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04 Dec 2023 at 01:46
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Bibliography on: Long Covid: Review Papers


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Long Covid: Review Papers

Wikipedia: Long Covid refers to a group of health problems persisting or developing after an initial COVID-19 infection. Symptoms can last weeks, months or years and are often debilitating. Long COVID is characterised by a large number of symptoms, which sometimes disappear and reappear. Commonly reported symptoms of long COVID are fatigue, memory problems, shortness of breath, and sleep disorder. Many other symptoms can also be present, including headaches, loss of smell or taste, muscle weakness, fever, and cognitive dysfunction and problems with mental health. Symptoms often get worse after mental or physical effort, a process called post-exertional malaise. The causes of long COVID are not yet fully understood. Hypotheses include lasting damage to organs and blood vessels, problems with blood clotting, neurological dysfunction, persistent virus or a reactivation of latent viruses and autoimmunity. Diagnosis of long COVID is based on suspected or confirmed COVID-19 infection, symptoms and by excluding alternative diagnoses. Estimates of the prevalence of long COVID vary based on definition, population studied, time period studied, and methodology, generally ranging between 5% and 50%. Prevalence is less after vaccination.

Created with PubMed® Query: ( "long covid" AND review[SB] ) NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)


RevDate: 2023-12-03

Kayla KA, Bédard-Matteau J, Rousseau S, et al (2023)

Sex differences in vascular endothelial function related to acute and long COVID-19.

Vascular pharmacology pii:S1537-1891(23)00110-6 [Epub ahead of print].

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has been at the forefront of health sciences research since its emergence in China in 2019 that quickly led to a global pandemic. As a result of this research, and the large numbers of infected patients globally, there were rapid enhancements made in our understanding of Coronavirus disease 2019 (COVID-19) pathology, including its role in the development of uncontrolled immune responses and its link to the development of endotheliitis and endothelial dysfunction. There were also some noted differences in the rate and severity of infection between males and females with acute COVID. Some individuals infected with SARS-CoV-2 also experience long-COVID, an important hallmark symptom of this being Myalgic Encephalomyelitis-Chronic Fatigue Syndrome (ME-CFS), also experienced differently between males and females. The purpose of this review is to discuss the impact of sex on the vasculature during acute and long COVID-19, present any link between ME-CFS and endothelial dysfunction, and provide evidence for the relationship between ME-CFS and the immune system. We also will delineate biological sex differences observed in other post viral infections and, assess if sex differences exist in how the immune system responds to viral infection causing ME-CFS.

RevDate: 2023-11-29

Hulscher N, Procter BC, Wynn C, et al (2023)

Clinical Approach to Post-acute Sequelae After COVID-19 Infection and Vaccination.

Cureus, 15(11):e49204.

The spike protein of SARS-CoV-2 has been found to exhibit pathogenic characteristics and be a possible cause of post-acute sequelae after SARS-CoV-2 infection or COVID-19 vaccination. COVID-19 vaccines utilize a modified, stabilized prefusion spike protein that may share similar toxic effects with its viral counterpart. The aim of this study is to investigate possible mechanisms of harm to biological systems from SARS-CoV-2 spike protein and vaccine-encoded spike protein and to propose possible mitigation strategies. We searched PubMed, Google Scholar, and 'grey literature' to find studies that (1) investigated the effects of the spike protein on biological systems, (2) helped differentiate between viral and vaccine-generated spike proteins, and (3) identified possible spike protein detoxification protocols and compounds that had signals of benefit and acceptable safety profiles. We found abundant evidence that SARS-CoV-2 spike protein may cause damage in the cardiovascular, hematological, neurological, respiratory, gastrointestinal, and immunological systems. Viral and vaccine-encoded spike proteins have been shown to play a direct role in cardiovascular and thrombotic injuries from both SARS-CoV-2 and vaccination. Detection of spike protein for at least 6-15 months after vaccination and infection in those with post-acute sequelae indicates spike protein as a possible primary contributing factor to long COVID. We rationalized that these findings give support to the potential benefit of spike protein detoxification protocols in those with long-term post-infection and/or vaccine-induced complications. We propose a base spike detoxification protocol, composed of oral nattokinase, bromelain, and curcumin. This approach holds immense promise as a base of clinical care, upon which additional therapeutic agents are applied with the goal of aiding in the resolution of post-acute sequelae after SARS-CoV-2 infection and COVID-19 vaccination. Large-scale, prospective, randomized, double-blind, placebo-controlled trials are warranted in order to determine the relative risks and benefits of the base spike detoxification protocol.

RevDate: 2023-11-29

Wu J, Yang H, Yu D, et al (2023)

Blood-derived product therapies for SARS-CoV-2 infection and long COVID.

MedComm, 4(6):e426 pii:MCO2426.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is capable of large-scale transmission and has caused the coronavirus disease 2019 (COVID-19) pandemic. Patients with COVID-19 may experience persistent long-term health issues, known as long COVID. Both acute SARS-CoV-2 infection and long COVID have resulted in persistent negative impacts on global public health. The effective application and development of blood-derived products are important strategies to combat the serious damage caused by COVID-19. Since the emergence of COVID-19, various blood-derived products that target or do not target SARS-CoV-2 have been investigated for therapeutic applications. SARS-CoV-2-targeting blood-derived products, including COVID-19 convalescent plasma, COVID-19 hyperimmune globulin, and recombinant anti-SARS-CoV-2 neutralizing immunoglobulin G, are virus-targeting and can provide immediate control of viral infection in the short term. Non-SARS-CoV-2-targeting blood-derived products, including intravenous immunoglobulin and human serum albumin exhibit anti-inflammatory, immunomodulatory, antioxidant, and anticoagulatory properties. Rational use of these products can be beneficial to patients with SARS-CoV-2 infection or long COVID. With evidence accumulated since the pandemic began, we here summarize the progress of blood-derived product therapies for COVID-19, discuss the effective methods and scenarios regarding these therapies, and provide guidance and suggestions for clinical treatment.

RevDate: 2023-11-29

Boccatonda A, Campello E, Simion C, et al (2023)

Long-term hypercoagulability, endotheliopathy and inflammation following acute SARS-CoV-2 infection.

Expert review of hematology [Epub ahead of print].

INTRODUCTION: both symptomatic and asymptomatic SARS-CoV-2 infections - coined Coronavirus disease 2019 (COVID-19) - have been linked to a higher risk of cardiovascular events after recovery.

AREAS COVERED: our review aims to summarize the latest evidence on the increased thrombotic and cardiovascular risk in recovered COVID-19 patients and to examine the pathophysiological mechanisms underlying the interplay among endothelial dysfunction, inflammatory response and coagulation in long-COVID. We performed a systematic search of studies on hypercoagulability, endothelial dysfunction and inflammation after SARS-CoV-2 infection.

EXPERT OPINION: endothelial dysfunction is a major pathophysiological mechanism responsible for most clinical manifestations in COVID-19. The pathological activation of endothelial cells by a virus infection results in a pro-adhesive and chemokine-secreting phenotype, which in turn promotes the recruitment of circulating leukocytes. Cardiovascular events after COVID-19 appear to be related to persistent immune dysregulation. Patients with long-lasting symptoms display higher amounts of proinflammatory molecules such as tumor necrosis factor-α, interferon γ and interleukins 2 and 6. Immune dysregulation can trigger the activation of the coagulation pathway. The formation of extensive microclots in vivo, both during acute COVID-19 and in long-COVID-19, appears to be a relevant mechanism responsible for persistent symptoms and cardiovascular events.

RevDate: 2023-11-29

Guo B, Zhao C, He MZ, et al (2023)

Identifying patterns of reported findings on long-term cardiac complications of COVID-19: a systematic review and meta-analysis.

BMC medicine, 21(1):468.

INTRODUCTION: Prior reviews synthesized findings of studies on long-term cardiac complications of COVID-19. However, the reporting and methodological quality of these studies has not been systematically evaluated. Here, we conducted a systematic review and meta-analysis on long-term cardiac complications of COVID-19 and examined patterns of reported findings by study quality and characteristics.

METHODS: We searched for studies examining long-term cardiac complications of COVID-19 that persisted for 4 weeks and over. A customized Newcastle-Ottawa scale (NOS) was used to evaluate the quality of included studies. Meta-analysis was performed to generate prevalence estimates of long-term cardiac complications across studies. Stratified analyses were further conducted to examine the prevalence of each complication by study quality and characteristics. The GRADE approach was used to determine the level of evidence for complications included in the meta-analysis.

RESULTS: A total number of 150 studies describing 57 long-term cardiac complications were included in this review, and 137 studies reporting 17 complications were included in the meta-analysis. Only 25.3% (n = 38) of studies were of high quality based on the NOS quality assessment. Chest pain and arrhythmia were the most widely examined long-term complications. When disregarding study quality and characteristics, summary prevalence estimates for chest and arrhythmia were 9.79% (95% CI 7.24-13.11) and 8.22% (95% CI 6.46-10.40), respectively. However, stratified analyses showed that studies with low-quality scores, small sample sizes, unsystematic sampling methods, and cross-sectional design were more likely to report a higher prevalence of complications. For example, the prevalence of chest pain was 22.17% (95% CI 14.40-32.55), 11.08% (95% CI 8.65-14.09), and 3.89% (95% CI 2.49-6.03) in studies of low, medium, and high quality, respectively. Similar patterns were observed for arrhythmia and other less examined long-term cardiac complications.

CONCLUSION: There is a wide spectrum of long-term cardiac complications of COVID-19. Reported findings from previous studies are strongly related to study quality, sample sizes, sampling methods, and designs, underscoring the need for high-quality epidemiologic studies to characterize these complications and understand their etiology.

RevDate: 2023-11-28

Volk P, Rahmani Manesh M, Warren ME, et al (2023)

Long-term neurological dysfunction associated with COVID-19: Lessons from influenza and inflammatory diseases?.

Journal of neurochemistry [Epub ahead of print].

As the COVID-19 pandemic persists, SARS-CoV-2 infection is increasingly associated with long-term neurological side effects including cognitive impairment, fatigue, depression, and anxiety, colloquially known as "long-COVID." While the full extent of long-COVID neuropathology across years or even decades is not yet known, we can perhaps take direction from long-standing research into other respiratory diseases, such as influenza, that can present with similar long-term neurological consequences. In this review, we highlight commonalities in the neurological impacts of influenza and COVID-19. We first focus on the common potential mechanisms underlying neurological sequelae of long-COVID and influenza, namely (1) viral neurotropism and (2) dysregulated peripheral inflammation. The latter, namely heightened peripheral inflammation leading to central nervous system dysfunction, is emerging as a shared mechanism in various peripheral inflammatory or inflammation-associated diseases and conditions. We then discuss historical and modern examples of influenza- and COVID-19-associated cognitive impairment, depression, anxiety, and fatigue, revealing key similarities in their neurological sequelae. Although we are learning that the effects of influenza and COVID differ somewhat in terms of their influence on the brain, as the impacts of long-COVID grow, such comparisons will likely prove valuable in guiding ongoing research into long-COVID, and perhaps foreshadow what could be in store for individuals with COVID-19 and their brain health.

RevDate: 2023-11-25

Mohan A, Iyer VA, Kumar D, et al (2023)

Navigating the Post-COVID-19 Immunological Era: Understanding Long COVID-19 and Immune Response.

Life (Basel, Switzerland), 13(11): pii:life13112121.

The COVID-19 pandemic has affected the world unprecedentedly, with both positive and negative impacts. COVID-19 significantly impacted the immune system, and understanding the immunological consequences of COVID-19 is essential for developing effective treatment strategies. The purpose of this review is to comprehensively explore and provide insights into the immunological aspects of long COVID-19, a phenomenon where individuals continue to experience a range of symptoms and complications, even after the acute phase of COVID-19 infection has subsided. The immune system responds to the initial infection by producing various immune cells and molecules, including antibodies, T cells, and cytokines. However, in some patients, this immune response becomes dysregulated, leading to chronic inflammation and persistent symptoms. Long COVID-19 encompasses diverse persistent symptoms affecting multiple organ systems, including the respiratory, cardiovascular, neurological, and gastrointestinal systems. In the post-COVID-19 immunological era, long COVID-19 and its impact on immune response have become a significant concern. Post-COVID-19 immune pathology, including autoimmunity and immune-mediated disorders, has also been reported in some patients. This review provides an overview of the current understanding of long COVID-19, its relationship to immunological responses, and the impact of post-COVID-19 immune pathology on patient outcomes. Additionally, the review addresses the current and potential treatments for long COVID-19, including immunomodulatory therapies, rehabilitation programs, and mental health support, all of which aim to improve the quality of life for individuals with long COVID-19. Understanding the complex interplay between the immune system and long COVID-19 is crucial for developing targeted therapeutic strategies and providing optimal care in the post-COVID-19 era.

RevDate: 2023-11-25

Hu Y, Liu Y, Zheng H, et al (2023)

Risk Factors for Long COVID in Older Adults.

Biomedicines, 11(11): pii:biomedicines11113002.

As time has passed following the COVID-19 pandemic, individuals infected with SARS-CoV-2 have gradually exhibited a variety of symptoms associated with long COVID in the postacute phase of infection. Simultaneously, in many countries worldwide, the process of population aging has been accelerating. Within this context, the elderly population has not only become susceptible and high-risk during the acute phase of COVID-19 but also has considerable risks when confronting long COVID. Elderly individuals possess specific immunological backgrounds, and during the process of aging, their immune systems can enter a state known as "immunosenescence". This further exacerbates "inflammaging" and the development of various comorbidities in elderly individuals, rendering them more susceptible to long COVID. Additionally, long COVID can inflict both physical and mental harm upon elderly people, thereby reducing their overall quality of life. Consequently, the impact of long COVID on elderly people should not be underestimated. This review seeks to summarize the infection characteristics and intrinsic factors of older adults during the COVID-19 pandemic, with a focus on the physical and mental impact of long COVID. Additionally, it aims to explore potential strategies to mitigate the risk of long COVID or other emerging infectious diseases among older adults in the future.

RevDate: 2023-11-21

Sánchez-García JC, Reinoso-Cobo A, Piqueras-Sola B, et al (2023)

Long COVID and Physical Therapy: A Systematic Review.

Diseases (Basel, Switzerland), 11(4): pii:diseases11040163.

Prolonged COVID is a persistent condition following the initial COVID-19 infection, which is characterized by a variety of symptoms that may include fatigue, muscle pain, sleep disturbances, "brain fog", respiratory, cardiovascular, digestive, neurological and dermatological symptoms. Physical therapy has been identified as a crucial aspect of the management of patients with long COVID, as it can help improve symptoms and overall physical function. The investigation of long COVID poses significant challenges due to the diversity and variability of symptoms, lack of clear diagnostic criteria, and limited understanding of the underlying mechanisms. The aim of this study is to conduct a systematic review of studies conducted in patients with long COVID in conjunction with interventions targeting respiratory function, particularly involving physical activity. To this end, we conducted a systematic review to analyze studies conducted on treatment programs for long COVID based on some form of physical activity. The protocol of the review was registered in the PROSPERO website, and the databases PubMed, Scopus, CINAHL and WOS were searched. Of the 62 initial articles, six were included in the review. The results obtained have positive implications for the advancement of physical activity as a therapeutic intervention for individuals with long COVID-19 and the conceptualization of evidence-based treatment protocols. Statistically significant results have been observed in studies of at least 6 weeks duration, in which inspiratory muscle training exercises are proposed. Further research is needed to better understand long COVID and develop effective treatment strategies.

RevDate: 2023-11-21

Sievers BL, Cheng MTK, Csiba K, et al (2023)

SARS-CoV-2 and innate immunity: the good, the bad, and the "goldilocks".

Cellular & molecular immunology [Epub ahead of print].

An ancient conflict between hosts and pathogens has driven the innate and adaptive arms of immunity. Knowledge about this interplay can not only help us identify biological mechanisms but also reveal pathogen vulnerabilities that can be leveraged therapeutically. The humoral response to SARS-CoV-2 infection has been the focus of intense research, and the role of the innate immune system has received significantly less attention. Here, we review current knowledge of the innate immune response to SARS-CoV-2 infection and the various means SARS-CoV-2 employs to evade innate defense systems. We also consider the role of innate immunity in SARS-CoV-2 vaccines and in the phenomenon of long COVID.

RevDate: 2023-11-20
CmpDate: 2023-11-20

Aiyegbusi OL (2023)

COVID-19 related headaches: epidemiology, pathophysiology, impacts, and management.

Current opinion in neurology, 36(6):609-614.

PURPOSE OF REVIEW: This is an expert overview of the recent literature on the nature, epidemiology, pathophysiology, impact, and management of COVID-19 related headache, in the acute phase of infection and in post-COVID-19 syndrome.

RECENT FINDINGS: Headache is one of the commonest symptoms of COVID-19 during acute infection and it is often experienced by individuals who go on to develop long COVID. There is a higher prevalence of headache in individuals with long COVID who contracted the Delta variant than in those who were infected with the Wuhan or Alpha variants. Headaches related to COVID-19 infection are commoner and may be more intense in women.There are indications that presence of headache might indicate a more benign COVID-19 infection and a better chance of survival. However, the impact of COVID-19 related headache could be substantial leading to poor quality of life in individuals affected. Headache that changes in its nature in terms of frequency and severity should be investigated to exclude cerebrovascular complications. There are promising new therapies for its treatment, but further research is needed.

SUMMARY: The findings of this review can promote a better understanding of COVID-19 related headache and guide clinicians in the management of patients.

RevDate: 2023-11-15

Pierre V, Draica F, Di Fusco M, et al (2023)

The impact of vaccination and outpatient treatment on the economic burden of covid-19 in the United States omicron era: a systematic literature review.

Journal of medical economics [Epub ahead of print].

AIMS: To identify and synthesize evidence regarding how coronavirus disease 2019 (COVID-19) interventions, including vaccines and outpatient treatments, have impacted healthcare resource use (HCRU) and costs in the United States (US) during the Omicron era.

MATERIALS AND METHODS: A systematic literature review (SLR) was performed to identify articles published between 1 January 2021 and 10 March 2023 that assessed the impact of vaccination and outpatient treatment on costs and HCRU outcomes associated with COVID-19. Screening was performed by two independent researchers using predefined inclusion/exclusion criteria.

