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Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans
Science ( IF 44.7 ) Pub Date : 2020-08-11 , DOI: 10.1126/science.abc6261
Prabhu S Arunachalam ₁ , Florian Wimmers ₁ , Chris Ka Pun Mok ₂ , Ranawaka A P M Perera ₃ , Madeleine Scott _{1,

4} , Thomas Hagan ₁ , Natalia Sigal ₁ , Yupeng Feng ₁ , Laurel Bristow ₅ , Owen Tak-Yin Tsang ₆ , Dhananjay Wagh ₇ , John Coller ₇ , Kathryn L Pellegrini ₈ , Dmitri Kazmin ₁ , Ghina Alaaeddine ₅ , Wai Shing Leung ₆ , Jacky Man Chun Chan ₆ , Thomas Shiu Hong Chik ₆ , Chris Yau Chung Choi ₆ , Christopher Huerta ₅ , Michele Paine McCullough ₅ , Huibin Lv ₂ , Evan Anderson ₉ , Srilatha Edupuganti ₅ , Amit A Upadhyay ₈ , Steve E Bosinger _{8,

10} , Holden Terry Maecker ₁ , Purvesh Khatri _{1,

4} , Nadine Rouphael ₅ , Malik Peiris _{2,

3} , Bali Pulendran _{1,

11,

12}

Affiliation

Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
HKU-Pasteur Research Pole, School of Public Health, HKU Li Ka Shing Faculty of Medicine, The University of Hong Kong (HKU), Hong Kong.
Centre of Influenza Research, School of Public Health, HKU Li Ka Shing Faculty of Medicine, HKU, Hong Kong.
Center for Biomedical Informatics, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA.
Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of Hong Kong, Hong Kong.
Stanford Functional Genomics Facility, Stanford University School of Medicine, Stanford, CA 94305, USA.
Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA.
Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA 30322, USA.
Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30329, USA.
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.

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.

更新日期：2020-08-11

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