Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 21(5), P. 319 - 329

Published: April 6, 2021

Language: Английский

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Complement and tissue factor–enriched neutrophil extracellular traps are key drivers in COVID-19 immunothrombosis

Journal of Clinical Investigation, Journal Year: 2020, Volume and Issue: 130(11), P. 6151 - 6157

Published: Aug. 6, 2020

Emerging data indicate that complement and neutrophils contribute to the maladaptive immune response fuels hyperinflammation thrombotic microangiopathy, thereby increasing coronavirus 2019 (COVID-19) mortality. Here, we investigated how interacts with platelet/neutrophil extracellular traps (NETs)/thrombin axis, using COVID-19 specimens, cell-based inhibition studies, NET/human aortic endothelial cell (HAEC) cocultures. Increased plasma levels of NETs, tissue factor (TF) activity, sC5b-9 were detected in patients. Neutrophils patients yielded high TF expression released NETs carrying active TF. Treatment control platelet-rich generated TF-bearing induced activity HAECs. Thrombin or NETosis C5aR1 blockade attenuated platelet-mediated NET-driven thrombogenicity. serum activation vitro, consistent clinical samples. Complement C3 compstatin Cp40 disrupted neutrophils. In conclusion, provide a mechanistic basis for pivotal role immunothrombosis. This study supports strategies against severe acute respiratory syndrome 2 exploit inhibition.

Language: Английский

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Thrombocytopathy and endotheliopathy: crucial contributors to COVID-19 thromboinflammation

Nature Reviews Cardiology, Journal Year: 2020, Volume and Issue: 18(3), P. 194 - 209

Published: Nov. 19, 2020

Language: Английский

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Direct activation of the alternative complement pathway by SARS-CoV-2 spike proteins is blocked by factor D inhibition

Blood, Journal Year: 2020, Volume and Issue: 136(18), P. 2080 - 2089

Published: Sept. 2, 2020

Language: Английский

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Central nervous system complications associated with SARS-CoV-2 infection: integrative concepts of pathophysiology and case reports

Journal of Neuroinflammation, Journal Year: 2020, Volume and Issue: 17(1)

Published: Aug. 6, 2020

Abstract Coronavirus disease 2019 (COVID-19) is a highly infectious pandemic caused by novel coronavirus called severe acute respiratory syndrome 2 (SARS-CoV-2). It frequently presents with unremitting fever, hypoxemic failure, and systemic complications (e.g., gastrointestinal, renal, cardiac, hepatic involvement), encephalopathy, thrombotic events. The symptoms are similar to those accompanying other genetically related beta-coronaviruses (CoVs) such as CoV (SARS-CoV) Middle East Respiratory Syndrome (MERS-CoV). Hypoxemic can rapidly progress Acute Distress (ARDS) secondary hemophagocytic lymphohistiocytosis, leading multi-organ system dysfunction syndrome. Severe cases typically associated aberrant excessive inflammatory responses. These include significant upregulation of cytokines, chemokines, pro-inflammatory mediators, increased acute-phase proteins (APPs) production hyperferritinemia elevated C-reactive protein (CRP), well lymphocytopenia. neurological SARS-CoV-2 infection high among critical illnesses. This review highlights the central nervous (CNS) COVID-19 attributed primary CNS involvement due rare direct neuroinvasion more commonly sequelae exuberant innate-mediated hyper-inflammation. also provides theoretical integration clinical experimental data elucidate pathogenesis these disorders. Specifically, how hyper-inflammation provoked maladaptive innate immunity may impair neurovascular endothelial function, disrupt BBB, activate immune signaling pathways, induce para-infectious autoimmunity, potentially contributing infection. Direct viral brain parenchyma causing encephalitis, possibly concurrent endotheliitis renin angiotensin (RAS) dysregulation, reviewed.