RESULTS: Fifty-eight unique studies were included in the SLR, of which all reported HCRU outcomes, and one reported costs. Overall, there was a significant reduction in the risk of COVID-19-related hospitalization for patients who received an original monovalent primary series vaccine plus booster dose vs. no vaccination. Moreover, receipt of a booster vaccine was associated with a lower risk of hospitalization vs. primary series vaccination. Evidence also indicated a significantly reduced risk of hospitalizations among recipients of nirmatrelvir/ritonavir (NMV/r), remdesivir, sotrovimab, and molnupiravir compared to non-recipients. Treated and/or vaccinated patients also experienced reductions in ICU admissions, length of stay, and emergency department (ED)/urgent care clinic encounters.

LIMITATIONS: The identified studies may not represent unique patient populations as many utilized the same regional/national data sources. Synthesis of the evidence was also limited by differences in populations, outcome definitions, and varying duration of follow-up across studies. Additionally, significant gaps, including HCRU associated with long COVID and various high-risk populations and cost data, were observed.

CONCLUSIONS: Despite evidence gaps, findings from the SLR highlight the significant positive impact that vaccination and outpatient treatment have had on HCRU in the US, including periods of Omicron predominance. Continued research is needed to inform clinical and policy decision-making in the US as COVID-19 continues to evolve as an endemic disease.

RevDate: 2023-11-14

Luchian ML, Higny J, Benoit M, et al (2023)

Unmasking Pandemic Echoes: An In-Depth Review of Long COVID's Unabated Cardiovascular Consequences beyond 2020.

Diagnostics (Basel, Switzerland), 13(21): pii:diagnostics13213368.

At the beginning of 2020, coronavirus disease 2019 (COVID-19) emerged as a new pandemic, leading to a worldwide health crisis and overwhelming healthcare systems due to high numbers of hospital admissions, insufficient resources, and a lack of standardized therapeutic protocols. Multiple genetic variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been detected since its first public declaration in 2020, some of them being considered variants of concern (VOCs) corresponding to several pandemic waves. Nevertheless, a growing number of COVID-19 patients are continuously discharged from hospitals, remaining symptomatic even months after their first episode of COVID-19 infection. Long COVID-19 or 'post-acute COVID-19 syndrome' emerged as the new pandemic, being characterized by a high variability of clinical manifestations ranging from cardiorespiratory and neurological symptoms such as chest pain, exertional dyspnoea or cognitive disturbance to psychological disturbances, e.g., depression, anxiety or sleep disturbance with a crucial impact on patients' quality of life. Moreover, Long COVID is viewed as a new cardiovascular risk factor capable of modifying the trajectory of current and future cardiovascular diseases, altering the patients' prognosis. Therefore, in this review we address the current definitions of Long COVID and its pathophysiology, with a focus on cardiovascular manifestations. Furthermore, we aim to review the mechanisms of acute and chronic cardiac injury and the variety of cardiovascular sequelae observed in recovered COVID-19 patients, in addition to the potential role of Long COVID clinics in the medical management of this new condition. We will further address the role of future research for a better understanding of the actual impact of Long COVID and future therapeutic directions.

RevDate: 2023-11-13

Gomaa AA, Abdel-Wadood YA, Thabet RH, et al (2023)

Pharmacological evaluation of vitamin D in COVID-19 and long COVID-19: recent studies confirm clinical validation and highlight metformin to improve VDR sensitivity and efficacy.

Inflammopharmacology [Epub ahead of print].

Nearly four years after its first appearance, and having gone from pandemic to endemic, the SARS-CoV-2 remains out of control globally. The purpose of this study was to evaluate the clinical efficacy of vitamin D (VD) in COVID-19 and long COVID-19, explain the discrepancy in clinical outcomes and highlight the potential impact of metformin on VD efficacy in recent articles. Articles from January 2022 to August 2023 were selected for this review. The objective of this study was achieved by reviewing, analyzing, and discussing articles demonstrating (1) the mechanism of action of VD (2) observational or randomized clinical trials (RCTs) that support or not the beneficial clinical effects of VD in COVID-19 or long COVID. (3) genetic and non-genetic reasons for the variation in the effects of VD. Articles were collected from electronic databases such as PubMed, Scopus, MEDLINE, Google Scholar, Egyptian Knowledge Bank, Science Direct, and Cochrane Database of Systematic Reviews. Twenty three studies conducted in vitro or in animal models indicated that VD may act in COVID-19 through protecting the respiratory system by antimicrobial peptide cathelicidins, reducing lung inflammation, regulating innate and adaptive immune functions and up regulation of autophagy gene activity. Our review identified 58 clinical studies that met the criteria. The number of publications supporting a beneficial clinical activity of VD in treating COVID-19 was 49 (86%), including 12 meta-analyses. Although the total patients included in all articles was 14,071,273, patients included in publications supporting a beneficial role of VD in COVID-19 were 14,029,411 (99.7%). Collectively, extensive observational studies indicated a decisive relationship between low VD levels and the severity of COVID-19 and mortality outcomes. Importantly, evidence from intervention studies has demonstrated the effectiveness of VD supplements in treating COVID-19. Furthermore, the results of 4 observational studies supported the beneficial role of VD in alleviating symptoms of long COVID-19 disease. However, eight RCTs and one meta-analysis of RCTs may contain low-grade evidence against a beneficial role of VD in COVID-19. Twenty-five articles have addressed the association between VDR and DBP genetic polymorphisms and treatment failure of VD in COVID-19. Impaired VDR signaling may underlie the variability of VD effects as non-genetic mechanisms. Interestingly, in recent studies, metformin has a beneficial therapeutic role in COVID-19 and long COVID-19, possibly by improving AMPK signaling of the VDR and enhancing the efficacy of the VD. In conclusion, evidence has been significantly strengthened over the past 18 months, with several meta-analyses and RCTs reporting conclusive beneficial effects of VD supplementation against COVID-19 and highlighting metformin to improve VDR sensitivity and efficacy in treating COVID-19 and long COVID-19.

RevDate: 2023-11-13

Marwaha B (2023)

Role of Tau protein in long COVID and potential therapeutic targets.

Frontiers in cellular and infection microbiology, 13:1280600.

INTRODUCTION: Long COVID is an emerging public health burden and has been defined as a syndrome with common symptoms of fatigue, shortness of breath, cognitive dysfunction, and others impacting day-to-day life, fluctuating or relapsing over, occurring for at least two months in patients with a history of probable or confirmed SARS CoV-2 infection; usually three months from the onset of illness and cannot be explained by an alternate diagnosis. The actual prevalence of long-term COVID-19 is unknown, but it is believed that more than 17 million patients in Europe may have suffered from it during pandemic.

PATHOPHYSIOLOGY: Currently, there is limited understanding of the pathophysiology of this syndrome, and multiple hypotheses have been proposed. Our literature review has shown studies reporting tau deposits in tissue samples of the brain from autopsies of COVID-19 patients compared to the control group, and the in-vitro human brain organoid model has shown aberrant phosphorylation of tau protein in response to SARS-CoV-2 infection. Tauopathies, a group of neurodegenerative disorders with the salient features of tau deposits, can manifest different symptoms based on the anatomical region of brain involvement and have been shown to affect the peripheral nervous system as well and explained even in rat model studies. Long COVID has more than 203 symptoms, with predominant symptoms of fatigue, dyspnea, and cognitive dysfunction, which tauopathy-induced CNS and peripheral nervous system dysfunction can explain. There have been no studies up till now to reveal the pathophysiology of long COVID. Based on our literature review, aberrant tau phosphorylation is a promising hypothesis that can be explored in future studies. Therapeutic approaches for tauopathies have multidimensional aspects, including targeting post-translational modifications, tau aggregation, and tau clearance through the autophagy process with the help of lysosomes, which can be potential targets for developing therapeutic interventions for the long COVID. In addition, future studies can attempt to find the tau proteins in CSF and use those as biomarkers for the long COVID.

RevDate: 2023-11-13
CmpDate: 2023-11-13

Grand RJ (2023)

SARS-CoV-2 and the DNA damage response.

The Journal of general virology, 104(11):.

The recent coronavirus disease 2019 (COVID-19) pandemic was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is characterized by respiratory distress, multiorgan dysfunction and, in some cases, death. The virus is also responsible for post-COVID-19 condition (commonly referred to as 'long COVID'). SARS-CoV-2 is a single-stranded, positive-sense RNA virus with a genome of approximately 30 kb, which encodes 26 proteins. It has been reported to affect multiple pathways in infected cells, resulting, in many cases, in the induction of a 'cytokine storm' and cellular senescence. Perhaps because it is an RNA virus, replicating largely in the cytoplasm, the effect of SARS-Cov-2 on genome stability and DNA damage responses (DDRs) has received relatively little attention. However, it is now becoming clear that the virus causes damage to cellular DNA, as shown by the presence of micronuclei, DNA repair foci and increased comet tails in infected cells. This review considers recent evidence indicating how SARS-CoV-2 causes genome instability, deregulates the cell cycle and targets specific components of DDR pathways. The significance of the virus's ability to cause cellular senescence is also considered, as are the implications of genome instability for patients suffering from long COVID.

RevDate: 2023-11-13
CmpDate: 2023-11-13

Bellanti JA, Novak P, Faitelson Y, et al (2023)

The Long Road of Long COVID: Specific Considerations for the Allergist/Immunologist.

The journal of allergy and clinical immunology. In practice, 11(11):3335-3345.

Long COVID (coronavirus disease 2019) syndrome, also known as post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is a new disorder that can develop after an acute infection with the SARS-CoV-2 virus. The condition is characterized by multiorgan system involvement with a wide range of symptoms that can vary in severity from mild to debilitating. Some of the common symptoms associated with long COVID syndrome include cardiovascular issues such as heart palpitations and chest pain; thrombotic events (eg, blood clotting disorders); metabolic problems (eg, type 2 diabetes); dysautonomia; paroxysmal orthostatic tachycardia syndrome; myalgic encephalomyelitis/chronic fatigue syndrome; reactivation of the Epstein-Barr virus; the presence of autoantibodies; chronic spontaneous urticaria (hives); and connective tissue diseases. Whereas long COVID syndrome can affect individuals from various backgrounds, certain populations may be at higher risk such as individuals of Hispanic and Latino heritage, as well as those with low socioeconomic status, although approximately one-third of affected patients have no known risk factors or preexisting conditions. Many survivors of COVID-19 struggle with multiple symptoms, increased disability, reduced function, and poor quality of life. Whereas vaccination has been the most significant intervention able to decrease the severity of acute SARS-Cov2 infection and curtail deaths, limited data are available related to its modulating effect on long COVID necessitating the need for further investigation. Furthermore, several inflammatory pathways have been proposed for the pathogenesis of long COVID that are the targets for ongoing clinical studies evaluating novel pharmacological agents. The purpose of the present report is to review the many factors associated with long COVID with a focus on those aspects that have relevance to the allergist-immunologist.

RevDate: 2023-11-13

Bradbury J, Wilkinson S, J Schloss (2023)

Nutritional Support During Long COVID: A Systematic Scoping Review.

Journal of integrative and complementary medicine, 29(11):695-704.

Introduction: Long COVID is a term that encompasses a range of signs, symptoms, and sequalae that continue or develop after an acute COVID-19 infection. The lack of early recognition of the condition contributed to delays in identifying factors that may contribute toward its development and prevention. The aim of this study was to scope the available literature to identify potential nutritional interventions to support people with symptoms associated with long COVID. Methods: This study was designed as a systematic scoping review of the literature (registration PROSPERO CRD42022306051). Studies with participants aged 18 years or older, with long COVID and who underwent a nutritional intervention were included in the review. Results: A total of 285 citations were initially identified, with five papers eligible for inclusion: two were pilot studies of nutritional supplements in the community, and three were nutritional interventions as part of inpatient or outpatient multidisciplinary rehabilitation programs. There were two broad categories of interventions: those that focused on compositions of nutrients (including micronutrients such as vitamin and mineral supplements) and those that were incorporated as part of multidisciplinary rehabilitation programs. Nutrients included in more than one study were multiple B group vitamins, vitamin C, vitamin D, and acetyl-l-carnitine. Discussion: Two studies trialed nutritional supplements for long COVID in community samples. Although these initial reports were positive, they are based on poorly designed studies and therefore cannot provide conclusive evidence. Nutritional rehabilitation was an important aspect of recovery from severe inflammation, malnutrition, and sarcopenia in hospital rehabilitation programs. Current gaps in the literature include a potential role for anti-inflammatory nutrients such as the omega 3 fatty acids, which are currently undergoing clinical trials, glutathione-boosting treatments such as N-acetylcysteine, alpha-lipoic acid, or liposomal glutathione in long COVID, and a possible adjunctive role for anti-inflammatory dietary interventions. This review provides preliminary evidence that nutritional interventions may be an important part of a rehabilitation program for people with severe long COVID symptomatology, including severe inflammation, malnutrition, and sarcopenia. For those in the general population with long COVID symptoms, the role of specific nutrients has not yet been studied well enough to recommend any particular nutrient or dietary intervention as a treatment or adjunctive treatment. Clinical trials of single nutrients are currently being conducted, and future systematic reviews could focus on single nutrient or dietary interventions to identify their nuanced mechanisms of action. Further clinical studies incorporating complex nutritional interventions are also warranted to strengthen the evidence base for using nutrition as a useful adjunctive treatment for people living with long COVID.

RevDate: 2023-11-11

Theoharides TC, Twahir A, D Kempuraj (2023)

Mast Cells in the Autonomic Nervous System and Potential Role in Disorders with Dysautonomia and Neuroinflammation.

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology pii:S1081-1206(23)01397-2 [Epub ahead of print].

Mast cells (MC) are ubiquitous in the body and are critical for allergic diseases, but also in immunity and inflammation, as well as potential involvement in the pathophysiology of dysautonomias and neuroinflammatory disorders. MC are located perivascularly close to nerve endings and sites such as the carotid bodies, heart, hypothalamus, the pineal and the adrenal glands that would allow them to regulate, but also be affected by the autonomic nervous system (ANS). MC are stimulated not only by allergens, but also many other triggers including some from the ANS that can affect MC release of neurosensitizing, proinflammatory and vasoactive mediators. Hence MC may be able to regulate homeostatic functions that appear to be dysfunctional in many conditions, such as postural orthostatic hypertension syndrome (POTS), autism spectrum disorder (ASD), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long-COVID syndrome. The evidence indicates that there is a possible association between these conditions and diseases associated with mast cell activation, There is no effective treatment for any form of these conditions other than minimizing symptoms. Given the many ways MC could be activated and the numerous mediators released, it would be important to develop ways to inhibit stimulation of MC and the release of ANS-relevant mediators.

RevDate: 2023-11-11

Ocampo FF, Promsena P, P Chan (2023)

Update on Central Nervous System Effects of the Intersection of HIV-1 and SARS-CoV-2.

Current HIV/AIDS reports [Epub ahead of print].

PURPOSE OF REVIEW: Research has shown myriad neurologic and mental health manifestations during the acute and subsequent stages of COVID-19 in people with HIV (PWH). This review summarizes the updates on central nervous system (CNS) outcomes following SARS-CoV-2 infection in PWH and highlight the existing knowledge gaps in this area.

RECENT FINDINGS: Studies leveraging electronic record systems have highlighted the excess risk of developing acute and lingering neurological complications of COVID-19 in PWH compared to people without HIV (PWoH). However, there is a notable scarcity of neuroimaging as well as blood and cerebrospinal fluid (CSF) marker studies that can confirm the potential synergy between these two infections, particularly in PWH receiving suppressive antiretroviral therapy. Considering the unclear potential interaction between SARS-CoV-2 and HIV, clinicians should remain vigilant regarding new-onset or worsening neurological symptoms in PWH following COVID-19, as they could be linked to either infection.

RevDate: 2023-11-10

Hira R, Karalasingham K, Baker JR, et al (2023)

Autonomic Manifestations of Long-COVID Syndrome.

Current neurology and neuroscience reports [Epub ahead of print].

PURPOSE OF REVIEW: Long-COVID is a novel condition emerging from the COVID-19 pandemic. Long-COVID is characterized by symptoms commonly seen in autonomic disorders including fatigue, brain fog, light-headedness, and palpitations. This article will critically evaluate recent findings and studies on Long-COVID and its physiological autonomic manifestations.

RECENT FINDINGS: Studies have reported on the prevalence of different symptoms and autonomic disorders in Long-COVID cohorts. Autonomic nervous system function, including both the parasympathetic and sympathetic limbs, has been studied using different testing techniques in Long-COVID patients. While numerous mechanisms may contribute to Long-COVID autonomic pathophysiology, it is currently unclear which ones lead to a Long-COVID presentation. To date, studies have not tested treatment options for autonomic disorders in Long-COVID patients. Long-COVID is associated with autonomic abnormalities. There is a high prevalence of clinical autonomic disorders among Long-COVID patients, with limited knowledge of the underlying mechanisms and the effectiveness of treatment options.

RevDate: 2023-11-09

Bhattacharjee N, Sarkar P, T Sarkar (2023)

Beyond the acute illness: Exploring long COVID and its impact on multiple organ systems.

Physiology international [Epub ahead of print].

Unprecedented worldwide health catastrophe due to the COVID-19 pandemic has ended up resulting in high morbidity and mortality rates. Even though many people recover from acute infection, there is rising concern regarding post-COVID-19 conditions (PCCs), often referred to as post-acute sequelae of SARS-CoV-2 infection (PASC) or "long COVID." The respiratory, cardiovascular, neurological, and endocrine systems are just a few of the many organ systems that can be impacted by this multifarious, complicated illness. The clinical manifestations of long COVID can vary among individuals and may include fatigue, dyspnea, chest pain, cognitive impairment, and new-onset diabetes, among others. Although the underlying processes of long COVID are not fully understood, they probably involve unregulated immune response, persistent generation of pro-inflammatory cytokines (chronic inflammation), autoimmune-like reactions, persistent viral replication, and micro-clot formation. To create successful treatments and care plans, it is essential to comprehend the immunological mechanisms causing these difficulties. The pathogenesis of long COVID should be clarified and potential biomarkers to help with diagnosis and treatment should be sought after. To reduce the burden of long COVID on people and healthcare systems around the world, the need for long-term monitoring and management of long COVID problems should be emphasized. It also underscores the significance of a multidisciplinary approach to patient care. The goal of this review is to carefully evaluate the clinical signs and symptoms of long COVID, their underlying causes, and any potential immunological implications.

RevDate: 2023-11-09

Müller L, S Di Benedetto (2023)

From aging to long COVID: exploring the convergence of immunosenescence, inflammaging, and autoimmunity.

Frontiers in immunology, 14:1298004.

