; Probiotics ; Pandemics ; },
abstract = {The gut microbiota (GM) plays an essential role in human health, influencing not only digestive processes but also the immune system´s functionality. The COVID-19 pandemic has highlighted the complex interaction between viral infections and the GM. Emerging evidence has demonstrated that SARS-CoV-2 can disrupt microbial homeostasis, leading to dysbiosis and compromised immune responses. The severity of COVID-19 has been associated with a reduction in the abundance of several beneficial bacteria in the gut. It has been proposed that consuming probiotics may help to re-colonize the GM. Although probiotics are important, prebiotics are essential for their metabolism, growth, and re-colonization capabilities. This chapter delves into the critical role of prebiotics in restoring GM after COVID-19 disease. The mechanisms by which prebiotics enhance the metabolism of beneficial bacteria will be described, and how prebiotics mediate the re-colonization of the gut with beneficial bacteria, thereby restoring microbial diversity and promoting the resilience of the gut-associated immune system. The benefits of consuming prebiotics from natural sources are superior to those from chemically purified commercial products.},
}

Humans
*Prebiotics/administration & dosage
*COVID-19/microbiology/immunology
*Gastrointestinal Microbiome/drug effects
SARS-CoV-2
Dysbiosis/microbiology
Probiotics
Pandemics

@article {pmid38381595,
year = {2025},
author = {Tsampasian, V and Bäck, M and Bernardi, M and Cavarretta, E and Dębski, M and Gati, S and Hansen, D and Kränkel, N and Koskinas, KC and Niebauer, J and Spadafora, L and Frias Vargas, M and Biondi-Zoccai, G and Vassiliou, VS},
title = {Cardiovascular disease as part of Long COVID: a systematic review.},
journal = {European journal of preventive cardiology},
volume = {32},
number = {6},
pages = {485-498},
doi = {10.1093/eurjpc/zwae070},
pmid = {38381595},
issn = {2047-4881},
mesh = {Humans ; *COVID-19/complications/epidemiology/diagnosis ; *Cardiovascular Diseases/epidemiology/diagnosis/therapy/etiology/physiopathology ; SARS-CoV-2 ; Risk Factors ; Risk Assessment ; Heart Disease Risk Factors ; },
abstract = {AIMS: Long COVID syndrome has had a major impact on million patients' lives worldwide. The cardiovascular system is an important aspect of this multifaceted disease that may manifest in many ways. We have hereby performed a narrative review in order to identify the extent of the cardiovascular manifestations of the Long COVID syndrome.

METHODS AND RESULTS: An in-depth systematic search of the literature has been conducted for this narrative review. The systematic search of PubMed and Cochrane databases yielded 3993 articles, of which 629 underwent full-text screening. A total of 78 studies were included in the final qualitative synthesis and data evaluation. The pathophysiology of the cardiovascular sequelae of Long COVID syndrome and the cardiac manifestations and complications of Long COVID syndrome are critically evaluated. In addition, potential cardiovascular risk factors are assessed, and preventive methods and treatment options are examined in this review.

CONCLUSION: This systematic review poignantly summarizes the evidence from the available literature regarding the cardiovascular manifestations of Long COVID syndrome and reviews potential mechanistic pathways, diagnostic approaches, preventive measures, and treatment options.},
}

Humans
*COVID-19/complications/epidemiology/diagnosis
*Cardiovascular Diseases/epidemiology/diagnosis/therapy/etiology/physiopathology
SARS-CoV-2
Risk Factors
Risk Assessment
Heart Disease Risk Factors

@article {pmid40246346,
year = {2025},
author = {Adilović, M},
title = {COVID-19 related complications.},
journal = {Progress in molecular biology and translational science},
volume = {213},
number = {},
pages = {259-314},
doi = {10.1016/bs.pmbts.2025.02.002},
pmid = {40246346},
issn = {1878-0814},
mesh = {Humans ; *COVID-19/complications ; *SARS-CoV-2 ; Pregnancy ; Pandemics ; Female ; },
abstract = {The COVID-19 pandemic has significantly impacted global healthcare systems, revealed vulnerabilities and prompted a re-evaluation of medical practices. Acute complications from the virus, including cardiovascular and neurological issues, have underscored the necessity for timely medical interventions. Advances in diagnostic methods and personalized therapies have been pivotal in mitigating severe outcomes. Additionally, Long COVID has emerged as a complex challenge, affecting various body systems and leading to respiratory, cardiovascular, neurological, psychological, and musculoskeletal problems. This broad spectrum of complications highlights the importance of multidisciplinary management approaches that prioritize therapy, rehabilitation, and patient-centered care. Vulnerable populations such as paediatric patients, pregnant women, and immunocompromised individuals face unique risks and complications, necessitating continuous monitoring and tailored management strategies to reduce morbidity and mortality associated with COVID-19.},
}

Humans
*COVID-19/complications
*SARS-CoV-2
Pregnancy
Pandemics
Female

@article {pmid40241147,
year = {2025},
author = {Morello, R and De Rose, C and Martino, L and Raffaelli, F and Zampino, G and Valentini, P and Buonsenso, D},
title = {Role of nutrient supplements in children with post-COVID condition: a retrospective preliminary observation and narrative review.},
journal = {Italian journal of pediatrics},
volume = {51},
number = {1},
pages = {119},
pmid = {40241147},
issn = {1824-7288},
mesh = {Humans ; *Dietary Supplements ; Retrospective Studies ; *COVID-19/complications ; Child ; Male ; Female ; Child, Preschool ; Adolescent ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Post-COVID Condition (PCC), emerging as a significant long-term consequence of SARS-CoV-2 infection, affects not only adults but also the pediatric population. Despite ongoing research, the precise pathophysiology of PCC remains elusive. However, several putative mechanisms have been identified, leading to the exploration of various therapeutic strategies. Notably, in the adult population, there has been substantial interest in the potential efficacy of nutritional supplements. Regrettably, information regarding the use of such supplements in the pediatric population is currently lacking.

METHODS: The present study was conducted to assess the impact of nutritional supplements on alleviating long COVID symptoms in children. To achieve this, we conducted a retrospective analysis of nutrient supplements administered by parents to children with Post-COVID Condition (PCC) between February 2020 and October 2022. Statistical analyses were employed to determine associations between categorical variables.

RESULTS: A total of 1243 children were enrolled following documented SARS-CoV-2 infection, with 940 (76.2%) diagnosed as recovered and 294 (23.8%) diagnosed with Long COVID. Among Long COVID patients experiencing disabling symptoms, treatment with oral lactoferrin and/or a Multi-Element Product (MEP) with antioxidant and anti-inflammatory properties was initiated. The correlation analysis between the use of supplements and persistence of long COVID at the next follow-up showed that the use of MEP alone (OR 5.7, 95% CI 3.8-8.5), or the combination of MEP and lactoferrin (OR 5.06, 95% CI 3.3-7.6) three months after the initial infection and for the following three months, were associated with a lower risk having long covid at six months following initial infection, when compared with the use of lactoferrin alone (OR 7.6 95% CI 5.1-11.4).

CONCLUSIONS: This proof-of-concept study revealed that MEP and lactoferrin, when administered three months after initial infection in patients with a new diagnosis of long covid, may have a positive impact on improving Long COVID symptoms in children during follow-up evaluations. This positive trend toward reducing Post-COVID Condition (PCC) exhibited by MEP and lactoferrin suggested a potential benefit worthy of exploration in future randomized controlled trials.},
}

Humans
*Dietary Supplements
Retrospective Studies
*COVID-19/complications
Child
Male
Female
Child, Preschool
Adolescent
SARS-CoV-2

@article {pmid40231214,
year = {2025},
author = {Serafini, RA and Frere, JJ and Giosan, IM and Nwaneshiudu, CA},
title = {SARS-CoV-2-induced sensory perturbations: A narrative review of clinical phenotypes, molecular pathologies, and possible interventions.},
journal = {Brain, behavior, & immunity - health},
volume = {45},
number = {},
pages = {100983},
pmid = {40231214},
issn = {2666-3546},
abstract = {BACKGROUND: The acute and post-acute sequelae of SARS-CoV-2 infection have been of great clinical interest since the inception of the COVID-19 pandemic. Despite a high prevalence of individuals with persistent symptoms, a wholistic view of the effects of SARS-CoV-2 on special sensory systems is lacking. Considering the significant impact of normal sensory function on quality of life, the goal of this review is to highlight unresolved issues related to SARS-CoV-2-associated insults to the sensory nervous system.

MAJOR FINDINGS: In this narrative review, we discuss the epidemiology of SARS-CoV-2-induced sensory perturbations, underlying pathological mechanisms, and possible therapeutic strategies across the olfactory, gustatory, somatosensory, visual, and auditory systems. Examined literature included studies with human biospecimens, human-derived cell lines, and naturally susceptible animal models, which highlighted evidence of persistent functional disruption in all sensory systems. SARS-CoV-2 infection was associated with persistent inflammation in the olfactory epithelium/bulb, somatosensory ganglia, and gustatory systems, long-term transcriptional perturbations in the sensory central nervous system and peripheral nervous system, and detectable degeneration/apoptosis in the gustatory and visual systems. Few studies have proposed evidence-based therapeutic strategies for attenuating specific sensory abnormalities after SARS-CoV-2 infection.

CONCLUSION: While the olfactory system, and to some extent the visual and somatosensory systems, have been more thoroughly investigated from symptomatology, behavioral and molecular perspectives, there is still an unmet need for the development of therapeutics to treat COVID-induced impairment of these systems. Further, additional attention must be placed on COVID-associated impairment of the gustatory, visual, and auditory systems, which lack detailed mechanistic investigations into their pathogenesis.},
}

@article {pmid40219044,
year = {2025},
author = {Marchesi, N and Allegri, M and Bruno, GM and Pascale, A and Govoni, S},
title = {Exploring the Potential of Dietary Supplements to Alleviate Pain Due to Long COVID.},
journal = {Nutrients},
volume = {17},
number = {7},
pages = {},
pmid = {40219044},
issn = {2072-6643},
mesh = {Humans ; *Dietary Supplements ; *COVID-19/complications ; SARS-CoV-2 ; *Chronic Pain/etiology ; Analgesics/therapeutic use ; *Pain Management/methods ; Post-Acute COVID-19 Syndrome ; *Pain/etiology/drug therapy ; },
abstract = {Long COVID, characterized by persistent symptoms following COVID-19 infection, significantly impacts individuals' health and daily functioning due to fatigue and pain. Focusing on pain, this review addresses nociplastic and chronic pain conditions. Interventions designed to reduce inflammation, oxidative stress, and enhance vagal activity may offer a promising approach to managing post-pandemic pain. This review presents individual components of food supplements with demonstrated efficacy in one or more pain conditions, focusing on their proposed mechanisms and clinical activity in pain, including their use in post-COVID-19 pain when available. Many of these substances have a long history of safe use and may offer an alternative to long-term analgesic drug treatment, which is often associated with potential side effects. This review also explores the potential for synergistic effects when combining these substances with each other or with conventional analgesics, considering the advantages for both patients and the healthcare system in using these substances as adjunctive or primary therapies for pain symptoms related to long COVID. While preclinical scientific literature provides a mechanistic basis for the action of several food supplements on pain control mechanisms and signaling pathways, clinical experience, particularly in the field of long COVID-associated pain, is still limited. However, the reviewed literature strongly suggests that the use of food supplements in long COVID-associated pain is an attainable goal, provided that rigorous clinical trials are conducted.},
}

Humans
*Dietary Supplements
*COVID-19/complications
SARS-CoV-2
*Chronic Pain/etiology
Analgesics/therapeutic use
*Pain Management/methods
Post-Acute COVID-19 Syndrome
*Pain/etiology/drug therapy

@article {pmid40212158,
year = {2025},
author = {Abbas, AH and Haji, MR and Shimal, AA and Kurmasha, YH and Al-Janabi, AAH and Azeez, ZT and Al-Ali, ARS and Al-Najati, HMH and Al-Waeli, ARA and Abdulhadi, NASA and Al-Tuaama, AZH and Al-Ashtary, MM and Hussin, OA},
title = {A multidisciplinary review of long COVID to address the challenges in diagnosis and updated management guidelines.},
journal = {Annals of medicine and surgery (2012)},
volume = {87},
number = {4},
pages = {2105-2117},
pmid = {40212158},
issn = {2049-0801},
abstract = {Long COVID has emerged as a significant challenge since the COVID-19 pandemic, which was declared as an outbreak in March 2020, marked by diverse symptoms and prolonged duration of disease. Defined by the WHO as symptoms persisting or emerging for at least two months post-SARS-CoV-2 infection without an alternative cause, its prevalence varies globally, with estimates of 10-20% in Europe, 7.3% in the USA, and 3.0% in the UK. The condition's etiology remains unclear, involving factors, such as renin-angiotensin system overactivation, persistent viral reservoirs, immune dysregulation, and autoantibodies. Reactivated viruses, like EBV and HSV-6, alongside epigenetic alterations, exacerbate mitochondrial dysfunction and energy imbalance. Emerging evidence links SARS-CoV-2 to chromatin and gut microbiome changes, further influencing long-term health impacts. Diagnosis of long COVID requires detailed systemic evaluation through medical history and physical examination. Management is highly individualized, focusing mainly on the patient's symptoms and affected systems. A multidisciplinary approach is essential, integrating diverse perspectives to address systemic manifestations, underlying mechanisms, and therapeutic strategies. Enhanced understanding of long COVID's pathophysiology and clinical features is critical to improving patient outcomes and quality of life. With a growing number of cases expected globally, advancing research and disseminating knowledge on long COVID remain vital for developing effective diagnostic and management frameworks, ultimately supporting better care for affected individuals.},
}

@article {pmid40211768,
year = {2025},
author = {Gao, J and Zhao, D and Nouri, HR and Chu, HW and Huang, H},
title = {Transcriptional Regulation of Mouse Mast Cell Differentiation and the Role of Human Lung Mast Cells in Airway Inflammation.},
journal = {Immunological reviews},
volume = {331},
number = {1},
pages = {e70026},
doi = {10.1111/imr.70026},
pmid = {40211768},
issn = {1600-065X},
support = {R01AI083986/NH/NIH HHS/United States ; R01AI107022/NH/NIH HHS/United States ; R01AI150082/NH/NIH HHS/United States ; R01AI152504/NH/NIH HHS/United States ; R01AI161296/NH/NIH HHS/United States ; U19AI125357/NH/NIH HHS/United States ; },
mesh = {Animals ; Humans ; *Mast Cells/immunology/metabolism ; Cell Differentiation/genetics ; Mice ; *Lung/immunology ; Gene Expression Regulation ; Inflammation/immunology ; *COVID-19/immunology ; Transcription Factors/metabolism ; *SARS-CoV-2/immunology ; },
abstract = {Mast cells (MCs) play a critical role in allergic inflammation, anaphylaxis, and chronic inflammatory diseases such as asthma, COPD, and osteoarthritis. Dysregulated MC activation can lead to MC activation syndrome (MACS), which is observed in patients with long COVID. MCs express the high-affinity receptor for IgE and, upon activation, release mediators and cytokines that trigger anaphylactic shock and promote allergic inflammation. They also interact with epithelial and nerve cells, which are crucial in forming a complex network of cell-cell and gene-gene interactions driving chronic inflammation that can confer resistance to treatment. In this review, in the context of the literature, we focus on experiments conducted in our laboratory investigating how transcription factors and enhancers regulate genes critical in mouse MC differentiation and function related to human lung inflammation.},
}

Animals
Humans
*Mast Cells/immunology/metabolism
Cell Differentiation/genetics
Mice
*Lung/immunology
Gene Expression Regulation
Inflammation/immunology
*COVID-19/immunology
Transcription Factors/metabolism
*SARS-CoV-2/immunology

@article {pmid40210368,
year = {2025},
author = {Verduzco-Gutierrez, M and Fleming, TK and Azola, AM},
title = {Considerations for Long COVID Rehabilitation in Women.},
journal = {Physical medicine and rehabilitation clinics of North America},
volume = {36},
number = {2},
pages = {371-387},
doi = {10.1016/j.pmr.2024.11.009},
pmid = {40210368},
issn = {1558-1381},
mesh = {Humans ; *COVID-19/rehabilitation/epidemiology ; Female ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Sex Factors ; },
abstract = {The coronavirus disease 2019 (COVID-19) pandemic has given rise to long COVID, a prolonged manifestation of severe acute respiratory syndrome coronavirus 2 infection, which presents with varied symptoms and conditions lasting beyond expected acute illness. Despite efforts, diagnostic and treatment approaches remain insufficient, particularly for women who experience higher prevalence rates. Rehabilitation professionals have played a crucial role during the pandemic. Individualized rehabilitation plans, encompassing various therapies and interdisciplinary collaborations, are essential. Addressing disparities and biological sex differences is paramount, requiring increased research, understanding, and advocacy for effective rehabilitative care tailored to all individuals affected by long COVID.},
}

Humans
*COVID-19/rehabilitation/epidemiology
Female
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Sex Factors

@article {pmid40199308,
year = {2024},
author = {Bona, JP},
title = {Knowledge Representation and Management in the Age of Long Covid and Large Language Models: a 2022-2023 Survey.},
journal = {Yearbook of medical informatics},
volume = {33},
number = {1},
pages = {216-222},
doi = {10.1055/s-0044-1800747},
pmid = {40199308},
issn = {2364-0502},
mesh = {*COVID-19 ; Humans ; *Artificial Intelligence ; *Language ; Surveys and Questionnaires ; Large Language Models ; },
abstract = {OBJECTIVES: To select, present, and summarize cutting edge work in the field of Knowledge Representation and Management (KRM) published in 2022 and 2023.