Language: Английский

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Impact of COVID-19 on the thyroid gland: an update

Reviews in Endocrine and Metabolic Disorders, Journal Year: 2020, Volume and Issue: 22(4), P. 803 - 815

Published: Nov. 25, 2020

Abstract Coronavirus disease 2019 (COVID-19) is the pandemic of new millennium. COVID-19 can cause both pulmonary and systemic inflammation, potentially determining multi-organ dysfunction. Data on relationship between thyroid have been emerging, rapidly increasing since March 2020. The gland virus infection with its associated inflammatory-immune responses are known to be engaged in complex interplay. SARS-CoV-2 uses ACE2 combined transmembrane protease serine 2 (TMPRSS2) as key molecular infect host cells. Interestingly, TMPRSS2 expression levels high more than lungs. Our literature search provided greater evidence that entire hypothalamic–pituitary–thyroid (HPT) axis could relevant targets damage by SARS-CoV-2. Specifically, COVID-19-related disorders include thyrotoxicosis, hypothyroidism, well nonthyroidal illness syndrome. Moreover, we noticed treatment plans for cancer considerably changing direction teleconsultations less diagnostic therapeutical procedures. current review includes findings changed soon results topic, considering rapidity worldwide research COVID-19.

Language: Английский

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Complement C3 vs C5 inhibition in severe COVID-19: Early clinical findings reveal differential biological efficacy

Clinical Immunology, Journal Year: 2020, Volume and Issue: 220, P. 108598 - 108598

Published: Sept. 19, 2020

Language: Английский

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Increased complement activation is a distinctive feature of severe SARS-CoV-2 infection

Science Immunology, Journal Year: 2021, Volume and Issue: 6(59)

Published: May 13, 2021

Complement activation has been implicated in the pathogenesis of severe SARS-CoV-2 infection. However, it remains to be determined whether increased complement is a broad indicator critical illness (and thus, no different COVID-19). It also unclear which pathways are contributing COVID-19, and if associated with certain features infection, such as endothelial injury hypercoagulability. To address these questions, we investigated plasma from patients COVID-19 prospectively enrolled at two tertiary care centers: Washington University School Medicine (n=134) Yale (n=49). We compared our non-COVID cohorts: (a) hospitalized influenza (n=54), (b) admitted intensive unit (ICU) acute respiratory failure requiring invasive mechanical ventilation (IMV, n=22). demonstrate that circulating markers elevated those non-COVID-19 failure. Further, results facilitate distinguishing who higher risk worse outcomes ICU admission, or IMV. Moreover, indicate enhanced alternative pathway most prevalent (i.e., angiopoietin-2) well hypercoagulability thrombomodulin von Willebrand factor). Our findings identify distinctive feature provide specific targets may utilized for prognostication, drug discovery personalized clinical trials.

Language: Английский

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A multi-omics investigation of the composition and function of extracellular vesicles along the temporal trajectory of COVID-19

Nature Metabolism, Journal Year: 2021, Volume and Issue: 3(7), P. 909 - 922

Published: June 22, 2021

Language: Английский

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Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): a Systemic Infection

Clinical Microbiology Reviews, Journal Year: 2021, Volume and Issue: 34(2)

Published: Jan. 12, 2021

To date, seven identified coronaviruses (CoVs) have been found to infect humans; of these, three highly pathogenic variants emerged in the 21st century. The newest member this group, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first detected at end 2019 Hubei province, China. Since then, novel has spread worldwide, causing a pandemic; disease caused by virus is called (COVID-19). clinical presentation ranges from asymptomatic mild tract infections and influenza-like illness with accompanying lung injury, multiorgan failure, death. Although lungs are believed be site which SARS-CoV-2 replicates, infected patients often report other symptoms, suggesting involvement gastrointestinal tract, heart, cardiovascular system, kidneys, organs; therefore, following question arises: COVID-19 or systemic disease? This review aims summarize existing data on replication different tissues both ex vivo models.

Language: Английский

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