The process of aging is accompanied by a dynamic restructuring of the immune response, a phenomenon known as immunosenescence. This mini-review navigates through the complex landscape of age-associated immune changes, chronic inflammation, age-related autoimmune tendencies, and their potential links with immunopathology of Long COVID. Immunosenescence serves as an introductory departure point, elucidating alterations in immune cell profiles and their functional dynamics, changes in T-cell receptor signaling, cytokine network dysregulation, and compromised regulatory T-cell function. Subsequent scrutiny of chronic inflammation, or "inflammaging," highlights its roles in age-related autoimmune susceptibilities and its potential as a mediator of the immune perturbations observed in Long COVID patients. The introduction of epigenetic facets further amplifies the potential interconnections. In this compact review, we consider the dynamic interactions between immunosenescence, inflammation, and autoimmunity. We aim to explore the multifaceted relationships that link these processes and shed light on the underlying mechanisms that drive their interconnectedness. With a focus on understanding the immunological changes in the context of aging, we seek to provide insights into how immunosenescence and inflammation contribute to the emergence and progression of autoimmune disorders in the elderly and may serve as potential mediator for Long COVID disturbances.

RevDate: 2023-11-08

Wolff D, Drewitz KP, Ulrich A, et al (2023)

Allergic diseases as risk factors for Long-COVID symptoms: Systematic review of prospective cohort studies.

Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology [Epub ahead of print].

OBJECTIVE: The role of allergy as a risk factor for Long-COVID (LC) is unclear and has not been thoroughly examined yet. We aimed to systematically review and appraise the epidemiological evidence on allergic diseases as risk factors for LC.

DESIGN: This is an initial systematic review. Two reviewers independently performed the study selection and data extraction using Covidence. Risk of bias (RoB) and certainty of evidence (GRADE) were assessed. Random effects meta-analyses were used to pool unadjusted ORs within homogeneous data subsets.

DATA SOURCES: We retrieved articles published between January 1st, 2020 and January 19th, 2023 from MEDLINE via PubMed, Scopus, the WHO-COVID-19 database and the LOVE platform (Epistemonikos Foundation). In addition, citations and reference lists were searched.

ELIGIBILITY CRITERIA: We included prospective cohort studies recruiting individuals of all ages with confirmed SARS-CoV-2 infection that were followed up for at least 12 months for LC symptoms where information on pre-existing allergic diseases was available. We excluded all study designs that were not prospective cohort studies and all publication types that were not original articles.

RESULTS: We identified 13 studies (9967 participants, range 39-1950 per study), all assessed as high RoB, due to population selection and methods used to ascertain the exposures and the outcome. Four studies did not provide sufficient data to calculate Odds Ratios. The evidence supported a possible relationship between LC and allergy, but was very uncertain. For example, pre-existing asthma measured in hospital-based populations (6 studies, 4019 participants) may be associated with increased risk of LC (Odds Ratio 1.94, 95% CI 1.08, 3.50) and findings were similar for pre-existing rhinitis (3 studies, 1141 participants; Odds Ratio 1.96, 95% CI 1.61, 2.39), both very low certainty evidence.

CONCLUSIONS: Pre-existing asthma or rhinitis may increase the risk of LC.

RevDate: 2023-11-06

Borczuk AC (2023)

Pathogenesis of pulmonary long COVID-19.

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc pii:S0893-3952(23)00283-1 [Epub ahead of print].

COVID-19 Is characterized by an acute respiratory illness that in some patients progresses to respiratory failure, largely demonstrating a pattern of acute respiratory distress syndrome. Excluding fatal cases, the outcome of this severe illness ranges from complete resolution to persistent respiratory dysfunction. This subacute to chronic respiratory illness has different manifestations, collectively called "long-COVID." The pathogenesis of organ dysfunction in acute injury stems from exaggerated innate immune response, complement activation and monocyte influx with a shift towards an organ injury state with abnormalities in cellular maturation. While the increased rate of thrombosis seen in acute COVID-19 does not appear to persist, interestingly, ongoing symptomatic COVID-19 and post-COVID pathogenesis appear to reflect persistence of the immune and cellular disturbance triggered by the acute and subacute period.

RevDate: 2023-11-06

Matveeva N, Kiselev I, Baulina N, et al (2023)

Shared genetic architecture of COVID-19 and Alzheimer's disease.

Frontiers in aging neuroscience, 15:1287322.

The severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and the сoronavirus disease 2019 (COVID-19) have become a global health threat. At the height of the pandemic, major efforts were focused on reducing COVID-19-associated morbidity and mortality. Now is the time to study the long-term effects of the pandemic, particularly cognitive impairment associated with long COVID. In recent years much attention has been paid to the possible relationship between COVID-19 and Alzheimer's disease, which is considered a main cause of age-related cognitive impairment. Genetic predisposition was shown for both COVID-19 and Alzheimer's disease. However, the analysis of the similarity of the genetic architecture of these diseases is usually limited to indicating a positive genetic correlation between them. In this review, we have described intrinsic linkages between COVID-19 and Alzheimer's disease, pointed out shared susceptibility genes that were previously identified in genome-wide association studies of both COVID-19 and Alzheimer's disease, and highlighted a panel of SNPs that includes candidate genetic risk markers of the long COVID-associated cognitive impairment.

RevDate: 2023-11-05

Gorst SL, Seylanova N, Dodd SR, et al (2023)

Core outcome measurement instruments for use in clinical and research settings for adults with post-COVID-19 condition: an international Delphi consensus study.

The Lancet. Respiratory medicine pii:S2213-2600(23)00370-3 [Epub ahead of print].

Post-COVID-19 condition (also known as long COVID) is a new, complex, and poorly understood disorder. A core outcome set (COS) for post-COVID-19 condition in adults has been developed and agreement is now required on the most appropriate measurement instruments for these core outcomes. We conducted an international consensus study involving multidisciplinary experts and people with lived experience of long COVID. The study comprised a literature review to identify measurement instruments for the core outcomes, a three-round online modified Delphi process, and an online consensus meeting to generate a core outcome measurement set (COMS). 594 individuals from 58 countries participated. The number of potential instruments for the 12 core outcomes was reduced from 319 to 19. Consensus was reached for inclusion of the modified Medical Research Council Dyspnoea Scale for respiratory outcomes. Measures for two relevant outcomes from a previously published COS for acute COVID-19 were also included: time until death, for survival, and the Recovery Scale for COVID-19, for recovery. Instruments were suggested for consideration for the remaining nine core outcomes: fatigue or exhaustion, pain, post-exertion symptoms, work or occupational and study changes, and cardiovascular, nervous system, cognitive, mental health, and physical outcomes; however, consensus was not achieved for instruments for these outcomes. The recommended COMS and instruments for consideration provide a foundation for the evaluation of post-COVID-19 condition in adults, which should help to optimise clinical care and accelerate research worldwide. Further assessment of this COMS is warranted as new data emerge on existing and novel measurement instruments.

RevDate: 2023-11-03
CmpDate: 2023-11-03

Assaf S, Stenberg H, Jesenak M, et al (2023)

Asthma in the era of COVID-19.

Respiratory medicine, 218:107373.

Since its global invasion in 2019, COVID-19 has affected several aspects of patients' lives and posed a significant impact on the health care system. Several patient populations were identified to be at high risk of contracting SARS-CoV-2 infection and/or developing severe COVID-19-related sequelae. Conversely, anyone who has contracted SARS-CoV-2 is at risk to experience symptoms and signs consistent with post-COVID manifestations. Patients with asthma were initially thought to be at increased risk and severity for SARS-CoV-2 infection. However, accumulating evidence demonstrates that asthma endotypes/phenotypes and comorbidities influence the risk stratification in this population. Furthermore, initial concerns about the potentially increased risk of poor outcomes with asthma treatments such as inhaled corticosteroids and biologics have not been substantiated. In this review, we provide an update on COVID-19 and asthma, including risk of susceptibility, clinical manifestations and course in this population as well as discuss recommendations for management.

RevDate: 2023-11-02

Marschalek R (2023)

SARS-CoV-2: The Virus, Its Biology and COVID-19 Disease-Counteracting Possibilities.

Frontiers in bioscience (Landmark edition), 28(10):273.

Since the end of 2019, the SARS-CoV-2 virus started to spread in different countries, leading to a world-wide pandemia, with today's infection numbers of more than 690 million and with a case fatality rate of more than 6.9 million. In addition, about 65 million patients suffer from post/long-Covid syndromes after having infections with the SARS-CoV-2 virus or variants thereof. This review highlights the biology of the virus, summarizes our knowledge of some of the viral mechanisms that counteract our immune responses, and finally also discusses the different vaccines and their specific safety profiles. Also, the possibility to fight this virus with recently available drugs (Veklury, Lagevrio and Paxlovid) will be discussed. All these data clearly argue that SARS-CoV-2 variants still exhibit a dangerous potential-although with a lower case fatality rate-and that vaccination in combination with drug intake upon infection may help to lower the risk of developing chronic or temporary autoimmune diseases.

RevDate: 2023-11-02
CmpDate: 2023-11-02

Riepl M, J Kaiser (2023)

Compounding for the Treatment of COVID-19 and Long COVID, Part 5: Associated Conditions, Prophylaxis, and Effective Treatment.

International journal of pharmaceutical compounding, 27(5):368-380.

The effects of infection with the highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the coronavirus- disease-2019 (COVID-19) it engenders continue to demonstrate that worldwide, the detection, prediction, and control of novel-pathogen pandemics remain largely unattained achievements. Key to successfully meeting those goals is a thorough understanding of the mechanisms of evolving causative agents and effective prophylaxis against them. In this article, we review common conditions that afflict people with COVID-19 or long COVID, examine the effectiveness of vaccines designed to prevent infection with SARS-CoV-2 and mitigate its sequelae, and provide formulations for 2 compounded preparations that can assist recovery from acute and chronic conditions caused by that virus when manufactured drugs are unavailable in required dosages or dosage forms or cannot be tolerated by the patient.

RevDate: 2023-11-02
CmpDate: 2023-11-02

De Vitis R, Passiatore M, Cilli V, et al (2023)


Georgian medical news.

COVID-19 may be asymptomatic or have a typical presentation with fever, cough, anosmia, lymphocytopenia. In some cases, it occurs with a "chimeric" presentation, with more subtle and ambiguous symptoms which may be initially misdiagnosed and are referred to in long covid condition. A possible central and peripheral nervous system involvement has been recognized. We present our experience and review the literature about association between carpal tunnel syndrome (CTS) and hand's arthritis presenting a case series of patients who firmly state that their condition of CTS arised or got worse during a typical presentation of COVID-19. The outbreak of COVID-19 has resulted in significant global healthcare implications. While the respiratory manifestations of COVID-19 have been widely studied, there is emerging evidence suggesting potential associations between COVID-19 and various other health conditions. This review of the literature aims to investigate the potential relationship between COVID-19 and the development or exacerbation of CTS. By synthesizing the available literature on this topic, we aim to provide a comprehensive overview of the current knowledge and enhance our understanding of the potential implications of COVID-19 on CTS. Case series: In this article we report 13 cases of typical presentations of COVID-19 with fever, myalgia, and respiratory system involvement, with a simultaneous aggravation of the median nerve pre-existing neuralgia and some cases that developed a median nerve neuralgia during COVID-19, which came to the attention of the hand surgeon. Some cases had stable symptomatic CTS and were on waiting list for surgical carpal tunnel release, some cases were previously asymptomatic and developed a median nerve neuralgia during COVID-19. All patients referred to a rapid worsening of acral paraesthesia and neuralgic pain of the same quality of CTS and in the median nerve topography. Some patients developed typical COVID-19 symptoms and died; the others were surgically treated. CTS could be an atypical presentations of COVID-19 or a condition of long-covid disease and clinical and epidemiological significance needs to be fully studied. We presented cases of worsening of the median nerve neuralgia which presented among other symptoms of COVID infection. We conclude a causal relation may exist and needs to be further investigated.

RevDate: 2023-11-02
CmpDate: 2023-11-02

Riepl M, J Kaiser (2023)

Compounding for the Treatment of COVID-19 and Long COVID, Part 4: The Legacy of Chronic COVID.

International journal of pharmaceutical compounding, 27(4):284-293.

People infected by severe acute respiratory coronavirus 2 (SARS-CoV-2) risk the development of not only acute coronavirus- disease-2019 (COVID-19) - the signs and symptoms of which range from none to severe illness that requires intensive treatment - but also long COVID (i.e., chronic COVID), a cyclical, progressive, multiphasic illness characterized by myriad debilitating conditions that persist long term. In some patients, those sequelae result in psychiatric disorders that can lead to suicide or other forms of self-harm, incidences of which have increased exponentially since before the COVID pandemic. It has been suggested that long COVID develops in an estimated 10% to 35% of people diagnosed as having COVID-19. Because the success of therapy for either form of COVID can be complicated by each patient's pharmacogenomic profile, personal treatment preferences, medical needs, and/or dosing requirements, we have found that in some people so afflicted, manufactured medications are ineffective or intolerable, and that for those individuals, a customized compound often provides relief and promotes recovery. The primary focus of this article is long COVID. The pathogenesis of that disease is reviewed, therapies for the signs and symptoms it engenders are examined, and 2 compounded formulations effective in treating both acute and chronic COVID-19 are presented.

RevDate: 2023-11-02
CmpDate: 2023-11-02

Kioi Y, Yorifuji H, Higami Y, et al (2023)

Serositis and lymphopenia are common features of systemic lupus erythematosus following SARS-CoV-2 infection: A case report and literature review.

International journal of rheumatic diseases, 26(11):2267-2271.

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect a number of human systems, including the respiratory, cardiovascular, neurological, gastrointestinal, and musculoskeletal systems. These symptoms persist long after the acute infection has healed and is called "long COVID". Interestingly, there have been a series of reports that SARS-CoV-2 infections trigger the development of various autoimmune diseases such as systemic lupus erythematosus (SLE), inflammatory arthritis, myositis, vasculitis. Here, we report a novel case of SLE characterized by persistent pleural effusion and lymphopenia following SARS-CoV-2 infection. This is the first case in the Western Pacific region to our knowledge. Furthermore, we reviewed 10 similar cases including our case. By looking at the characteristics of each case, we found that serositis and lymphopenia are common features of SLE following SARS-CoV-2 infection. Our finding suggests that patients with prolonged pleural effusion and/or lymphopenia after COVID-19 should be checked for autoantibodies.

RevDate: 2023-11-01

Li J, Zhou Y, Ma J, et al (2023)

The long-term health outcomes, pathophysiological mechanisms and multidisciplinary management of long COVID.

Signal transduction and targeted therapy, 8(1):416.

There have been hundreds of millions of cases of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the growing population of recovered patients, it is crucial to understand the long-term consequences of the disease and management strategies. Although COVID-19 was initially considered an acute respiratory illness, recent evidence suggests that manifestations including but not limited to those of the cardiovascular, respiratory, neuropsychiatric, gastrointestinal, reproductive, and musculoskeletal systems may persist long after the acute phase. These persistent manifestations, also referred to as long COVID, could impact all patients with COVID-19 across the full spectrum of illness severity. Herein, we comprehensively review the current literature on long COVID, highlighting its epidemiological understanding, the impact of vaccinations, organ-specific sequelae, pathophysiological mechanisms, and multidisciplinary management strategies. In addition, the impact of psychological and psychosomatic factors is also underscored. Despite these crucial findings on long COVID, the current diagnostic and therapeutic strategies based on previous experience and pilot studies remain inadequate, and well-designed clinical trials should be prioritized to validate existing hypotheses. Thus, we propose the primary challenges concerning biological knowledge gaps and efficient remedies as well as discuss the corresponding recommendations.

RevDate: 2023-10-30
CmpDate: 2023-10-30

Koleničová V, Vňuková MS, Anders M, et al (2023)

A Review Article on Exercise Intolerance in Long COVID: Unmasking the Causes and Optimizing Treatment Strategies.

Medical science monitor : international medical journal of experimental and clinical research, 29:e941079 pii:941079.

There is a growing body of research on SARS-CoV-2 (PASC), previously known as the post-COVID syndrome, a chronic condition characterized by symptoms that persist after SARS-CoV-2 infection. Among these symptoms, feelings of physical exhaustion and prolonged fatigue are particularly prevalent and can significantly impact patients' quality of life. These symptoms are associated with reduced overall physical capacity, decreased daily physical activity, malaise after intense training, and intolerance to physical activity (IFA). IFA, described as a reduced ability to perform physical activities typical for the patient's age, can often lead to a sedentary lifestyle. Prolonged physical inactivity can cause deterioration in the overall physical condition and disrupt mitochondrial function, triggering a vicious cycle of gradual symptom worsening. The underlying causes of PASC remain unclear; however, several biochemical mechanisms have been discussed to explain the body's energy depletion, and a multidisciplinary approach that combines physical and cognitive rehabilitation and lifestyle interventions such as exercise and diet modifications has been suggested to improve the overall health and well-being of PASC patients. This critical review aims to review the existing research on the possible causes and links among chronic fatigue, reduced physical activity, and exercise intolerance in patients with PASC. Further research into the underlying causes and treatment of PASC and the importance of developing individualized treatment is needed to address each patient's unique health requirements.

RevDate: 2023-10-30
CmpDate: 2023-10-30

Edward JA, Peruri A, Rudofker E, et al (2023)

Characteristics and Treatment of Exercise Intolerance in Patients With Long COVID.

Journal of cardiopulmonary rehabilitation and prevention, 43(6):400-406.

The post-acute sequalae of SARS-CoV-2, also known as "Long COVID," is characterized by profound fatigue, impaired functional capacity with post-exertional malaise, orthostatic intolerance, and tachycardia. At least 25-30% of individuals impacted by SARS-CoV-2 will go on to experience the Long COVID syndrome, underscoring the detrimental impact this condition has on society. Although efforts are underway to further understand risk factors for Long COVID and identify strategies to prevent disease development entirely, implementation of treatment strategies is warranted to alleviate symptom burden among those affected. This review provides a rationale for exercise prescriptions tailored to the Long COVID patient based on the pathophysiology underlying this syndrome, as well as the previously demonstrated benefits of exercise training in other similar populations whose clinical manifestations result from cardiac deconditioning. Herein, we discuss methods to tailor exercise protocols, accommodating exercise intolerance and post-exertional malaise that may otherwise limit the ability to participate in a training protocol, as well as data demonstrating that a focused exercise prescription may effectively alleviate symptom burden in these patients. Long COVID results, in large part, from deconditioning, which may result from as little as 20 hr of inactivity. Exercise prescriptions tailored to patients with Long COVID may effectively alleviate symptom burden associated with this condition and in the absence of overt contraindications should be considered in management.

