PMID- 32788292
OWN - NLM
STAT- MEDLINE
DCOM- 20200918
LR  - 20211204
IS  - 1095-9203 (Electronic)
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 369
IP  - 6508
DP  - 2020 Sep 4
TI  - Systems biological assessment of immunity to mild versus severe COVID-19 
      infection in humans.
PG  - 1210-1220
LID - 10.1126/science.abc6261 [doi]
AB  - 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-alpha (IFN-alpha) 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-alpha levels in plasma during infection. These results reveal 
      mechanisms and potential therapeutic targets for COVID-19.
CI  - Copyright (c) 2020 The Authors, some rights reserved; exclusive licensee American 
      Association for the Advancement of Science. No claim to original U.S. Government 
      Works.
FAU - Arunachalam, Prabhu S
AU  - Arunachalam PS
AUID- ORCID: 0000-0003-0090-5689
AD  - Institute for Immunity, Transplantation and Infection, Stanford University School 
      of Medicine, Stanford, CA 94305, USA.
FAU - Wimmers, Florian
AU  - Wimmers F
AUID- ORCID: 0000-0002-6482-2228
AD  - Institute for Immunity, Transplantation and Infection, Stanford University School 
      of Medicine, Stanford, CA 94305, USA.
FAU - Mok, Chris Ka Pun
AU  - Mok CKP
AUID- ORCID: 0000-0002-0525-6772
AD  - HKU-Pasteur Research Pole, School of Public Health, HKU Li Ka Shing Faculty of 
      Medicine, The University of Hong Kong (HKU), Hong Kong.
FAU - Perera, Ranawaka A P M
AU  - Perera RAPM
AUID- ORCID: 0000-0003-3936-1535
AD  - Centre of Influenza Research, School of Public Health, HKU Li Ka Shing Faculty of 
      Medicine, HKU, Hong Kong.
FAU - Scott, Madeleine
AU  - Scott M
AUID- ORCID: 0000-0001-9350-5451
AD  - Institute for Immunity, Transplantation and Infection, Stanford University School 
      of Medicine, Stanford, CA 94305, USA.
AD  - Center for Biomedical Informatics, Department of Medicine, Stanford University 
      School of Medicine, Stanford, CA 94305, USA.
FAU - Hagan, Thomas
AU  - Hagan T
AUID- ORCID: 0000-0002-5254-5251
AD  - Institute for Immunity, Transplantation and Infection, Stanford University School 
      of Medicine, Stanford, CA 94305, USA.
FAU - Sigal, Natalia
AU  - Sigal N
AUID- ORCID: 0000-0003-2831-7053
AD  - Institute for Immunity, Transplantation and Infection, Stanford University School 
      of Medicine, Stanford, CA 94305, USA.
FAU - Feng, Yupeng
AU  - Feng Y
AUID- ORCID: 0000-0001-8550-2787
AD  - Institute for Immunity, Transplantation and Infection, Stanford University School 
      of Medicine, Stanford, CA 94305, USA.
FAU - Bristow, Laurel
AU  - Bristow L
AUID- ORCID: 0000-0001-9050-0057
AD  - Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of 
      Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA.
FAU - Tak-Yin Tsang, Owen
AU  - Tak-Yin Tsang O
AD  - Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of 
      Hong Kong, Hong Kong.
FAU - Wagh, Dhananjay
AU  - Wagh D
AUID- ORCID: 0000-0002-6937-003X
AD  - Stanford Functional Genomics Facility, Stanford University School of Medicine, 
      Stanford, CA 94305, USA.
FAU - Coller, John
AU  - Coller J
AD  - Stanford Functional Genomics Facility, Stanford University School of Medicine, 
      Stanford, CA 94305, USA.
FAU - Pellegrini, Kathryn L
AU  - Pellegrini KL
AUID- ORCID: 0000-0002-5089-5477
AD  - Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, 
      USA.
FAU - Kazmin, Dmitri
AU  - Kazmin D
AD  - Institute for Immunity, Transplantation and Infection, Stanford University School 
      of Medicine, Stanford, CA 94305, USA.
FAU - Alaaeddine, Ghina
AU  - Alaaeddine G
AUID- ORCID: 0000-0001-9570-7989
AD  - Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of 
      Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA.
FAU - Leung, Wai Shing
AU  - Leung WS
AUID- ORCID: 0000-0001-8377-085X
AD  - Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of 
      Hong Kong, Hong Kong.
FAU - Chan, Jacky Man Chun
AU  - Chan JMC
AD  - Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of 
      Hong Kong, Hong Kong.
FAU - Chik, Thomas Shiu Hong
AU  - Chik TSH
AUID- ORCID: 0000-0002-0481-1420
AD  - Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of 
      Hong Kong, Hong Kong.
FAU - Choi, Chris Yau Chung
AU  - Choi CYC
AUID- ORCID: 0000-0002-3695-2770
AD  - Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of 
      Hong Kong, Hong Kong.
FAU - Huerta, Christopher
AU  - Huerta C
AD  - Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of 
      Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA.
FAU - Paine McCullough, Michele
AU  - Paine McCullough M
AD  - Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of 
      Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA.
FAU - Lv, Huibin
AU  - Lv H
AD  - HKU-Pasteur Research Pole, School of Public Health, HKU Li Ka Shing Faculty of 
      Medicine, The University of Hong Kong (HKU), Hong Kong.
FAU - Anderson, Evan
AU  - Anderson E
AUID- ORCID: 0000-0002-1576-4420
AD  - Department of Pediatrics, Division of Infectious Disease, Emory University School 
      of Medicine, Atlanta, GA 30322, USA.
FAU - Edupuganti, Srilatha
AU  - Edupuganti S
AUID- ORCID: 0000-0001-6566-9969
AD  - Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of 
      Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA.
FAU - Upadhyay, Amit A
AU  - Upadhyay AA
AUID- ORCID: 0000-0002-0952-4164
AD  - Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, 
      USA.
FAU - Bosinger, Steve E
AU  - Bosinger SE
AUID- ORCID: 0000-0002-2116-5061
AD  - Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, 
      USA.
AD  - Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 
      30329, USA.
FAU - Maecker, Holden Terry
AU  - Maecker HT
AUID- ORCID: 0000-0003-0795-9946
AD  - Institute for Immunity, Transplantation and Infection, Stanford University School 
      of Medicine, Stanford, CA 94305, USA.
FAU - Khatri, Purvesh
AU  - Khatri P
AUID- ORCID: 0000-0002-4143-4708
AD  - Institute for Immunity, Transplantation and Infection, Stanford University School 
      of Medicine, Stanford, CA 94305, USA.
AD  - Center for Biomedical Informatics, Department of Medicine, Stanford University 
      School of Medicine, Stanford, CA 94305, USA.
FAU - Rouphael, Nadine
AU  - Rouphael N
AD  - Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of 
      Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA.
FAU - Peiris, Malik
AU  - Peiris M
AUID- ORCID: 0000-0001-8217-5995
AD  - HKU-Pasteur Research Pole, School of Public Health, HKU Li Ka Shing Faculty of 
      Medicine, The University of Hong Kong (HKU), Hong Kong.
AD  - Centre of Influenza Research, School of Public Health, HKU Li Ka Shing Faculty of 
      Medicine, HKU, Hong Kong.
FAU - Pulendran, Bali
AU  - Pulendran B
AUID- ORCID: 0000-0001-6517-4333
AD  - Institute for Immunity, Transplantation and Infection, Stanford University School 
      of Medicine, Stanford, CA 94305, USA. bpulend@stanford.edu.
AD  - Department of Pathology, Stanford University School of Medicine, Stanford, CA 
      94305, USA.
AD  - Department of Microbiology and Immunology, Stanford University School of 
      Medicine, Stanford, CA 94305, USA.
LA  - eng
GR  - R38 AI140299/AI/NIAID NIH HHS/United States
GR  - U19 AI090023/AI/NIAID NIH HHS/United States
GR  - U24 AI120134/AI/NIAID NIH HHS/United States
GR  - U19 AI057266/AI/NIAID NIH HHS/United States
GR  - HHSN272201400006C/AI/NIAID NIH HHS/United States
GR  - S10 OD021763/OD/NIH HHS/United States
GR  - S10 OD026799/OD/NIH HHS/United States
GR  - R01 AI048638/AI/NIAID NIH HHS/United States
GR  - S10 OD018220/OD/NIH HHS/United States
GR  - P51 OD011132/OD/NIH HHS/United States
GR  - UM1 AI148576/AI/NIAID NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200811
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Cytokines)
RN  - 0 (DNA, Bacterial)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Immunoglobulins)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interferon Type I)
RN  - 0 (Lipopolysaccharides)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Betacoronavirus/*immunology
MH  - COVID-19
MH  - Coronavirus Infections/*immunology
MH  - Cytokines/blood
MH  - DNA, Bacterial/blood
MH  - Dendritic Cells/immunology/metabolism
MH  - Female
MH  - Flow Cytometry
MH  - HLA-DR Antigens/analysis
MH  - Humans
MH  - Immunity
MH  - Immunity, Innate
MH  - Immunoglobulins/blood/immunology
MH  - Inflammation Mediators/blood
MH  - Interferon Type I/metabolism
MH  - Leukocytes, Mononuclear/immunology/metabolism
MH  - Lipopolysaccharides/blood
MH  - Male
MH  - Myeloid Cells/immunology/metabolism
MH  - Pandemics
MH  - Pneumonia, Viral/*immunology
MH  - SARS-CoV-2
MH  - Signal Transduction
MH  - Single-Cell Analysis
MH  - Systems Biology
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Transcription, Genetic
MH  - Transcriptome
PMC - PMC7665312
EDAT- 2020/08/14 06:00
MHDA- 2020/09/20 06:00
PMCR- 2020/11/13
CRDT- 2020/08/14 06:00
PHST- 2020/05/05 00:00 [received]
PHST- 2020/07/10 00:00 [revised]
PHST- 2020/08/04 00:00 [accepted]
PHST- 2020/08/14 06:00 [pubmed]
PHST- 2020/09/20 06:00 [medline]
PHST- 2020/08/14 06:00 [entrez]
PHST- 2020/11/13 00:00 [pmc-release]
AID - science.abc6261 [pii]
AID - abc6261 [pii]
AID - 10.1126/science.abc6261 [doi]
PST - ppublish
SO  - Science. 2020 Sep 4;369(6508):1210-1220. doi: 10.1126/science.abc6261. Epub 2020 
      Aug 11.