METHODS: A comprehensive set of KRM-relevant articles published in 2022 and 2023 was retrieved by querying PubMed. Topic modeling with Latent Dirichlet Allocation was used to further refine this query and suggest areas of focus. Selected articles were chosen based on a review of their title and abstract.

RESULTS: An initial set of 8,706 publications were retrieved from PubMed. From these, fifteen papers were ultimately selected matching one of two main themes: KRM for long COVID, and KRM approaches used in combination with generative large language models.

CONCLUSIONS: This survey shows the ongoing development and versatility of KRM approaches, both to improve our understanding of a global health crisis and to augment and evaluate cutting edge technologies from other areas of artificial intelligence.},
}

*COVID-19
Humans
*Artificial Intelligence
*Language
Surveys and Questionnaires
Large Language Models

@article {pmid40195851,
year = {2025},
author = {Chung, J and Pierce, J and Franklin, C and Olson, RM and Morrison, AR and Amos-Landgraf, J},
title = {Translating animal models of SARS-CoV-2 infection to vascular, neurological and gastrointestinal manifestations of COVID-19.},
journal = {Disease models & mechanisms},
volume = {18},
number = {9},
pages = {},
doi = {10.1242/dmm.052086},
pmid = {40195851},
issn = {1754-8411},
support = {U42OD010918//Institutes of Health (NIH)/ ; T32OD011126//NIH Office of the Director/ ; IK2BX002527//U.S. Department of Veterans Affairs/ ; },
mesh = {*COVID-19/complications/pathology/virology ; Animals ; *Disease Models, Animal ; *SARS-CoV-2/physiology ; *Gastrointestinal Diseases/virology/etiology/pathology ; Humans ; *Nervous System Diseases/virology/etiology/pathology ; *Vascular Diseases/virology/etiology ; Gastrointestinal Tract/pathology/virology ; *Translational Research, Biomedical ; },
abstract = {Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) initiated a global pandemic resulting in an estimated 775 million infections with over 7 million deaths, it has become evident that COVID-19 is not solely a pulmonary disease. Emerging evidence has shown that, in a subset of patients, certain symptoms - including chest pain, stroke, anosmia, dysgeusia, diarrhea and abdominal pain - all indicate a role of vascular, neurological and gastrointestinal (GI) pathology in the disease process. Many of these disease processes persist long after the acute disease has been resolved, resulting in 'long COVID' or post-acute sequelae of COVID-19 (PASC). The molecular mechanisms underlying the acute and systemic conditions associated with COVID-19 remain incompletely defined. Appropriate animal models provide a method of understanding underlying disease mechanisms at the system level through the study of disease progression, tissue pathology, immune system response to the pathogen and behavioral responses. However, very few studies have addressed PASC and whether existing models hold promise for studying this challenging problem. Here, we review the current literature on cardiovascular, neurological and GI pathobiology caused by COVID-19 in patients, along with established animal models of the acute disease manifestations and their prospects for use in PASC studies. Our aim is to provide guidance for the selection of appropriate models in order to recapitulate certain aspects of the disease to enhance the translatability of mechanistic studies.},
}

*COVID-19/complications/pathology/virology
Animals
*Disease Models, Animal
*SARS-CoV-2/physiology
*Gastrointestinal Diseases/virology/etiology/pathology
Humans
*Nervous System Diseases/virology/etiology/pathology
*Vascular Diseases/virology/etiology
Gastrointestinal Tract/pathology/virology
*Translational Research, Biomedical

@article {pmid40193038,
year = {2025},
author = {Sadowski, J and Ostrowska, SA and Klaudel, T and Zaborska, M and Chruszcz, M and Sztangreciak-Lehun, A and Bułdak, RJ},
title = {Neuropsychiatric disorders in the course to SARS-CoV-2 virus infection, including biological pathomechanisms, psychosocial factors and long COVID-19 associated with "brain fog".},
journal = {Journal of neurovirology},
volume = {},
number = {},
pages = {},
pmid = {40193038},
issn = {1538-2443},
abstract = {During the COVID-19 pandemic, neuropsychiatric disorders began to be observed in a significant proportion of patients, occurring at different times after infection and characterised by varying degrees of severity. This article discusses neurological and psychiatric disorders associated with SARS-CoV-2 virus infection, taking into account biological pathomechanisms and psychosocial factors. The long COVID-19 along with the "brain fog" phenomenon were considered in the study. The purpose of the study is to analyse and discuss the available information from the scientific literature on the possible association between SARS-CoV-2 virus infection and the occurrence of neuropsychiatric disorders with different degrees of severity and temporal correlation. To discuss the correlation of COVID-19 with the occurrence of neuropsychiatric disorders, a systematic literature review was conducted using the following databases: PubMed, Elsevier and Google Scholar. The following keywords were used when searching the materials used: "neuropsychiatric disorders", "COVID-19", "SARS-CoV-2", "NeuroCOVID", "cytokine storm" and "long COVID-19". Focusing on the characteristics of the materials and methods used, as well as the results obtained and conclusions reached in each article, 164 publications of research, meta-analysis, review and case reports were included in the study. Neuropsychiatric disorders resulting from SARS-CoV-2 virus infection are multifactorial in nature. The main elements responsible for the varied pattern of symptoms include direct and indirect central nervous system effects of the disease, individual patient conditions, psychosocial factors, severity of immune responses and severity of infection. The neuropsychiatric effects of SARS-CoV-2 infection can be divided into symptoms directly related to the neurological and psychiatric zones and mixed disorders.},
}

@article {pmid40180726,
year = {2025},
author = {Diener, HC},
title = {[Not Available].},
journal = {MMW Fortschritte der Medizin},
volume = {167},
number = {6},
pages = {30},
doi = {10.1007/s15006-025-4871-1},
pmid = {40180726},
issn = {1613-3560},
}

@article {pmid39800813,
year = {2025},
author = {Mohd Yusoff, H and Yew, SQ and Mohammed Nawi, A and Htwe, O and Mohd Tohit, N and Mohamed, Z and Muhamad Noordin, MA and Che Mohamed, N and Mohd, FH},
title = {Prevalence and symptoms of Long Covid-19 in the workplace.},
journal = {Occupational medicine (Oxford, England)},
volume = {75},
number = {1},
pages = {33-41},
doi = {10.1093/occmed/kqae128},
pmid = {39800813},
issn = {1471-8405},
support = {UKMP-S230424//National Institute of Occupational Safety and Health (NIOSH) Malaysia/ ; },
mesh = {Humans ; *COVID-19/epidemiology/complications ; Prevalence ; *Workplace/statistics & numerical data ; SARS-CoV-2 ; Fatigue/epidemiology/etiology ; Dyspnea/epidemiology/etiology ; Post-Acute COVID-19 Syndrome ; Male ; },
abstract = {BACKGROUND: The symptoms of Long coronavirus disease 2019 (Covid-19) are heterogeneous, creating uncertainty for employers regarding the diagnosis. The prevalence of Long Covid-19 in the workforce is also unknown. Furthermore, workers affected by Long Covid-19 encounter considerable difficulties in ensuring work safety and returning to their jobs due to this condition.

AIMS: This review is aimed to identify the prevalence of Long Covid-19 in the workplace and to determine the various symptoms of Long Covid-19 experienced by the workers.

METHODS: A meta-analysis was conducted to calculate the pooled estimates for the prevalence of Long Covid-19. Heterogeneity among the estimates was evaluated using the I² statistic.

RESULTS: The pooled prevalence of Long Covid-19 among workers across the 11 studies was 38% (95% CI 23-56). A total of 43 symptoms associated with Long Covid-19 were identified in the workplace, with the top five symptoms being dyspnoea at moderate activity (51%, 95% CI 39-62), mental symptoms (38%, 95% CI 6-87), dyspnoea at mild activity (35%, 95% CI 25-47), fatigue (26%, 95% CI 3-78) and effort intolerance (24%, 95% CI 15-35).

CONCLUSIONS: The review indicates a significant burden of long-lasting symptoms within the workforce. The top five reported symptoms of Long Covid-19 were dyspnoea during mild and moderate activities, mental symptoms, fatigue and effort intolerance.},
}

Humans
*COVID-19/epidemiology/complications
Prevalence
*Workplace/statistics & numerical data
SARS-CoV-2
Fatigue/epidemiology/etiology
Dyspnea/epidemiology/etiology
Post-Acute COVID-19 Syndrome
Male

@article {pmid40175252,
year = {2025},
author = {Tarasco, MC and Iacomino, N and Mantegazza, R and Cavalcante, P},
title = {COVID-19, Epstein-Barr virus reactivation and autoimmunity: Casual or causal liaisons?.},
journal = {Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jmii.2025.03.014},
pmid = {40175252},
issn = {1995-9133},
abstract = {The coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 virus infection, has been associated with a substantial risk of autoimmune disease development or exacerbation. The postulated pathophysiological mechanisms linking COVID-19 with autoimmunity include reactivation of latent Epstein-Barr virus (EBV), whose dysregulated infection in the host can trigger or promote an autoimmune response. This review summarizes recent studies highlighting a potential immunopathogenetic link between SARS-CoV-2 infection and EBV reactivation, which could underlie autoimmunity onset or worsening, as well as immune-related long COVID manifestations in COVID-19 patients. We offer our perspective on the direction that research should take to disentangle the nature (whether causal or casual) of the "COVID-19-EBV-autoimmunity" liaisons. Further advances in this research area may be crucial for designing strategies to prevent or treat EBV reactivation-related autoimmune conditions in COVID-19 patients, or patients with inflammatory co-infectious diseases, at the same time promising to improve our knowledge on the viral contribution to autoimmune phenomena.},
}

@article {pmid40152069,
year = {2025},
author = {Chen, YH and Jan, JS and Yang, CH and Yen, TL and Linh, TTD and Annavajjula, S and Satapathy, MK and Tsao, SY and Hsieh, CY},
title = {Cognitive Sequelae of COVID-19: Mechanistic Insights and Therapeutic Approaches.},
journal = {CNS neuroscience & therapeutics},
volume = {31},
number = {3},
pages = {e70348},
doi = {10.1111/cns.70348},
pmid = {40152069},
issn = {1755-5949},
support = {R113-020//Ditmanson Medical Foundation Chia-Yi Christian Hospital/ ; CGH-A10610//Cathay General Hospital/ ; },
mesh = {Humans ; *COVID-19/complications/psychology ; *Cognitive Dysfunction/etiology/therapy ; SARS-CoV-2 ; Animals ; Neuroinflammatory Diseases ; },
abstract = {BACKGROUND: The COVID-19 pandemic has left an indelible mark on the world, with mounting evidence suggesting that it not only posed acute challenges to global healthcare systems but has also unveiled a complex array of long-term consequences, particularly cognitive impairment (CI). As the persistence of post-COVID-19 neurological syndrome could evolve into the next public health crisis, it is imperative to gain a better understanding of the intricate pathophysiology of CI in COVID-19 patients and viable treatment strategies.

METHODS: This comprehensive review explores the pathophysiology and management of cognitive impairment across the phases of COVID-19, from acute infection to Long-COVID, by synthesizing findings from clinical, preclinical, and mechanistic studies to identify key contributors to CI, as well as current therapeutic approaches.

RESULTS: Key mechanisms contributing to CI include persistent neuroinflammation, cerebrovascular complications, direct neuronal injury, activation of the kynurenine pathway, and psychological distress. Both pharmacological interventions, such as anti-inflammatory therapies and agents targeting neuroinflammatory pathways, and non-pharmacological strategies, including cognitive rehabilitation, show promise in addressing these challenges. Although much of the current evidence is derived from preclinical and animal studies, these findings provide foundational insights into potential treatment approaches.

CONCLUSION: By synthesizing current knowledge, this review highlights the importance of addressing COVID-19-related cognitive impairment and offers actionable insights for mitigation and recovery as the global community continues to grapple with the pandemic's long-term impact.},
}

Humans
*COVID-19/complications/psychology
*Cognitive Dysfunction/etiology/therapy
SARS-CoV-2
Animals
Neuroinflammatory Diseases

@article {pmid40141784,
year = {2025},
author = {Caliman-Sturdza, OA and Gheorghita, R and Lobiuc, A},
title = {Neuropsychiatric Manifestations of Long COVID-19: A Narrative Review of Clinical Aspects and Therapeutic Approaches.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {3},
pages = {},
doi = {10.3390/life15030439},
pmid = {40141784},
issn = {2075-1729},
abstract = {The COVID-19 (C-19) pandemic has highlighted the significance of understanding the long-term effects of this disease on the quality of life of those infected. Long COVID-19 (L-C19) presents as persistent symptoms that continue beyond the main illness period, usually lasting weeks to years. One of the lesser-known but significant aspects of L-C19 is its impact on neuropsychiatric manifestations, which can have a profound effect on an individual's quality of life. Research shows that L-C19 creates neuropsychiatric issues such as mental fog, emotional problems, and brain disease symptoms, along with sleep changes, extreme fatigue, severe head pain, tremors with seizures, and pain in nerves. People with cognitive problems plus fatigue and mood disorders experience great difficulty handling everyday activities, personal hygiene, and social interactions. Neuropsychiatric symptoms make people withdraw from social activity and hurt relationships, thus causing feelings of loneliness. The unpredictable state of L-C19 generates heavy psychological pressure through emotional suffering, including depression and anxiety. Neuropsychiatric changes such as cognitive impairment, fatigue, and mood swings make it hard for people to work or study effectively, which decreases their output at school or work and lowers their job contentment. The purpose of this narrative review is to summarize the clinical data present in the literature regarding the neuropsychiatric manifestations of L-C19, to identify current methods of diagnosis and treatment that lead to correct management of the condition, and to highlight the impact of these manifestations on patients' quality of life.},
}

@article {pmid40141748,
year = {2025},
author = {Stasi, C},
title = {Post-COVID-19 Pandemic Sequelae in Liver Diseases.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {3},
pages = {},
doi = {10.3390/life15030403},
pmid = {40141748},
issn = {2075-1729},
abstract = {During the coronavirus disease 2019 (COVID-19) pandemic, several studies highlighted a worse prognosis for patients with alterations in liver function tests, especially those with pre-existing liver diseases. However, further studies are needed to define the long-term impact of the COVID-19 pandemic on liver diseases. Long COVID-19 encompasses a wide range of signs and symptoms, including exacerbations of pre-existing chronic conditions or new onset conditions developed after the COVID-19 acute phase. Therefore, the long-term effects of COVID-19 extensively include hepatic manifestations. The co-expression of angiotensin-converting receptor 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) has been demonstrated also in enterocytes, cholangiocytes, and hepatocytes. Studies on the post-COVID-19 sequelae have shown the presence of steatosis and necroinflammation in the liver, concomitantly with an alteration of inflammation, cytolysis and cholestasis indices. Some studies also demonstrated an increased risk for hepatobiliary pathologies, including secondary biliary cholangitis and worsening of the severity of metabolic-associated fatty liver disease (MASLD). Based on these premises, this review aims to provide an overview of the pathophysiological mechanisms contributing to COVID-19-related liver and hepatobiliary damage; explore its implications for liver inflammation and fibrosis, with a particular focus on MASLD and metabolic dysfunction-associated steatohepatitis (MASH); and analyze the short- and long-term COVID-19 sequelae. A literature search was conducted using the PubMed database for relevant studies published in English.},
}

@article {pmid40140333,
year = {2025},
author = {Wei, C and Jiang, W and Luo, M and Shao, F},
title = {BBB breakdown caused by plasma membrane pore formation.},
journal = {Trends in cell biology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tcb.2025.02.012},
pmid = {40140333},
issn = {1879-3088},
abstract = {The blood-brain barrier, recently reintroduced as the blood-brain border (BBB), is a dynamic interface between the central nervous system (CNS) and the bloodstream. Disruption of the BBB exposes the CNS to peripheral pathogens and harmful substances, causing or worsening various CNS diseases. While traditional views attribute BBB failure to tight junction disruption or increased transcytosis, recent studies highlight the critical role of gasdermin D (GSDMD) pore formation in brain endothelial cells (bECs) during BBB disruption by lipopolysaccharide (LPS) or bacterial infections. This mechanism may also be involved in neurological complications like the 'brain fog' seen in long COVID. Pore formation in bECs may represent a prevalent mechanism causing BBB leakage. Investigating membrane-permeabilizing pores or channels and their effects on BBB integrity is a growing area of research. Further exploration of molecular processes that maintain, disrupt, and restore bEC membrane integrity will advance our understanding of brain vasculature and aid in developing new therapies for BBB-related diseases.},
}

@article {pmid39902608,
year = {2025},
author = {Tcheroyan, R and Makhoul, P and Simpson, S},
title = {An updated review of pulmonary radiological features of acute and chronic COVID-19.},
journal = {Current opinion in pulmonary medicine},
volume = {31},
number = {3},
pages = {183-195},
doi = {10.1097/MCP.0000000000001152},
pmid = {39902608},
issn = {1531-6971},
mesh = {Humans ; *COVID-19/complications/diagnostic imaging ; *Tomography, X-Ray Computed/methods ; *SARS-CoV-2 ; *Lung/diagnostic imaging ; Chronic Disease ; Acute Disease ; Pulmonary Fibrosis/diagnostic imaging ; },
abstract = {PURPOSE OF REVIEW: Significant progress has been made in our understanding of the acute and chronic clinical and radiological manifestations of coronavirus-19 (COVID-19). This article provides an updated review on pulmonary COVID-19, while highlighting the key imaging features that can identify and distinguish acute COVID-19 pneumonia and its chronic sequelae from other diseases.

RECENT FINDINGS: Acute COVID-19 pneumonia typically presents with manifestations of organizing pneumonia on computed tomography (CT). In cases of severe disease, patients clinically progress to acute respiratory distress syndrome, which manifests as diffuse alveolar damage on CT. The most common chronic imaging finding is ground-glass opacities, which commonly resolves, as well as subpleural bands and reticulation. Pulmonary fibrosis is an overall rare complication of COVID-19, with characteristic features, including architectural distortion, and traction bronchiectasis.

SUMMARY: Chest CT can be a helpful adjunct tool in both diagnosing and managing acute COVID-19 pneumonia and its chronic sequelae. It can identify high-risk cases and guide decision-making, particularly in cases of severe or complicated disease. Follow-up imaging can detect persistent lung abnormalities associated with long COVID and guide appropriate management.},
}

Humans
*COVID-19/complications/diagnostic imaging
*Tomography, X-Ray Computed/methods
*SARS-CoV-2
*Lung/diagnostic imaging
Chronic Disease
Acute Disease
Pulmonary Fibrosis/diagnostic imaging

@article {pmid40137051,
year = {2025},
author = {Kukreti, S and Lu, MT and Yeh, CY and Ko, NY},
title = {Physiological Sensors Equipped in Wearable Devices for Management of Long COVID Persisting Symptoms: Scoping Review.},
journal = {Journal of medical Internet research},
volume = {27},
number = {},
pages = {e69506},
doi = {10.2196/69506},
pmid = {40137051},
issn = {1438-8871},
mesh = {Humans ; *Wearable Electronic Devices ; *COVID-19/therapy/diagnosis ; Monitoring, Physiologic/instrumentation/methods ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Wearable technology has evolved in managing COVID-19, offering early monitoring of key physiological parameters. However, the role of wearables in tracking and managing long COVID is less understood and requires further exploration of their potential.

OBJECTIVE: This review assessed the application and effectiveness of wearable devices in managing long COVID symptoms, focusing on commonly used sensors and their potential for improving long-term patient care.

METHODS: A literature search was conducted across databases including PubMed, Embase, Web of Science, and Cochrane Central, adhering to PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) reporting guidelines. The search was updated regularly throughout 2024. Abstract and full-text screening and selection were facilitated using Rayyan software developed by Qatar Computing Research Institute. Quality appraisal was conducted using the Joanna Briggs Institute (JBI) critical appraisal tool to ensure the methodological rigor of the included studies. Data were extracted on study characteristics, wearable devices, sensors used, and monitored physiological parameters, and the results were synthesized in a narrative format.

RESULTS: A total of 1186 articles were identified, and after duplicate removal and screening, 15 studies were initially included, with 11 studies meeting the criteria for final data synthesis. The included studies varied in design, ranging from observational to interventional trials, and involved sample sizes from 3 to 17,667 participants across different countries. In total, 10 different wearable devices were used to monitor long COVID symptoms, capturing key metrics such as heart rate variability, body temperature, sleep, and physical activity. Smartwatches were the most used wearable devices and fitness trackers with electrocardiography and photoplethysmography sensors were used to monitor heart rate, oxygen saturation, and respiratory rate. Of the 10 devices, 4 were Food and Drug Administration-approved, emphasizing the reliability and validation of the physiological data collected. Studies were primarily conducted in the United States and Europe, reflecting significant regional research interest in wearable technology for long COVID management.

CONCLUSIONS: This review highlights the potential of wearable technology in providing continuous and personalized monitoring for long COVID patients. Although wearables show promise in tracking persistent symptoms, further research is needed to improve usability, validate long-term efficacy, and enhance patient engagement.},
}

Humans
*Wearable Electronic Devices
*COVID-19/therapy/diagnosis
Monitoring, Physiologic/instrumentation/methods
SARS-CoV-2

@article {pmid40126325,
year = {2025},
author = {Nyasulu, PS and Tamuzi, JL and Oliveira, RKF and Oliveira, SD and Petrosillo, N and de Jesus Perez, V and Dhillon, N and Butrous, G},
title = {COVID-19 and Parasitic Co-Infection: A Hypothetical Link to Pulmonary Vascular Disease.},
journal = {Infectious disease reports},
volume = {17},
number = {2},
pages = {},
pmid = {40126325},
issn = {2036-7430},
abstract = {Background/Objectives: Before the Coronavirus disease 2019 (COVID-19) era, the global prevalence of pulmonary arterial hypertension (PAH) was between 0.4 and 1.4 per 100,000 people. The long-term effects of protracted COVID-19 associated with pulmonary vascular disease (PVD) risk factors may increase this prevalence. According to preliminary data, the exact prevalence of early estimates places the prevalence of PVD in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at 22%, although its predictive value remains unknown. PVD caused by COVID-19 co-infections is understudied and underreported, and its future impact is unclear. However, due to COVID-19/co-infection pathophysiological effects on pulmonary vascularization, PVD mortality and morbidity may impose a genuine concern-both now and in the near future. Based on reported studies, this literature review focused on the potential link between COVID-19, parasitic co-infection, and PVD. This review article also highlights hypothetical pathophysiological mechanisms between COVID-19 and parasitic co-infection that could trigger PVD. Methods: We conducted a systematic literature review (SLR) searching peer-reviewed articles, including link between COVID-19, parasitic co-infection, and PVD. Results: This review hypothesized that multiple pathways associated with pathogens such as underlying schistosomiasis, human immunodeficiency virus (HIV), pulmonary tuberculosis (PTB), pulmonary aspergillosis, Wuchereria bancrofti, Clonorchis sinensis, paracoccidioidomycosis, human herpesvirus 8, and scrub typhus coupled with acute or long COVID-19, may increase the burden of PVD and worsen its mortality in the future. Conclusions: Further experimental studies are also needed to determine pathophysiological pathways between PVD and a history of COVID-19/co-infections.},
}

@article {pmid40122540,
year = {2025},
author = {McDowell, CP and Tyner, B and Shrestha, S and McManus, L and Comaskey, F and Harrington, P and Walsh, KA and O'Neill, M and Ryan, M},
title = {Effectiveness and tolerance of exercise interventions for long COVID: a systematic review of randomised controlled trials.},
journal = {BMJ open},
volume = {15},
number = {3},
pages = {e082441},
pmid = {40122540},
issn = {2044-6055},
mesh = {Humans ; *COVID-19/prevention & control/therapy ; *Randomized Controlled Trials as Topic ; *Exercise Therapy/methods ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Quality of Life ; Treatment Outcome ; },
abstract = {OBJECTIVES: To examine the effectiveness of exercise interventions to improve long COVID symptoms and the tolerance of exercise interventions among people with long COVID.

DESIGN: Systematic review.

DATA SOURCES: Medline via EBSCOhost, Embase via OVID and CENTRAL via the Cochrane Library up to 28 February 2023.

Inclusion criteria were: (1) participants with long COVID, as defined by study authors; (2) random assignment to either an exercise intervention or a comparison group and (3) a quantitative measure of at least 1 of the 12 core long COVID outcomes. Exclusion criteria were: (1) signs or symptoms not reasonably attributable to prior SARS-CoV-2 infection; (2) pre-exposure or postexposure prophylaxis for COVID-19 or the prevention of long COVID symptoms and (3) interventions where the primary exercise component is breathing or respiratory muscle training.

DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data, and studies were narratively synthesised.

RESULTS: Eight studies were included. Follow-up periods ranged from 2 to 28 weeks (mean=8.5 weeks). Sample sizes ranged from 39 to 119 (mean=56). All studies were in adults (mean age=49.9 years) and both sexes (mean female proportion=53.9%). Four studies were at low risk of bias, two were unclear and two were high. The evidence suggests that exercise interventions lead to short-term improvements in dyspnoea, fatigue, physical function and the physical domain of quality of life among people with long COVID. Of the five studies that reported adverse events, rates were low and, when reported, mild. Of the seven studies that reported sufficient relevant information, 1 of 252 participants who received exercise discontinued the intervention due to tolerance-related issues.

CONCLUSION: Available evidence suggests that exercise interventions may be beneficial and tolerable among some people with long COVID. However, the evidence base consists of a limited number of studies with small sample sizes and short follow-up periods.},
}

Humans
*COVID-19/prevention & control/therapy
*Randomized Controlled Trials as Topic
*Exercise Therapy/methods
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Quality of Life
Treatment Outcome

@article {pmid40120171,
year = {2025},
author = {Das Sarma, J},
title = {Murine β-coronavirus spike protein: A major determinant of neuropathogenic properties.},
journal = {Virology},
volume = {606},
number = {},
pages = {110499},
doi = {10.1016/j.virol.2025.110499},
pmid = {40120171},
issn = {1096-0341},
abstract = {Coronaviruses have emerged as a significant challenge to human health. While earlier outbreaks of coronaviruses such as SARS-CoV and MERS-CoV posed serious threats, the recent SARS-CoV-2 pandemic has heightened interest in coronavirus research due to its pulmonary pathology, in addition to its neurological manifestations. In addition, the patients who have recovered from SARS-CoV-2 infection show long-term symptoms such as anosmia, brain fog and long COVID. A major hurdle in studying these viruses is the limited availability of specialized research facilities, emphasizing the need for prototype virus-based models to investigate the pathophysiology. The mouse hepatitis virus (MHV), a member of the β-coronavirus family, serves as an excellent model to unravel the mechanisms underlying virus-induced pathogenesis. This review highlights two decades of research efforts aimed at understanding the pathophysiological mechanism of coronavirus-induced diseases, focusing on the development of targeted recombinant strains to identify the minimal essential motif of the spike protein responsible for fusogenicity and neuropathogenicity. By synthesizing findings from these studies, the review identifies the most promising therapeutic targets against coronaviruses, paving the way for the development of pan-coronavirus antivirals.},
}

@article {pmid40094929,
year = {2025},
author = {Patrascu, R and Dumitru, CS},
title = {Advances in Understanding Inflammation and Tissue Damage: Markers of Persistent Sequelae in COVID-19 Patients.},
journal = {Journal of clinical medicine},
volume = {14},
number = {5},
pages = {},
pmid = {40094929},
issn = {2077-0383},
abstract = {This review explores the crucial role of established and emerging biomarkers in the diagnosis, management, and understanding of post-COVID-19 conditions. With COVID-19 affecting multiple organ systems, biomarkers have been instrumental in identifying ongoing inflammation and tissue damage, facilitating early diagnosis and prognostication. Specifically, markers like C-reactive protein (CRP), interleukin-6 (IL-6), and novel entities such as soluble urokinase plasminogen activator receptor (suPAR) and neutrophil extracellular traps (NETs) provide insights into the pathophysiological mechanisms and predict long-term outcomes. This review highlights the integration of these biomarkers into clinical workflows and their implications for personalized medicine, emphasizing their potential in guiding therapeutic interventions and monitoring recovery. Future directions suggest a focus on longitudinal studies to explore biomarker trajectories and their interaction with therapeutic outcomes, aiming to enhance the management of post-COVID-19 conditions and refine public health strategies.},
}

@article {pmid40094893,
year = {2025},
author = {Mara, G and Nini, G and Cotoraci, C},
title = {Impact of Pulmonary Comorbidities on COVID-19: Acute and Long-Term Evaluations.},
journal = {Journal of clinical medicine},
volume = {14},
number = {5},
pages = {},
pmid = {40094893},
issn = {2077-0383},
abstract = {Background/Objectives: Pulmonary comorbidities, such as chronic obstructive pulmonary disease (COPD), asthma, and interstitial lung diseases (ILDs), have emerged as critical factors influencing the severity and outcomes of COVID-19. This review aims to evaluate the interplay between these comorbidities and COVID-19, both during the acute phase and in long-term recovery, focusing on their impact on clinical management and outcomes. Methods: This systematic review examined studies sourced from major medical databases, including PubMed and Scopus, using keywords such as "COVID-19", "pulmonary comorbidities", "long COVID", and "respiratory sequelae". Peer-reviewed articles published from January 2020 to the present were included, with data extracted to evaluate both the acute and long-term effects of these comorbidities on COVID-19 patients. Results: Patients with COPD demonstrated significantly higher risks of severe COVID-19, including increased hospitalization and mortality. Asthma, while less consistently associated with severe outcomes, showed a variable risk based on disease control. ILDs were strongly correlated with poor outcomes, including higher rates of respiratory failure and mortality. Long-term complications, such as persistent dyspnea, impaired lung function, and structural changes like fibrosis, were prevalent in patients recovering from moderate to severe COVID-19. These complications adversely affected quality of life and increased healthcare dependency. Conclusions: Pulmonary comorbidities amplify both the acute severity and long-term respiratory consequences of COVID-19. Effective management necessitates tailored strategies addressing both phases, integrating rehabilitation and continuous monitoring to mitigate chronic impairments. Future research should prioritize understanding the mechanisms behind these interactions to inform public health interventions and improve patient outcomes.},
}