RevDate: 2023-10-28

Tziolos NR, Ioannou P, Baliou S, et al (2023)

Long COVID-19 Pathophysiology: What Do We Know So Far?.

Microorganisms, 11(10): pii:microorganisms11102458.

Long COVID-19 is a recognized entity that affects millions of people worldwide. Its broad clinical symptoms include thrombotic events, brain fog, myocarditis, shortness of breath, fatigue, muscle pains, and others. Due to the binding of the virus with ACE-2 receptors, expressed in many organs, it can potentially affect any system; however, it most often affects the cardiovascular, central nervous, respiratory, and immune systems. Age, high body mass index, female sex, previous hospitalization, and smoking are some of its risk factors. Despite great efforts to define its pathophysiology, gaps remain to be explained. The main mechanisms described in the literature involve viral persistence, hypercoagulopathy, immune dysregulation, autoimmunity, hyperinflammation, or a combination of these. The exact mechanisms may differ from system to system, but some share the same pathways. This review aims to describe the most prevalent pathophysiological pathways explaining this syndrome.

RevDate: 2023-10-27

Moyo E, Chimene M, Moyo P, et al (2023)

Risk factors and clinical presentations of long COVID in Africa: A scoping review.

Journal of infection and public health, 16(12):1982-1988 pii:S1876-0341(23)00317-9 [Epub ahead of print].

COVID-19-related complications can last for years, even in patients who are asymptomatic during the acute phase, a phenomenon referred to as long COVID. This scoping review aimed to summarize the risk factors and clinical symptoms of long COVID in Africa between 2020 and 2022. Five studies were included. Three of the studies used in this review were retrospective cross-sectional studies, one was a prospective cohort study while another one was a case-control study. The review identified several risk factors for long COVID, including being female, being older than 40 years, having more than four acute COVID-19 symptoms, and having concomitant conditions such as asthma, hypertension, and depression. General, respiratory, cardiovascular, otolaryngological, gastrointestinal, and neurological symptoms were among the reported long COVID symptoms. To ensure that patients with long COVID are diagnosed and treated early, the risk factors and clinical symptoms of long COVID need to be identified for different population groups.

RevDate: 2023-10-25

Zhang Y, Y Li (2023)

Clinical Translation of Aptamers for COVID-19.

Journal of medicinal chemistry [Epub ahead of print].

The COVID-19 etiologic agent, SARS-CoV-2, continues to be one of the leading causes of death on a global scale. Although efficient methods for diagnosis and treatment of COVID-19 have been developed, new methods of battling SARS-CoV-2 variants and long COVID are still urgently needed. A number of aptamers have demonstrated tremendous potential to be developed into diagnostic and therapeutic agents for COVID-19. The translation of the aptamers for clinical uses, however, has been extremely slow. Overcoming the difficulties faced by aptamers would advance this technology toward clinical use for COVID-19 and other serious disorders.

RevDate: 2023-10-23

Shah B, Ahmad MN, Khalid M, et al (2023)

Long COVID and Wavering Incidence of Pulmonary Embolism: A Systematic Review.

Journal of community hospital internal medicine perspectives, 13(5):23-31.

Pulmonary embolism (PE) is a serious medical condition that can occur as a result of venous thromboembolism (VTE). COVID-19, also known as Post-Acute Sequelae of SARS-CoV-2 infection (PASC), can potentially lead to PE due to the formation of blood clots in the lungs. This study aims to collate and report trends of PE in patients with long COVID (4-12 weeks since infection) and post-COVID-19 syndrome (>12 weeks since infection). The study adhered to PRISMA Statement 2020 guidelines, and a systematic search was conducted in four databases. In total, nine observational studies were included with a total patient count of 45,825,187. The incidence of PE with long COVID/post-COVID-19 syndrome was seen among 31,885 individuals out of 44,967,887 participants. The incidence rate of PE was observed as 0.07%, given that the studies included matched controls. While we cannot state with certainty that COVID-19 infection in itself leads to higher risks of PE at a later time, this study emphasizes the need for optimized care and longitudinal studies during the COVID-19 era to account for deviations from the norm.

RevDate: 2023-10-23
CmpDate: 2023-10-23

Ortega-Paz L, Talasaz AH, Sadeghipour P, et al (2023)

COVID-19-Associated Pulmonary Embolism: Review of the Pathophysiology, Epidemiology, Prevention, Diagnosis, and Treatment.

Seminars in thrombosis and hemostasis, 49(8):816-832.

COVID-19 is associated with endothelial activation in the setting of a potent inflammatory reaction and a hypercoagulable state. The end result of this thromboinflammatory state is an excess in thrombotic events, in particular venous thromboembolism. Pulmonary embolism (PE) has been of special interest in patients with COVID-19 given its association with respiratory deterioration, increased risk of intensive care unit admission, and prolonged hospital stay. The pathophysiology and clinical characteristics of COVID-19-associated PE may differ from the conventional non-COVID-19-associated PE. In addition to embolic events from deep vein thrombi, in situ pulmonary thrombosis, particularly in smaller vascular beds, may be relevant in patients with COVID-19. Appropriate prevention of thrombotic events in COVID-19 has therefore become of critical interest. Several changes in viral biology, vaccination, and treatment management during the pandemic may have resulted in changes in incidence trends. This review provides an overview of the pathophysiology, epidemiology, clinical characteristics, and risk factors of COVID-19-associated PE. Furthermore, we briefly summarize the results from randomized controlled trials of preventive antithrombotic therapies in COVID-19, focusing on their findings related to PE. We discuss the acute treatment of COVID-19-associated PE, which is substantially similar to the management of conventional non-COVID-19 PE. Ultimately, we comment on the current knowledge gaps in the evidence and the future directions in the treatment and follow-up of COVID-19-associated PE, including long-term management, and its possible association with long-COVID.

RevDate: 2023-10-22

Luo D, Mei B, Wang P, et al (2023)

Prevalence and risk factors for persistent symptoms after COVID-19: a systematic review and meta-analysis.

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases pii:S1198-743X(23)00526-8 [Epub ahead of print].

BACKGROUND: Long-term physical and mental persistent symptoms following COVID-19 represent a growing global public health concern. However, there remains a substantial knowledge gap regarding their prevalence and risk factors.

OBJECTIVES: To estimate the prevalence and risk factors for persistent symptoms after COVID-19.

DATA SOURCES: Electronic databases were searched for studies published from December 2019 to January 2023.

STUDY ELIGIBILITY CRITERIA: Eligible studies that reported the prevalence and risk factors for persistent symptoms following COVID-19 were included.

PARTICIPANTS: Patients who recovered from COVID-19.

ASSESSMENT OF RISK OF BIAS: The Joanna Briggs Institute critical appraisal tool was used to assess the risk of bias in prevalence studies, while the risk of bias in cohort studies was evaluated with the Newcastle-Ottawa Scale.

METHODS: We used a random-effects model to pool persistent symptom prevalence and risk ratios comparing COVID-19 patients with non-COVID-19 individuals.

RESULTS: After screening 4,359 studies, a total of 211 eligible studies were included, covering a population of 13,368,074 individuals. Fatigue, dyspnea, post-traumatic stress disorder, anxiety, and depression were the most frequently reported persistent symptoms after COVID-19. Subgroup analyses revealed that individuals with more severe illness in the acute phase or from Europe exhibited a higher prevalence of certain symptoms, whereas children demonstrated a lower prevalence. Furthermore, COVID-19 patients had a significantly higher prevalence of most persistent symptoms compared to non-COVID-19 individuals. Factors frequently associated with a higher prevalence of persistent symptoms included female gender, advanced age, severe illness during the acute phase of COVID-19, multiple comorbidities, an extended duration of hospital stay, and a high body mass index.

CONCLUSION: This meta-analysis provides a thorough review of the prevalence and risk factors for persistent symptoms following COVID-19. The findings underscore the importance of long-term monitoring and support for individuals recovering from COVID-19.

RevDate: 2023-10-22
CmpDate: 2023-10-22

Hon KLE, Leung AKC, Leung KKY, et al (2024)

Impact of "Long Covid" on Children: Global and Hong Kong Perspectives.

Current pediatric reviews, 20(1):59-65.

BACKGROUND: The coronavirus disease (COVID-19) pandemic spares no nation or city, and the virus is responsible for the escalating incidence and mortality worldwide.

OBJECTIVE: This article reviews the impact of "Long Covid" on Children.

METHODS: A PubMed search was conducted in December 2021 in Clinical Queries using the key terms "COVID-19" OR "long COVID". The search was restricted to children and adolescent aged < 18 years and English literature.

RESULTS: Many large-scale studies have provided strong scientific evidence as to the detrimental and irreversible sequelae of COVID-19 on the health, psychology, and development of affected children. Many insights into managing this disease can be obtained from comparing the management of influenza. COVID-19 is generally a mild respiratory disease in children. Several syndromes, such as multisystem inflammatory syndrome in children (MIS-C) and COVID toe, are probably not specific to SARS-CoV-2. "Long COVID", or the long-term effects of SARS-CoV-2 infection, or the prolonged isolation and containment strategies on education and psychosocial influences on children associated with the pandemic, are significant.

CONCLUSION: Healthcare providers must be aware of the potential effects of quarantine on children's mental health. More importantly, healthcare providers must appreciate the importance of the decisions and actions made by governments, non-governmental organizations, the community, schools, and parents in reducing the possible effects of this situation. Multifaceted age-specific and developmentally appropriate strategies must be adopted by healthcare authorities to lessen the negative impact of quarantine on the psychological well-being of children.

RevDate: 2023-10-22
CmpDate: 2023-10-22

Ormiston CK, Świątkiewicz I, PR Taub (2022)

Postural orthostatic tachycardia syndrome as a sequela of COVID-19.

Heart rhythm, 19(11):1880-1889.

Postural orthostatic tachycardia syndrome (POTS) is a complex multisystem disorder characterized by orthostatic intolerance and tachycardia and may be triggered by viral infection. Recent reports indicate that 2%-14% of coronavirus disease 2019 (COVID-19) survivors develop POTS and 9%-61% experience POTS-like symptoms, such as tachycardia, orthostatic intolerance, fatigue, and cognitive impairment within 6-8 months of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Pathophysiological mechanisms of post-COVID-19 POTS are not well understood. Current hypotheses include autoimmunity related to SARS-CoV-2 infection, autonomic dysfunction, direct toxic injury by SARS-CoV-2 to the autonomic nervous system, and invasion of the central nervous system by SARS-CoV-2. Practitioners should actively assess POTS in patients with post-acute COVID-19 syndrome symptoms. Given that the symptoms of post-COVID-19 POTS are predominantly chronic orthostatic tachycardia, lifestyle modifications in combination with the use of heart rate-lowering medications along with other pharmacotherapies should be considered. For example, ivabradine or β-blockers in combination with compression stockings and increasing salt and fluid intake has shown potential. Treatment teams should be multidisciplinary, including physicians of various specialties, nurses, psychologists, and physiotherapists. Additionally, more resources to adequately care for this patient population are urgently needed given the increased demand for autonomic specialists and clinics since the start of the COVID-19 pandemic. Considering our limited understanding of post-COVID-19 POTS, further research on topics such as its natural history, pathophysiological mechanisms, and ideal treatment is warranted. This review evaluates the current literature available on the associations between COVID-19 and POTS, possible mechanisms, patient assessment, treatments, and future directions to improving our understanding of post-COVID-19 POTS.

RevDate: 2023-10-20

Luchting B, Behrends U, Eigner B, et al (2023)

[Interdisciplinary multimodal pain therapy in postviral syndromes and ME/CFS : Features, pitfalls and model concept].

Schmerz (Berlin, Germany) [Epub ahead of print].

BACKGROUND: Multimodal pain therapy usually take place in the context of group therapy lasting several weeks and is based on a generally activating approach. Due to the specificity of stress intolerance with postexertional malaise (PEM) in patients with postviral syndromes, physical as well as psychological overload must be urgently avoided in these cases; however, these aspects can only be insufficiently considered in current medical pain therapy concepts.

METHODS: Summary of the current literature and presentation of clinical characteristics as well as presentation of a model project for a multimodal pain therapy in postviral syndromes with PEM.

MODEL CONCEPT: The presented model project describes a day clinic treatment setting for interdisciplinary multimodal pain therapy adapted to the individual resilience with minimization of the risk of strain-induced deterioration of the condition.

RevDate: 2023-10-19

Thierry AR (2023)

Netosis creates a link between diabetes and Long COVID.

Physiological reviews [Epub ahead of print].

RevDate: 2023-10-18

Houweling L, Maitland-Van der Zee AH, Holtjer JCS, et al (2023)

The effect of the urban exposome on COVID-19 health outcomes: A systematic review and meta-analysis.

Environmental research pii:S0013-9351(23)02155-2 [Epub ahead of print].

BACKGROUND: The global severity of SARS-CoV-2 illness has been associated with various urban characteristics, including exposure to ambient air pollutants. This systematic review and meta-analysis aims to synthesize findings from ecological and non-ecological studies to investigate the impact of multiple urban-related features on a variety of COVID-19 health outcomes.

METHODS: On December 5, 2022, PubMed was searched to identify all types of observational studies that examined one or more urban exposome characteristics in relation to various COVID-19 health outcomes such as infection severity, the need for hospitalization, ICU admission, COVID pneumonia, and mortality.

RESULTS: A total of 38 non-ecological and 241 ecological studies were included in this review. Non-ecological studies highlighted the significant effects of population density, urbanization, and exposure to ambient air pollutants, particularly PM2.5. The meta-analyses revealed that a 1 μg/m[3] increase in PM2.5 was associated with a higher likelihood of COVID-19 hospitalization (pooled OR 1.08 (95% CI:1.02-1.14)) and death (pooled OR 1.06 (95% CI:1.03-1.09)). Ecological studies, in addition to confirming the findings of non-ecological studies, also indicated that higher exposure to nitrogen dioxide (NO2), ozone (O3), sulphur dioxide (SO2), and carbon monoxide (CO), as well as lower ambient temperature, humidity, ultraviolet (UV) radiation, and less green and blue space exposure, were associated with increased COVID-19 morbidity and mortality.

CONCLUSION: This systematic review has identified several key vulnerability features related to urban areas in the context of the recent COVID-19 pandemic. The findings underscore the importance of improving policies related to urban exposures and implementing measures to protect individuals from these harmful environmental stressors.

RevDate: 2023-10-16

Yang L, Wu Y, Jin W, et al (2023)

The potential role of ferroptosis in COVID-19-related cardiovascular injury.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 168:115637 pii:S0753-3322(23)01435-X [Epub ahead of print].

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged as a global health threat in 2019. An important feature of the disease is that multiorgan symptoms of SARS-CoV-2 infection persist after recovery. Evidence indicates that people who recovered from COVID-19, even those under the age of 65 years without cardiovascular risk factors such as smoking, obesity, hypertension, and diabetes, had a significantly increased risk of cardiovascular disease for up to one year after diagnosis. Therefore, it is important to closely monitor individuals who have recovered from COVID-19 for potential cardiovascular damage that may manifest at a later stage. Ferroptosis is an iron-dependent form of non-apoptotic cell death characterized by the production of reactive oxygen species (ROS) and increased lipid peroxide levels. Several studies have demonstrated that ferroptosis plays an important role in cancer, ischemia/reperfusion injury (I/RI), and other cardiovascular diseases. Altered iron metabolism, upregulation of reactive oxygen species, and glutathione peroxidase 4 inactivation are striking features of COVID-19-related cardiovascular injury. SARS-CoV-2 can cause cardiovascular ferroptosis, leading to cardiovascular damage. Understanding the mechanism of ferroptosis in COVID-19-related cardiovascular injuries will contribute to the development of treatment regimens for preventing or reducing COVID-19-related cardiovascular complications. In this article, we go over the pathophysiological underpinnings of SARS-CoV-2-induced acute and chronic cardiovascular injury, the function of ferroptosis, and prospective treatment approaches.

RevDate: 2023-10-16

Martino L, Morello R, De Rose C, et al (2023)

Persistent respiratory symptoms associated with post-covid condition (Long covid) in children: a systematic review and analysis of current gaps and future perspectives.

Expert review of respiratory medicine [Epub ahead of print].

INTRODUCTION: There is increasing evidence that also children can develop Long Covid. However, there are no specific reviews providing a clear description of reported respiratory symptoms and potential diagnostics.

AREAS COVERED: we performed on Pubmed a systematic search of studies conducted on children aged less than 18 years with previous SARS-CoV-2 infection complaining about persistent respiratory symptoms; the aim of our review is to characterize the incidence, pattern and duration of respiratory symptoms after the acute infection in pediatric population.

EXPERT OPINION: children can develop persisting respiratory symptoms, as documented by several follow-up studies both including or not control groups of non-infected children. However, the methodological variabilities of the analyzed studies does not allow to provide firm conclusions about the rate, type and best diagnostics for children with persistent respiratory symptoms. Future studies should investigate on larger pediatric cohorts the role of noninvasive diagnostics and new biomarkers as well as investigating therapeutic options both during acute infection or when Long Covid has been diagnosed.

RevDate: 2023-10-16

Meng QT, Song WQ, Churilov LP, et al (2023)

Psychophysical therapy and underlying neuroendocrine mechanisms for the rehabilitation of long COVID-19.

Frontiers in endocrinology, 14:1120475.

With the global epidemic and prevention of the COVID-19, long COVID-19 sequelae and its comprehensive prevention have attracted widespread attention. Long COVID-19 sequelae refer to that three months after acute COVID-19, the test of SARS-CoV-2 is negative, but some symptoms still exist, such as cough, prolonged dyspnea and fatigue, shortness of breath, palpitations and insomnia. Its pathological mechanism is related to direct viral damage, immunopathological response, endocrine and metabolism disorders. Although there are more effective methods for treating COVID-19, the treatment options available for patients with long COVID-19 remain quite limited. Psychophysical therapies, such as exercise, oxygen therapy, photobiomodulation, and meditation, have been attempted as treatment modalities for long COVID-19, which have the potential to promote recovery through immune regulation, antioxidant effects, and neuroendocrine regulation. Neuroendocrine regulation plays a significant role in repairing damage after viral infection, regulating immune homeostasis, and improving metabolic activity in patients with long COVID-19. This review uses oxytocin as an example to examine the neuroendocrine mechanisms involved in the psychophysical therapies of long COVID-19 syndrome and proposes a psychophysical strategy for the treatment of long COVID-19.

