Immune mechanisms underlying COVID-19 pathology and post-acute sequelae of SARS-CoV-2 infection (PASC) DOI Creative Commons
Sindhu Mohandas, Prasanna Jagannathan, Timothy J. Henrich

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: May 26, 2023

With a global tally of more than 500 million cases severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections to date, there are growing concerns about the post-acute sequelae SARS-CoV-2 infection (PASC), also known as long COVID. Recent studies suggest that exaggerated immune responses key determinants severity and outcomes initial well subsequent PASC. The complexity innate adaptive in period requires in-depth mechanistic analyses identify specific molecular signals cell populations which promote PASC pathogenesis. In this review, we examine current literature on mechanisms dysregulation COVID-19 limited emerging data immunopathology While phases may share some parallel immunopathology, it is likely quite distinct heterogeneous, thus requiring large-scale longitudinal patients with without after an infection. By outlining knowledge gaps PASC, hope provide avenues for novel research directions will ultimately lead precision therapies restore healthy function patients.

Language: Английский

Nitric oxide signalling in kidney regulation and cardiometabolic health DOI Open Access
Mattias Carlström

Nature Reviews Nephrology, Journal Year: 2021, Volume and Issue: 17(9), P. 575 - 590

Published: June 1, 2021

Language: Английский

Citations

188

Maternal-fetal immune responses in pregnant women infected with SARS-CoV-2 DOI Creative Commons
Valeria Garcia‐Flores, Roberto Romero,

Yi Xu

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Jan. 18, 2022

Pregnant women represent a high-risk population for severe/critical COVID-19 and mortality. However, the maternal-fetal immune responses initiated by SARS-CoV-2 infection, whether this virus is detectable in placenta, are still under investigation. Here we show that infection during pregnancy primarily induces unique inflammatory at interface, which largely governed maternal T cells fetal stromal cells. also associated with humoral cellular blood, as well mild cytokine response neonatal circulation (i.e., umbilical cord blood), without compromising T-cell repertoire or initiating IgM responses. Importantly, not detected placental tissues, nor sterility of placenta compromised viral infection. This study provides insight into triggered emphasizes rarity

Language: Английский

Citations

184

SARS-CoV-2 spike protein S1 induces fibrin(ogen) resistant to fibrinolysis: implications for microclot formation in COVID-19 DOI Creative Commons

Lize M. Grobbelaar,

Chantelle Venter,

Maré Vlok

et al.

Bioscience Reports, Journal Year: 2021, Volume and Issue: 41(8)

Published: July 30, 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection, the cause of disease 2019 (COVID-19), is characterized by unprecedented clinical pathologies. One most important pathologies, hypercoagulation and microclots in lungs patients. Here we study effect isolated SARS-CoV-2 spike protein S1 subunit as potential inflammagen sui generis. Using scanning electron fluorescence microscopy well mass spectrometry, investigate this to interact with platelets fibrin(ogen) directly blood hypercoagulation. platelet-poor plasma (PPP), show that may interfere flow. Mass spectrometry also showed when added healthy PPP, it results structural changes β γ fibrin(ogen), complement 3, prothrombin. These proteins were substantially resistant trypsinization, presence S1. suggest that, part, circulation contribute COVID-19 positive patients substantial impairment fibrinolysis. Such lytic result persistent large have noted here previously samples This observation relevance treatment hypercoagulability

Language: Английский

Citations

161

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

153

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

141

SARS-CoV-2 Infects Endothelial Cells In Vivo and In Vitro DOI Creative Commons
Fengming Liu, Kun Han, Robert V. Blair

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2021, Volume and Issue: 11

Published: July 6, 2021

SARS-CoV-2 infection can cause fatal inflammatory lung pathology, including thrombosis and increased pulmonary vascular permeability leading to edema hemorrhage. In addition the lung, cytokine storm-induced cascade also affects other organs. infection-related inflammation is characterized by endotheliopathy in Whether causes directly infecting endothelial cells not known focus of present study. We observed 1) co-localization with cell marker CD31 lungs SARS-CoV-2-infected mice expressing hACE2 intranasal delivery adenovirus 5-hACE2 (Ad5-hACE2 mice) non-human primates at both protein RNA levels, 2) proteins immunogold labeling electron microscopic analysis. detected autopsied tissue obtained from patients who died severe COVID-19. Comparative analysis sequencing data infected Ad5-hACE2 Ad5-empty (control) revealed upregulated KRAS signaling pathway, a well-known pathway for cellular activation dysfunction. Further, we showed that infects mature mouse aortic (AoECs) were activated performing an sprouting assay prior exposure SARS-CoV-2. This was demonstrated CD34 immunostaining detection viral particles studies. Moreover, AoECs became positive ACE-2 but quiescent AoECs. Together, our results indicate pneumocytes, vivo ex vivo, which may contribute cardiovascular complications infection, multipleorgan failure.