@article {pmid40093756,
year = {2025},
author = {Sanger, BD and Alarachi, A and McNeely, HE and McKinnon, MC and McCabe, RE},
title = {Brain Fog and Cognitive Dysfunction in Posttraumatic Stress Disorder: An Evidence-Based Review.},
journal = {Psychology research and behavior management},
volume = {18},
number = {},
pages = {589-606},
pmid = {40093756},
issn = {1179-1578},
abstract = {The term "brain fog" has long been used both colloquially and in research literature in reference to various neurocognitive phenomenon that detract from cognitive efficiency. We define "brain fog" as the subjective experience of cognitive difficulties, in keeping with the most common colloquial and research use of the term. While a recent increase in use of this term has largely been in the context of the post-coronavirus-19 condition known as long COVID, "brain fog" has also been discussed in relation to several other conditions including mental health conditions such as post-traumatic stress disorder (PTSD). PTSD is associated with both subjective cognitive complaints and relative deficits on cognitive testing, but the phenomenology and mechanisms contributing to "brain fog" in this population are poorly understood. PTSD psychopathology across cognitive, affective and physiological symptom domains have been tied to "brain fog". Furthermore, dissociative symptoms common in PTSD also contribute to the experience of "brain fog". Comorbid physical and mental health conditions may also increase the risk of experiencing "brain fog" among individuals with PTSD. Considerations for the assessment of "brain fog" in PTSD as part of psychodiagnostic assessment are discussed. While standard psychological intervention for PTSD is associated with a reduction in subjective cognitive deficits, other cognitive interventions may be valuable when "brain fog" persists following PTSD remission or when "brain fog" interferes with treatment. Limitations of current research on "brain fog" in PTSD include a lack of consistent definition and operationalization of "brain fog" in the literature, as well as limited tools for measurement. Future research should address these limitations, as well as further evaluate the use of cognitive remediation as an intervention for "brain fog".},
}

@article {pmid40084919,
year = {2025},
author = {Baalbaki, N and Slob, EMA and Kazer, SW and I Abdel-Aziz, M and Bogaard, HJ and Golebski, K and Maitland-van der Zee, AH},
title = {The Omics Landscape of Long COVID-A Comprehensive Systematic Review to Advance Biomarker, Target and Drug Discovery.},
journal = {Allergy},
volume = {},
number = {},
pages = {},
doi = {10.1111/all.16526},
pmid = {40084919},
issn = {1398-9995},
support = {//Health~Holland/ ; },
abstract = {An estimated 10% of coronavirus disease (COVID-19) survivors suffer from persisting symptoms referred to as long COVID (LC), a condition for which approved treatment options are still lacking. This systematic review (PROSPERO: CRD42024499281) aimed to explore the pathophysiological mechanisms underlying LC and potential treatable traits across symptom-based phenotypes. We included studies with primary data, written in English, focusing on omics analyses of human samples from LC patients with persistent symptoms of at least 3 months. Our search in PubMed and Embase, conducted on January 8, 2024, identified 642 studies, of which 29 met the inclusion criteria after full-text assessment. The risk of bias was evaluated using the Joanna Briggs Institute appraisal tool. The synthesis of omics data, including genomics, transcriptomics, proteomics, metabolomics, and metagenomics, revealed common findings associated with fatigue, cardiovascular, pulmonary, neurological, and gastrointestinal phenotypes. Key findings included mitochondrial dysfunction, dysregulated microRNAs associated with pulmonary dysfunction, tissue impairment, blood-brain barrier disruption, coagulopathy, vascular dysfunction, microbiome disturbances, microbial-derived metabolite production and persistent inflammation. Limitations include cross-study heterogeneity and variability in sampling methods. Our review emphasizes the complexity of LC and the need for further longitudinal omics-integrated studies to advance the development of biomarkers and targeted treatments.},
}

@article {pmid40083165,
year = {2025},
author = {Li, S and Dai, B and Hou, Y and Zhang, L and Liu, J and Hou, H and Song, D and Wang, S and Li, X and Zhao, H and Wang, W and Kang, J and Tan, W},
title = {Effect of pulmonary rehabilitation for patients with long COVID-19: a systematic review and meta-analysis of randomized controlled trials.},
journal = {Therapeutic advances in respiratory disease},
volume = {19},
number = {},
pages = {17534666251323482},
pmid = {40083165},
issn = {1753-4666},
mesh = {Humans ; *COVID-19/rehabilitation/physiopathology ; *Randomized Controlled Trials as Topic ; *Quality of Life ; Post-Acute COVID-19 Syndrome ; Lung/physiopathology ; Treatment Outcome ; Exercise Tolerance ; Respiratory Function Tests ; Recovery of Function ; Male ; Middle Aged ; Female ; },
abstract = {BACKGROUND: Pulmonary rehabilitation (PR) has demonstrated efficacy in managing long COVID-19, underscoring the need to refine and tailor PR strategies for optimal patient outcomes.

OBJECTIVES: To evaluate the impact of PR on patients with long COVID-19 and to compare the efficacy of different types and durations of PR interventions.

DESIGN: Systematic review and meta-analysis.

DATA SOURCES AND METHODS: We systematically searched randomized controlled trials (RCTs) of the effectiveness of PR in long COVID-19 patients published before April 2024. The primary outcomes were physical capacity assessed by the 6-minute walking test (6MWT), lung function measured by forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC), health-related quality of life (HRQoL), and fatigue. Secondary outcomes were thirty-second sit-to-stand test (30STST), handgrip strength tests, maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), dyspnea, depression, anxiety, perceived effort, and adverse events.

RESULTS: A total of 37 studies with 3363 patients were included. Compared to controls, PR improved physical capacity (6MWT, 30STST, handgrip), lung function (FEV1, FVC, MIP, MEP), HRQoL, fatigue, dyspnea, and anxiety but did not reach statistical significance for depression. Subgroup analyses of PR duration indicated that programs of ⩽4 weeks improved 6MWT; those between 4 and 8 weeks significantly improved 6MWT, lung function (FEV1, FVC), HRQoL, and reduced fatigue; and programs over 8 weeks improved HRQoL and reduced fatigue. Exercise type analysis revealed that breathing exercises improved 6MWT, lung function (FEV1, FVC), and HRQoL; multicomponent exercises enhanced 6MWT performance and reduced fatigue; the combination of both types improved 6MWT, FEV1 (L), FVC (%pred), HRQoL, and reduced fatigue.

CONCLUSION: PR improves physical capacity, lung function, and quality of life and alleviates dyspnea, fatigue, and anxiety in long COVID-19 patients. A 4- to 8-week PR program and a combination of both breath exercises and multicomponent training is most effective for managing long-term COVID-19 syndromes.

TRIAL REGISTRATION: PROSPERO ID: CRD42024455008.},
}

Humans
*COVID-19/rehabilitation/physiopathology
*Randomized Controlled Trials as Topic
*Quality of Life
Post-Acute COVID-19 Syndrome
Lung/physiopathology
Treatment Outcome
Exercise Tolerance
Respiratory Function Tests
Recovery of Function
Male
Middle Aged
Female

@article {pmid40080079,
year = {2025},
author = {Li, D and Long, F and Zhang, S and Yu, B},
title = {Mechanisms and treatment progress of neurological diseases of COVID and L-C19 in children.},
journal = {Physiology international},
volume = {},
number = {},
pages = {},
doi = {10.1556/2060.2025.00484},
pmid = {40080079},
issn = {2498-602X},
abstract = {OBJECTIVE: Although SARS-CoV-2 primarily targets the respiratory system, there is evidence that it can also infect the central nervous system, especially in children, leading to neurological symptoms and long-term consequences. It is imperative to summarize the possible mechanisms, main symptoms, and treatments of neurological symptoms of COVID-19 in children.

METHODS: We performed a literature search using the PubMed online database to find studies investigating the mechanisms of COVID-19 infection of the central nervous system and therapies for COVID-19 neurological symptoms in children.

RESULTS: The main mechanisms of action of SARS-CoV-2 virus on the nervous system are direct invasion, systemic inflammation and molecular mimicry. Although the incidence of adverse reactions to intravenous IgG therapy (IVIG) varies greatly and the contraindications are not yet clear, IVIG has been shown to be clearly effective for the neurological symptoms of COVID-19 in children.

CONCLUSION: However, due to insufficient data, more clinical studies are still needed to confirm its safety and efficacy, further improve the treatment plan, and determine the appropriate dosage to better serve clinical practice.

SIGNIFICANCE: The specific regimen of IVIG treatment for COVID-19 in children was explored, which further improved the understanding of COVID-19 and L-C19 neurological diseases in children.},
}

@article {pmid40079963,
year = {2025},
author = {Rudolph, AE and Al Akoury, N and Bogdanenko, N and Markus, K and Whittle, I and Wright, O and Haridy, H and Spinardi, JR and McLaughlin, JM and Kyaw, MH},
title = {Factors affecting the impact of COVID-19 vaccination on post COVID-19 conditions among adults: A systematic literature review.},
journal = {Human vaccines & immunotherapeutics},
volume = {21},
number = {1},
pages = {2474772},
pmid = {40079963},
issn = {2164-554X},
mesh = {Humans ; *COVID-19/prevention & control/immunology ; *COVID-19 Vaccines/administration & dosage/immunology ; *Vaccination/statistics & numerical data ; *SARS-CoV-2/immunology ; *Vaccine Efficacy ; Adult ; },
abstract = {This systematic literature review summarizes the evidence across 56 publications and pre-prints (January 2020-July 2023) with low-risk of bias based on JBI critical appraisal, that report adjusted estimates for the relationship between COVID-19 vaccination and Post-COVID-19 Condition (PCC) by timing of vaccination relative to infection or PCC-onset. Comparisons of adjusted vaccine effectiveness (aVE) against ≥1 PCC (vs. unvaccinated) across study characteristics known to impact PCC burden or VE against other COVID-19 endpoints were possible for 31 studies where vaccination preceded infection. Seventy-seven percent of pre-infection aVE estimates were statistically significant (range: 7%-95%). Statistically significant pre-infection aVE estimates were slightly higher for mRNA (range: 14%-84%) than non-mRNA vaccines (range: 16%-38%) and aVE ranges before and during Omicron overlapped. Our findings suggest that COVID-19 vaccination before SARS-CoV-2 infection reduces the risk of PCC regardless of vaccine type, number of doses received, PCC definition, predominant variant, and severity of acute infections included.},
}

Humans
*COVID-19/prevention & control/immunology
*COVID-19 Vaccines/administration & dosage/immunology
*Vaccination/statistics & numerical data
*SARS-CoV-2/immunology
*Vaccine Efficacy
Adult

@article {pmid40076527,
year = {2025},
author = {Sun, DS and Lien, TS and Chang, HH},
title = {Virus-Induced Pathogenic Antibodies: Lessons from Long COVID and Dengue Hemorrhage Fever.},
journal = {International journal of molecular sciences},
volume = {26},
number = {5},
pages = {},
pmid = {40076527},
issn = {1422-0067},
support = {104-2320-B-320 -009 -MY3, 107-2311-B-320-002-MY3, 111-2320-B320-006-MY3, 112-2320-B-320-007//National Science and Technology Council, Taiwan/ ; TCMMP104-06, TCMMP108-04, TCMMP 111-01, TCAS111-02, TCAS-112-02, TCAS113-04, TCRD112-033, TCRD113-041//Tzu-Chi Medical Foundation/ ; },
mesh = {Humans ; *Severe Dengue/immunology/virology ; *COVID-19/immunology/virology ; *Dengue Virus/immunology ; *SARS-CoV-2/immunology ; *Antibodies, Viral/immunology ; *Antibody-Dependent Enhancement/immunology ; Autoantibodies/immunology ; Post-Acute COVID-19 Syndrome ; Animals ; },
abstract = {Virus-induced antibodies represent a dual-edged sword in the immune response to viral infections. While antibodies are critical for neutralizing pathogens, some can paradoxically exacerbate disease severity through mechanisms such as antibody-dependent enhancement (ADE), autoantibody, and prolonged inflammation. Long coronavirus disease (COVID) and dengue hemorrhagic fever (DHF) exemplify conditions where pathogenic antibodies play a pivotal role in disease progression. Long COVID is associated with persistent immune dysregulation and autoantibody production, leading to chronic symptoms and tissue damage. In DHF, pre-existing antibodies against dengue virus contribute to ADE, amplifying viral replication, immune activation, and vascular permeability. This review explores the mechanisms underlying these pathogenic antibody responses, highlighting the shared pathways of immune dysregulation and comparing the distinct features of both conditions. By examining these studies, we identify key lessons for therapeutic strategies, vaccine design, and future research aimed at mitigating the severe outcomes of viral infections.},
}

Humans
*Severe Dengue/immunology/virology
*COVID-19/immunology/virology
*Dengue Virus/immunology
*SARS-CoV-2/immunology
*Antibodies, Viral/immunology
*Antibody-Dependent Enhancement/immunology
Autoantibodies/immunology
Post-Acute COVID-19 Syndrome
Animals

@article {pmid40075382,
year = {2025},
author = {Weigel, B and Inderyas, M and Eaton-Fitch, N and Thapaliya, K and Marshall-Gradisnik, S},
title = {Health-related quality of life in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post COVID-19 Condition: a systematic review.},
journal = {Journal of translational medicine},
volume = {23},
number = {1},
pages = {318},
pmid = {40075382},
issn = {1479-5876},
support = {489798//Stafford Fox Medical Research Foundation/ ; 1199502//National Health and Medical Research Council/ ; 47107//Mason Foundation/ ; 49979//McCusker Charitable Foundation/ ; 4676//Buxton Foundation/ ; 4879//Henty Community/ ; 4579//Blake Beckett Trust Foundation/ ; 4570//Alison Hunter Memorial Foundation/ ; 4575//Change for ME Charity/ ; },
mesh = {Humans ; *Fatigue Syndrome, Chronic ; *Quality of Life ; *COVID-19/psychology/epidemiology ; SARS-CoV-2 ; Female ; },
abstract = {PURPOSE: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Post COVID-19 Condition (PCC) are debilitating, chronic multi-systemic illnesses that require multidisciplinary care. However, people with ME/CFS (pwME/CFS) and people with PCC (pwPCC) are often precluded from accessing necessary disability and social support services. These unmet care needs exacerbate the existing illness burdens experienced by pwME/CFS and pwPCC. To deliver appropriate care and optimise health outcomes for pwME/CFS and pwPCC, the development of evidence-based healthcare policies that recognise the disabling impacts of these illnesses must be prioritised. This systematic review summarises the health-related quality of life (HRQoL) of pwME/CFS and pwPCC when compared with healthy controls (HCs) to elucidate the impacts of these illnesses and guide healthcare policy reform.

METHODS: CINAHL, Embase, MEDLINE, PubMed, PsycINFO and the Web of Science Core Collection were systematically searched from 1st January 2003 to 23rd July 2024. Eligible publications included observational studies capturing quantitative HRQoL data among pwME/CFS or pwPCC when compared with HCs. The use of validated patient-reported outcome measures (PROMs) was mandatory. Eligible studies were also required to employ the most stringent diagnostic criteria currently available, including the Canadian Consensus Criteria or International Consensus Criteria for ME/CFS and the World Health Organization case definition for PCC (PROSPERO ID: CRD42024501309).

