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

作者：Prabhu S. Arunachalam, Florian Wimmers, Chris Ka Pun Mok, Ranawaka A. P. M. Perera, Madeleine K. D. Scott, Thomas Hagan, Natalia G. Sigal, Yupeng Feng, Laurel Bristow, Owen Tak‐Yin Tsang, Dhananjay A. Wagh, John A. Coller, Kathryn L. Pellegrini, Dmitri A. Kazmin, Ghina Alaaeddine, Wai-Shing Leung, Jacky Man Chun Chan, Thomas Shiu Hong Chik, Chris Yau Chung Choi, Christopher Huerta, Michele Paine McCullough, Huibin Lv, Evan J. Anderson, Srilatha Edupuganti, Amit A. Upadhyay, Steve E. Bosinger, Holden Terry Maecker, Purvesh Khatri, Nadine Rouphael, Malik J. S. Peiris, Bali Pulendran · 发表于：Science · 年份：2020 · DOI：10.1126/science.abc6261 · 被引用次数：1351 · 研究领域：SARS-CoV-2 and COVID-19 Research、COVID-19 Clinical Research Studies、Immune responses and vaccinations

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.