Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination

New England Journal of Medicine, Год журнала: 2021, Номер 384(22), С. 2124 - 2130

Опубликована: Апрель 9, 2021

We report findings in five patients who presented with venous thrombosis and thrombocytopenia 7 to 10 days after receiving the first dose of ChAdOx1 nCoV-19 adenoviral vector vaccine against coronavirus disease 2019 (Covid-19). The were health care workers 32 54 years age. All had high levels antibodies platelet factor 4-polyanion complexes; however, they no previous exposure heparin. Because cases occurred a population more than 130,000 vaccinated persons, we propose that represent rare vaccine-related variant spontaneous heparin-induced refer as vaccine-induced immune thrombotic thrombocytopenia.

Язык: Английский

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The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity

The Lancet Respiratory Medicine, Год журнала: 2021, Номер 9(6), С. 622 - 642

Опубликована: Май 7, 2021

The zoonotic SARS-CoV-2 virus that causes COVID-19 continues to spread worldwide, with devastating consequences. While the medical community has gained insight into epidemiology of COVID-19, important questions remain about clinical complexities and underlying mechanisms disease phenotypes. Severe most commonly involves respiratory manifestations, although other systems are also affected, acute is often followed by protracted complications. Such complex manifestations suggest dysregulates host response, triggering wide-ranging immuno-inflammatory, thrombotic, parenchymal derangements. We review intricacies pathophysiology, its various phenotypes, anti-SARS-CoV-2 response at humoral cellular levels. Some similarities exist between failure origins, but evidence for many distinctive mechanistic features indicates constitutes a new entity, emerging data suggesting involvement an endotheliopathy-centred pathophysiology. Further research, combining basic studies, needed advance understanding pathophysiological characterise immuno-inflammatory derangements across range phenotypes enable optimum care patients COVID-19.

Язык: Английский

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Systemic complement activation is associated with respiratory failure in COVID-19 hospitalized patients

Proceedings of the National Academy of Sciences, Год журнала: 2020, Номер 117(40), С. 25018 - 25025

Опубликована: Сен. 17, 2020

Significance The new SARS-CoV-2 pandemic leads to COVID-19 with respiratory failure, substantial morbidity, and significant mortality. Overactivation of the innate immune response is postulated trigger this detrimental process. complement system a key player in immunity. Despite few reports local activation, there lack evidence that degree systemic activation occurs early patients, whether associated failure. This study shows number products are systemically, consistently, long-lastingly increased from admission during hospital stay. Notably, terminal sC5b-9 complex was Thus, inhibition an attractive therapeutic approach for treatment COVD-19.

Язык: Английский

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Understanding COVID-19-associated coagulopathy

Nature reviews. Immunology, Год журнала: 2022, Номер 22(10), С. 639 - 649

Опубликована: Авг. 5, 2022

Язык: Английский

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Current and novel biomarkers of thrombotic risk in COVID-19: a Consensus Statement from the International COVID-19 Thrombosis Biomarkers Colloquium

Nature Reviews Cardiology, Год журнала: 2022, Номер 19(7), С. 475 - 495

Опубликована: Янв. 13, 2022

Язык: Английский

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The state of complement in COVID-19

Nature reviews. Immunology, Год журнала: 2021, Номер 22(2), С. 77 - 84

Опубликована: Дек. 15, 2021

Язык: Английский

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

Science Immunology, Год журнала: 2021, Номер 6(59)

Опубликована: Май 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.

Язык: Английский

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Innate immunological pathways in COVID-19 pathogenesis

Science Immunology, Год журнала: 2022, Номер 7(67)

Опубликована: Янв. 7, 2022

Coronavirus disease 2019 (COVID-19) is a characterized by profound dysregulation of the innate immune system. This knowledge has emerged from large body single-cell omics studies patients with COVID-19, which have provided one most detailed cellular atlases human ever. However, we are only beginning to understand immunological pathways that govern host defense and immunopathology in COVID-19. In this review, discuss emerging understanding how SARS-CoV-2 host-derived molecules activate specific pattern recognition receptors elicit protective interferon responses pathological cytokine responses, particular focus on acute infection lung pathophysiology critical addition, these modulated virus-host interactions stress-sensing pathways. In-depth mechanisms will likely uncover molecular targets for treatment COVID-19 other viral infections. it reveal fine balance between beneficial versus causing responses.

Язык: Английский

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Immune dysregulation and immunopathology induced by SARS-CoV-2 and related coronaviruses — are we our own worst enemy?

Nature reviews. Immunology, Год журнала: 2021, Номер 22(1), С. 47 - 56

Опубликована: Ноя. 26, 2021

Human coronaviruses cause a wide spectrum of disease, ranging from mild common colds to acute respiratory distress syndrome and death. Three highly pathogenic human — severe coronavirus (SARS-CoV), Middle East SARS-CoV-2 have illustrated the epidemic pandemic potential coronaviruses, better understanding their disease-causing mechanisms is urgently needed for rational design therapeutics. Analyses patients revealed marked dysregulation immune system in cases infection, there ample evidence that aberrant responses are typified by impaired induction interferons, exuberant inflammatory delayed adaptive responses. In addition, various viral proteins been shown impair interferon signalling induce inflammasome activation. This suggests disease associated with mediated both dysregulated host active interference. Here we discuss our current involved each these scenarios. this Perspective, Lok-Yin Roy Wong Stanley Perlman consider how 2 (SARS-CoV-2) related able drive immunopathology. They provide an overview coronavirus-derived molecules interfere key innate responses, including pathways complement, NF-κB activation, as well activation immunity.

Язык: Английский

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Endothelium Infection and Dysregulation by SARS-CoV-2: Evidence and Caveats in COVID-19

Viruses, Год журнала: 2020, Номер 13(1), С. 29 - 29

Опубликована: Дек. 26, 2020

The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) poses a persistent threat to global public health. Although primarily illness, extrapulmonary manifestations COVID-19 include gastrointestinal, cardiovascular, renal and neurological diseases. Recent studies suggest that dysfunction endothelium during may exacerbate these deleterious events inciting inflammatory microvascular thrombotic processes. controversial, there is evidence SARS-CoV-2 infect endothelial cells binding angiotensin-converting enzyme 2 (ACE2) cellular receptor using viral Spike protein. In this review, we explore current insights into relationship between infection, due ACE2 downregulation, pulmonary extra-pulmonary immunothrombotic complications in severe COVID-19. We also discuss preclinical clinical development therapeutic agents targeting SARS-CoV-2-mediated dysfunction. Finally, present replication primary human lung cardiac cells. Accordingly, striving understand parameters lead patients, it important consider how direct infection contribute process.

Язык: Английский

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