RESULTS: This review captured 16 studies, including eight studies among pwME/CFS, seven studies among pwPCC and one study among both illness cohorts. Most participants were female and middle-aged. All pwPCC had experienced prolonged COVID-19 symptoms for at least three months. When compared with HCs, all HRQoL domains were significantly impaired among pwME/CFS and pwPCC. Both illnesses had a salient impact on physical health, including pain and ability to perform daily and work activities. While direct comparisons between pwME/CFS and pwPCC were limited by inconsistencies in the PROMs employed, comparable impact trends across HRQoL domain scores were observed.

CONCLUSION: ME/CFS and PCC have similar, profound impacts on HRQoL that warrant access to multidisciplinary disability and social support services. Future research must harmonise HRQoL data collection and prioritise longitudinal investigations among pwME/CFS and pwPCC to characterise PCC subgroups (including those fulfilling ME/CFS criteria) and predictors of prognosis.},
}

Humans
*Fatigue Syndrome, Chronic
*Quality of Life
*COVID-19/psychology/epidemiology
SARS-CoV-2
Female

@article {pmid40074704,
year = {2025},
author = {Schwartz, J and Capistrano, K and Hussein, H and Hafedi, A and Shukla, D and Naqvi, A},
title = {Oral SARS-CoV-2 Infection and Risk for Long Covid.},
journal = {Reviews in medical virology},
volume = {35},
number = {2},
pages = {e70029},
pmid = {40074704},
issn = {1099-1654},
support = {R56DE033249//NIDCR/NIH/ ; R01EY033622//NEI/NIH/ ; R01DE027980//NIDCR/NIH/ ; R01 DE027980/DE/NIDCR NIH HHS/United States ; R56 DE033249/DE/NIDCR NIH HHS/United States ; /NH/NIH HHS/United States ; R01 EY033622/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/immunology/virology ; *SARS-CoV-2/immunology/physiology ; Post-Acute COVID-19 Syndrome ; Microbiota ; Dysbiosis ; Mouth Mucosa/virology/immunology/microbiology ; Virus Internalization ; Mouth Diseases/virology/microbiology/immunology ; Angiotensin-Converting Enzyme 2/metabolism ; },
abstract = {SARS-CoV-2 is an oral pathogen that infects and replicates in mucosal and salivary epithelial cells, contributing to oral post-acute sequelae COVID-19 (PASC) and other oral and non-oral pathologies. While pre-existing inflammatory oral diseases provides a conducive environment for the virus, acute infection and persistence of SARS-CoV-2 can also results in oral microbiome dysbiosis that further worsens poor oral mucosal health. Indeed, oral PASC includes periodontal diseases, dysgeusia, xerostomia, pharyngitis, oral keratoses, and pulpitis suggesting significant bacterial contributions to SARS-CoV-2 and oral tissue tropism. Dysbiotic microbiome-induced inflammation can promote viral entry via angiotensin-converting enzyme receptor-2 (ACE2), serine transmembrane TMPRSS2 and possibly other non-canonical pathways. Additionally, metabolites derived from a dysbiotic microbiome can alter the physiological and biochemical pathways related to the metabolism of lipids, carbohydrates, and amino acids. This may promote a pro-inflammatory microenvironment, leading to immune exhaustion, loss of tolerance, and susceptibility to a variety of oral pathogens, causing acute and later chronic inflammation. Microbial release of mimics of host metallopeptidases related to furin, ADAM17 (A disintegrin and metalloproteinase 17), and glycoprotein metabolites can further aid viral attachment to T cell immunoglobulin-like (TIMs), enhancing viral entry while simultaneously depressing oral mucosal immune resistance and clearance. Membrane reorganization characterised by neuroproteins, such as neuropilins, also functionally assists with SARS-CoV-2 entry and extends the pathogenesis of PASC from the oral cavity to the brain, gut, or other non-oral tissues. Thus, poor oral health, characterised by disrupted oral microbiomes can promote viral tropism, weaken antiviral resistance, and heightens susceptibility to SARS-CoV-2 infection. This immune dysfunction also increases the risk of additional viral infections, exacerbating oral conditions like periodontal and endodontic diseases. These persistent oral health issues can contribute to systemic inflammation, creating bidirectional effects between oral and non-oral tissues, potentially leading to Post-Acute Sequelae of COVID-19 (PASC).},
}

Humans
*COVID-19/immunology/virology
*SARS-CoV-2/immunology/physiology
Post-Acute COVID-19 Syndrome
Microbiota
Dysbiosis
Mouth Mucosa/virology/immunology/microbiology
Virus Internalization
Mouth Diseases/virology/microbiology/immunology
Angiotensin-Converting Enzyme 2/metabolism

@article {pmid40073162,
year = {2025},
author = {Taher, MK and Salzman, T and Banal, A and Morissette, K and Domingo, FR and Cheung, AM and Cooper, CL and Boland, L and Zuckermann, AM and Mullah, MA and Laprise, C and Colonna, R and Hashi, A and Rahman, P and Collins, E and Corrin, T and Waddell, LA and Pagaduan, JE and Ahmad, R and Jaramillo Garcia, AP},
title = {Global prevalence of post-COVID-19 condition: a systematic review and meta-analysis of prospective evidence.},
journal = {Health promotion and chronic disease prevention in Canada : research, policy and practice},
volume = {45},
number = {3},
pages = {112-138},
doi = {10.24095/hpcdp.45.3.02},
pmid = {40073162},
issn = {2368-738X},
mesh = {Humans ; *COVID-19/epidemiology ; Prevalence ; Prospective Studies ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Global Health/statistics & numerical data ; Survivors/statistics & numerical data ; },
abstract = {INTRODUCTION: We investigated the prevalence of new or persistent manifestations experienced by COVID-19 survivors at 3 or more months after their initial infection, collectively known as post-COVID-19 condition (PCC).

METHODS: We searched four electronic databases and major grey literature resources for prospective studies, systematic reviews, authoritative reports and population surveys. A random-effects meta-analysis pooled the prevalence data of 22 symptoms and outcomes. The GRADE approach was used to assess the certainty of evidence. PROSPERO CRD42021231476.

RESULTS: Of 20 731 identified references, 194 met our inclusion criteria. These studies followed 483 531 individuals with confirmed COVID-19 diagnosis over periods of up to 2 years. Most focused on adults, nearly two-thirds were conducted in Europe and 63% were of high or moderate quality. The supplementary search identified 17 systematic reviews, five authoritative reports and four population surveys that reported on PCC prevalence. Our analysis revealed that more than half of COVID-19 survivors experienced one or more symptoms more than a year after their initial infection. The most common symptoms were fatiguedyspneamemory, sleep or concentration disturbances; depressionand pain. Limitation in returning to work was the most common outcome. Prevalence tended to be higher among females, individuals hospitalized during their initial infection and those who experienced severe COVID-19 illness.

CONCLUSION: PCC presents a significant health burden, affecting some groups more than others. This information will help inform health care system policies and services for people living with PCC and those caring for them.},
}

Humans
*COVID-19/epidemiology
Prevalence
Prospective Studies
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Global Health/statistics & numerical data
Survivors/statistics & numerical data

@article {pmid40071259,
year = {2025},
author = {Velati, D and Puoti, M},
title = {Real-world experience with therapies for SARS-CoV-2: Lessons from the Italian COVID-19 studies.},
journal = {Le infezioni in medicina},
volume = {33},
number = {1},
pages = {64-75},
pmid = {40071259},
issn = {2532-8689},
abstract = {The therapeutic armamentarium that has been made available from the beginning of the emergency phase of the COVID-19 pandemic to date is briefly reviewed, and an overview of the real-world clinical evidence published by the Italian medical and scientific community during the last three years is presented herein. Prior to the introduction of a vaccine for SARS-CoV-2, several treatment options were implemented from the onset given the evidence that a "cytokine storm" was present during infection with SARS-CoV-2. However, with the exception of tocilizumab, baricitinib and perhaps anakinra, most studies with anti-cytokine biological agents in patients with severe COVID-19 did not show any significant clinical improvement or decrease in mortality at day 28. The same is true of several repurposed drugs including ivermectin, lactoferrin, interferon ß-1a, lopinavir/ritonavir alone or combined with hydroxychloroquine, and darunavir/ cobicistat, which did not show any benefits in clinical status or mortality. Treatment with neutralizing monoclonal antibodies (mAbs) for COVID-19 is changing continually with the evolution of new viral variants. In Italy, current indications for treatment of COVID-19 outpatients underline that the use of specific mAbs may vary over time depending on the prevalent SARS-CoV-2 variant and the sensitivity to the different mAbs available. Three antiviral drugs against SARS-CoV-2 were studied extensively and initially available in Italy: remdesivir, molnupiravir, and nirmaltrelvir/ritonavir, but at present the latter is the only oral antiviral for SARS-CoV-2 available in Italy. Several real-world studies for the use of nirmatrelvir/ ritonavir in the Italian population have been published. Among the current unmet needs, a clear and universal definition for long COVID along with treatments and prevention are still lacking as is clarity of the pathogenetic mechanisms responsible for it.},
}

@article {pmid40071133,
year = {2025},
author = {Monsalve, DM and Acosta-Ampudia, Y and Acosta, NG and Celis-Andrade, M and Şahin, A and Yilmaz, AM and Shoenfeld, Y and Ramírez-Santana, C},
title = {NETosis: A key player in autoimmunity, COVID-19, and long COVID.},
journal = {Journal of translational autoimmunity},
volume = {10},
number = {},
pages = {100280},
pmid = {40071133},
issn = {2589-9090},
abstract = {NETosis, the process through which neutrophils release neutrophil extracellular traps (NETs), has emerged as a crucial mechanism in host defense and the pathogenesis of autoimmune responses. During the SARS-CoV-2 pandemic, this process received significant attention due to the central role of neutrophil recruitment and activation in infection control. However, elevated neutrophil levels and dysregulated NET formation have been linked to coagulopathy and endothelial damage, correlating with disease severity and poor prognosis in COVID-19. Moreover, it is known that SARS-CoV-2 can induce persistent low-grade systemic inflammation, known as long COVID, although the underlying causes remain unclear. It has been increasingly acknowledged that excessive NETosis and NET generation contribute to further pathophysiological abnormalities following SARS-CoV-2 infection. This review provides an updated overview of the role of NETosis in autoimmune diseases, but also the relationship between COVID-19 and long COVID with autoimmunity (e.g., latent and overt autoimmunity, molecular mimicry, epitope spreading) and NETosis (e.g., immune responses, NET markers). Finally, we discuss potential therapeutic strategies targeting dysregulated NETosis to mitigate the severe complications of COVID-19 and long COVID.},
}

@article {pmid40068974,
year = {2025},
author = {Emery, I and Rosen, C},
title = {Adult Long Coronavirus Disease 2019: Definition, Prevalence Pathophysiology, and Clinical Manifestations.},
journal = {Infectious disease clinics of North America},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.idc.2025.02.007},
pmid = {40068974},
issn = {1557-9824},
abstract = {Long coronavirus disease 2019 (COVID-19) is a multisystem disorder with variable manifestations and duration. One in 10 people with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection will develop some manifestation of long COVID-19. Currently, there is no one single etiologic factor for the symptoms and signs of long COVID-19 beyond exposure to the SARS-CoV-2 virus. There are multiple theories about the pathophysiology ranging from viral persistence, reactivation, autoimmunity, and immune depletion. Certain risk factors have been identified including female sex, severe acute/hospitalized COVID-19, previous infections with SARS-CoV-2, and absence of vaccinations.},
}

@article {pmid40062993,
year = {2025},
author = {Cavarelli, M},
title = {Ghosts of the virus : unmasking the persistent threat of SARS-CoV-2 in Long COVID.},
journal = {Virologie (Montrouge, France)},
volume = {29},
number = {1},
pages = {57-68},
doi = {10.1684/vir.2025.1074},
pmid = {40062993},
issn = {1267-8694},
mesh = {Humans ; *COVID-19/immunology/virology ; *SARS-CoV-2/physiology/immunology ; *Post-Acute COVID-19 Syndrome ; Inflammation/virology ; Gastrointestinal Tract/virology ; },
abstract = {Long COVID has emerged as a debilitating condition, severely impacting the daily functioning and quality of life of affected individuals. The pathogenesis of Long COVID is complex and multifactorial, involving immune dysregulation, persistent inflammation, and potential reactivation of other pathogens. A key driver of Long COVID is the potential persistence of SARS-CoV-2 in various tissues beyond the respiratory tract, leading to the formation of viral reservoirs that contribute to ongoing symptoms, several months after initial infection. These reservoirs have been suggested in the gastrointestinal tract, central nervous system, cardiovascular system, and other tissues, often persisting months after the initial infection. Additionally, viral RNA and proteins in these tissues are associated with chronic inflammation and immune system disruptions, which are primary contributors to Long COVID symptoms. This article explores the mechanisms and consequences of SARS-CoV-2 persistence in respiratory and non-respiratory tissues, highlighting its impact on the immune system and underscoring critical areas for future research to improve outcomes for individuals suffering from Long COVID.},
}

Humans
*COVID-19/immunology/virology
*SARS-CoV-2/physiology/immunology
*Post-Acute COVID-19 Syndrome
Inflammation/virology
Gastrointestinal Tract/virology

@article {pmid40062991,
year = {2025},
author = {Cavarelli, M},
title = {[Ghosts of the virus : unmasking the persistent threat of SARS-CoV-2 in Long COVID].},
journal = {Virologie (Montrouge, France)},
volume = {29},
number = {1},
pages = {41-53},
doi = {10.1684/vir.2025.1073},
pmid = {40062991},
issn = {1267-8694},
mesh = {Humans ; *COVID-19/immunology/virology ; *SARS-CoV-2/physiology ; *Post-Acute COVID-19 Syndrome ; Inflammation/virology ; },
abstract = {Long COVID has emerged as a debilitating condition, severely impacting the daily functioning and quality of life of affected individuals. The pathogenesis of Long COVID is complex and multifactorial, involving immune dysregulation, persistent inflammation, and potential reactivation of other pathogens. A key driver of Long COVID is the potential persistence of SARS-CoV-2 in various tissues beyond the respiratory tract, leading to the formation of viral reservoirs that contribute to ongoing symptoms, several months after initial infection. These reservoirs have been suggested in the gastrointestinal tract, central nervous system, cardiovascular system, and other tissues, often persisting months after the initial infection. Additionally, viral RNA and proteins in these tissues are associated with chronic inflammation and immune system disruptions, which are primary contributors to Long COVID symptoms. This article explores the mechanisms and consequences of SARS-CoV-2 persistence in respiratory and non-respiratory tissues, highlighting its impact on the immune system and underscoring critical areas for future research to improve outcomes for individuals suffering from Long COVID.},
}

Humans
*COVID-19/immunology/virology
*SARS-CoV-2/physiology
*Post-Acute COVID-19 Syndrome
Inflammation/virology

@article {pmid40051665,
year = {2025},
author = {Sakellaropoulos, SG and Sakellaropoulos, PG and Steinberg, BS and Rogers, C and Ismael, O and Scholl, EW and Mohammed, M and Mitsis, A and Patrinou, NG},
title = {Five Years of Long COVID Syndrome: An Updated Review on Cardiometabolic and Psychiatric Aspects.},
journal = {Cardiology research},
volume = {16},
number = {2},
pages = {81-85},
pmid = {40051665},
issn = {1923-2829},
abstract = {Five years after the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, there is still a significant number of people who have survived COVID-19 but never fully recovered from the disease. They go through an odyssey of doctor visits and a multitude of diagnostic tests, which ultimately do not provide concrete correlations and answers to the question of how exactly long COVID (LC) affects both physical and mental health, and performance. Often, not even highly technical and highly specialized methods, such as cardiac magnetic resonance imaging (MRI), can provide further explanation. Various research efforts continue to investigate the causes, effects and possible treatments of LC, particularly its impact on cognition and mental health. Patients with LC may experience persistent symptoms, but new symptoms also occur. Based on available studies, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) does not only affect the pulmonary system, but nearly every major system and organ, from the brain and heart to the kidneys and immune system. What mechanisms could explain the persistent symptoms of LC and the inadequate recovery? How valuable is an early internal and neurological examination, particularly in the context of psychotherapy? In this review, we examined which factors could contribute to the persistence of LC symptoms and to what extent mitochondrial impairment by LC can explain the symptoms of LC.},
}

