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Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans.
Arunachalam, Prabhu S; Wimmers, Florian; Mok, Chris Ka Pun; Perera, Ranawaka A P M; Scott, Madeleine; Hagan, Thomas; Sigal, Natalia; Feng, Yupeng; Bristow, Laurel; Tak-Yin Tsang, Owen; Wagh, Dhananjay; Coller, John; Pellegrini, Kathryn L; Kazmin, Dmitri; Alaaeddine, Ghina; Leung, Wai Shing; Chan, Jacky Man Chun; Chik, Thomas Shiu Hong; Choi, Chris Yau Chung; Huerta, Christopher; Paine McCullough, Michele; Lv, Huibin; Anderson, Evan; Edupuganti, Srilatha; Upadhyay, Amit A; Bosinger, Steve E; Maecker, Holden Terry; Khatri, Purvesh; Rouphael, Nadine; Peiris, Malik; Pulendran, Bali.
  • Arunachalam PS; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Wimmers F; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Mok CKP; HKU-Pasteur Research Pole, School of Public Health, HKU Li Ka Shing Faculty of Medicine, The University of Hong Kong (HKU), Hong Kong.
  • Perera RAPM; Centre of Influenza Research, School of Public Health, HKU Li Ka Shing Faculty of Medicine, HKU, Hong Kong.
  • Scott M; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Hagan T; Center for Biomedical Informatics, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Sigal N; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Feng Y; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Bristow L; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Tak-Yin Tsang O; Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA.
  • Wagh D; Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of Hong Kong, Hong Kong.
  • Coller J; Stanford Functional Genomics Facility, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Pellegrini KL; Stanford Functional Genomics Facility, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Kazmin D; Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA.
  • Alaaeddine G; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Leung WS; Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA.
  • Chan JMC; Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of Hong Kong, Hong Kong.
  • Chik TSH; Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of Hong Kong, Hong Kong.
  • Choi CYC; Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of Hong Kong, Hong Kong.
  • Huerta C; Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of Hong Kong, Hong Kong.
  • Paine McCullough M; Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA.
  • Lv H; Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA.
  • Anderson E; HKU-Pasteur Research Pole, School of Public Health, HKU Li Ka Shing Faculty of Medicine, The University of Hong Kong (HKU), Hong Kong.
  • Edupuganti S; Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Upadhyay AA; Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA.
  • Bosinger SE; Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA.
  • Maecker HT; Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA.
  • Khatri P; Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30329, USA.
  • Rouphael N; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Peiris M; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Pulendran B; Center for Biomedical Informatics, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Science ; 369(6508): 1210-1220, 2020 09 04.
Article in English | MEDLINE | ID: covidwho-704393
Semantic information from SemMedBD (by NLM)
1. Severe infection PROCESS_OF Homo sapiens
Subject
Severe infection
Predicate
PROCESS_OF
Object
Homo sapiens
2. Immunity PROCESS_OF Homo sapiens
Subject
Immunity
Predicate
PROCESS_OF
Object
Homo sapiens
3. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
4. Immune response PROCESS_OF Patients
Subject
Immune response
Predicate
PROCESS_OF
Object
Patients
5. Peripheral blood mononuclear cell (cell) PART_OF Patients
Subject
Peripheral blood mononuclear cell (cell)
Predicate
PART_OF
Object
Patients
6. Bacterial product COEXISTS_WITH human plasma
Subject
Bacterial product
Predicate
COEXISTS_WITH
Object
human plasma
7. Borg Category-Ratio 10 Perceived Exertion Score 5 PROCESS_OF Patients
Subject
Borg Category-Ratio 10 Perceived Exertion Score 5
Predicate
PROCESS_OF
Object
Patients
8. Myeloid Cells LOCATION_OF IFNA1
Subject
Myeloid Cells
Predicate
LOCATION_OF
Object
IFNA1
9. Myeloid Cells PART_OF Patients
Subject
Myeloid Cells
Predicate
PART_OF
Object
Patients
10. Severe infection PROCESS_OF Homo sapiens
Subject
Severe infection
Predicate
PROCESS_OF
Object
Homo sapiens
11. Immunity PROCESS_OF Homo sapiens
Subject
Immunity
Predicate
PROCESS_OF
Object
Homo sapiens
12. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
13. Immune response PROCESS_OF Patients
Subject
Immune response
Predicate
PROCESS_OF
Object
Patients
14. Peripheral blood mononuclear cell (cell) PART_OF Patients
Subject
Peripheral blood mononuclear cell (cell)
Predicate
PART_OF
Object
Patients
15. Bacterial product COEXISTS_WITH human plasma
Subject
Bacterial product
Predicate
COEXISTS_WITH
Object
human plasma
16. Borg Category-Ratio 10 Perceived Exertion Score 5 PROCESS_OF Patients
Subject
Borg Category-Ratio 10 Perceived Exertion Score 5
Predicate
PROCESS_OF
Object
Patients
17. Myeloid Cells LOCATION_OF IFNA1
Subject
Myeloid Cells
Predicate
LOCATION_OF
Object
IFNA1
18. Myeloid Cells PART_OF Patients
Subject
Myeloid Cells
Predicate
PART_OF
Object
Patients
ABSTRACT
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.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Coronavirus Infections / Betacoronavirus Limits: Female / Humans / Male Language: English Journal: Science Year: 2020 Document Type: Article Affiliation country: Science.abc6261

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Coronavirus Infections / Betacoronavirus Limits: Female / Humans / Male Language: English Journal: Science Year: 2020 Document Type: Article Affiliation country: Science.abc6261