Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans
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Open Access
- 4 September 2020
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 369 (6508), 1210-1220
- https://doi.org/10.1126/science.abc6261
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-alpha (IFN-alpha) 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-alpha levels in plasma during infection. These results reveal mechanisms and potential therapeutic targets for COVID-19.Keywords
Funding Information
- National Institutes of Health (U19AI090023)
This publication has 44 references indexed in Scilit:
- Dysregulated Type I Interferon and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected MiceCell Host & Microbe, 2016
- Parsing the Interferon Transcriptional Network and Its Disease AssociationsCell, 2016
- limma powers differential expression analyses for RNA-sequencing and microarray studiesNucleic Acids Research, 2015
- An Endotoxin Tolerance Signature Predicts Sepsis and Organ Dysfunction at Initial Clinical PresentationEBioMedicine, 2014
- Homogenous 96-Plex PEA Immunoassay Exhibiting High Sensitivity, Specificity, and Excellent ScalabilityPLOS ONE, 2014
- Molecular signatures of antibody responses derived from a systems biology study of five human vaccinesNature Immunology, 2013
- S100A9 a new marker for monocytic human myeloid‐derived suppressor cellsImmunology, 2012
- Toll-like receptor–mediated induction of type I interferon in plasmacytoid dendritic cells requires the rapamycin-sensitive PI(3)K-mTOR-p70S6K pathwayNature Immunology, 2008
- Relationship between Plasma Levels of Lipopolysaccharide (LPS) and LPS‐Binding Protein in Patients with Severe Sepsis and Septic ShockThe Journal of Infectious Diseases, 1999
- Plasma Cytokine and Endotoxin Levels Correlate with Survival in Patients with the Sepsis SyndromeAnnals of Internal Medicine, 1993