@article {pmid40046430,
year = {2024},
author = {Talkington, GM and Kolluru, P and Gressett, TE and Ismael, S and Meenakshi, U and Acquarone, M and Solch-Ottaiano, RJ and White, A and Ouvrier, B and Paré, K and Parker, N and Watters, A and Siddeeque, N and Sullivan, B and Ganguli, N and Calero-Hernandez, V and Hall, G and Longo, M and Bix, GJ},
title = {Neurological sequelae of long COVID: a comprehensive review of diagnostic imaging, underlying mechanisms, and potential therapeutics.},
journal = {Frontiers in neurology},
volume = {15},
number = {},
pages = {1465787},
pmid = {40046430},
issn = {1664-2295},
support = {TL1 TR003106/TR/NCATS NIH HHS/United States ; },
abstract = {One lingering effect of the COVID-19 pandemic created by SARS-CoV-2 is the emergence of Long COVID (LC), characterized by enduring neurological sequelae affecting a significant portion of survivors. This review provides a thorough analysis of these neurological disruptions with respect to cognitive dysfunction, which broadly manifest as chronic insomnia, fatigue, mood dysregulation, and cognitive impairments with respect to cognitive dysfunction. Furthermore, we characterize how diagnostic tools such as PET, MRI, EEG, and ultrasonography provide critical insight into subtle neurological anomalies that may mechanistically explain the Long COVID disease phenotype. In this review, we explore the mechanistic hypotheses of these neurological changes, which describe CNS invasion, neuroinflammation, blood-brain barrier disruption, and gut-brain axis dysregulation, along with the novel vascular disruption hypothesis that highlights endothelial dysfunction and hypoperfusion as a core underlying mechanism. We lastly evaluate the clinical treatment landscape, scrutinizing the efficacy of various therapeutic strategies ranging from antivirals to anti-inflammatory agents in mitigating the multifaceted symptoms of LC.},
}

@article {pmid40029778,
year = {2025},
author = {Wang, J and Xiong, Y and Song, Z and Li, Y and Zhang, L and Qin, C},
title = {Progress in research on osteoporosis secondary to SARS-CoV-2 infection.},
journal = {Animal models and experimental medicine},
volume = {},
number = {},
pages = {},
doi = {10.1002/ame2.12573},
pmid = {40029778},
issn = {2576-2095},
support = {2060204//State Key Laboratory Special Fund/ ; 2022B1111020005//Key-Area Research and Development Program of Guangdong Province/ ; 2021-I2M-1-034,2023-I2M-2-001//Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences/ ; 82221004//The Foundation for Innovative Research Groups of the National Natural Science Foundation of China/ ; },
abstract = {The World Health Organization has declared that COVID-19 no longer constitutes a "public health emergency of international concern," yet the long-term impact of SARS-CoV-2 infection on bone health continues to pose new challenges for global public health. In recent years, numerous animal model and clinical studies have revealed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to secondary osteoporosis. The mechanisms involved are related to the virus's direct effects on bone tissue, dysregulation of the body's inflammatory response, hypoxia, noncoding RNA imbalance, and metabolic abnormalities. Although these studies have unveiled the connection between SARS-CoV-2 infection and osteoporosis, current research is not comprehensive and in depth. Future studies are needed to evaluate the long-term effects of SARS-CoV-2 on bone density and metabolism, elucidate the specific mechanisms of pathogenesis, and explore potential interventions. This review aims to collate existing research literature on SARS-CoV-2 infection-induced secondary osteoporosis, summarize the underlying mechanisms, and provide direction for future research.},
}

@article {pmid40012912,
year = {2024},
author = {Naiditch, H and Betts, MR and Larman, HB and Levi, M and Rosenberg, AZ},
title = {Immunologic and inflammatory consequences of SARS-CoV-2 infection and its implications in renal disease.},
journal = {Frontiers in immunology},
volume = {15},
number = {},
pages = {1376654},
pmid = {40012912},
issn = {1664-3224},
support = {F32 MD019534/MD/NIMHD NIH HHS/United States ; T32 HL007563/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/immunology ; *SARS-CoV-2/immunology ; *Inflammation/immunology ; Kidney Diseases/immunology/virology/etiology ; Cytokines/metabolism/immunology ; },
abstract = {The emergence of the COVID-19 pandemic made it critical to understand the immune and inflammatory responses to the SARS-CoV-2 virus. It became increasingly recognized that the immune response was a key mediator of illness severity and that its mechanisms needed to be better understood. Early infection of both tissue and immune cells, such as macrophages, leading to pyroptosis-mediated inflammasome production in an organ system critical for systemic oxygenation likely plays a central role in the morbidity wrought by SARS-CoV-2. Delayed transcription of Type I and Type III interferons by SARS-CoV-2 may lead to early disinhibition of viral replication. Cytokines such as interleukin-1 (IL-1), IL-6, IL-12, and tumor necrosis factor α (TNFα), some of which may be produced through mechanisms involving nuclear factor kappa B (NF-κB), likely contribute to the hyperinflammatory state in patients with severe COVID-19. Lymphopenia, more apparent among natural killer (NK) cells, CD8+ T-cells, and B-cells, can contribute to disease severity and may reflect direct cytopathic effects of SARS-CoV-2 or end-organ sequestration. Direct infection and immune activation of endothelial cells by SARS-CoV-2 may be a critical mechanism through which end-organ systems are impacted. In this context, endovascular neutrophil extracellular trap (NET) formation and microthrombi development can be seen in the lungs and other critical organs throughout the body, such as the heart, gut, and brain. The kidney may be among the most impacted extrapulmonary organ by SARS-CoV-2 infection owing to a high concentration of ACE2 and exposure to systemic SARS-CoV-2. In the kidney, acute tubular injury, early myofibroblast activation, and collapsing glomerulopathy in select populations likely account for COVID-19-related AKI and CKD development. The development of COVID-19-associated nephropathy (COVAN), in particular, may be mediated through IL-6 and signal transducer and activator of transcription 3 (STAT3) signaling, suggesting a direct connection between the COVID-19-related immune response and the development of chronic disease. Chronic manifestations of COVID-19 also include systemic conditions like Multisystem Inflammatory Syndrome in Children (MIS-C) and Adults (MIS-A) and post-acute sequelae of COVID-19 (PASC), which may reflect a spectrum of clinical presentations of persistent immune dysregulation. The lessons learned and those undergoing continued study likely have broad implications for understanding viral infections' immunologic and inflammatory consequences beyond coronaviruses.},
}

Humans
*COVID-19/immunology
*SARS-CoV-2/immunology
*Inflammation/immunology
Kidney Diseases/immunology/virology/etiology
Cytokines/metabolism/immunology

@article {pmid40011942,
year = {2025},
author = {Leitzke, M and Roach, DT and Hesse, S and Schönknecht, P and Becker, GA and Rullmann, M and Sattler, B and Sabri, O},
title = {Long COVID - a critical disruption of cholinergic neurotransmission?.},
journal = {Bioelectronic medicine},
volume = {11},
number = {1},
pages = {5},
pmid = {40011942},
issn = {2332-8886},
abstract = {BACKGROUND: Following the COVID-19 pandemic, there are many chronically ill Long COVID (LC) patients with different symptoms of varying degrees of severity. The pathological pathways of LC remain unclear until recently and make identification of path mechanisms and exploration of therapeutic options an urgent challenge. There is an apparent relationship between LC symptoms and impaired cholinergic neurotransmission.

METHODS: This paper reviews the current literature on the effects of blocked nicotinic acetylcholine receptors (nAChRs) on the main affected organ and cell systems and contrasts this with the unblocking effects of the alkaloid nicotine. In addition, mechanisms are presented that could explain the previously unexplained phenomenon of post-vaccination syndrome (PVS). The fact that not only SARS-CoV-2 but numerous other viruses can bind to nAChRs is discussed under the assumption that numerous other post-viral diseases and autoimmune diseases (ADs) may also be due to impaired cholinergic transmission. We also present a case report that demonstrates changes in cholinergic transmission, specifically, the availability of α4β2 nAChRs by using (-)-[[18]F]Flubatine whole-body positron emission tomography (PET) imaging of cholinergic dysfunction in a LC patient along with a significant neurological improvement before and after low-dose transcutaneous nicotine (LDTN) administration. Lastly, a descriptive analysis and evaluation were conducted on the results of a survey involving 231 users of LDTN.

RESULTS: A substantial body of research has emerged that offers a compelling explanation for the phenomenon of LC, suggesting that it can be plausibly explained because of impaired nAChR function in the human body. Following a ten-day course of transcutaneous nicotine administration, no enduring neuropathological manifestations were observed in the patient. This observation was accompanied by a significant increase in the number of free ligand binding sites (LBS) of nAChRs, as determined by (-)-[[18]F]Flubatine PET imaging. The analysis of the survey shows that the majority of patients (73.5%) report a significant improvement in the symptoms of their LC/MEF/CFS disease as a result of LDTN.

CONCLUSIONS: In conclusion, based on current knowledge, LDTN appears to be a promising and safe procedure to relieve LC symptoms with no expected long-term harm.},
}

@article {pmid40004799,
year = {2025},
author = {Aliberti, A and Gasparro, R and Mignogna, M and Canfora, F and Spagnuolo, G and Sammartino, G and Coppola, N},
title = {Unveiling the Oral Lesions, Dysgeusia and Osteonecrosis Related to COVID-19: A Comprehensive Systematic Review.},
journal = {Journal of clinical medicine},
volume = {14},
number = {4},
pages = {},
pmid = {40004799},
issn = {2077-0383},
abstract = {Background/Objectives: The oral cavity has garnered increasing attention as a site for viral infection and related pathological manifestations in coronavirus disease-19. This article aims to provide a comprehensive overview of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2)-related oral manifestations, including taste disturbances, oral lesions and osteonecrosis. Methods: A search was conducted up to September 2024 according to PRISMA (Preferred Reporting Items for Systematic Reviews) guidelines using the databases PubMed and Scopus. All the observational, case-series, case-report and cross-sectional studies written in English on oral manifestations related to COVID-19 disease and long-COVID disease were included. All other types of studies and studies based on oral manifestation after COVID-19 vaccination and oral impairment due to lockdown were excluded. The risk of bias of included studies was assessed using the Joanna Briggs Appraisal checklist. Results: A total of 104 articles including 23 case-report, 15 case-series, 8 case-control, 18 cohort and 40 cross-sectional studies were selected. The results showed that patients with COVID-19 were found to have a significantly higher prevalence of xerostomia (45-74%) and dysgeusia (32-59%) compared to non-infected individuals. Regarding oral mucosal lesions, ulcers, candidiasis and herpes simplex infections were frequently observed. As for osteonecrosis, a significant number of patients with COVID-19-associated rhinomaxillary mucormycosis presented with maxillary osteonecrosis due to fungal infection, primarily mucormycosis. The methodological quality of most of the studies was moderate/high. Conclusions: COVID-19 has been associated with a range of oral manifestations. The complex interplay of viral infection, immune response, medication use and stress likely contributes to these oral complications. Early recognition and management of these oral manifestations are crucial for improving patient outcomes and developing targeted preventive and therapeutic strategies for COVID-19-related oral health issues.},
}

@article {pmid40003500,
year = {2025},
author = {Smyth, NJ and Blitshteyn, S},
title = {Language Matters: What Not to Say to Patients with Long COVID, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, and Other Complex Chronic Disorders.},
journal = {International journal of environmental research and public health},
volume = {22},
number = {2},
pages = {},
pmid = {40003500},
issn = {1660-4601},
mesh = {Humans ; *Fatigue Syndrome, Chronic/therapy ; *COVID-19/psychology ; Chronic Disease ; Language ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; },
abstract = {People with Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and other complex chronic disorders consistently report having difficulty obtaining effective and compassionate medical care and being disbelieved, judged, gaslighted, and even dismissed by healthcare professionals. We believe that these adversarial interactions and language are more likely to arise when healthcare professionals are confronting complex chronic illnesses without proper training, diagnostic biomarkers, or FDA-approved therapies. These problematic conversations between practitioners and patients often involve specific words and phrases-termed the "never-words"-can leave patients in significant emotional distress and negatively impact the clinician-patient relationship and recovery. Seeking to prevent these destructive interactions, we review key literature on best practices for difficult clinical conversations and discuss the application of these practices for people with Long COVID, ME/CFS, dysautonomia, and other complex chronic disorders. We provide recommendations for alternative, preferred phrasing to the never-words, which can enhance therapeutic relationship and chronic illness patient care via compassionate, encouraging, and non-judgmental language.},
}

Humans
*Fatigue Syndrome, Chronic/therapy
*COVID-19/psychology
Chronic Disease
Language
Post-Acute COVID-19 Syndrome
SARS-CoV-2

@article {pmid40002834,
year = {2025},
author = {Whitaker-Hardin, B and McGregor, KM and Uswatte, G and Lokken, K},
title = {A Narrative Review of the Efficacy of Long COVID Interventions on Brain Fog, Processing Speed, and Other Related Cognitive Outcomes.},
journal = {Biomedicines},
volume = {13},
number = {2},
pages = {},
pmid = {40002834},
issn = {2227-9059},
abstract = {In the years following the global emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or COVID-19, researchers have become acutely aware of long-term symptomology associated with this disease, often termed long COVID. Long COVID is associated with pervasive symptoms affecting multiple organ systems. Neurocognitive symptoms are reported by up to 40% of long COVID patients, with resultant effects of loss of daily functioning, employment issues, and enormous economic impact and high healthcare utilization. The literature on effective, safe, and non-invasive interventions for the remediation of the cognitive consequences of long COVID is scarce and poorly described. Of specific interest to this narrative review is the identification of potential interventions for long COVID-associated neurocognitive deficits. Articles were sourced from PubMed, EBSCO, Scopus, and Embase following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles published between the dates of January 2020 and 30 June 2024 were included in the search. Twelve studies were included in the narrative review, including a feasibility study, a pilot study, a case series, a case study, and an observational study, in addition to three randomized clinical trials and four interventional studies. Overall, treatment interventions such as cognitive training, non-invasive brain stimulation therapy, exercise rehabilitation, targeted pharmacological intervention, and other related treatment paradigms show promise in reducing long COVID cognitive issues. This narrative review highlights the need for more rigorous experimental designs and future studies are needed to fully evaluate treatment interventions for persistent cognitive deficits associated with long COVID.},
}

