Low avidity circulating SARS-CoV-2 reactive CD8+ T cells with proinflammatory TEMRA phenotype are associated with post-acute sequelae of COVID-19 DOI Creative Commons
Krystallenia Paniskaki,

Margarethe Konik,

Moritz Anft

et al.

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: June 2, 2023

The role of adaptive SARS-CoV-2 specific immunity in post-acute sequelae COVID-19 (PASC) is not well explored, although a growing population convalescent patients with manifestation PASC observed. We analyzed the SARS-CoV-2-specific immune response, via pseudovirus neutralizing assay and multiparametric flow cytometry 40 non-specific 15 healthy donors. Although frequencies SARS-CoV-2-reactive CD4+ T cells were similar between studied cohorts, stronger reactive CD8+ cell characterized by IFNγ production predominant TEMRA phenotype but low functional TCR avidity was detected compared to controls. Of interest, high comparable groups demonstrating sufficient cellular antiviral response PASC. In line immunity, capacity inferior conclusion, our data suggest that may be driven an inflammatory triggered expanded pro-inflammatory cells. These are known activated or even without stimulation lead tissue damage. Further studies including animal models required for better understanding underlying immunopathogensis. Summary: A persistent responsible observed patients.

Language: Английский

Long COVID: major findings, mechanisms and recommendations DOI Open Access
Hannah Davis, Lisa McCorkell, Julia Moore Vogel

et al.

Nature Reviews Microbiology, Journal Year: 2023, Volume and Issue: 21(3), P. 133 - 146

Published: Jan. 13, 2023

Language: Английский

Citations

2751
Persistent complement dysregulation with signs of thromboinflammation in active Long Covid DOI Creative Commons
Carlo Cervia, Sarah C. Brüningk, Tobias Hoch

et al.

Science, Journal Year: 2024, Volume and Issue: 383(6680)

Published: Jan. 18, 2024

Long Covid is a debilitating condition of unknown etiology. We performed multimodal proteomics analyses blood serum from COVID-19 patients followed up to 12 months after confirmed severe acute respiratory syndrome coronavirus 2 infection. Analysis >6500 proteins in 268 longitudinal samples revealed dysregulated activation the complement system, an innate immune protection and homeostasis mechanism, individuals experiencing Covid. Thus, active was characterized by terminal system dysregulation ongoing alternative classical pathways, latter associated with increased antibody titers against several herpesviruses possibly stimulating this pathway. Moreover, markers hemolysis, tissue injury, platelet activation, monocyte-platelet aggregates were Machine learning thromboinflammatory as top biomarkers, warranting diagnostic therapeutic interrogation these systems.

Language: Английский

Citations

199
Long COVID: pathophysiological factors and abnormalities of coagulation DOI Creative Commons
Simone Turner, Asad Khan, David Putrino

et al.

Trends in Endocrinology and Metabolism, Journal Year: 2023, Volume and Issue: 34(6), P. 321 - 344

Published: April 19, 2023

Acute COVID-19 infection is followed by prolonged symptoms in approximately one ten cases: known as Long COVID. The disease affects ~65 million individuals worldwide. Many pathophysiological processes appear to underlie COVID, including viral factors (persistence, reactivation, and bacteriophagic action of SARS CoV-2); host (chronic inflammation, metabolic endocrine dysregulation, immune autoimmunity); downstream impacts (tissue damage from the initial infection, tissue hypoxia, dysbiosis, autonomic nervous system dysfunction). These mechanisms culminate long-term persistence disorder characterized a thrombotic endothelialitis, endothelial hyperactivated platelets, fibrinaloid microclots. abnormalities blood vessels coagulation affect every organ represent unifying pathway for various

Language: Английский

Citations

148
Post-acute sequelae of COVID-19: understanding and addressing the burden of multisystem manifestations DOI Creative Commons
Matteo Parotto, Mariann Gyöngyösi, Kathryn L. Howe

et al.

The Lancet Respiratory Medicine, Journal Year: 2023, Volume and Issue: 11(8), P. 739 - 754

Published: July 17, 2023

Individuals with SARS-CoV-2 infection can develop symptoms that persist well beyond the acute phase of COVID-19 or emerge after phase, lasting for weeks months initial illness. The post-acute sequelae COVID-19, which include physical, cognitive, and mental health impairments, are known collectively as long COVID post-COVID-19 condition. substantial burden this multisystem condition is felt at individual, health-care system, socioeconomic levels, on an unprecedented scale. Survivors COVID-19-related critical illness risk respiratory distress syndrome, sepsis, chronic illness, these multidimensional morbidities might be difficult to differentiate from specific effects COVID-19. We provide overview manifestations in adults. explore various organ systems, describe potential pathophysiological mechanisms, consider challenges providing clinical care support survivors manifestations. Research needed reduce incidence optimise therapeutic rehabilitative patients.

Language: Английский

Citations

137
Long COVID: An inevitable sequela of SARS-CoV-2 infection DOI Creative Commons
Chih‐Cheng Lai, Chi‐Kuei Hsu, Muh‐Yong Yen

et al.

Journal of Microbiology Immunology and Infection, Journal Year: 2022, Volume and Issue: 56(1), P. 1 - 9

Published: Oct. 15, 2022

At present, there are more than 560 million confirmed cases of the coronavirus disease 2019 (COVID-19) worldwide. Although 98% patients with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection can survive COVID, a significant portion survivors develop residual health problems, which is termed as long COVID. COVID-19 generally associated high risk asymptomatic or mild also show The definition COVID inconsistent and its clinical manifestations protean. In addition to general symptoms, such fatigue, affect many organ systems, including respiratory, neurological, psychosocial, cardiovascular, gastrointestinal, metabolic systems. Moreover, may experience exercise intolerance impaired daily function quality life. Long be caused by SARS-CoV-2 direct injury immune/inflammatory response. Assessment requires comprehensive evaluation, history taking, physical examination, laboratory tests, radiography, functional tests. However, no known effective treatment for Based on limited evidence, vaccines help prevent development As new entity that constantly evolving, still unknowns, further investigation warranted enhance our understanding this disease.

Language: Английский

Citations

105
Combining L-Arginine with vitamin C improves long-COVID symptoms: The LINCOLN Survey DOI
Raffaele Izzo, Valentina Trimarco, Pasquale Mone

et al.

Pharmacological Research, Journal Year: 2022, Volume and Issue: 183, P. 106360 - 106360

Published: July 19, 2022

Language: Английский

Citations

75
Long COVID: a review and proposed visualization of the complexity of long COVID DOI Creative Commons
Rubeshan Perumal, Letitia Shunmugam, Kogieleum Naidoo

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: April 20, 2023

Post-Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus - 2 (SARS-CoV-2) infection, or Long COVID, is a prevailing second pandemic with nearly 100 million affected individuals globally and counting. We propose visual description the complexity COVID its pathogenesis that can be used by researchers, clinicians, public health officials to guide global effort toward an improved understanding eventual mechanism-based provision care afflicted patients. The proposed visualization framework for should evidence-based, dynamic, modular, systems-level approach condition. Furthermore, further research such could establish strength relationships between pre-existing conditions (or risk factors), biological mechanisms, resulting clinical phenotypes outcomes COVID. Notwithstanding significant contribution disparities in access social determinants have on disease course long our model focuses primarily mechanisms. Accordingly, sets out scientific, clinical, efforts better understand abrogate burden imposed

Language: Английский

Citations

63
The knowns and unknowns of long COVID-19: from mechanisms to therapeutical approaches DOI Creative Commons
Roxana Gheorghiţă, Iuliana Șoldănescu, Andrei Lobiuc

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: March 4, 2024

The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has been defined as the greatest global health and socioeconomic crisis of modern times. While most people recover after being infected with virus, a significant proportion them continue to experience issues weeks, months even years acute infection SARS-CoV-2. This persistence clinical symptoms in individuals for at least three onset or emergence new lasting more than two months, without any other explanation alternative diagnosis have named long COVID, long-haul post-COVID-19 conditions, chronic post-acute sequelae (PASC). Long COVID characterized constellation disorders that vary widely their manifestations. Further, mechanisms underlying are not fully understood, which hamper efficient treatment options. review describes predictors common related COVID's effects on central peripheral nervous system organs tissues. Furthermore, transcriptional markers, molecular signaling pathways risk factors such sex, age, pre-existing condition, hospitalization during phase COVID-19, vaccination, lifestyle presented. Finally, recommendations patient rehabilitation management, well therapeutical approaches discussed. Understanding complexity this disease, its across multiple organ systems overlapping pathologies possible paramount developing diagnostic tools treatments.

Language: Английский

Citations

23
Pathophysiological, immunological, and inflammatory features of long COVID DOI Creative Commons
Karen Böhmwald, Benjamín Diethelm‐Varela,

Linmar Rodríguez-Guilarte

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 28, 2024

The COVID-19 pandemic continues to cause severe global disruption, resulting in significant excess mortality, overwhelming healthcare systems, and imposing substantial social economic burdens on nations. While most of the attention therapeutic efforts have concentrated acute phase disease, a notable proportion survivors experience persistent symptoms post-infection clearance. This diverse set symptoms, loosely categorized as long COVID, presents potential additional public health crisis. It is estimated that 1 5 exhibit clinical manifestations consistent with COVID. Despite this prevalence, mechanisms pathophysiology COVID remain poorly understood. Alarmingly, evidence suggests cases within condition develop debilitating or disabling symptoms. Hence, urgent priority should be given further studies equip systems for its management. review provides an overview available information emerging condition, focusing affected individuals’ epidemiology, pathophysiological mechanisms, immunological inflammatory profiles.

Language: Английский

Citations

21
Increased Levels of Inflammatory and Endothelial Biomarkers in Blood of Long COVID Patients Point to Thrombotic Endothelialitis DOI
Simone Turner,

Caitlin A. Naidoo,

Thomas J. Usher

et al.

Seminars in Thrombosis and Hemostasis, Journal Year: 2023, Volume and Issue: 50(02), P. 288 - 294

Published: May 19, 2023

Abstract The prevailing hypotheses for the persistent symptoms of Long COVID have been narrowed down to immune dysregulation and autoantibodies, widespread organ damage, viral persistence, fibrinaloid microclots (entrapping numerous inflammatory molecules) together with platelet hyperactivation. Here we demonstrate significantly increased concentrations von Willebrand factor (VWF), 4 (PF4), serum amyloid A (SAA), α-2 antiplasmin (α-2AP), endothelial-leukocyte adhesion molecule 1 (E-selectin), endothelial cell (PECAM-1) in soluble part blood. It was noteworthy that mean level exceeded upper limit laboratory reference range patients, other 5 were elevated patients as compared controls. This is alarming if take into consideration a significant amount total burden these molecules has previously shown be entrapped inside fibrinolysis-resistant (thus decreasing apparent molecules). We conclude presence microclotting, relatively high levels six biomarkers known key drivers clotting pathology, points thrombotic endothelialitis pathological process COVID.

Language: Английский

Citations

34