Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans

• Type of Material: Article
• Authors: Prabhu S. Arunachalam, Stanford University; Florian Wimmers, Stanford University; Chris Ka Pun Mok, University of Hong Kong; Evan Anderson, Emory University; Srilatha Edupuganti, Emory University; Amit Upadhyay, Emory University; Steven Bosinger, Emory University; Nadine Rouphael, Emory University; Malik Peiris, University of Hong Kong; Bali Pulendran, Emory University
• Language: English
• Date: 2020-09-04
• Publisher: AMER ASSOC ADVANCEMENT SCIENCE
• Publication Version: Final Published Version
• Copyright Statement: © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1126/science.abc6261
• Title of Journal or Parent Work: SCIENCE
• Volume: 369
• Issue: 6508
• Start Page: 1210
• End Page: +
• Grant/Funding Information: This work was supported by NIH grants HIPC U19AI090023 (to B.P.), U19AI057266 (to B.P. and principal investigator R. Ahmed from Emory University), and U24AI120134 (to S.E.B.); the Sean Parker Cancer Institute; the Soffer endowment (to B.P.); the Violetta Horton endowment (to B.P.); a Calmette and Yersin scholarship from the Pasteur International Network Association (to H.L.); the National Natural Science Foundation of China (NSFC)–Research Grants Council (RGC) Joint Research Scheme (N_HKU737/18) (to C.K.P.M. and M.P.); the Guangzhou Medical University High-level University Innovation Team Training Program [Guangzhou Medical University released (2017) no. 159] (to C.K.P.M. and M.P.); the U.S. NIH (contract no. HHSN272201400006C) (to M.P.); and the RGC of the Hong Kong Special Administrative Region, China (project no. T11-712/19-N) (to M.P.). Next-generation sequencing services were provided by the Yerkes NHP Genomics Core, which is supported in part by NIH P51 OD 011132, and the data were acquired on a NovaSeq 6000 funded by NIH S10 OD 026799.
• Keywords: CYTOKINE; Multidisciplinary Sciences; Science & Technology; I INTERFERON; SEPSIS; DISEASE; Science & Technology - Other Topics; RECEPTOR
• Research Categories: Health Sciences, Immunology; Biology, Virology; Health Sciences, Public Health

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-a (IFN-a) 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-a levels in plasma during infection. These results reveal mechanisms and potential therapeutic targets for COVID-19.