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Journal ArticleDOI

Histopathology and ultrastructural findings of fatal COVID-19 infections in Washington State: a case series

TL;DR: In this paper, the authors provide a clinicopathological report of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases by documenting histopathological changes and evidence of SARS CoV2 tissue tropism.
About: This article is published in The Lancet.The article was published on 2020-08-01 and is currently open access. It has received 587 citations till now. The article focuses on the topics: Diffuse alveolar damage & Kidney disease.
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Journal ArticleDOI
TL;DR: In this paper, the authors proposed that SARS-CoV-2 infection induces a process known as immunothrombosis, in which activated neutrophils and monocytes interact with platelets and the coagulation cascade, leading to intravascular clot formation in small and larger vessels.
Abstract: Coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with severe disease show hyperactivation of the immune system, which can affect multiple organs besides the lungs. Here, we propose that SARS-CoV-2 infection induces a process known as immunothrombosis, in which activated neutrophils and monocytes interact with platelets and the coagulation cascade, leading to intravascular clot formation in small and larger vessels. Microthrombotic complications may contribute to acute respiratory distress syndrome (ARDS) and other organ dysfunctions. Therapeutic strategies aimed at reducing immunothrombosis may therefore be useful. Several antithrombotic and immunomodulating drugs have been proposed as candidates to treat patients with SARS-CoV-2 infection. The growing understanding of SARS-CoV-2 infection pathogenesis and how it contributes to critical illness and its complications may help to improve risk stratification and develop targeted therapies to reduce the acute and long-term consequences of this disease.

448 citations

Journal ArticleDOI
TL;DR: In this series of seven COVID-19 autopsies, thrombosis was a prominent feature in multiple organs, in some cases despite full anticoagulation and regardless of timing of the disease course, suggesting that thROMbosis plays a role very early in the disease process.

440 citations

Journal ArticleDOI
12 Nov 2020-Cell
TL;DR: A new mouse-adapted SARS-CoV-2 virus that captures multiple aspects of severe COVID-19 disease in standard laboratory mice is generated and characterized to provide a robust platform for studies of ALI and ARDS to evaluate vaccine and antiviral drug performance.

376 citations

Journal ArticleDOI
TL;DR: A timeline and correlating histopathological findings with clinical stages of COVID-19 are constructed and found to be consistent with knowledge regarding clinical patterns of viral infection, development of hyperinflammation and hypercoagulability, and fibrosis.

362 citations

Journal ArticleDOI
28 Jan 2021-Nature
TL;DR: Transgenic K18-hACE2 mice are a useful model for studying the pathological basis of both mild and lethal COVID-19 and for assessing therapeutic interventions; infection of these mice resulted in severe pneumonia and, in some cases, infection in the brain, which was prevented by convalescent plasma.
Abstract: The ongoing coronavirus disease 2019 (COVID-19) pandemic is associated with substantial morbidity and mortality. Although much has been learned in the first few months of the pandemic, many features of COVID-19 pathogenesis remain to be determined. For example, anosmia is a common presentation, and many patients with anosmia show no or only minor respiratory symptoms1. Studies in animals infected experimentally with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of COVID-19, provide opportunities to study aspects of the disease that are not easily investigated in human patients. Although the severity of COVID-19 ranges from asymptomatic to lethal2, most experimental infections provide insights into mild disease3. Here, using K18-hACE2 transgenic mice that were originally developed for SARS studies4, we show that infection with SARS-CoV-2 causes severe disease in the lung and, in some mice, the brain. Evidence of thrombosis and vasculitis was detected in mice with severe pneumonia. Furthermore, we show that infusion of convalescent plasma from a recovered patient with COVID-19 protected against lethal disease. Mice developed anosmia at early time points after infection. Notably, although pre-treatment with convalescent plasma prevented most signs of clinical disease, it did not prevent anosmia. Thus, K18-hACE2 mice provide a useful model for studying the pathological basis of both mild and lethal COVID-19 and for assessing therapeutic interventions.

328 citations

References
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Journal ArticleDOI
TL;DR: Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily, which is the seventh member of the family of coronaviruses that infect humans.
Abstract: In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.).

21,455 citations

Journal ArticleDOI
16 Apr 2020-Cell
TL;DR: It is demonstrated that SARS-CoV-2 uses the SARS -CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming, and it is shown that the sera from convalescent SARS patients cross-neutralized Sars-2-S-driven entry.

15,362 citations

Journal ArticleDOI
07 Apr 2020-JAMA
TL;DR: Hospitalised COVID-19 patients are frequently elderly subjects with co-morbidities receiving polypharmacy, all of which are known risk factors for d
Abstract: Background: Hospitalised COVID-19 patients are frequently elderly subjects with co-morbidities receiving polypharmacy, all of which are known risk factors for d

14,343 citations

Journal ArticleDOI
TL;DR: The phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans.

9,474 citations

Journal ArticleDOI
TL;DR: O surto do novo coronavírus (COVID-19) em Wuhan, China, iniciado em dezembro de 2019, evoluiu para se tornar uma pandemia global A.

6,850 citations

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