Language: Английский

Citations

136

The Relevance of a Physical Active Lifestyle and Physical Fitness on Immune Defense: Mitigating Disease Burden, With Focus on COVID-19 Consequences DOI Creative Commons
Tayrine Ordonio Filgueira, Ângela Castoldi, Lucas Eduardo Rodrigues Santos

et al.

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Feb. 5, 2021

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a fast spreading virus leading to the development of Disease-2019 (COVID-19). and critical cases are characterized by damage respiratory system, endothelial inflammation, multiple organ failure triggered an excessive production proinflammatory cytokines, culminating in high number deaths all over world. Sedentarism induces worse, continuous, progressive consequences health. On other hand, physical activity provides benefits health improves low-grade systemic inflammation. aim this review elucidate effects fitness, immune defense, its contribution mitigate severe inflammatory response mediated SARS-CoV-2. Physical exercise effective therapeutic strategy SARS-CoV-2 infection. In sense, studies have shown that acute myokines secreted tissues into bloodstream, supporting modulatory effect. Therefore, maintaining influence balance system increases vigilance, also might promote potent against infectious diseases chronic associated with forms COVID-19. Protocols maintain practice suggested been strongly established, such as home-based (HBE) outdoor-based (OBE). regard, HBE help reduce levels inactivity, bed rest, sitting time, impacting on adherence activity, promoting related exercise, attracting patients different stages treatment for parallel, OBE must improve health, but prevent COVID-19 outcomes populations. conclusion, or models can be progress infection, coadjutant therapy at ages conditions.

Language: Английский

Citations

133

Cerebrospinal fluid findings in COVID-19: a multicenter study of 150 lumbar punctures in 127 patients DOI Creative Commons
Sven Jarius, Florence Pache, Peter Körtvélyessy

et al.

Journal of Neuroinflammation, Journal Year: 2022, Volume and Issue: 19(1)

Published: Jan. 20, 2022

Abstract Background Comprehensive data on the cerebrospinal fluid (CSF) profile in patients with COVID-19 and neurological involvement from large-scale multicenter studies are missing so far. Objective To analyze systematically CSF COVID-19. Methods Retrospective analysis of 150 lumbar punctures 127 PCR-proven symptoms seen at 17 European university centers Results The most frequent pathological finding was blood-CSF barrier (BCB) dysfunction (median QAlb 11.4 [6.72–50.8]), which present 58/116 (50%) samples without pre-/coexisting CNS diseases (group I). remained elevated > 14d (47.6%) even 30d (55.6%) after onset. total protein 54/118 (45.8%) 65.35 mg/dl [45.3–240.4]) strongly correlated QAlb. white cell count (WCC) increased 14/128 (11%) (mostly lympho-monocytic; median 10 cells/µl, 100 only 4). An albuminocytological dissociation (ACD) found 43/115 (37.4%) samples. l -lactate 26/109 (24%; 3.04 mmol/l [2.2–4]). CSF-IgG 50/100 (50%), but peripheral origin, since QIgG normal almost all cases, as were QIgA QIgM. In 58/103 (56%) pattern 4 oligoclonal bands (OCB) compatible systemic inflammation present, while CSF-restricted OCB 2/103 (1.9%). SARS-CoV-2-CSF-PCR negative 76/76 Routine findings 35%. Cytokine levels frequently (often associated BCB dysfunction) serum, partly remaining positive high for weeks/months (939 tests). Of note, a SARS-CoV-2-IgG-antibody index (AI) 2/19 (10.5%) unusually WCC both them interleukin-6 (IL-6) one (not tested other). Anti-neuronal/anti-glial autoantibodies mostly absent serum (1509 disorders II [ N = 19]; including multiple sclerosis, JC-virus-associated immune reconstitution inflammatory syndrome, HSV/VZV encephalitis/meningitis, lymphoma, anti-Yo subarachnoid hemorrhage), representative respective disease. Conclusions is mainly characterized by disruption absence intrathecal inflammation, endotheliopathy. Persistent cytokine may contribute to acute ‘long COVID’. Direct infection SARS-CoV-2, if occurring all, seems be rare. Broad differential diagnostic considerations recommended avoid misinterpretation treatable coexisting complications

Language: Английский

Citations

133

Beyond neutralization: Fc-dependent antibody effector functions in SARS-CoV-2 infection DOI Open Access
Ali Zhang, Hannah D. Stacey, Michael R. D’Agostino

et al.

Nature reviews. Immunology, Journal Year: 2022, Volume and Issue: 23(6), P. 381 - 396

Published: Dec. 19, 2022

Language: Английский

Citations

131

Long-term follow-up of recovered patients with COVID-19 DOI Creative Commons
Monica Cortinovis, Norberto Perico, Giuseppe Remuzzi

et al.

The Lancet, Journal Year: 2021, Volume and Issue: 397(10270), P. 173 - 175

Published: Jan. 1, 2021

Language: Английский

Citations

123