RevDate: 2023-10-16

Yang J, Lim KH, Lim KT, et al (2023)

Complementary and alternative medicine for long COVID: a systematic review of randomized controlled trials.

Therapeutic advances in chronic disease, 14:20406223231204727.

BACKGROUND: Complementary and alternative medicine (CAM) interventions are growing in popularity as possible treatments for long COVID symptoms. However, comprehensive analysis of current evidence in this setting is still lacking.

OBJECTIVE: This study aims to review existing published studies on the use of CAM interventions for patients experiencing long COVID through a systematic review.

DESIGN: Systematic review of randomized controlled trials (RCTs).

METHODS: A comprehensive electronic literature search was performed in multiple databases and clinical trial registries from September 2019 to January 2023. RCTs evaluating efficacy and safety of CAM for long COVID were included. Methodological quality of each included trial was appraised with the Cochrane 'risk of bias' tool. A qualitative analysis was conducted due to heterogeneity of included studies.

RESULTS: A total of 14 RCTs with 1195 participants were included in this review. Study findings demonstrated that CAM interventions could benefit patients with long COVID, especially those suffering from neuropsychiatric disorders, olfactory dysfunction, cognitive impairment, fatigue, breathlessness, and mild-to-moderate lung fibrosis. The main interventions reported were self-administered transcutaneous auricular vagus nerve stimulation, neuro-meditation, dietary supplements, olfactory training, aromatherapy, inspiratory muscle training, concurrent training, and an online breathing and well-being program.

CONCLUSION: CAM interventions may be effective, safe, and acceptable to patients with symptoms of long COVID. However, the findings from this systematic review should be interpreted with caution due to various methodological limitations. More rigorous trials focused on CAM for long COVID are warranted in the future.

RevDate: 2023-10-15

Fry L, Logemann A, Waldron E, et al (2023)

Emotional functioning in long COVID: Comparison to post-concussion syndrome using the Personality Assessment Inventory.

The Clinical neuropsychologist [Epub ahead of print].

Objective: Recent studies on Long COVID found that patients report prominent emotional distress and significant correlations between distress and cognitive performance have been identified, raising the question of how to manage or treat these issues. To understand psychological functioning in Long COVID further, this study examined personality responses on the Personality Assessment Inventory (PAI) to compare psychological functioning in a Long COVID group with a post-concussion syndrome (PCS) group, a syndrome with a significant psychological component. Participants and methods: Participants included 201 consecutive Long COVID outpatients (Mean age = 48.87 years, mean education = 14.82, 71.6% Female, 82.6% White) and a comparison group of 102 consecutively referred PCS outpatients (Mean age = 46.08, mean education = 14.17, 63.7% Female, 88.2% White). Effect sizes and t-tests were calculated using the PAI validity, clinical, interpersonal, and treatment consideration scales as well as clinical subscales. Results: The results replicated earlier findings on the PAI in Long COVID by demonstrating that both Long COVID and PCS groups had the highest mean elevations on SOM and DEP scales but no statistically significant between group differences in mean scale elevations. Results support similarities in psychological functioning between Long COVID and PCS patients emphasizing the importance of evaluating psychological functioning in neuropsychological evaluations for these populations. Further, results suggest that psychological treatment strategies for PCS patients may be helpful for Long COVID patients, but more research is needed.

RevDate: 2023-10-14

Sanal-Hayes NEM, Mclaughlin M, Hayes LD, et al (2023)

A scoping review of 'Pacing' for management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): lessons learned for the long COVID pandemic.

Journal of translational medicine, 21(1):720.

BACKGROUND: Controversy over treatment for people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a barrier to appropriate treatment. Energy management or pacing is a prominent coping strategy for people with ME/CFS. Whilst a definitive definition of pacing is not unanimous within the literature or healthcare providers, it typically comprises regulating activity to avoid post exertional malaise (PEM), the worsening of symptoms after an activity. Until now, characteristics of pacing, and the effects on patients' symptoms had not been systematically reviewed. This is problematic as the most common approach to pacing, pacing prescription, and the pooled efficacy of pacing was unknown. Collating evidence may help advise those suffering with similar symptoms, including long COVID, as practitioners would be better informed on methodological approaches to adopt, pacing implementation, and expected outcomes.

OBJECTIVES: In this scoping review of the literature, we aggregated type of, and outcomes of, pacing in people with ME/CFS.

ELIGIBILITY CRITERIA: Original investigations concerning pacing were considered in participants with ME/CFS.

SOURCES OF EVIDENCE: Six electronic databases (PubMed, Scholar, ScienceDirect, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials [CENTRAL]) were searched; and websites MEPedia, Action for ME, and ME Action were also searched for grey literature, to fully capture patient surveys not published in academic journals.

METHODS: A scoping review was conducted. Review selection and characterisation was performed by two independent reviewers using pretested forms.

RESULTS: Authors reviewed 177 titles and abstracts, resulting in 17 included studies: three randomised control trials (RCTs); one uncontrolled trial; one interventional case series; one retrospective observational study; two prospective observational studies; four cross-sectional observational studies; and five cross-sectional analytical studies. Studies included variable designs, durations, and outcome measures. In terms of pacing administration, studies used educational sessions and diaries for activity monitoring. Eleven studies reported benefits of pacing, four studies reported no effect, and two studies reported a detrimental effect in comparison to the control group.

CONCLUSIONS: Highly variable study designs and outcome measures, allied to poor to fair methodological quality resulted in heterogenous findings and highlights the requirement for more research examining pacing. Looking to the long COVID pandemic, our results suggest future studies should be RCTs utilising objectively quantified digitised pacing, over a longer duration of examination (i.e. longitudinal studies), using the core outcome set for patient reported outcome measures. Until these are completed, the literature base is insufficient to inform treatment practises for people with ME/CFS and long COVID.

RevDate: 2023-10-14

Ambalavanan R, Snead RS, Marczika J, et al (2023)

Advancing the Management of Long COVID by Integrating into Health Informatics Domain: Current and Future Perspectives.

International journal of environmental research and public health, 20(19): pii:ijerph20196836.

The ongoing COVID-19 pandemic has profoundly affected millions of lives globally, with some individuals experiencing persistent symptoms even after recovering. Understanding and managing the long-term sequelae of COVID-19 is crucial for research, prevention, and control. To effectively monitor the health of those affected, maintaining up-to-date health records is essential, and digital health informatics apps for surveillance play a pivotal role. In this review, we overview the existing literature on identifying and characterizing long COVID manifestations through hierarchical classification based on Human Phenotype Ontology (HPO). We outline the aspects of the National COVID Cohort Collaborative (N3C) and Researching COVID to Enhance Recovery (RECOVER) initiative in artificial intelligence (AI) to identify long COVID. Through knowledge exploration, we present a concept map of clinical pathways for long COVID, which offers insights into the data required and explores innovative frameworks for health informatics apps for tackling the long-term effects of COVID-19. This study achieves two main objectives by comprehensively reviewing long COVID identification and characterization techniques, making it the first paper to explore incorporating long COVID as a variable risk factor within a digital health informatics application. By achieving these objectives, it provides valuable insights on long COVID's challenges and impact on public health.

RevDate: 2023-10-14

Georgieva E, Ananiev J, Yovchev Y, et al (2023)

COVID-19 Complications: Oxidative Stress, Inflammation, and Mitochondrial and Endothelial Dysfunction.

International journal of molecular sciences, 24(19): pii:ijms241914876.

SARS-CoV-2 infection, discovered and isolated in Wuhan City, Hubei Province, China, causes acute atypical respiratory symptoms and has led to profound changes in our lives. COVID-19 is characterized by a wide range of complications, which include pulmonary embolism, thromboembolism and arterial clot formation, arrhythmias, cardiomyopathy, multiorgan failure, and more. The disease has caused a worldwide pandemic, and despite various measures such as social distancing, various preventive strategies, and therapeutic approaches, and the creation of vaccines, the novel coronavirus infection (COVID-19) still hides many mysteries for the scientific community. Oxidative stress has been suggested to play an essential role in the pathogenesis of COVID-19, and determining free radical levels in patients with coronavirus infection may provide an insight into disease severity. The generation of abnormal levels of oxidants under a COVID-19-induced cytokine storm causes the irreversible oxidation of a wide range of macromolecules and subsequent damage to cells, tissues, and organs. Clinical studies have shown that oxidative stress initiates endothelial damage, which increases the risk of complications in COVID-19 and post-COVID-19 or long-COVID-19 cases. This review describes the role of oxidative stress and free radicals in the mediation of COVID-19-induced mitochondrial and endothelial dysfunction.

RevDate: 2023-10-14

Moreno-Corona NC, López-Ortega O, Pérez-Martínez CA, et al (2023)

Dynamics of the Microbiota and Its Relationship with Post-COVID-19 Syndrome.

International journal of molecular sciences, 24(19): pii:ijms241914822.

Coronavirus disease (COVID-19) is an infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can be asymptomatic or present with multiple organ dysfunction. Many infected individuals have chronic alterations associated with neuropsychiatric, endocrine, gastrointestinal, and musculoskeletal symptoms, even several months after disease onset, developing long-COVID or post-acute COVID-19 syndrome (PACS). Microbiota dysbiosis contributes to the onset and progression of many viral diseases, including COVID-19 and post-COVID-19 manifestations, which could serve as potential diagnostic and prognostic biomarkers. This review aimed to discuss the most recent findings on gut microbiota dysbiosis and its relationship with the sequelae of PACS. Elucidating these mechanisms could help develop personalized and non-invasive clinical strategies to identify individuals at a higher risk of experiencing severe disease progression or complications associated with PACS. Moreover, the review highlights the importance of targeting the gut microbiota composition to avoid dysbiosis and to develop possible prophylactic and therapeutic measures against COVID-19 and PACS in future studies.

RevDate: 2023-10-13

Voss JG, Pinto MD, CW Burton (2023)

How do the Social Determinants of Health Impact the Post-Acute Sequelae of COVID-19: A Critical Review.

The Nursing clinics of North America, 58(4):541-568.

The review critically analyzes the social determinants of health (SDOH) variables in the current literature of patients with post-acute sequelae (PASC) of COVID-19 in the United States. Race, gender, and age were discussed as well as health outcomes, severity of illness, and phenotypes of long-COVID. Most research was retrospectively with samples that had access to health insurance, which did not capture populations with poor or no access to health care. More research is needed that directly addresses the impact on SDOH on PASC. The current literature is sparse and provides little actionable information.

RevDate: 2023-10-13

Shafqat A, Omer MH, Albalkhi I, et al (2023)

Neutrophil extracellular traps and long COVID.

Frontiers in immunology, 14:1254310.

Post-acute COVID-19 sequelae, commonly known as long COVID, encompasses a range of systemic symptoms experienced by a significant number of COVID-19 survivors. The underlying pathophysiology of long COVID has become a topic of intense research discussion. While chronic inflammation in long COVID has received considerable attention, the role of neutrophils, which are the most abundant of all immune cells and primary responders to inflammation, has been unfortunately overlooked, perhaps due to their short lifespan. In this review, we discuss the emerging role of neutrophil extracellular traps (NETs) in the persistent inflammatory response observed in long COVID patients. We present early evidence linking the persistence of NETs to pulmonary fibrosis, cardiovascular abnormalities, and neurological dysfunction in long COVID. Several uncertainties require investigation in future studies. These include the mechanisms by which SARS-CoV-2 brings about sustained neutrophil activation phenotypes after infection resolution; whether the heterogeneity of neutrophils seen in acute SARS-CoV-2 infection persists into the chronic phase; whether the presence of autoantibodies in long COVID can induce NETs and protect them from degradation; whether NETs exert differential, organ-specific effects; specifically which NET components contribute to organ-specific pathologies, such as pulmonary fibrosis; and whether senescent cells can drive NET formation through their pro-inflammatory secretome in long COVID. Answering these questions may pave the way for the development of clinically applicable strategies targeting NETs, providing relief for this emerging health crisis.

RevDate: 2023-10-10

Megha KB, Reshma S, Amir S, et al (2023)

Comprehensive Risk Assessment of Infection Induced by SARS-CoV-2.

Molecular neurobiology [Epub ahead of print].

The pandemic COVID-19 (coronavirus disease 2019) is caused by the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), which devastated the global economy and healthcare system. The infection caused an unforeseen rise in COVID-19 patients and increased the mortality rate globally. This study gives an overall idea about host-pathogen interaction, immune responses to COVID-19, recovery status of infection, targeted organs and complications associated, and comparison of post-infection immunity in convalescent subjects and non-infected individuals. The emergence of the variants and episodes of COVID-19 infections made the situation worsen. The timely introduction of vaccines and precautionary measures helped control the infection's severity. Later, the population that recovered from COVID-19 grew significantly. However, understanding the impact of healthcare issues resulting after infection is paramount for improving an individual's health status. It is now recognised that COVID-19 infection affects multiple organs and exhibits a broad range of clinical manifestations. So, post COVID-19 infection creates a high risk in individuals with already prevailing health complications. The identification of post-COVID-19-related health issues and their appropriate management is of greater importance to improving patient's quality of life. The persistence, sequelae and other medical complications that normally last from weeks to months after the recovery of the initial infection are involved with COVID-19. A multi-disciplinary approach is necessary for the development of preventive measures, techniques for rehabilitation and strategies for clinical management when it comes to long-term care.

RevDate: 2023-10-10

Lim JK, B Njei (2023)

Clinical and Histopathological Discoveries in Patients with Hepatic Injury and Cholangiopathy Who Have Died of COVID-19: Insights and Opportunities for Intervention.

Hepatic medicine : evidence and research, 15:151-164.

The COVID-19 pandemic has had a profound impact on global health, necessitating a comprehensive understanding of its diverse manifestations. Cholangiopathy, a condition characterized by biliary dysfunction, has emerged as a significant complication in COVID-19 patients. In this review, we report the epidemiology of COVID-19, describe the hepatotropism of SARS-CoV-2, and present the histopathology of acute liver injury (ALI) in COVID-19. Additionally, we explore the relationship between pre-existing chronic liver disease and COVID-19, shedding light on the increased susceptibility of these individuals to develop cholangiopathy. Through an in-depth analysis of cholangiopathy in COVID-19 patients, we elucidate its clinical manifestations, diagnostic criteria, and underlying pathogenesis involving inflammation, immune dysregulation, and vascular changes. Furthermore, we provide a summary of studies investigating post-COVID-19 cholangiopathy, highlighting the long-term effects and potential management strategies for this condition, and discussing opportunities for intervention, including therapeutic targets, diagnostic advancements, supportive care, and future research needs.

RevDate: 2023-10-09

Muyayalo KP, Gong GS, Kiyonga Aimeé K, et al (2023)

Impaired immune response against SARS-CoV-2 infection is the major factor indirectly altering reproductive function in COVID-19 patients: a narrative review.

Human fertility (Cambridge, England) [Epub ahead of print].

Coronavirus disease 2019 (COVID-19) is an infectious disease affecting multiple systems and organs, including the reproductive system. SARS-CoV-2, the virus that causes COVID-19, can damage reproductive organs through direct (angiotensin converting enzyme-2, ACE-2) and indirect mechanisms. The immune system plays an essential role in the homeostasis and function of the male and female reproductive systems. Therefore, an altered immune response related to infectious and inflammatory diseases can affect reproductive function and fertility in both males and females. This narrative review discussed the dysregulation of innate and adaptive systems induced by SARS-CoV-2 infection. We reviewed the evidence showing that this altered immune response in COVID-19 patients is the major indirect mechanism leading to adverse reproduction outcomes in these patients. We summarized studies reporting the long-term effect of SARS-CoV-2 infection on women's reproductive function and proposed the chronic inflammation and chronic autoimmunity characterizing long COVID as potential underlying mechanisms. Further studies are needed to clarify the role of autoimmunity and chronic inflammation (long COVID) in altered female reproduction function in COVID-19.

RevDate: 2023-10-09

Luo S, Zheng Z, Bird SR, et al (2023)

An Overview of Long COVID Support Services in Australia and International Clinical Guidelines, With a Proposed Care Model in a Global Context.

Public health reviews, 44:1606084.

Objective: To identify gaps among Australian Long COVID support services and guidelines alongside recommendations for future health programs. Methods: Electronic databases and seven government health websites were searched for Long COVID-specific programs or clinics available in Australia as well as international and Australian management guidelines. Results: Five Long COVID specific guidelines and sixteen Australian services were reviewed. The majority of Australian services provided multidisciplinary rehabilitation programs with service models generally consistent with international and national guidelines. Most services included physiotherapists and psychologists. While early investigation at week 4 after contraction of COVID-19 is recommended by the Australian, UK and US guidelines, this was not consistently implemented. Conclusion: Besides Long COVID clinics, future solutions should focus on early identification that can be delivered by General Practitioners and all credentialed allied health professions. Study findings highlight an urgent need for innovative care models that address individual patient needs at an affordable cost. We propose a model that focuses on patient-led self-care with further enhancement via multi-disciplinary care tools.

RevDate: 2023-10-09
CmpDate: 2023-10-09

Baker MG, Kvalsvig A, Plank MJ, et al (2023)

Continued mitigation needed to minimise the high health burden from COVID-19 in Aotearoa New Zealand.

The New Zealand medical journal, 136(1583):67-91.

In this article we review the COVID-19 pandemic experience in Aotearoa New Zealand and consider the optimal ongoing response strategy. We note that this pandemic virus looks likely to result in future waves of infection that diminish in size over time, depending on such factors as viral evolution and population immunity. However, the burden of disease remains high with thousands of infections, hundreds of hospitalisations and tens of deaths each week, and an unknown burden of long-term illness (long COVID). Alongside this there is a considerable burden from other important respiratory illnesses, including influenza and RSV, that needs more attention. Given this impact and the associated health inequities, particularly for Māori and Pacific Peoples, we consider that an ongoing respiratory disease mitigation strategy is appropriate for New Zealand. As such, the previously described "vaccines plus" approach (involving vaccination and public health and social measures), should now be integrated with the surveillance and control of other important respiratory infections. Now is also a time for New Zealand to build on the lessons from the COVID-19 pandemic to enhance preparedness nationally and internationally. New Zealand's experience suggests elimination (or ideally exclusion) should be the default first choice for future pandemics of sufficient severity.

RevDate: 2023-10-09

Zhou X, Zhang K, Liu L, et al (2022)

Anti-fatigue effect from Ginseng Radix et Rhizoma: a suggestive and promising treatment for long COVID.

Acupuncture and herbal medicine, 2(2):69-77.

