P. S. Arunachalam, F. Wimmers, C. Mok, R. Perera, M. Scott, T. Hagan, N. Sigal, Yupeng Feng, Laurel Bristow, Owen Tak-Yin Tsang, D. Wagh, J. Coller, Kathryn L Pellegrini, D. Kazmin, Ghina Alaaeddine, W. Leung, J. Chan, T. Chik, Chris Yau-Chung Choi, Christopher Huerta, Michele Paine McCullough, Huibin Lv, E. Anderson, S. Edupuganti, Amit A. Upadhyay, S. Bosinger, H. Maecker, P. Khatri, N. Rouphael, M. Peiris, B. Pulendran
Science, 2020
Immune profiling of COVID-19 patients Coronavirus disease 2019 (COVID-19) has affected millions of people globally, yet how the human immune system responds to and influences COVID-19 severity remains unclear. Mathew et al. present a comprehensive atlas of immune modulation associated with COVID-19. They performed high-dimensional flow cytometry of hospitalized COVID-19 patients and found three prominent and distinct immunotypes that are related to disease severity and clinical parameters. Arunachalam et al. report a systems biology approach to assess the immune system of COVID-19 patients with mild-to-severe disease. These studies provide a compendium of immune cell information and roadmaps for potential therapeutic interventions. Science, this issue p. eabc8511, p. 1210 Immune responses of COVID-19 patients are cataloged and compared with those of healthy individuals. 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.
Cited by 311 publications.
Field of study: Medicine