In:
Science, American Association for the Advancement of Science (AAAS), Vol. 369, No. 6508 ( 2020-09-04), p. 1210-1220
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.
Type of Medium:
Online Resource
ISSN:
0036-8075
,
1095-9203
DOI:
10.1126/science.abc6261
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2020
detail.hit.zdb_id:
128410-1
detail.hit.zdb_id:
2066996-3
detail.hit.zdb_id:
2060783-0
SSG:
11
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