Two years after the coronavirus disease 2019 (COVID-19) outbreak, an increasing number of patients continue to suffer from long COVID (LC), persistent symptoms, and/or delayed or long-term complications beyond the initial 4 weeks from the onset of symptoms. Constant fatigue is one of the most common LC symptoms, leading to severely reduced quality of life among patients. Ginseng Radix et Rhizoma-known as the King of Herbs in traditional Chinese medicine-has shown clinical anti-fatigue effects. In this review, we summarize the underlying anti-fatigue mechanisms of Ginseng Radix et Rhizoma extracts and their bioactive compounds, with a special focus on anti-viral, immune remodeling, endocrine system regulation, and metabolism, suggesting that Ginseng Radix et Rhizoma is a potentially promising treatment for LC, especially in regard to targeting fatigue.

RevDate: 2023-10-06

El-Maradny YA, Rubio-Casillas A, Mohamed KI, et al (2023)

Intrinsic factors behind long-COVID: II. SARS-CoV-2, extracellular vesicles, and neurological disorders.

Journal of cellular biochemistry [Epub ahead of print].

With the decline in the number of new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections, the World Health Organization announced the end of the SARS-CoV-2 pandemic. However, the repercussions of this viral pandemic may remain with us for a longer period of time, as it has remodeled the lives of humankind in many ways, including social and economic. Of course, its most important repercussions remain on the human health level. Long-coronavirus disease (COVID) or post-COVID is a state for which we do not have a concrete definition, a specific international classification of diseases Code, clear diagnostic tools, or well-known effective cures as of yet. In this second article from the Intrinsic Factors behind long-COVID Series, we try to link long-COVID symptoms with their causes, starting from the nervous system. Extracellular vesicles (ECVs) play very complex and ramified roles in the bodies of both healthy and not-healthy individuals. ECVs may facilitate the entry of many bioactive molecules and pathogens into the tissues and cells of the nervous system across the blood-brain barrier. Based on the size, quantity, and quality of their cargo, ECVs are directly proportional to the pathological condition and its severity through intertwined mechanisms that evoke inflammatory immune responses typically accompanied by pathological symptoms over variable time periods according to the type of these symptoms.

RevDate: 2023-10-05

Sapna F, Deepa F, Sakshi F, et al (2023)

Unveiling the Mysteries of Long COVID Syndrome: Exploring the Distinct Tissue and Organ Pathologies Linked to Prolonged COVID-19 Symptoms.

Cureus, 15(9):e44588.

The ongoing battle against the coronavirus disease 2019 (COVID-19) pandemic has encountered a complex aspect with the emergence of long COVID syndrome. There has been a growing prevalence of COVID-19-affected individuals experiencing persistent and diverse symptoms that extend beyond the initial infection phase. The phenomenon known as long COVID syndrome raises significant questions about the underlying mechanisms driving these enduring symptoms. This comprehensive analysis explores the complex domain of long COVID syndrome with a view to shed light on the specific tissue and organ pathologies contributing to its intricate nature. This review aims to analyze the various clinical manifestations of this condition across different bodily systems and explore potential mechanisms such as viral persistence, immune dysregulation, autoimmunity, and molecular mimicry. The goal is to gain a better understanding of the intricate network of pathologies contributing to long COVID syndrome. Understanding these distinct pathological indicators provides valuable insights into comprehending the complexities of long COVID and presents opportunities for developing more accurate diagnostic and therapeutic strategies, thereby improving the quality of patient care by effectively addressing the ever-changing medical challenge in a more focused manner.

RevDate: 2023-10-04

Grach SL, Seltzer J, Chon TY, et al (2023)

Diagnosis and Management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Mayo Clinic proceedings, 98(10):1544-1551.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic neurologic disease often preceded by infection. There has been increased interest in ME/CFS recently because of its significant overlap with the post-COVID syndrome (long COVID or post-acute sequelae of COVID), with several studies estimating that half of patients with post-COVID syndrome fulfill ME/CFS criteria. Our concise review describes a generalist approach to ME/CFS, including diagnosis, evaluation, and management strategies.

RevDate: 2023-10-04

Esposito S, Deolmi M, Ramundo G, et al (2023)

True prevalence of long COVID in children: a narrative review.

Frontiers in microbiology, 14:1225952.

Contrary to what is true for adults, little is known about pediatric long COVID (LC). Studies enrolling children are relatively few and extremely heterogeneous. This does not allow to draw definitive conclusions on the frequency and pathogenesis of pediatric LC and limits the development of appropriate and effective measures to contain the clinical, social and economic impact of this condition on the pediatric population. Depending on the methods used to collect and analyze data, studies have found that the incidence rate of pediatric LC may vary from about 25% to less than 5%. However, despite true prevalence of pediatric LC cannot be exactly defined, studies comparing children with previous COVID-19 and uninfected controls have shown that most of the clinical manifestations detected in infected children, mainly mood symptoms, mental health disorders and heart abnormalities could be diagnosed with similar frequency and severity in uninfected subjects also. This seems to indicate that SARS-CoV-2 is the cause of pediatric LC only in a part of children and other factors play a relevant role in this regard. Pandemic itself with the persistent disruption of child lives may have caused persistent stress in all the pediatric population causing mood symptoms, mental health disorders or several organ and body system functional alterations, regardless SARS-CoV-2 infection. These suppositions suggest the need for long-term physical control of all the children after COVID-19 especially when they were already suffering from an underlying disease or have had a severe disease. Moreover, attention should be paid to the assessment of change in children's emotional and behavioral functioning in order to assure adequate interventions for the best emotional and behavioral well being. However, whatever its origin, it seems highly likely that the prevalence of the pediatric LC is set to decline in the future. Preliminary observations seem to suggest that recently developed SARS-CoV-2 variants are associated with less severe COVID-19. This suggests that, as already seen in adults, a lower number of pediatric virus-associated LC cases should occur. Furthermore, the use of COVID-19 vaccines, reducing incidence and severity of SARS-CoV-2 infection, may reduce risk of LC development. Finally, elimination of restrictive measures should significantly reduce mood symptoms and mental health disorders.

RevDate: 2023-10-02

Ogbonna O, Bull F, Spinks B, et al (2023)

The Impact of Being Homeless on the Clinical Outcomes of COVID-19: Systematic Review.

International journal of public health, 68:1605893.

Objective: The homeless population experiences inequality in health compared with the general population, which may have widened during the COVID-19 pandemic. However, the impact of being homeless on the outcomes of COVID-19 is uncertain. This systematic review aimed to analyse the impact of experiencing homelessness on the clinical outcomes of COVID-19, including the effects on health inequalities. Methods: A review protocol was developed and registered in PROSPERO (PROSPERO registration 2022 CRD42022304941). Nine databases were searched in November 2022 to identify studies on homeless populations which contained primary research on the following outcomes of COVID-19: incidence, hospitalisation, mortality, long COVID, mental wellbeing, and evidence of inequalities. Included studies were summarised with narrative synthesis. Results: The searches yielded 8,233 initial hits; after screening, 41 studies were included. Overall, evidence showed that those in crowded living settings had a higher risk of COVID-19 infection compared to rough sleepers and the general population. The homeless population had higher rates of hospitalisation and mortality than the general population, lower vaccination rates, and suffered negative mental health impacts. Conclusion: This systematic review shows the homeless population is more susceptible to COVID-19 outcomes. Further research is needed to determine the actual impact of the pandemic on this population, and of interventions to mitigate overall risk, given the low certainty of findings from some of the low-quality evidence available. In addition, further research is required to ascertain the impact of long COVID on those experiencing homelessness, since the present review yielded no studies on this topic.

RevDate: 2023-09-28

Calvache-Mateo A, Heredia-Ciuró A, Martín-Núñez J, et al (2023)

Efficacy and Safety of Respiratory Telerehabilitation in Patients with Long COVID-19: A Systematic Review and Meta-Analysis.

Healthcare (Basel, Switzerland), 11(18):.

The aim of this review was to identify, map, and synthesize the extent and nature of research activity on the use of telerehabilitation to support Long COVID-19 rehabilitation and examine the efficacy and safety of respiratory telerehabilitation in patients with Long COVID-19. A systematic review and meta-analysis of randomized controlled trials were performed. We included controlled trials that tested the effect of respiratory telerehabilitation interventions in patients with Long COVID-19 versus no intervention, usual care, placebo, or face-to-face intervention. The data were pooled, and a meta-analysis was completed for quality of life, dyspnea, lung function, anxiety and depression, respiratory muscle strength, functional capacity, and lower limb strength. Finally, 10 studies were included. The meta-analysis results show significant differences in favor of respiratory telerehabilitation in quality of life (p = 0.02), dyspnea (p < 0.00001), respiratory muscle strength (p < 0.001), functional capacity (p < 0.0001), and lower limb strength (p = 0.01) but not in lung function (p = 0.28) and anxiety and depression (p = 0.55). In addition, there were no statistically significant differences in adverse effects (p = 0.06) between the telerehabilitation and comparator groups. The results suggest that these interventions can improve quality of life, reduce dyspnea, and increase respiratory and lower extremity muscle strength as well as functional capacity in patients with Long COVID-19.

RevDate: 2023-09-28

Boura I, Qamar MA, Daddoveri F, et al (2023)

SARS-CoV-2 and Parkinson's Disease: A Review of Where We Are Now.

Biomedicines, 11(9):.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has been discussed in the context of Parkinson's disease (PD) over the last three years. Now that we are entering the long-term phase of this pandemic, we are intrigued to look back and see how and why the community of patients with PD was impacted and what knowledge we have collected so far. The relationship between COVID-19 and PD is likely multifactorial in nature. Similar to other systemic infections, a probable worsening of PD symptoms secondary to COVID-19, either transient or persistent (long COVID), has been demonstrated, while the COVID-19-related mortality of PD patients may be increased compared to the general population. These observations could be attributed to direct or indirect damage from SARS-CoV-2 in the central nervous system (CNS) or could result from general infection-related parameters (e.g., hospitalization or drugs) and the sequelae of the COVID-19 pandemic (e.g., quarantine). A growing number of cases of new-onset parkinsonism or PD following SARS-CoV-2 infection have been reported, either closely (post-infectious) or remotely (para-infectious) after a COVID-19 diagnosis, although such a link remains hypothetical. The pathophysiological substrate of these phenomena remains elusive; however, research studies, particularly pathology studies, have suggested various COVID-19-induced degenerative changes with potential associations with PD/parkinsonism. We review the literature to date for answers considering the relationship between SARS-CoV-2 infection and PD/parkinsonism, examining pathophysiology, clinical manifestations, vaccination, and future directions.

RevDate: 2023-09-28

Ogarek N, Oboza P, Olszanecka-Glinianowicz M, et al (2023)

SARS-CoV-2 infection as a potential risk factor for the development of cancer.

Frontiers in molecular biosciences, 10:1260776.

The COVID-19 pandemic has a significant impact on public health and the estimated number of excess deaths may be more than three times higher than documented in official statistics. Numerous studies have shown an increased risk of severe COVID-19 and death in patients with cancer. In addition, the role of SARS-CoV-2 as a potential risk factor for the development of cancer has been considered. Therefore, in this review, we summarise the available data on the potential effects of SARS-CoV-2 infection on oncogenesis, including but not limited to effects on host signal transduction pathways, immune surveillance, chronic inflammation, oxidative stress, cell cycle dysregulation, potential viral genome integration, epigenetic alterations and genetic mutations, oncolytic effects and reactivation of dormant cancer cells. We also investigated the potential long-term effects and impact of the antiviral therapy used in COVID-19 on cancer development and its progression.

RevDate: 2023-09-28
CmpDate: 2023-09-27

Clark IA, B Vissel (2023)

Autocrine positive feedback of tumor necrosis factor from activated microglia proposed to be of widespread relevance in chronic neurological disease.

Pharmacology research & perspectives, 11(5):e01136.

Over a decade's experience of post-stroke rehabilitation by administering the specific anti-TNF biological, etanercept, by the novel perispinal route, is consistent with a wide range of chronically diminished neurological function having been caused by persistent excessive cerebral levels of TNF. We propose that this TNF persistence, and cerebral disease chronicity, largely arises from a positive autocrine feedback loop of this cytokine, allowing the persistence of microglial activation caused by the excess TNF that these cells produce. It appears that many of these observations have never been exploited to construct a broad understanding and treatment of certain chronic, yet reversible, neurological illnesses. We propose that this treatment allows these chronically activated microglia to revert to their normal quiescent state, rather than simply neutralizing the direct harmful effects of this cytokine after its release from microglia. Logically, this also applies to the chronic cerebral aspects of various other neurological conditions characterized by activated microglia. These include long COVID, Lyme disease, post-stroke syndromes, traumatic brain injury, chronic traumatic encephalopathy, post-chemotherapy, post-irradiation cerebral dysfunction, cerebral palsy, fetal alcohol syndrome, hepatic encephalopathy, the antinociceptive state of morphine tolerance, and neurogenic pain. In addition, certain psychiatric states, in isolation or as sequelae of infectious diseases such as Lyme disease and long COVID, are candidates for being understood through this approach and treated accordingly. Perispinal etanercept provides the prospect of being able to treat various chronic central nervous system illnesses, whether they are of infectious or non-infectious origin, through reversing excess TNF generation by microglia.

RevDate: 2023-09-24

Steiner S, Fehrer A, Hoheisel F, et al (2023)

Understanding, diagnosing, and treating Myalgic encephalomyelitis/chronic fatigue syndrome - State of the art: Report of the 2nd international meeting at the Charité fatigue center.

Autoimmunity reviews pii:S1568-9972(23)00186-6 [Epub ahead of print].

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a devastating disease affecting millions of people worldwide. Due to the 2019 pandemic of coronavirus disease (COVID-19), we are facing a significant increase of ME/CFS prevalence. On May 11th to 12th, 2023, the second international ME/CFS conference of the Charité Fatigue Center was held in Berlin, Germany, focusing on pathomechanisms, diagnosis, and treatment. During the two-day conference, more than 100 researchers from various research fields met on-site and over 700 attendees participated online to discuss the state of the art and novel findings in this field. Key topics from the conference included: the role of the immune system, dysfunction of endothelial and autonomic nervous system, and viral reactivation. Furthermore, there were presentations on innovative diagnostic measures and assessments for this complex disease, cutting-edge treatment approaches, and clinical studies. Despite the increased public attention due to the COVID-19 pandemic, the subsequent rise of Long COVID-19 cases, and the rise of funding opportunities to unravel the pathomechanisms underlying ME/CFS, this severe disease remains highly underresearched. Future adequately funded research efforts are needed to further explore the disease etiology and to identify diagnostic markers and targeted therapies.

RevDate: 2023-09-22

Röltgen K, SD Boyd (2023)

Antibody and B Cell Responses to SARS-CoV-2 Infection and Vaccination: The End of the Beginning.

Annual review of pathology [Epub ahead of print].

As the COVID-19 pandemic has evolved during the past years, interactions between human immune systems, rapidly mutating and selected SARS-CoV-2 viral variants, and effective vaccines have complicated the landscape of individual immunological histories. Here, we review some key findings for antibody and B cell-mediated immunity, including responses to the highly mutated omicron variants; immunological imprinting and other impacts of successive viral antigenic variant exposures on antibody and B cell memory; responses in secondary lymphoid and mucosal tissues and non-neutralizing antibody-mediated immunity; responses in populations vulnerable to severe disease such as those with cancer, immunodeficiencies, and other comorbidities, as well as populations showing apparent resistance to severe disease such as many African populations; and evidence of antibody involvement in postacute sequelae of infection or long COVID. Despite the initial phase of the pandemic ending, human populations will continue to face challenges presented by this unpredictable virus. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 19 is January 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

RevDate: 2023-09-28

Weissert R (2023)

Nervous system-related tropism of SARS-CoV-2 and autoimmunity in COVID-19 infection.

European journal of immunology [Epub ahead of print].

The effects of SARS-CoV-2 in COVID-19 on the nervous system are incompletely understood. SARS-CoV-2 can infect endothelial cells, neurons, astrocytes, and oligodendrocytes with consequences for the host. There are indications that infection of these CNS-resident cells may result in long-term effects, including emergence of neurodegenerative diseases. Indirect effects of infection with SARS-CoV-2 relate to the induction of autoimmune disease involving molecular mimicry or/and bystander activation of T- and B cells and emergence of autoantibodies against various self-antigens. Data obtained in preclinical models of coronavirus-induced disease gives important clues for the understanding of nervous system-related assault of SARS-CoV-2. The pathophysiology of long-COVID syndrome and post-COVID syndrome in which autoimmunity and immune dysregulation might be the driving forces are still incompletely understood. A better understanding of nervous-system-related immunity in COVID-19 might support the development of therapeutic approaches. In this review, the current understanding of SARS-CoV-2 tropism for the nervous system, the associated immune responses, and diseases are summarized. The data indicates that there is viral tropism of SARS-CoV-2 in the nervous system resulting in various disease conditions. Prevention of SARS-CoV-2 infection by means of vaccination is currently the best strategy for the prevention of subsequent tissue damage involving the nervous system.

RevDate: 2023-09-21

Easter QT, Matuck BF, Warner BM, et al (2023)

Biogeographical Impacts of Dental, Oral, and Craniofacial Microbial Reservoirs.

Journal of dental research [Epub ahead of print].

The human mouth, or oral cavity, is at the crossroads of our external and internal environments, and it is increasingly evident that local colonization of dental, oral, and craniofacial (DOC) tissues and cells by bacteria and viruses may also have systemic effects across myriad diseases and disorders. Better understanding of this phenomenon will require a holistic understanding of host-microbial interactions in both spatiotemporal and biogeographical contexts while also considering person-, organ-, tissue-, cell-, and molecular-level variation. After the acute phase interaction with microbes, the establishment of site-specific reservoirs constitutes an important relationship to understand within the human body; however, despite a preliminary understanding of how viral reservoirs originate and persist across the human body, the landscape of single-cell and spatial multiomic tools has challenged our current understanding of what cells and niches can support microbial reservoirs. The lack of complete understanding impacts research into these relevant topics and implementing precision care for microbial-induced or microbial-influenced diseases. Here, via the lens of acute and chronic microbial infections of the DOC tissues, the goal of this review is to highlight and link the emerging spatiotemporal biogeography of host-viral interactomics at 3 levels: (1) DOC cell types in distinct tissues, (2) DOC-associated microbes, and (3) niche-specific DOC pathologies. Further, we will focus on the impact of postacute infectious syndromes such as long COVID, neurodegenerative disorders, and other underappreciated postviral conditions. We will provide hypotheses about how DOC tissues may play roles systemically in these conditions. Throughout, we will underscore how COVID-19 has catalyzed a new understanding of these biological questions, discuss future directions to study these phenomena, and highlight the utility of noninvasive oral biofluids in screening, monitoring, and intervening to prevent and/or ameliorate human infectious diseases.

