학술논문
Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans
CORONAVIRUS
CORONAVIRUS
Document Type
Academic Journal
Author
Arunachalam, Prabhu S.; Wimmers, Florian; Mok, Chris Ka Pun; Perera, Ranawaka A.P.M.; Scott, Madeleine; Hagan, Thomas; Sigal, Natalia; Feng, Yupeng; Bristow, Laurel; Tsang, Owen Tak Yin; Wagh, Dhananjay; Coller, John; Pellegrini, Kathryn L.; Kazmin, Dmitri; Alaaeddine, Ghina; Leung, Wai Shing; Chan, Jacky Man Chun; Chik, Thomas Shiu Hong; Choi, Chris Yau Chung; Huerta, Christopher; McCullough, Michele Paine; Lv, Huibin; Anderson, Evan; Edupuganti, Srilatha; Upadhyay, Amit A.; Bosinger, Steve E.; Maecker, Holden Terry; Khatri, Purvesh; Rouphael, Nadine; Peiris, Malik; Pulendran, Bali
Source
Science. Sept 2020, Vol. 369 Issue 6508, p1210, 11 p.
Subject
Language
English
ISSN
0036-8075
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.