Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans.
Science
; 369(6508): 1210-1220, 2020 09 04.
Article
em En
| MEDLINE
| ID: mdl-32788292
ABSTRACT
Coronavirus disease 2019 (COVID-19) represents a global crisis, yet major knowledge gaps remain about human immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We analyzed immune responses in 76 COVID-19 patients and 69 healthy individuals from Hong Kong and Atlanta, Georgia, United States. In the peripheral blood mononuclear cells (PBMCs) of COVID-19 patients, we observed reduced expression of human leukocyte antigen class DR (HLA-DR) and proinflammatory cytokines by myeloid cells as well as impaired mammalian target of rapamycin (mTOR) signaling and interferon-α (IFN-α) production by plasmacytoid dendritic cells. By contrast, we detected enhanced plasma levels of inflammatory mediators-including EN-RAGE, TNFSF14, and oncostatin M-which correlated with disease severity and increased bacterial products in plasma. Single-cell transcriptomics revealed a lack of type I IFNs, reduced HLA-DR in the myeloid cells of patients with severe COVID-19, and transient expression of IFN-stimulated genes. This was consistent with bulk PBMC transcriptomics and transient, low IFN-α levels in plasma during infection. These results reveal mechanisms and potential therapeutic targets for COVID-19.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pneumonia Viral
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Infecções por Coronavirus
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Betacoronavirus
Limite:
Female
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Humans
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Male
Idioma:
En
Revista:
Science
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos