Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans.
Prabhu S Arunachalam, Florian Wimmers, Chris Ka Pun Mok, Ranawaka A P M Perera, Madeleine Scott, Thomas Hagan, Natalia Sigal, Yupeng Feng, Laurel Bristow, Owen Tak-Yin Tsang, Dhananjay Wagh, John Coller, Kathryn L Pellegrini, Dmitri 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 Anderson, Srilatha Edupuganti, Amit A Upadhyay, Steve E Bosinger, Holden Terry Maecker, Purvesh Khatri, Nadine Rouphael, Malik Peiris, Bali Pulendran
Author Information
Prabhu S Arunachalam: Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA. ORCID
Florian Wimmers: Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA. ORCID
Chris Ka Pun Mok: HKU-Pasteur Research Pole, School of Public Health, HKU Li Ka Shing Faculty of Medicine, The University of Hong Kong (HKU), Hong Kong. ORCID
Ranawaka A P M Perera: Centre of Influenza Research, School of Public Health, HKU Li Ka Shing Faculty of Medicine, HKU, Hong Kong. ORCID
Madeleine Scott: Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA. ORCID
Thomas Hagan: Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA. ORCID
Natalia Sigal: Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA. ORCID
Yupeng Feng: Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA. ORCID
Laurel Bristow: Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA. ORCID
Owen Tak-Yin Tsang: Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of Hong Kong, Hong Kong.
Dhananjay Wagh: Stanford Functional Genomics Facility, Stanford University School of Medicine, Stanford, CA 94305, USA. ORCID
John Coller: Stanford Functional Genomics Facility, Stanford University School of Medicine, Stanford, CA 94305, USA.
Kathryn L Pellegrini: Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA. ORCID
Dmitri Kazmin: Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
Ghina Alaaeddine: Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA. ORCID
Wai Shing Leung: Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of Hong Kong, Hong Kong. ORCID
Jacky Man Chun Chan: Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of Hong Kong, Hong Kong.
Thomas Shiu Hong Chik: Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of Hong Kong, Hong Kong. ORCID
Chris Yau Chung Choi: Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of Hong Kong, Hong Kong. ORCID
Christopher Huerta: Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA.
Michele Paine McCullough: Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA.
Huibin Lv: HKU-Pasteur Research Pole, School of Public Health, HKU Li Ka Shing Faculty of Medicine, The University of Hong Kong (HKU), Hong Kong.
Evan Anderson: Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA 30322, USA. ORCID
Srilatha Edupuganti: Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA. ORCID
Amit A Upadhyay: Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA. ORCID
Steve E Bosinger: Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA. ORCID
Holden Terry Maecker: Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA. ORCID
Purvesh Khatri: Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA. ORCID
Nadine Rouphael: Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA.
Malik Peiris: HKU-Pasteur Research Pole, School of Public Health, HKU Li Ka Shing Faculty of Medicine, The University of Hong Kong (HKU), Hong Kong. ORCID
Bali Pulendran: Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA. bpulend@stanford.edu. ORCID
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.