@article {pmid39997467,
year = {2025},
author = {Ayyoub, S and Dhillon, NK and Tura-Ceide, O},
title = {Genetics of Long COVID: Exploring the Molecular Drivers of Persistent Pulmonary Vascular Disease Symptoms.},
journal = {Infectious disease reports},
volume = {17},
number = {1},
pages = {},
pmid = {39997467},
issn = {2036-7430},
support = {CP17/00114, CPII22/00006)//Miguel Servet type grants from the Institute of Health Carlos III/ ; PI21/01212//Catalan Pneumology Foundation (FUCAP) and from the Institute of Health Carlos III/ ; 2024 FI-3 00065//AGAUR-FI ajuts Joan Oró, backed by the Secretariat of Universities and Research of the Department of Research and Universities of the Generalitat of Catalonia, and the European Social Plus Fund/ ; R01HL1528322//NIH Funding/ ; },
abstract = {Background/ Objectives: Long COVID or post-acute sequelae of SARS-CoV-2 infection (PASC) are symptoms that manifest despite passing the acute infection phase. These manifestations encompass a wide range of symptoms, the most common being fatigue, shortness of breath, and cognitive dysfunction. Genetic predisposition is clearly involved in the susceptibility of individuals to developing these persistent symptoms and the variation in the severity and forms. This review summarizes the role of genetic factors and gene polymorphisms in the development of major pulmonary vascular disorders associated with long COVID. Methods: A comprehensive review of current literature was conducted to examine the genetic contributions to pulmonary complications following SARS-CoV-2 infection. Studies investigating genetic polymorphisms linked to pulmonary hypertension, pulmonary thromboembolism, and pulmonary vascular endothelialitis were reviewed and summarized. Results: Findings show that specific genetic variants contribute to increased susceptibility to pulmonary vascular complications in long COVID patients. Variants associated with endothelial dysfunction, coagulation pathways, and inflammatory responses have been implicated in the development of pulmonary hypertension and thromboembolic events. Genetic predispositions influencing vascular integrity and immune responses appear to influence disease severity and progression. Conclusions: Understanding these mechanisms and genetic predispositions could pave the way for targeted therapeutic interventions to alleviate the burden on patients experiencing long COVID.},
}

@article {pmid39993991,
year = {2025},
author = {Mink, S and Wilhelm, F and Cadamuro, J and Reimann, P and Fraunberger, P},
title = {Anti-SARS-CoV-2 Antibodies in Long-COVID-Markers of Protection or Elevated Risk? A Systematic Review.},
journal = {Reviews in medical virology},
volume = {35},
number = {2},
pages = {e70027},
doi = {10.1002/rmv.70027},
pmid = {39993991},
issn = {1099-1654},
mesh = {Humans ; *COVID-19/immunology/prevention & control/virology ; *Antibodies, Viral/blood/immunology ; *SARS-CoV-2/immunology ; Biomarkers/blood ; Post-Acute COVID-19 Syndrome ; },
abstract = {Long-COVID affects a significant number of COVID-19 survivors, profoundly impacting daily life and work. Although research suggests a potential link between antibody levels and long-COVID risk, findings remain inconclusive. Understanding antibody dynamics could support the identification of patients at risk, improve long-COVID diagnosis, and guide protective strategies such as vaccination. Despite growing evidence, no systematic review has yet evaluated the current literature on this topic. We therefore aimed to synthesise and evaluate existing evidence on the association between anti-SARS-CoV-2 antibody titres and long-COVID, with the goal of clarifying their potential role in predicting long-COVID risk, guiding patient management, and informing future research directions. Studies published in PubMed/Medline databases between January 2020 and October 2024 were included without language restrictions. Studies on body fluids other than serum/blood were excluded. Study selection and quality assessment was conducted independently by two researchers. After screening 949 studies, 58 studies encompassing 53,739 individuals, and 7812 long-COVID patients, were included. Evidence was highly heterogenous but most studies reported an association between anti-SARS-CoV-2-spike antibodies and long-COVID, although the nature of the association appeared to be dependent on time from acute infection. Low anti-SARS-CoV-2-spike antibodies during acute COVID-19 were associated with increased risk of long-COVID. The association between low anti-SARS-CoV-2-spike antibodies during acute COVID-19 and long-COVID suggests that maintaining sufficiently high antibody levels may be protective. However, the current evidence level is low and further studies with sufficient power are required to confirm this association and to potentially determine protective cutoffs.},
}

Humans
*COVID-19/immunology/prevention & control/virology
*Antibodies, Viral/blood/immunology
*SARS-CoV-2/immunology
Biomarkers/blood
Post-Acute COVID-19 Syndrome

@article {pmid39990183,
year = {2025},
author = {Łukomska, E and Kloc, K and Kowalska, M and Matjaszek, A and Joshi, K and Scholz, S and Van de Velde, N and Beck, E},
title = {Healthcare Resource Utilization (HCRU) and Direct Medical Costs Associated with Long COVID or Post-COVID-19 Conditions: Findings from a Literature Review.},
journal = {Journal of market access & health policy},
volume = {13},
number = {1},
pages = {7},
pmid = {39990183},
issn = {2001-6689},
abstract = {Approximately 10-20% of individuals suffering from COVID-19 develop prolonged symptoms known as long COVID or post-COVID condition (LC). This review aimed to assess healthcare resource use (HCRU) and healthcare costs associated with LC. Because LC is not clearly defined and often remains undiagnosed, studies reporting on long-term follow-up of individuals with a COVID-19 diagnosis were also included. Among the 41 publications included, 36 reported on HCRU and 16 on costs. Individuals with LC had significantly elevated HCRU and healthcare costs vs. controls without a COVID-19 diagnosis over ≥15 months, with a 7.6-13.1% increase in total healthcare costs per person per month as assessed by difference-in-difference analysis. Among studies that did not specifically refer to LC, having a COVID-19 diagnosis was associated with a significant 4-10% increase in long-term total HCRU over 6-8 months and a 1.3- to 2.9-fold relative increase in total healthcare costs over 6 months. Due to the heterogeneity of the included studies, high-quality evidence is needed to better understand the economic burden of LC. In the absence of effective treatments, prioritizing the prevention of acute COVID-19, e.g., through vaccination, may be crucial for preventing LC and the associated long-term HCRU and medical spending.},
}

@article {pmid39984803,
year = {2025},
author = {Ivlev, I and Wagner, J and Phillips, T and Treadwell, JR},
title = {Interventions for Long COVID: A Narrative Review.},
journal = {Journal of general internal medicine},
volume = {},
number = {},
pages = {},
pmid = {39984803},
issn = {1525-1497},
support = {MSA-SOW#05-ECRI-ENG-11-07-2022/PCORI/Patient-Centered Outcomes Research Institute/United States ; },
abstract = {Long COVID continues to impose a significant burden on COVID-19 survivors, presenting with diverse symptoms and clinical uncertainty. This review synthesized evidence from 97 studies, including 26 randomized controlled trials and 15 non-randomized comparative studies, which explored the effectiveness, comparative effectiveness, and potential risks of proposed interventions for managing common long COVID symptoms: fatigue, neurocognitive symptoms, anxiety, depression, and sleep issues. Our comprehensive analysis, encompassing English-language articles, gray literature, and feedback from 14 Key Informants (i.e., patients, caregivers, clinicians, payors, and researchers), reveals a persistently weak body of evidence, characterized by high imprecision and considerable uncertainty regarding the benefits and harms of the interventions. The studies examined a wide array of treatment categories, including multi-component rehabilitation, supplements, complementary treatments, prescription medications, and the COVID-19 vaccine. Key informants emphasized the critical need for establishing robust diagnostic criteria and utilizing functional outcomes while also highlighting significant barriers to care, including dismissive attitudes from healthcare providers, inadequate insurance coverage, and restricted access to specialty care. Given the evolving definitions of long COVID and the variable mechanisms of its management, our findings underscore the pressing need for further rigorous research to refine and validate effective treatment protocols. Until more definitive evidence is available, both clinicians and patients face substantial uncertainty in treatment decisions, with many resorting to self-treatment using costly and potentially ineffective options.},
}

@article {pmid39981885,
year = {2025},
author = {Zhang, Y and Chen, H and Li, Y and Luo, C and Zhu, Y and Zhou, X and Wang, R and He, J and Guo, H and Xu, X and Qiu, M and Li, J},
title = {Animal Models for Long COVID: Current Advances, Limitations, and Future Directions.},
journal = {Journal of medical virology},
volume = {97},
number = {2},
pages = {e70237},
doi = {10.1002/jmv.70237},
pmid = {39981885},
issn = {1096-9071},
mesh = {Animals ; *Disease Models, Animal ; *COVID-19/epidemiology ; Humans ; Mice ; *SARS-CoV-2/pathogenicity ; Post-Acute COVID-19 Syndrome ; Primates ; Cricetinae ; Mesocricetus ; },
abstract = {Long COVID (LC) represents a chronic, systemic, and often disabling condition that poses a significant ongoing threat to public health. Foundational scientific studies are needed to unravel the underlying mechanisms, with the ultimate goal of developing effective preventative and therapeutic strategies. Therefore, there is an urgent demand for animal models that can accurately replicate the clinical features of LC. This review integrates clinical epidemiological data to summarize the pathological changes in extrapulmonary systems involved in LC. Additionally, it critically examines the capacity of existing animal models, including nonhuman primates, genetically modified mice, and Syrian hamsters, to exhibit enduring postinfection symptoms that align with human clinical manifestations, and identifies key areas requiring further development. The objective is to offer insights that will aid in the development of next-generation animal models, thereby accelerating our understanding of how acute respiratory viral infections transition into chronic conditions, and ensuring preparedness for future pandemics.},
}

Animals
*Disease Models, Animal
*COVID-19/epidemiology
Humans
Mice
*SARS-CoV-2/pathogenicity
Post-Acute COVID-19 Syndrome
Primates
Cricetinae
Mesocricetus

@article {pmid39974559,
year = {2025},
author = {Ewing, AG and Salamon, S and Pretorius, E and Joffe, D and Fox, G and Bilodeau, S and Bar-Yam, Y},
title = {Review of organ damage from COVID and Long COVID: a disease with a spectrum of pathology.},
journal = {Medical review (2021)},
volume = {5},
number = {1},
pages = {66-75},
pmid = {39974559},
issn = {2749-9642},
abstract = {Long COVID, as currently defined by the World Health Organization (WHO) and other authorities, is a symptomatic condition that has been shown to affect an estimated 10 %-30 % of non-hospitalized patients after one infection. However, COVID-19 can also cause organ damage in individuals without symptoms, who would not fall under the current definition of Long COVID. This organ damage, whether symptomatic or not, can lead to various health impacts such as heart attacks and strokes. Given these observations, it is necessary to either expand the definition of Long COVID to include organ damage or recognize COVID-19-induced organ damage as a distinct condition affecting many symptomatic and asymptomatic individuals after COVID-19 infections. It is important to consider that many known adverse health outcomes, including heart conditions and cancers, can be asymptomatic until harm thresholds are reached. Many more medical conditions can be identified by testing than those that are recognized through reported symptoms. It is therefore important to similarly recognize that while Long COVID symptoms are associated with organ damage, there are many individuals that have organ damage without displaying recognized symptoms and to include this harm in the characterization of COVID-19 and in the monitoring of individuals after COVID-19 infections.},
}

@article {pmid39971694,
year = {2025},
author = {Tsang, MS and Zhou, IW and Zhang, AL and Xue, CC},
title = {Chinese herbal medicine for dyspnea and persistent symptoms of long COVID: A systematic review and meta-analysis of randomized controlled trials.},
journal = {Journal of integrative medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.joim.2025.01.001},
pmid = {39971694},
issn = {2095-4964},
abstract = {BACKGROUND: Over 65 million people have long COVID. Evidence for using Chinese herbal medicine (CHM) to treat long COVID is growing. A systematic review of evidence for guiding clinical decision is warranted.

OBJECTIVE: To examine the effects and safety of CHM in alleviating the severity of dyspnea, fatigue, exercise intolerance, depression, anxiety and insomnia in long COVID adults based on registered randomized clinical trials (RCT).

SEARCH STRATEGY: World Health Organization International Clinical Trials Registry Platform and Chinese Clinical Trial Registry were searched for registered trial protocols from database inception to February 10, 2023. English (PubMed, Embase, AMED and CINAHL) and Chinese databases (CNKI, Wanfang Data and CQVIP) were then searched to identify relevant publications from December 2019 through April 6, 2023.

INCLUSION CRITERIA: Registered RCTs that compared the effects of Chinese herbal medicines or Chinese herbal formulas against a control treatment (i.e., the placebo or usual care) in adults with persistent symptoms of long COVID. The primary outcome of dyspnea, and secondary outcomes of fatigue, exercise intolerance, depression, anxiety and insomnia were measured using validated tools at the end of the treatment.

DATA EXTRACTION AND ANALYSIS: Data were extracted, and eligible RCTs were evaluated using version 2 of the Cochrane risk-of-bias tool for randomized trials and Grading of Recommendations, Assessment, Development and Evaluations independently by two researchers. Effect sizes were estimated by random-effects modelling and mean difference (MD). Heterogeneity between trials was quantified by I[2].

RESULTS: Among the 38 registered clinical trials we identified, seven RCTs (1,519 patients) were included in the systematic review. One RCT had a low overall risk of bias. Compared to the control, CHM reduces dyspnea on the Borg Dyspnea Scale score (MD = -0.2, 95% confidence interval [CI] = -0.65 to 0.25) with moderate certainty, and reduces fatigue on the Borg Scale (MD = -0.48, 95% CI = -0.74 to -0.22) with low certainty. CHM clinically reduces depression on Hamilton Depression Rating Scale score (MD = -6.00, 95% CI = -7.56 to -4.44) and anxiety on Hamilton Anxiety Rating Scale score (MD = -6.10, 95% CI = -7.67 to -4.53), and reduces insomnia on the Insomnia Severity Index (MD = -4.86, 95% CI = -12.50 to 2.79) with moderate certainty. Meta-analysis of two RCTs (517 patients) showed that CHM clinically improves exercise intolerance by increasing 6-minute walking distance (MD = -15.92, 95% CI = -10.20 to 42.05) with substantial heterogeneity (I[2] = 68%) and low certainty.

CONCLUSION: CHM is associated with a post-treatment clinical reduction in depression and anxiety in long COVID adults, compared to the control, but it does not have a strong treatment effect on dyspnea and insomnia. Effects of CHM on exercise intolerance and fatigue are uncertain, and the safety of using CHM remains questionable. Please cite this article as: Tsang MS, Zhou IW, Zhang AL, Xue CC. Chinese herbal medicine for dyspnea and persistent symptoms of long COVID: a systematic review and meta-analysis of randomized controlled trials. J Integr Med. 2025; Epub ahead of print.},
}

@article {pmid39967901,
year = {2024},
author = {Panesar, A and Gharanei, P and Khovanova, N and Young, L and Grammatopoulos, D},
title = {Thyroid function during COVID-19 and post-COVID complications in adults: a systematic review.},
journal = {Frontiers in endocrinology},
volume = {15},
number = {},
pages = {1477389},
pmid = {39967901},
issn = {1664-2392},
mesh = {Humans ; *COVID-19/complications/epidemiology ; *Thyroid Gland/physiopathology ; *SARS-CoV-2 ; Thyroid Diseases/complications/physiopathology ; Adult ; Post-Acute COVID-19 Syndrome ; Thyroid Function Tests ; Thyroid Hormones/blood ; Thyroiditis/etiology ; },
abstract = {The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, has presented multifaceted health challenges. COVID-19 primarily targets the respiratory system but also affects multiple organ systems, including the endocrine system. Emerging evidence suggests interactions between thyroid function, the acute phase of COVID-19, and the prolonged symptoms known as post-COVID sequalae or long COVID. Several studies have reported that COVID-19 can induce thyroid dysfunction, leading to conditions such as thyroiditis and alterations in thyroid hormone levels. The mechanisms through which SARS-CoV-2 affects the thyroid include direct viral infection of thyroid cells, leading to viral thyroiditis, which causes inflammation and transient or sustained thyroid dysfunction, as well as an excessive systemic immune response (cytokine storm). This is associated with elevated levels of cytokines, such as IL-6, that disrupt thyroid function and lead to nonthyroidal illness syndrome (NTIS). Medications administered during the acute illness phase, such as corticosteroids and antiviral drugs, can also impact thyroid hormone actions. The involvement of the thyroid gland in long COVID, or postacute sequelae of SARS-CoV-2 infection, is an area not well defined, with potential implications for understanding and managing this condition. Persistent low-grade inflammation affecting thyroid function over time can lead to ongoing thyroiditis or exacerbate pre-existing thyroid conditions. Viral infections, including SARS-CoV-2, can trigger or worsen autoimmune thyroid diseases, such as Hashimoto's thyroiditis and Graves' disease. Long COVID may disrupt the hypothalamic-pituitary-adrenal (HPA) axis, which can, in turn, affect the hypothalamic-pituitary-thyroid (HPT) axis, leading to abnormal thyroid function. This review was designed to systematically capture recent literature on COVID-19-related thyroid dysfunction in the adult population, the prognostic consequences of thyroid dysfunction during COVID-19, and the effects of thyroid dysfunction on patients with long COVID. A comprehensive search of PubMed and EMBASE databases was conducted. The systematic review was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Study quality was assessed using the Critical Appraisal Skills Programme (CASP). A total of 53 studies met the inclusion criteria. The review summarises recent findings and provides an update of the current understanding of thyroid dysfunction in COVID-19-related spectrum of disorders, underscoring the complex nature of SARS-CoV-2 infection and its far-reaching impacts on human health.},
}