RevDate: 2023-09-20

Wang J, Liu R, Ma H, et al (2023)

The Pathogenesis of COVID-19-Related Taste Disorder and Treatments.

Journal of dental research [Epub ahead of print].

COVID-19, mainly manifested as acute respiratory distress syndrome, has afflicted millions of people worldwide since 2019. Taste dysfunction is a common early-stage symptom of COVID-19 infection that burdens patients for weeks or even permanently in some cases. Owing to its subjectivity and complexity, the mechanism of taste disorder is poorly studied. Previous studies have reported that the COVID-19 entry receptors are highly expressed in taste buds, thereby intensifying the cytocidal effect. Taste receptor cells are vulnerable to inflammation, and the COVID-19-induced cytokine storm causes secondary damage to taste function. Interferon and various proinflammatory cytokines can trigger cell apoptosis and disrupt the renewal of taste bud stem cells. This immune response can be further enhanced by the accumulation of Angiotensin II (Ang II) caused by an unbalanced local renin-angiotensin system (RAS) system. In addition, severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is neurotropic and can invade the brain through the olfactory bulb, affecting the nervous system. Other factors, such as host zinc deficiency, genetic susceptibility, sialic acid, and some neurotransmitters, also contribute to the pathogenesis process. Although several medical interventions have displayed effectiveness, only a few strategies exist for the treatment of postinfectious dysgeusia. Stem cell-based taste regeneration offers promise for long-term taste disorders. Clinical studies have demonstrated that stem cells can treat long COVID-19 through immune regulation. In dysgeusia, the differentiation of taste bud stem cells can be stimulated through exogenous epithelial-derived and neural-derived factors to regenerate taste buds. Tongue organoids are also emerging as functional taste buds, offering new insights into the study of taste regeneration. This review presents the current evidence of the pathogenesis of COVID-19-related dysgeusia, summarizes currently available treatments, and suggests future directions of taste regeneration therapy.

RevDate: 2023-09-19

Shmueli M, Lendner I, S Ben-Shimol (2023)

Effect of the COVID-19 pandemic on the pediatric infectious disease landscape.

European journal of pediatrics [Epub ahead of print].

This narrative review aims to present an overview of the COVID-19 pandemic's effects on the landscape of pediatric infectious diseases. While COVID-19 generally results in mild symptoms and a favorable prognosis in children, the pandemic brought forth significant consequences. These included persistent symptoms among infected children ("long COVID"), a profound transformation in healthcare utilization (notably through the widespread adoption of telemedicine), and the implementation of optimization strategies within healthcare settings. Furthermore, the pandemic resulted in alterations in the circulation patterns of respiratory pathogens, including influenza, RSV, and Streptococcus pneumoniae. The possible reasons for those changes are discussed in this review. COVID-19 effect was not limited to respiratory infectious diseases, as other diseases, including urinary tract and gastrointestinal infections, have displayed decreased transmission rates, likely attributable to heightened hygiene measures and shifts in care-seeking behaviors. Finally, the disruption of routine childhood vaccination programs has resulted in reduced immunization coverage and an upsurge in vaccine hesitancy. In addition, the pandemic was associated with issues of antibiotic misuse and over-prescription. Conclusion: In conclusion, the COVID-19 pandemic has left a profound and multifaceted impact on the landscape of pediatric infectious diseases, ranging from the emergence of "long COVID" in children to significant changes in healthcare delivery, altered circulation patterns of various pathogens, and concerning disruptions in vaccination programs and antibiotic usage. What is Known: • COVID-19 usually presents with mild symptoms in children, although severe and late manifestations are possible. • The pandemic resulted in a dramatically increased use of health care services, as well as alterations in the circulation patterns of respiratory pathogens, decreased rates of other, non-respiratory, infections, disruption of routine childhood vaccination programs, and antibiotic misuse. What is New: • Possible strategies to tackle future outbreaks are presented, including changes in health care services utilization, implementation of updated vaccine programs and antibiotic stewardship protocols. • The decline in RSV and influenza circulation during COVID-19 was probably not primarily related to NPI measures, and rather related to other, non-NPI measures implementation, including specific pathogen-host interactions on the level of the biological niche (the nasopharynx).

RevDate: 2023-09-19

Li H, Xia J, Bennett D, et al (2023)

Long-COVID-19 clinical and health outcomes: an umbrella review.

Therapeutic advances in infectious disease, 10:20499361231198335.

BACKGROUND: A growing interest in long-term sequelae of COVID-19 has prompted several systematic literature reviews (SLRs) to evaluate long-COVID-19 effects. However, many of these reviews lack in-depth information on the timing, duration, and severity of these conditions.

OBJECTIVES: Our aim was to synthesize both qualitative and quantitative evidence on prevalence and outcomes of long-term effect of COVID-19 through an umbrella review.

DESIGN: Umbrella review of relevant SLRs on long-COVID-19 in terms of prolonged symptoms and clinical conditions, and comprehensively synthesized the latest existing evidence.

DATA SOURCES AND METHODS: We systematically identified and appraised prior systematic reviews/meta-analyses using MEDLINE, Embase, and Cochrane database of systematic review from 2020 to 2021 following the preferred reporting items for systematic reviews and meta-analyses guidance. We summarized and categorized all relevant clinical symptoms and outcomes in adults with COVID-19 using the Medical Dictionary for Regulatory Activities System Organ Class (MedDRA SOC).

RESULTS: We identified 967 systematic reviews/meta-analyses; 36 were retained for final data extraction. The most prevalent SOC were social circumstances (40%), blood and lymphatic system disorders (39%), and metabolism and nutrition disorder (38%). The most frequently reported SOC outcomes within each MedDRA category were poor quality of life (59%), wheezing and dyspnea (19-49%), fatigue (30-64%), chest pain (16%), decreased or loss of appetite (14-17%), abdominal discomfort or digestive disorder (12-18%), arthralgia with or without myalgia (16-24%), paresthesia (27%) and hair loss (14-25%), and hearing loss or tinnitus (15%).

CONCLUSION: This study confirmed a high prevalence of several long COVID-19 outcomes according to the MedDRA categories and indicated that the majority of evidence was rated as moderate to low.

REGISTRATION: The review was registered at PROSPERO (https://www.crd.york.ac.uk/prospero/) (CRD42022303557).

RevDate: 2023-09-19
CmpDate: 2023-09-19

Ng CYJ, Bun HH, Zhao Y, et al (2023)

TCM "medicine and food homology" in the management of post-COVID disorders.

Frontiers in immunology, 14:1234307.

BACKGROUND: The World Health Organization declared that COVID-19 is no longer a public health emergency of global concern on May 5, 2023. Post-COVID disorders are, however, becoming more common. Hence, there lies a growing need to develop safe and effective treatment measures to manage post-COVID disorders. Investigating the use of TCM medicinal foods in the long-term therapy of post-COVID illnesses may be beneficial given contemporary research's emphasis on the development of medicinal foods.

SCOPE AND APPROACH: The use of medicinal foods for the long-term treatment of post-COVID disorders is highlighted in this review. Following a discussion of the history of the TCM "Medicine and Food Homology" theory, the pathophysiological effects of post-COVID disorders will be briefly reviewed. An analysis of TCM medicinal foods and their functions in treating post-COVID disorders will then be provided before offering some insight into potential directions for future research and application.

KEY FINDINGS AND DISCUSSION: TCM medicinal foods can manage different aspects of post-COVID disorders. The use of medicinal foods in the long-term management of post-COVID illnesses may be a safe and efficient therapy choice because they are typically milder in nature than chronic drug use. These findings may also be applied in the long-term post-disease treatment of similar respiratory disorders.

RevDate: 2023-09-19

Marques KC, Quaresma JAS, LFM Falcão (2023)

Cardiovascular autonomic dysfunction in "Long COVID": pathophysiology, heart rate variability, and inflammatory markers.

Frontiers in cardiovascular medicine, 10:1256512.

Long COVID is characterized by persistent signs and symptoms that continue or develop for more than 4 weeks after acute COVID-19 infection. Patients with Long COVID experience a cardiovascular autonomic imbalance known as dysautonomia. However, the underlying autonomic pathophysiological mechanisms behind this remain unclear. Current hypotheses include neurotropism, cytokine storms, and inflammatory persistence. Certain immunological factors indicate autoimmune dysfunction, which can be used to identify patients at a higher risk of Long COVID. Heart rate variability can indicate autonomic imbalances in individuals suffering from Long COVID, and measurement is a non-invasive and low-cost method for assessing cardiovascular autonomic modulation. Additionally, biochemical inflammatory markers are used for diagnosing and monitoring Long COVID. These inflammatory markers can be used to improve the understanding of the mechanisms driving the inflammatory response and its effects on the sympathetic and parasympathetic pathways of the autonomic nervous system. Autonomic imbalances in patients with Long COVID may result in lower heart rate variability, impaired vagal activity, and substantial sympathovagal imbalance. New research on this subject must be encouraged to enhance the understanding of the long-term risks that cardiovascular autonomic imbalances can cause in individuals with Long COVID.

RevDate: 2023-09-21

Oliveira A, Fabbri G, Gille T, et al (2023)

Holistic management of patients with progressive pulmonary fibrosis.

Breathe (Sheffield, England), 19(3):230101.

UNLABELLED: Progressive pulmonary fibrosis (PF) is a complex interstitial lung disease that impacts substantially on patients' daily lives, requiring personalised and integrated care. We summarise the main needs of patients with PF and their caregivers, and suggest a supportive care approach. Individualised care, education, emotional and psychological support, specialised treatments, and better access to information and resources are necessary. Management should start at diagnosis, be tailored to the patient's needs, and consider end-of-life care. Pharmacological and non-pharmacological interventions should be individualised, including oxygen therapy and pulmonary rehabilitation, with digital healthcare utilised as appropriate. Further research is needed to address technical issues related to oxygen delivery and digital healthcare.

EDUCATIONAL AIMS: To identify the main needs of patients with PF and their caregivers.To describe the components of a comprehensive approach to a supportive care programme for patients with PF.To identify further areas of research to address technical issues related to the management of patients with PF.

RevDate: 2023-09-20
CmpDate: 2023-09-19

Ruiz-Pablos M, Paiva B, A Zabaleta (2023)

Epstein-Barr virus-acquired immunodeficiency in myalgic encephalomyelitis-Is it present in long COVID?.

Journal of translational medicine, 21(1):633.

Both myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) and long COVID (LC) are characterized by similar immunological alterations, persistence of chronic viral infection, autoimmunity, chronic inflammatory state, viral reactivation, hypocortisolism, and microclot formation. They also present with similar symptoms such as asthenia, exercise intolerance, sleep disorders, cognitive dysfunction, and neurological and gastrointestinal complaints. In addition, both pathologies present Epstein-Barr virus (EBV) reactivation, indicating the possibility of this virus being the link between both pathologies. Therefore, we propose that latency and recurrent EBV reactivation could generate an acquired immunodeficiency syndrome in three steps: first, an acquired EBV immunodeficiency develops in individuals with "weak" EBV HLA-II haplotypes, which prevents the control of latency I cells. Second, ectopic lymphoid structures with EBV latency form in different tissues (including the CNS), promoting inflammatory responses and further impairment of cell-mediated immunity. Finally, immune exhaustion occurs due to chronic exposure to viral antigens, with consolidation of the disease. In the case of LC, prior to the first step, there is the possibility of previous SARS-CoV-2 infection in individuals with "weak" HLA-II haplotypes against this virus and/or EBV.

RevDate: 2023-09-17

Shaver N, Katz M, Darko Asamoah G, et al (2023)

Protocol for a living evidence synthesis on variants of concern and COVID-19 vaccine effectiveness.

Vaccine pii:S0264-410X(23)01065-4 [Epub ahead of print].

BACKGROUND: It is evident that COVID-19 will remain a public health concern in the coming years, largely driven by variants of concern (VOC). It is critical to continuously monitor vaccine effectiveness as new variants emerge and new vaccines and/or boosters are developed. Systematic surveillance of the scientific evidence base is necessary to inform public health action and identify key uncertainties. Evidence syntheses may also be used to populate models to fill in research gaps and help to prepare for future public health crises. This protocol outlines the rationale and methods for a living evidence synthesis of the effectiveness of COVID-19 vaccines in reducing the morbidity and mortality associated with, and transmission of, VOC of SARS-CoV-2.

METHODS: Living evidence syntheses of vaccine effectiveness will be carried out over one year for (1) a range of potential outcomes in the index individual associated with VOC (pathogenesis); and (2) transmission of VOC. The literature search will be conducted up to May 2023. Observational and database-linkage primary studies will be included, as well as RCTs. Information sources include electronic databases (MEDLINE; Embase; Cochrane, L*OVE; the CNKI and Wangfang platforms), pre-print servers (medRxiv, BiorXiv), and online repositories of grey literature. Title and abstract and full-text screening will be performed by two reviewers using a liberal accelerated method. Data extraction and risk of bias assessment will be completed by one reviewer with verification of the assessment by a second reviewer. Results from included studies will be pooled via random effects meta-analysis when appropriate, or otherwise summarized narratively.

DISCUSSION: Evidence generated from our living evidence synthesis will be used to inform policy making, modelling, and prioritization of future research on the effectiveness of COVID-19 vaccines against VOC.

RevDate: 2023-09-16

Lewthwaite H, Byrne A, Brew B, et al (2023)

Treatable traits for long COVID.

Respirology (Carlton, Vic.) [Epub ahead of print].

Long COVID, or post-acute COVID-19 sequelae, is experienced by an estimated one in eight adults following acute COVID-19. Long COVID is a new and complex chronic health condition that typically includes multiple symptoms that cross organ systems and fluctuate over time; a one-size-fits-all approach is, therefore, not likely to be appropriate nor relevant for long COVID treatment. 'Treatable Traits' is a personalized medicine approach, purpose-built to address the complexity and heterogeneity of complex chronic conditions. This comprehensive review aimed to understand how a treatable traits approach could be applied to long COVID, by first identifying the most prevalent long COVID treatable traits and then the available evidence for strategies to target these traits. An umbrella review of 22 systematic reviews identified 34 symptoms and complications common with long COVID, grouped into eight long COVID treatable trait clusters: neurological, chest, psychological, pain, fatigue, sleep impairment, functional impairment and other. A systematic review of randomized control trials identified 18 studies that explored different intervention approaches for long COVID prevention (k = 4) or management (k = 14). While a single study reported metformin as effective for long COVID prevention, the findings need to be replicated and consensus is required around how to define long COVID as a clinical trial endpoint. For long COVID management, current evidence supports exercise training or respiratory muscle training for long COVID treatable traits in the chest and functional limitation clusters. While there are studies exploring interventions targeting other long COVID treatable traits, further high-quality RCTs are needed, particularly targeting treatable traits in the clusters of fatigue, psychological, pain and sleep impairment.

RevDate: 2023-09-14

Martínez-Lavín M, A Miguel-Álvarez (2023)

Hypothetical framework for post-COVID 19 condition based on a fibromyalgia pathogenetic model.

Clinical rheumatology [Epub ahead of print].

There is a clear clinical overlap between fibromyalgia, myalgic encephalomyelitis, and post-COVID 19 condition. Chronic fatigue, cognitive impairment, and widespread pain characterize these 3 syndromes. A steady line of investigation posits fibromyalgia as stress-evoked sympathetically maintained neuropathic pain syndrome and places dorsal root ganglia dysregulation with the ensuing small fiber neuropathy at the epicenter of fibromyalgia pathogenesis. This article discusses emerging evidence suggesting that similar mechanism may operate in post-COVID 19 condition.

RevDate: 2023-09-14

Udeh R, Utrero-Rico A, Dolja-Gore X, et al (2023)

Lactate dehydrogenase contribution to symptom persistence in long COVID: A pooled analysis.

Reviews in medical virology [Epub ahead of print].

There's critical need for risk predictors in long COVID. This meta-analysis evaluates the evidence for an association between plasma lactate dehydrogenase (LDH) and long COVID and explores the contribution of LDH to symptoms persistent across the distinct post-acute sequelae of COVID-19 (PASC) domains. PubMed, EMBASE, Web of Science, and Google Scholar were searched for articles published up to 20 March 2023 for studies that reported data on LDH levels in COVID-19 survivors with and without PASC. Random-effect meta-analysis was employed to estimate the standardized mean difference (SMD) with corresponding 95% confidence interval of each outcome. There were a total of 8289 study participants (3338 PASC vs. 4951 controls) from 46 studies. Our meta-analysis compared to the controls showed a significant association between LDH elevation and Resp-PASC [SMD = 1.07, 95%CI = 0.72, 1.41, p = 0.01] but not Cardio-PASC [SMD = 1.79, 95%CI = -0.02, 3.61, p = 0.05], Neuro-PASC [SMD = 0.19, 95%CI = -0.24, 0.61, p = 0.40], and Gastrointestinal-PASC [SMD = 0.45, 95%CI = -1.08, 1.98, p = 0.56]. This meta-analysis suggests elevated LDH can be used for predicting Resp-PASC, but not Cardio-PASC, Neuro-PASC or gastrointestinal-PASC. Thus, elevated plasma LDH following COVID infection may be considered as a disease biomarker.

RevDate: 2023-09-13

Hawley HB (2023)

Long COVID: Clinical Findings, Pathology, and Endothelial Molecular Mechanisms.

The American journal of medicine pii:S0002-9343(23)00539-9 [Epub ahead of print].

Persistence of COVID-19 symptoms may follow SARS-CoV-2 infection. The incidence of long COVID increases with the severity of acute disease, but even mild disease can be associated with sequelae. The symptoms vary widely with fatigue, shortness of breath, and cognitive dysfunction being the most common. Abnormalities of multiple organs have been documented and histopathology has revealed widespread microthrombi. Elevated levels of complement are present in acute COVID-19 patients and may persist at lower levels in long COVID. Evidence supports complement activation with endotheliopathy associated disease as the molecular mechanism causing both acute and long COVID.

RevDate: 2023-09-13

Cotugno N, Amodio D, Buonsenso D, et al (2023)

Susceptibility of SARS-CoV2 infection in children.

European journal of pediatrics [Epub ahead of print].

