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Cell ; 183(5): 1354-1366.e13, 2020 11 25.
Article in English | MEDLINE | ID: covidwho-871817


The COVID-19 pandemic has led to extensive morbidity and mortality throughout the world. Clinical features that drive SARS-CoV-2 pathogenesis in humans include inflammation and thrombosis, but the mechanistic details underlying these processes remain to be determined. In this study, we demonstrate endothelial disruption and vascular thrombosis in histopathologic sections of lungs from both humans and rhesus macaques infected with SARS-CoV-2. To define key molecular pathways associated with SARS-CoV-2 pathogenesis in macaques, we performed transcriptomic analyses of bronchoalveolar lavage and peripheral blood and proteomic analyses of serum. We observed macrophage infiltrates in lung and upregulation of macrophage, complement, platelet activation, thrombosis, and proinflammatory markers, including C-reactive protein, MX1, IL-6, IL-1, IL-8, TNFα, and NF-κB. These results suggest a model in which critical interactions between inflammatory and thrombosis pathways lead to SARS-CoV-2-induced vascular disease. Our findings suggest potential therapeutic targets for COVID-19.

COVID-19/complications , COVID-19/immunology , SARS-CoV-2/genetics , Thrombosis/complications , Vascular Diseases/complications , Aged, 80 and over , Animals , Bronchoalveolar Lavage , C-Reactive Protein/analysis , COVID-19/blood , COVID-19/pathology , Complement Activation , Cytokines/blood , Female , Humans , Inflammation/blood , Inflammation/immunology , Inflammation/virology , Lung/pathology , Macaca mulatta , Macrophages/immunology , Male , Platelet Activation , Thrombosis/blood , Thrombosis/pathology , Transcriptome , Vascular Diseases/blood , Vascular Diseases/pathology
Science ; 369(6505): 812-817, 2020 08 14.
Article in English | MEDLINE | ID: covidwho-327276


An understanding of protective immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for vaccine and public health strategies aimed at ending the global coronavirus disease 2019 (COVID-19) pandemic. A key unanswered question is whether infection with SARS-CoV-2 results in protective immunity against reexposure. We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. After the initial viral clearance, animals were rechallenged with SARS-CoV-2 and showed 5 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa compared with after the primary infection. Anamnestic immune responses after rechallenge suggested that protection was mediated by immunologic control. These data show that SARS-CoV-2 infection induced protective immunity against reexposure in nonhuman primates.

Betacoronavirus , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , Animals , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Betacoronavirus/immunology , Betacoronavirus/physiology , Bronchoalveolar Lavage Fluid/virology , COVID-19 , Coronavirus Infections/pathology , Coronavirus Infections/virology , Disease Models, Animal , Female , Immunity, Cellular , Immunity, Humoral , Immunologic Memory , Lung/immunology , Lung/pathology , Lung/virology , Lung Diseases, Interstitial/immunology , Lung Diseases, Interstitial/pathology , Lung Diseases, Interstitial/virology , Macaca mulatta , Male , Nasal Mucosa/virology , Pandemics , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Recurrence , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/immunology , Viral Load , Virus Replication