Humans
*COVID-19/complications/epidemiology
*Thyroid Gland/physiopathology
*SARS-CoV-2
Thyroid Diseases/complications/physiopathology
Adult
Post-Acute COVID-19 Syndrome
Thyroid Function Tests
Thyroid Hormones/blood
Thyroiditis/etiology

@article {pmid39967803,
year = {2025},
author = {Smadja, DM and Abreu, MM},
title = {Hyperthermia and targeting heat shock proteins: innovative approaches for neurodegenerative disorders and Long COVID.},
journal = {Frontiers in neuroscience},
volume = {19},
number = {},
pages = {1475376},
pmid = {39967803},
issn = {1662-4548},
abstract = {Neurodegenerative diseases (NDs) and Long COVID represent critical and growing global health challenges, characterized by complex pathophysiological mechanisms including neuronal deterioration, protein misfolding, and persistent neuroinflammation. The emergence of innovative therapeutic approaches, such as whole-body hyperthermia (WBH), offers promising potential to modulate underlying pathophysiological mechanisms in NDs and related conditions like Long COVID. WBH, particularly in fever-range, enhances mitochondrial function, induces heat shock proteins (HSPs), and modulates neuroinflammation-benefits that pharmacological treatments often struggle to replicate. HSPs such as HSP70 and HSP90 play pivotal roles in protein folding, aggregation prevention, and cellular protection, directly targeting pathological processes seen in NDs like Alzheimer's, Parkinson's, and Huntington's disease. Preliminary findings also suggest WBH's potential to alleviate neurological symptoms in Long COVID, where persistent neuroinflammation and serotonin dysregulation are prominent. Despite the absence of robust clinical trials, the therapeutic implications of WBH extend to immune modulation and the restoration of disrupted physiological pathways. However, the dual nature of hyperthermia's effects-balancing pro-inflammatory and anti-inflammatory responses-emphasizes the need for dose-controlled applications and stringent patient monitoring to minimize risks in vulnerable populations. While WBH shows potential interest, significant challenges remain. These include individual variability in response, limited accessibility to advanced hyperthermia technologies, and the need for standardized clinical protocols. Future research must focus on targeted clinical trials, biomarker identification, and personalized treatment strategies to optimize WBH's efficacy in NDs and Long COVID. The integration of WBH into therapeutic paradigms could mark a transformative step in addressing these complex conditions.},
}

@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 = {171},
number = {},
pages = {106067},
doi = {10.1016/j.neubiorev.2025.106067},
pmid = {39965723},
issn = {1873-7528},
mesh = {Humans ; *COVID-19/psychology/complications ; *Cognitive Reserve/physiology ; *Cognitive Dysfunction/physiopathology/etiology ; Cognition/physiology ; SARS-CoV-2 ; },
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 5604 studies, 87 were eligible (10,950 COVID-19 cases; 78,305 controls), and IPD was obtained for 29 datasets (3919 COVID-19 cases; 8267 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.},
}

Humans
*COVID-19/psychology/complications
*Cognitive Reserve/physiology
*Cognitive Dysfunction/physiopathology/etiology
Cognition/physiology
SARS-CoV-2

@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.},
}

@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},
mesh = {Humans ; *COVID-19 Vaccines/economics/immunology/administration & dosage ; *Cost-Benefit Analysis ; *COVID-19/prevention & control/epidemiology/economics ; *Immunization, Secondary/economics ; *SARS-CoV-2/immunology ; Australia/epidemiology ; Vaccine Efficacy ; Canada/epidemiology ; },
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.},
}

Humans
*COVID-19 Vaccines/economics/immunology/administration & dosage
*Cost-Benefit Analysis
*COVID-19/prevention & control/epidemiology/economics
*Immunization, Secondary/economics
*SARS-CoV-2/immunology
Australia/epidemiology
Vaccine Efficacy
Canada/epidemiology

@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},
mesh = {Humans ; *Transcranial Magnetic Stimulation/methods ; *Transcranial Direct Current Stimulation/methods ; *Stroke/complications/therapy/physiopathology/diagnostic imaging ; *Fatigue/therapy/etiology/physiopathology ; Brain/diagnostic imaging/physiopathology ; },
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.},
}

Humans
*Transcranial Magnetic Stimulation/methods
*Transcranial Direct Current Stimulation/methods
*Stroke/complications/therapy/physiopathology/diagnostic imaging
*Fatigue/therapy/etiology/physiopathology
Brain/diagnostic imaging/physiopathology

@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},
mesh = {Humans ; *COVID-19/therapy/psychology ; *Psychotherapy/methods ; SARS-CoV-2 ; Feasibility Studies ; Patient Acceptance of Health Care ; Treatment Outcome ; },
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.},
}

Humans
*COVID-19/therapy/psychology
*Psychotherapy/methods
SARS-CoV-2
Feasibility Studies
Patient Acceptance of Health Care
Treatment Outcome

@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},
support = {K23 AI157875/AI/NIAID NIH HHS/United States ; R01 NS136197/NS/NINDS NIH HHS/United States ; },
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.},
}

@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].},
}

@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},
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.},
}

Humans
*COVID-19/complications
*Post-Acute COVID-19 Syndrome
*SARS-CoV-2
*Cardiovascular Diseases/etiology
Pandemics
Congresses as Topic
COVID-19 Drug Treatment

@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 = {},
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.},
}

Humans
*Proteome/metabolism/analysis
*Thrombosis/metabolism
*Amyloid/metabolism
*Blood Coagulation
COVID-19/metabolism
Sepsis/metabolism/blood
SARS-CoV-2/metabolism

@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 = {},
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.},
}

@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 = {},
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.},
}

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

@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.},
}

Humans
*COVID-19/psychology
Adult
SARS-CoV-2
Outcome Assessment, Health Care
Europe
Post-Acute COVID-19 Syndrome
Consensus

@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.},
}

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

@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 Postexertional 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 postexertional malaise (PEM) in people with post-COVID-19 condition (PCC); and the change in prevalence of PEM after rehabilitation interventions in people with PCC.

DATA SOURCES: We searched MEDLINE, Embase, CENTRAL, CINAHL, PsychINFO, and clinical trial registries from inception until February 11, 2025.

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 after 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.

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. Discrepancies were resolved with a senior research team member. For the prevalence studies we used the ROBINS-E tool. For randomized controlled trials we used the RoB2 tool. For non-randomized interventional studies we used the ROBINS-I tool to assess the non-randomized studies. We used the GRADE system to assess the certainty 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. We used a random effects model. Results were reported as proportions with corresponding 95% confidence intervals (95% CI) or presented descriptively when statistical analysis was not applied. This study is registered with PROSPERO (CRD42024516682). The prevalence of PEM in community-dwelling adults living with PCC was 25% (95% CI: 0.17-0.36; 10 studies; 4,076 low certainty after the word participants). Five of the included studies (193 patients) found a decrease in the frequency and intensity of PEM episodes in adults with PCC after a tailored rehabilitation program centered on integrating pacing approaches. Eight studies (1080 patients) measured PEM as an adverse event following an individually tailored rehabilitation intervention with a therapeutic exercise component. Seven of these studies did not find indications of post exertional symptom exacerbation related to the exercise component of the intervention. All of the studies had high to very high risk of bias.

CONCLUSIONS: Our research confirms that there is a large burden of PEM in adults living with PCC, highlighting a critical challenge for health care 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 who 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 nonvalidated, unstandardized tools to measure PEM in people with PCC; hence, there is an urgent need to strengthen the methods of future trials.},
}

@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.},
}

*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

@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.},
}

Humans
*COVID-19/complications
*Post-Acute COVID-19 Syndrome
Longitudinal Studies
Cognition
Cognitive Dysfunction/etiology
Time Factors

@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 = {137},
number = {},
pages = {111279},
doi = {10.1016/j.pnpbp.2025.111279},
pmid = {39909170},
issn = {1878-4216},
mesh = {Humans ; *Hallucinogens/therapeutic use ; *COVID-19/complications ; *Post-Acute COVID-19 Syndrome ; Serotonin Agents/therapeutic use ; },
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.},
}

Humans
*Hallucinogens/therapeutic use
*COVID-19/complications
*Post-Acute COVID-19 Syndrome
Serotonin Agents/therapeutic use

@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.},
}

Humans
*COVID-19/immunology/mortality
*Autoantibodies/blood
Prognosis
*SARS-CoV-2/immunology
Prospective Studies

@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.},
}

Female
Humans
Male
*COVID-19/epidemiology
Dyspnea/epidemiology
Post-Acute COVID-19 Syndrome
Prevalence
Risk Factors
SARS-CoV-2
Sex Factors

@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.},
}

@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.},
}

@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.},
}

Humans
*Cerebrovascular Circulation/physiology
*Orthostatic Intolerance/physiopathology/diagnosis
COVID-19/complications/physiopathology
Ultrasonography, Doppler, Transcranial
Spectroscopy, Near-Infrared
Postural Orthostatic Tachycardia Syndrome/physiopathology/diagnosis

@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},
mesh = {Humans ; *COVID-19 Vaccines/immunology ; *COVID-19/prevention & control/virology/immunology ; *SARS-CoV-2/immunology/drug effects/genetics ; *Antiviral Agents/therapeutic use ; COVID-19 Drug Treatment ; Animals ; },
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.},
}

Humans
*COVID-19 Vaccines/immunology
*COVID-19/prevention & control/virology/immunology
*SARS-CoV-2/immunology/drug effects/genetics
*Antiviral Agents/therapeutic use
COVID-19 Drug Treatment
Animals

@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.},
}

@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.},
}

Humans
*COVID-19/complications/epidemiology
*Asthma/epidemiology/complications
*Pulmonary Disease, Chronic Obstructive/epidemiology/complications
*SARS-CoV-2
Risk Factors
Post-Acute COVID-19 Syndrome

@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.},
}

@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.},
}

@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.},
}

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

@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.},
}

Humans
*Probiotics/therapeutic use
*COVID-19
*Dysbiosis
*Gastrointestinal Microbiome/drug effects
*Post-Acute COVID-19 Syndrome
SARS-CoV-2
Phenotype

@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.},
}

Animals
*COVID-19/complications/virology
*Disease Models, Animal
Mice
*SARS-CoV-2
*Post-Acute COVID-19 Syndrome
Humans
Cricetinae
Primates

@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.},
}

@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.},
}

@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.},
}

@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.},
}

@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.},
}

*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

@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).},
}

@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.},
}

Humans
*COVID-19/immunology/complications
*Dysbiosis
*Gastrointestinal Microbiome
*Post-Acute COVID-19 Syndrome
*SARS-CoV-2/physiology
*Brain-Gut Axis
Inflammation

@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 = {68},
number = {3},
pages = {2089-2094},
doi = {10.1021/acs.jmedchem.4c00691},
pmid = {39836023},
issn = {1520-4804},
mesh = {Humans ; *Autoantibodies/immunology ; *SARS-CoV-2/immunology ; *COVID-19/immunology/virology ; *Receptors, Muscarinic/metabolism/immunology ; COVID-19 Drug Treatment ; Post-Acute COVID-19 Syndrome ; },
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.},
}

Humans
*Autoantibodies/immunology
*SARS-CoV-2/immunology
*COVID-19/immunology/virology
*Receptors, Muscarinic/metabolism/immunology
COVID-19 Drug Treatment
Post-Acute COVID-19 Syndrome

@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.},
}

Humans
*COVID-19/immunology
*Autoantibodies/immunology
*SARS-CoV-2/immunology
*Severity of Illness Index
Autoimmunity
Autoimmune Diseases/immunology

@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.},
}

Humans
*COVID-19/epidemiology/economics/mortality
*SARS-CoV-2
Efficiency
Pandemics/economics
Absenteeism
Global Health/economics
Cost of Illness

@article {pmid39826380,
year = {2025},
author = {Hu, LY and Cai, AQ and Li, B and Sun, YQ and Li, Z and Liu, JP and Cao, HJ},
title = {Prevalence and risk factors for long COVID in China: A systematic review and meta-analysis of observational studies.},
journal = {Journal of infection and public health},
volume = {18},
number = {3},
pages = {102652},
doi = {10.1016/j.jiph.2025.102652},
pmid = {39826380},
issn = {1876-035X},
mesh = {Humans ; *COVID-19/epidemiology ; China/epidemiology ; Risk Factors ; Prevalence ; *SARS-CoV-2 ; Observational Studies as Topic ; Pandemics ; Post-Acute COVID-19 Syndrome ; Female ; Coronavirus Infections/epidemiology ; Betacoronavirus ; Pneumonia, Viral/epidemiology ; Male ; },
abstract = {BACKGROUND: With the outbreak of COVID-19 in China, a large number of COVID-19 patients are at risk of long COVID after recovery. The purpose of our research is to systematically review the existing clinical studies to understand the current prevalence and related risk factors of long COVID in COVID-19 patients in China.

METHODS: The protocol of this systematic review was registered on PROSPERO (CRD42024519375). We searched six electronic databases from 1st January 2020-1st March 2024. Literature screening, data extraction, and risk bias assessment were independently carried out by two reviewers. Quality of the included studies was evaluated by AHRQ and NOS. The meta-analysis was performed by R software 4.2.3 to derive the prevalence of long COVID and risk factors.

RESULTS: Overall, 50 studies with 65880 participants were included. The results showed that the prevalence of long COVID (with at least one symptom) among the COVID-19 patients was approximately 50 % (95 %Confidence Interval (CI) 42-58 %) in China. Although we conducted meta-regression and subgroup analysis, the heterogeneity of the study was high. But the Omicron BA.2 variant had a statistically significant effect on the prevalence of long COVID (P = 0.0004). The three most common symptoms of long COVID were fatigue (0.33, 95 %CI 0.28-0.39), cognitive decline (0.30, 95 %CI 0.14-0.46) and shortness of breath (0.29, 95 %CI 0.15-0.43). Patients with severe acute phase of COVID-19 (Odds Ratio (OR) 1.57, 95 % CI 1.39-1.77), combined 2 comorbidities (OR 1.80, 95 % CI 1.40-2.32), combined 3 comorbidities (OR 2.13, 95 % CI 1.64-2.77), advanced age (OR 1.02, 95 % CI 1.01-1.04), female (OR 1.58, 95 % CI 1.44-1.73) were the risk factors for long COVID prevalence.

CONCLUSION: Current systematic review found that nearly half of COVID-19 patients may suffering from long COVID in China. Establishing a long COVID recovery-support platform and regular follow-up would help to long-term monitor and manage the patients, especially those high-risk population.},
}

Humans
*COVID-19/epidemiology
China/epidemiology
Risk Factors
Prevalence
*SARS-CoV-2
Observational Studies as Topic
Pandemics
Post-Acute COVID-19 Syndrome
Female
Coronavirus Infections/epidemiology
Betacoronavirus
Pneumonia, Viral/epidemiology
Male

@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.},
}

Humans
*COVID-19/epidemiology/psychology/prevention & control
*Social Isolation/psychology
*Exercise
Aged
*Sleep Quality
SARS-CoV-2