Coronavirus disease 2019 in children presents with distinct phenotype in comparison to adults. Overall, the pediatric infection with a generally milder clinical course of the acute infection compared to adults still faces several unknown aspects. Specifically, the presence of a wide range of inflammatory manifestations, including multisystem inflammatory syndrome in children (MIS-C), myocarditis, and long COVID in the period after infection suggests a particular susceptibility of some children upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Albeit peculiar complications such as long covid are less frequent in children compared to adults, research on the relationship between inflammatory syndromes and SARS-CoV-2 is rapidly evolving. Conclusions: new studies and findings continue to emerge, providing further insights into the underlying mechanisms and potential therapeutic strategies. In the present work, we revised current knowledge of the main factors accounting for such variability upon SARS-CoV-2 infection over the pediatric age group. What is Known: • COVID19 in children overall showed a milder course compared to adults during the acute phase of the infection. • Children showed to be susceptible to a wide range of post infectious complications including multisystem inflammatory syndrome in children (MIS-C), myocarditis, neuroinflammation, and long COVID. What is New: • Mechanisms underlying susceptibility to a severe course of the infection were recently shown to pertain to the host. • A specific combination of HLA was recently shown to be associated to higher susceptibility to MIS-C in children.

RevDate: 2023-09-11

Kiyak C, Ijezie OA, Ackah JA, et al (2023)

Topographical Distribution of Neuroanatomical Abnormalities Following COVID-19 Invasion : A Systematic Literature Review.

Clinical neuroradiology [Epub ahead of print].

PURPOSE: This systematic review is aimed at synthesising the literature base to date on the frequency and topographical distribution of neuroanatomical changes seen on imaging following COVID-19 invasion with a focus on both the acute and chronic phases of the disease.

METHODS: In this study, 8 databases were systematically searched to identify relevant articles published from December 2019 to March 2022 and supplemented with a manual reference search. Data were extracted from the included studies and narrative synthesis was employed to integrate the findings.

RESULTS: A total of 110 studies met the inclusion criteria and comprised 119,307 participants (including 31,073 acute and 143 long COVID-19 patients manifesting neurological alterations) and controls. Considerable variability in both the localisation and nature of neuroanatomical abnormalities are noted along the continuum with a wide range of neuropathologies relating to the cerebrovascular/neurovascular system, (sub)cortical structures (including deep grey and white matter structures), brainstem, and predominant regional and/or global alterations in the cerebellum with varying degrees of spinal involvement.

CONCLUSION: Structural regional alterations on neuroimaging are frequently demonstrated in both the acute and chronic phases of SARS-CoV‑2 infection, particularly prevalent across subcortical, prefrontal/frontal and cortico-limbic brain areas as well as the cerebrovascular/neurovascular system. These findings contribute to our understanding of the acute and chronic effects of the virus on the nervous system and has the potential to provide information on acute and long-term treatment and neurorehabilitation decisions.

RevDate: 2023-09-11

Kempuraj D, Aenlle KK, Cohen J, et al (2023)

COVID-19 and Long COVID: Disruption of the Neurovascular Unit, Blood-Brain Barrier, and Tight Junctions.

The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry [Epub ahead of print].

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), could affect brain structure and function. SARS-CoV-2 can enter the brain through different routes, including the olfactory, trigeminal, and vagus nerves, and through blood and immunocytes. SARS-CoV-2 may also enter the brain from the peripheral blood through a disrupted blood-brain barrier (BBB). The neurovascular unit in the brain, composed of neurons, astrocytes, endothelial cells, and pericytes, protects brain parenchyma by regulating the entry of substances from the blood. The endothelial cells, pericytes, and astrocytes highly express angiotensin converting enzyme 2 (ACE2), indicating that the BBB can be disturbed by SARS-CoV-2 and lead to derangements of tight junction and adherens junction proteins. This leads to increased BBB permeability, leakage of blood components, and movement of immune cells into the brain parenchyma. SARS-CoV-2 may also cross microvascular endothelial cells through an ACE2 receptor-associated pathway. The exact mechanism of BBB dysregulation in COVID-19/neuro-COVID is not clearly known, nor is the development of long COVID. Various blood biomarkers could indicate disease severity and neurologic complications in COVID-19 and help objectively diagnose those developing long COVID. This review highlights the importance of neurovascular and BBB disruption, as well as some potentially useful biomarkers in COVID-19, and long COVID/neuro-COVID.

RevDate: 2023-09-10

Gupta T, Najumuddin , Rajendran D, et al (2023)

Metabolism configures immune response across multi-systems: Lessons from COVID-19.

Advances in biological regulation, 90:100977 pii:S2212-4926(23)00023-4 [Epub ahead of print].

Several studies over the last decade demonstrate the recruitment of immune cells, increased inflammatory cytokines, and chemokine in patients with metabolic diseases, including heart failure, parenchymal inflammation, obesity, tuberculosis, and diabetes mellitus. Metabolic rewiring of immune cells is associated with the severity and prevalence of these diseases. The risk of developing COVID-19/SARS-CoV-2 infection increases in patients with metabolic dysfunction (heart failure, diabetes mellitus, and obesity). Several etiologies, including fatigue, dyspnea, and dizziness, persist even months after COVID-19 infection, commonly known as Post-Acute Sequelae of CoV-2 (PASC) or long COVID. A chronic inflammatory state and metabolic dysfunction are the factors that contribute to long COVID. Here, this study explores the potential link between pathogenic metabolic and immune alterations across different organ systems that could underlie COVID-19 and PASC. These interactions could be utilized for targeted future therapeutic approaches.

RevDate: 2023-09-22

Seibert FS, Stervbo U, Wiemers L, et al (2023)

Severity of neurological Long-COVID symptoms correlates with increased level of autoantibodies targeting vasoregulatory and autonomic nervous system receptors.

Autoimmunity reviews, 22(11):103445 pii:S1568-9972(23)00179-9 [Epub ahead of print].

BACKGROUND: The Long-COVID syndrome constitutes a plethora of persisting symptoms with neurological disorders being the most disabling ones. The pathogenesis of Long-COVID is currently under heavy scrutiny and existing data on the role of auto-immune reaction to G-protein coupled receptors (GPCR) are conflicting.

METHODS: This monocentric, cross-sectional study included patients who suffered a mild to moderate SARS-CoV-2 infection up to 12 months prior to enrollment with (n = 72) or without (n = 58) Long-COVID diagnosis according to the German S1 guideline or with no known history of SARS-CoV-2 infection (n = 70). While autoantibodies specific for the vasoregulation associated Adrenergic Receptor (ADR) B1 and B2 and the CNS and vasoregulation associated muscarinic acetylcholine receptor (CHR) M3 and M4 were measured by ELISA, neurological disorders were quantified by internationally standardized questionnaires.

RESULTS: The prevalence and concentrations of evaluated autoantibodes were significantly higher in Long-COVID compared to the 2 other groups (p = 2.1*10[-9]) with a significantly higher number of patients with simultaneous detection of more than one autoantibody in the Long-COVID group (p = 0.0419). Importantly, the overall inflammatory state was low in all 3 groups. ARB1 and ARB2 correlated negatively CERAD Trail Marking A and B (R ≤ -0.26, p ≤ 0.043), while CHRM3 correlated positively with Chadler Fatigue Scale (R = 0.37, p = 0.0087).

CONCLUSIONS: Concentrations of autoantibodies correlates to the intensity of neurological disorders including psychomotor speed, visual search, attention, and fatigue.

RevDate: 2023-09-09

Fundora MP, Kamidani S, ME Oster (2023)

COVID Vaccination as a Strategy for Cardiovascular Disease Prevention.

Current cardiology reports [Epub ahead of print].

PURPOSE OF REVIEW: Cardiovascular (CV) disease is a known complication of SARS-CoV-2 infection. A clear benefit of COVID-19 vaccination is a reduction mortality; however, COVID-19 vaccination may also prevent cardiovascular disease (CVD). We aim to describe CV pathology associated with SARS-CoV-2 infection and describe how COVID-19 vaccination is a strategy for CVD prevention.

RECENT FINDINGS: The risks and benefits of COVID-19 vaccination have been widely studied. Analysis of individuals with and without pre-existing CVD has shown that COVID-19 vaccination can prevent morbidity associated with SARS-CoV-2 infection and reduce mortality. COVID-19 vaccination is effective in preventing myocardial infarction, cerebrovascular events, myopericarditis, and long COVID, all associated with CVD risk factors. Vaccination reduces mortality in patients with pre-existing CVD. Further study investigating ideal vaccination schedules for individuals with CVD should be undertaken to protect this vulnerable group and address new risks from variants of concern.

RevDate: 2023-09-12
CmpDate: 2023-09-11

Chen TB, Chang CM, Yang CC, et al (2023)

Neuroimmunological Effect of Vitamin D on Neuropsychiatric Long COVID Syndrome: A Review.

Nutrients, 15(17):.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19). COVID-19 is now recognized as a multiorgan disease with a broad spectrum of manifestations. A substantial proportion of individuals who have recovered from COVID-19 are experiencing persistent, prolonged, and often incapacitating sequelae, collectively referred to as long COVID. To date, definitive diagnostic criteria for long COVID diagnosis remain elusive. An emerging public health threat is neuropsychiatric long COVID, encompassing a broad range of manifestations, such as sleep disturbance, anxiety, depression, brain fog, and fatigue. Although the precise mechanisms underlying the neuropsychiatric complications of long COVID are presently not fully elucidated, neural cytolytic effects, neuroinflammation, cerebral microvascular compromise, breakdown of the blood-brain barrier (BBB), thrombosis, hypoxia, neurotransmitter dysregulation, and provoked neurodegeneration are pathophysiologically linked to long-term neuropsychiatric consequences, in addition to systemic hyperinflammation and maladaptation of the renin-angiotensin-aldosterone system. Vitamin D, a fat-soluble secosteroid, is a potent immunomodulatory hormone with potential beneficial effects on anti-inflammatory responses, neuroprotection, monoamine neurotransmission, BBB integrity, vasculometabolic functions, gut microbiota, and telomere stability in different phases of SARS-CoV-2 infection, acting through both genomic and nongenomic pathways. Here, we provide an up-to-date review of the potential mechanisms and pathophysiology of neuropsychiatric long COVID syndrome and the plausible neurological contributions of vitamin D in mitigating the effects of long COVID.

RevDate: 2023-09-16

Nazari P, P Pozzilli (2023)

Type 2 diabetes and Covid-19: Lessons learnt, unanswered questions and hints for the future.

Diabetes research and clinical practice, 204:110896 pii:S0168-8227(23)00659-9 [Epub ahead of print].

Type 2 diabetes (T2DM) and COVID-19 represent a considerable burden of disease for patients and healthcare systems. New evidence is transpiring detailing the existence of a bidirectional relationship between T2DM and COVID-19. Alongside the acute influence of pre-existing T2DM on the course of COVID-19 and the exacerbation of dysglycemia following acute infection, long-term sequalae resulting from the synergistic interplay between the two is emerging, namely the development of COVID-induced diabetes and long-COVID in patients with pre-existing diabetes. This review presents our current understanding of the bidirectionality between these two conditions with a view to highlighting questions which remain unanswered and suggesting avenues for future research. In doing so, it emphasises critical gaps where concentrated research efforts are likely to yield the most beneficial improvements in understanding of the relationship between the two conditions, translating to tangible optimisations in care for the affected population.

RevDate: 2023-09-11
CmpDate: 2023-09-11

Vishwakarma N, Goud RB, Tirupattur MP, et al (2023)

The Eye of the Storm: Investigating the Long-Term Cardiovascular Effects of COVID-19 and Variants.

Cells, 12(17):.

COVID-19 had stormed through the world in early March of 2019, and on 5 May 2023, SARS-CoV-2 was officially declared to no longer be a global health emergency. The rise of new COVID-19 variants XBB.1.5 and XBB.1.16, a product of recombinant variants and sub-strains, has fueled a need for continued surveillance of the pandemic as they have been deemed increasingly infectious. Regardless of the severity of the variant, this has caused an increase in hospitalizations, a strain in resources, and a rise of concern for public health. In addition, there is a growing population of patients experiencing cardiovascular complications as a result of post-acute sequelae of COVID-19. This review aims to focus on what was known about SARS-CoV-2 and its past variants (Alpha, Delta, Omicron) and how the knowledge has grown today with new emerging variants, with an emphasis on cardiovascular complexities. We focus on the possible mechanisms that cause the observations of chronic cardiac conditions seen even after patients have recovered from the infection. Further understanding of these mechanisms will help to close the gap in knowledge on post-acute sequelae of COVID-19 and the differences between the effects of variants.

RevDate: 2023-09-22

Løkke FB, Hansen KS, Dalgaard LS, et al (2023)

Long-term complications after infection with SARS-CoV-1, influenza and MERS-CoV - Lessons to learn in long COVID?.

Infectious diseases now, 53(8):104779 pii:S2666-9919(23)00141-0 [Epub ahead of print].

The COVID-19 pandemic has affected millions of people worldwide, and while the mortality rate remains the primary concern, it is becoming increasingly apparent that many COVID-19 survivors experience long-term sequelae, representing a major concern for both themselves and healthcare providers. Comparing long-term sequelae following COVID-19 to those of other respiratory viruses such as influenza, MERS-CoV, and SARS-CoV-1 is an essential step toward understanding the extent and impact of these sequelae. A literature search was carried out using the PubMed. database. Search-terms included "persistent", "long-term", "chronic", and MeSH-terms for SARS-CoV-1, MERS-CoV and Influenza. Only English-language articles were selected. Articles were screened by title/abstract and full-text readings. Key points for comparison were persistent symptoms > 4 weeks, virus type, study design, population size, admission status, methods, and findings. Thirty-one articles were included: 19 on SARS-CoV-1, 10 on influenza, and 2 on MERS-CoV-survivors. Damage to the respiratory system was the main long-term manifestation after the acute phase of infection. Quality of life-related and psychological sequelae were the second and third most widely reported symptoms, respectively. Consistent with long-term sequelae from COVID-19, persisting cardiovascular, neurological, musculoskeletal, gastrointestinal impairments were also reported. In summary, the long-term sequelae following COVID-19 are a significant concern, and while long-term sequelae following influenza, MERS-CoV, and SARS-CoV-1 have also been reported, their prevalence and severity are less clear. It is essential to continue to study and monitor the long-term effects of all respiratory viruses so as to improve our understanding and develop strategies for prevention and treatment.

RevDate: 2023-09-08

Nyasulu PS, Tamuzi JL, RT Erasmus (2023)

Burden, causation, and particularities of Long COVID in African populations: A rapid systematic review.

IJID regions, 8:137-144.

OBJECTIVES: To determine the prevalence of long COVID, its most common symptoms, comorbidities, and pathophysiological mechanisms in African populations.

METHODS: A systematic review of long COVID in African populations was conducted. The random effects model was used to calculate the pooled prevalence rates (95% CI). A narrative synthesis was also performed.

RESULTS: We included 14 studies from seven African countries, totaling 6030 previously SARS-CoV-2 infected participants and 2954 long COVID patients. Long COVID had a pooled prevalence of 41% (26-56%). Fatigue, dyspnea, and confusion or lack of concentration were the most common symptoms, with prevalence rates (95% CI) of 41% (26-56%), 25% (12-38%), and 40% (12-68%), respectively. Long COVID was mainly associated with advanced age, being female, more than three long COVID symptoms in the acute phase, initial fatigue and dyspnea, COVID-19 severity, pre-existing obesity, hypertension, diabetes mellitus, and the presence of any chronic illness (P ≤0.05). High microclot and platelet-poor plasma viscosity explained the pathophysiology of long COVID.

CONCLUSION: Long COVID prevalence in Africa was comparable to the global prevalence. The most common symptoms were higher in Africa. Comorbidities associated with long COVID may lead to additional complications in African populations due to hypercoagulation and thrombosis.Systematic review registration: PROSPERO CRD42023430024.


RJR Experience and Expertise


Robbins holds BS, MS, and PhD degrees in the life sciences. He served as a tenured faculty member in the Zoology and Biological Science departments at Michigan State University. He is currently exploring the intersection between genomics, microbial ecology, and biodiversity — an area that promises to transform our understanding of the biosphere.


Robbins has extensive experience in college-level education: At MSU he taught introductory biology, genetics, and population genetics. At JHU, he was an instructor for a special course on biological database design. At FHCRC, he team-taught a graduate-level course on the history of genetics. At Bellevue College he taught medical informatics.


Robbins has been involved in science administration at both the federal and the institutional levels. At NSF he was a program officer for database activities in the life sciences, at DOE he was a program officer for information infrastructure in the human genome project. At the Fred Hutchinson Cancer Research Center, he served as a vice president for fifteen years.


Robbins has been involved with information technology since writing his first Fortran program as a college student. At NSF he was the first program officer for database activities in the life sciences. At JHU he held an appointment in the CS department and served as director of the informatics core for the Genome Data Base. At the FHCRC he was VP for Information Technology.


While still at Michigan State, Robbins started his first publishing venture, founding a small company that addressed the short-run publishing needs of instructors in very large undergraduate classes. For more than 20 years, Robbins has been operating The Electronic Scholarly Publishing Project, a web site dedicated to the digital publishing of critical works in science, especially classical genetics.


Robbins is well-known for his speaking abilities and is often called upon to provide keynote or plenary addresses at international meetings. For example, in July, 2012, he gave a well-received keynote address at the Global Biodiversity Informatics Congress, sponsored by GBIF and held in Copenhagen. The slides from that talk can be seen HERE.


Robbins is a skilled meeting facilitator. He prefers a participatory approach, with part of the meeting involving dynamic breakout groups, created by the participants in real time: (1) individuals propose breakout groups; (2) everyone signs up for one (or more) groups; (3) the groups with the most interested parties then meet, with reports from each group presented and discussed in a subsequent plenary session.


Robbins has been engaged with photography and design since the 1960s, when he worked for a professional photography laboratory. He now prefers digital photography and tools for their precision and reproducibility. He designed his first web site more than 20 years ago and he personally designed and implemented this web site. He engages in graphic design as a hobby.

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Although new treatments and vaccines have greatly reduced the acute threat of covid-19, many people who contract the disease find themselves with a persistent set of symptoms that are at best uncomfortable and at worst debilitating — long covid. R. Robbins

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Collection of publications by R J Robbins

Reprints and preprints of publications, slide presentations, instructional materials, and data compilations written or prepared by Robert Robbins. Most papers deal with computational biology, genome informatics, using information technology to support biomedical research, and related matters.

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Curriculum Vitae for R J Robbins

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Curriculum Vitae for R J Robbins

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