[Source: Science, full page: (LINK). Abstract, edited.]
Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans
Prabhu S. Arunachalam1,*, Florian Wimmers1,*, Chris Ka Pun Mok2,*, Ranawaka A. P. M. Perera3,*, Madeleine Scott1,4,†, Thomas Hagan1,†, Natalia Sigal1,†, Yupeng Feng1,†, Laurel Bristow5, Owen Tak-Yin Tsang6, Dhananjay Wagh7, John Coller7, Kathryn L. Pellegrini8, Dmitri Kazmin1, Ghina Alaaeddine5, Wai Shing Leung6, Jacky Man Chun Chan6, Thomas Shiu Hong Chik6, Chris Yau Chung Choi6, Christopher Huerta5, Michele Paine McCullough5, Huibin Lv2, Evan Anderson9, Srilatha Edupuganti5, Amit A. Upadhyay8, Steve E. Bosinger8,10, Holden Terry Maecker1, Purvesh Khatri1,4, Nadine Rouphael5, Malik Peiris2,3, Bali Pulendran1,11,12,‡
1 Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA 94305, USA. 2 HKU-Pasteur Research Pole, School of Public Health, HKU Li Ka Shing Faculty of Medicine, The University of Hong Kong (HKU), Hong Kong. 3 Centre of Influenza Research, School of Public Health, HKU Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong. 4 Center for Biomedical informatics, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. 5 Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA. 6 Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of Hong Kong, Hong Kong. 7 Stanford Functional Genomics Facility, Stanford University School of Medicine, Stanford, CA 94305, USA. 8 Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA. 9 Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA 30322, USA. 10 Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30329, USA. 11 Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. 12 Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
‡Corresponding author. Email: firstname.lastname@example.org
* These authors contributed equally to this work.
† These authors contributed equally to this work.
Science 11 Aug 2020: eabc6261 | DOI: 10.1126/science.abc6261
COVID-19 represents a global crisis, yet major knowledge gaps remain about human immunity to SARS-CoV-2. We analyzed immune responses in 76 COVID-19 patients and 69 healthy individuals from Hong Kong and Atlanta. In PBMCs of COVID-19 patients, there was reduced expression of HLA-DR and pro-inflammatory cytokines by myeloid cells, and impaired mTOR-signaling and IFN-α production by plasmacytoid DCs. In contrast, there were enhanced plasma levels of inflammatory mediators, including EN-RAGE, TNFSF14, and oncostatin-M, which correlated with disease severity and increased bacterial products in human plasma. Single-cell transcriptomics revealed no type-I IFN, reduced HLA-DR in myeloid cells of severe patients, and transient expression of IFN-stimulated genes. This was consistent with bulk PBMC transcriptomics, and transient, low plasma IFN-α levels during infection. These results reveal mechanisms and potential therapeutic targets for COVID-19.
Keywords: SARS-CoV-2; COVID-19; Immunopathology; Immunology.