Immune mechanisms underlying COVID-19 pathology and post-acute sequelae of SARS-CoV-2 infection (PASC)

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

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Neutrophil extracellular traps in homeostasis and disease

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Sept. 20, 2024

Language: Английский

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COVID-19 and autoimmune diseases: is there a connection?

Current Opinion in Allergy and Clinical Immunology, Journal Year: 2023, Volume and Issue: 23(2), P. 185 - 192

Published: Jan. 11, 2023

Purpose of review This summarizes current evidence on the potential link between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and autoimmunity. Recent findings Several viral infections are triggers reactive autoimmune diseases by inducing type II IV hypersensitivity reactions. demonstrated that SARS-CoV-2 is not an exception, triggering production tissue-specific autoantibodies during phase disease 2019 (COVID-19) leading to development as long-term complication. The significant immune dysregulation with cytokine storm organ damage observed in patients critical COVID-19 considered main mechanism explaining high levels autoantibodies, which also implicated severity need for intensive care assessment. Multisystem inflammatory children (MIS-C) immune-mediated where recent leads systemic inflammation, already other diseases. Summary Autoimmunity may be a complication SAR-CoV-2 infection. Understanding pathogenesis manifestations might help prevent incidence or exacerbation disorders design better more efficient treatment strategies adult populations.

Language: Английский

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Neutrophil extracellular traps (NET): not only antimicrobial but also modulators of innate and adaptive immunities in inflammatory autoimmune diseases

RMD Open, Journal Year: 2023, Volume and Issue: 9(3), P. e003104 - e003104

Published: Aug. 1, 2023

Polymorphonuclear neutrophils (PMN) represent one of the first lines defence against invading pathogens and are most abundant leucocytes in circulation. Generally described as pro-inflammatory cells, recent data suggest that PMN also have immunomodulatory capacities. In response to certain stimuli, activated expel neutrophil extracellular traps (NET), structures made DNA associated proteins. Although originally an innate immune mechanism fighting bacterial infection, NET formation (or probably rather excess together with impaired clearance NET) may be deleterious. Indeed, been implicated development several inflammatory autoimmune diseases rheumatoid arthritis or systemic lupus erythematosus, well fibrosis cancer. They suggested a source (neo)autoantigens regulatory proteins like proteases act physical barrier. Different mechanisms described, leading death not, depending on stimulus. Interestingly, both anti-inflammatory this partly depends mechanism, thus triggering formation. Within review, we will describe activities especially how modulate responses.

Language: Английский

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What is the actual relationship between neutrophil extracellular traps and COVID-19 severity? A longitudinal study

Respiratory Research, Journal Year: 2024, Volume and Issue: 25(1)

Published: Jan. 19, 2024

Abstract Background Neutrophil extracellular traps (NETs) have repeatedly been related to COVID-19 severity and mortality. However, there is no consensus on their quantification, are scarce data evolution during the disease. We studied circulating NET markers in patients with throughout hospitalization. Methods prospectively included 93 (201 blood samples), evaluating disease 3 evolutionary phases (viral, early, late inflammation). Of these, 72 had 180 samples various phases. also evaluated 55 controls similar age, sex comorbidities. measured 4 serum: cfDNA, CitH3, MPO-DNA NE-DNA complexes; as well neutrophil-related cytokines IL-8 G-CSF. Results The group higher CitH3 (28.29 vs 20.29 pg/mL, p = 0.022), MPO-DNA, (7.87 2.56 ng/mL; 0.80 0.52 1.04 0.72, respectively, < 0.001 for all) than hospitalisation. cfDNA was only marker clearly severity, it remained non-survivors Only an independent risk factor mortality need intensive care. count, IL-8, G-CSF were significantly severity. showed significant correlations (r: 0.483, 0.001), including all across grades, they days 10–16 of those who died. Correlations among other lower expected. Conclusions biomarkers NETs present associated mortality, but three little or association these outcomes. activity neutrophil count better reflected formation. appeared be more overall tissue damage; previous widespread use this could overestimated relationship between Currently, limitations accurate measurement that make difficult assess its true role pathogenesis.

Language: Английский

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Impaired balance between neutrophil extracellular trap formation and degradation by DNases in COVID-19 disease

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: March 7, 2024

Abstract Background Thrombo-inflammation and neutrophil extracellular traps (NETs) are exacerbated in severe cases of COVID-19, potentially contributing to disease exacerbation. However, the mechanisms underpinning this dysregulation remain elusive. We hypothesised that lower DNase activity may be associated with higher NETosis clinical worsening patients COVID-19. Methods Biological samples were obtained from hospitalized (15 severe, 37 critical at sampling) 93 non-severe ambulatory cases. Our aims compare NET biomarkers, functional levels, explore driving any imbalance concerning severity. Results Functional levels diminished most patients, paralleling an between markers activity. DNase1 antigen but patients. DNase1L3 remained consistent across subgroups, not rising alongside markers. DNASE1 polymorphisms correlated reduced levels. Moreover, a quantitative deficiency plasmacytoid dendritic cells (pDCs), which primarily express , was observed Analysis public single-cell RNAseq data revealed expression pDCs COVID-19 patient. Conclusion Severe exhibited quantity. Early identification could guide targeted therapies against thrombo-inflammation COVID-19-related sepsis, such as administration, avert deterioration. Trial registration : COVERAGE trial (NCT04356495) COLCOV19-BX study (NCT04332016). Graphical

Language: Английский

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Protein kinase C isoforms mediate the formation of neutrophil extracellular traps

International Immunopharmacology, Journal Year: 2022, Volume and Issue: 114, P. 109448 - 109448

Published: Nov. 24, 2022

Language: Английский

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Neutrophils and COVID-19

Progress in molecular biology and translational science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Multisystem Inflammatory Syndrome in Children: A Comprehensive Review Over the Past Five Years

Journal of Intensive Care Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: March 17, 2025

Multisystem Inflammatory Syndrome in Children: A Comprehensive Review over the Past Five Years This review explores many facets of Children (MIS-C) previous 5 years. In time since COVID 19 pandemic gripped our medical systems, we can now explore data that has been collected from The literature allowed us to better understand impact and post illness occurrence a severe systemic inflammatory disease on youngest patient populations. paper will outline pathophysiology MIS-C, treatments utilized, short long-term outcomes including epidemiological factors.

Language: Английский

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What do we know about pathological mechanism and pattern of lung injury related to SARS-CoV-2 Omicron variant?

Diagnostic Pathology, Journal Year: 2023, Volume and Issue: 18(1)

Published: Feb. 10, 2023

Abstract Pulmonary damage in SARS-CoV-2 is characterized pathologically by diffuse alveolar (DAD) and thrombosis. In addition, nosocomial bacterial superinfections ventilator-induced lung injury (VILI) are likely to occur. The Omicron variant have manifested itself as a more diffusive virus which mainly affects the upper airways, such nose pharynx. mechanism leading with complex clinical course for remains unclear. A key question whether organ due direct targeting of or downstream effects an altered immune response. An escape process being studied, could lead prolonged viral shedding increase hospitalization times patients comorbidities, increased risk pulmonary co-infections/superinfections damage. This brief commentary reports current knowledge on provides some useful suggestions scientific community.

Language: Английский

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