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Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans.

Identifieur interne : 000038 ( Main/Exploration ); précédent : 000037; suivant : 000039

Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans.

Auteurs : Prabhu S. Arunachalam [États-Unis] ; Florian Wimmers [États-Unis] ; Chris Ka Pun Mok [Hong Kong] ; Ranawaka A P M. Perera [Hong Kong] ; Madeleine Scott [États-Unis] ; Thomas Hagan [États-Unis] ; Natalia Sigal [États-Unis] ; Yupeng Feng [États-Unis] ; Laurel Bristow [États-Unis] ; Owen Tak-Yin Tsang [Hong Kong] ; Dhananjay Wagh [États-Unis] ; John Coller [États-Unis] ; Kathryn L. Pellegrini [États-Unis] ; Dmitri Kazmin [États-Unis] ; Ghina Alaaeddine [États-Unis] ; Wai Shing Leung [Hong Kong] ; Jacky Man Chun Chan [Hong Kong] ; Thomas Shiu Hong Chik [Hong Kong] ; Chris Yau Chung Choi [Hong Kong] ; Christopher Huerta [États-Unis] ; Michele Paine Mccullough [États-Unis] ; Huibin Lv [Hong Kong] ; Evan Anderson [États-Unis] ; Srilatha Edupuganti [États-Unis] ; Amit A. Upadhyay [États-Unis] ; Steve E. Bosinger [États-Unis] ; Holden Terry Maecker [États-Unis] ; Purvesh Khatri [États-Unis] ; Nadine Rouphael [États-Unis] ; Malik Peiris [Hong Kong] ; Bali Pulendran [États-Unis]

Source :

RBID : pubmed:32788292

Descripteurs français

English descriptors

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.

DOI: 10.1126/science.abc6261
PubMed: 32788292
PubMed Central: PMC7665312


Affiliations:


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Le document en format XML

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<name sortKey="Feng, Yupeng" sort="Feng, Yupeng" uniqKey="Feng Y" first="Yupeng" last="Feng">Yupeng Feng</name>
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<name sortKey="Alaaeddine, Ghina" sort="Alaaeddine, Ghina" uniqKey="Alaaeddine G" first="Ghina" last="Alaaeddine">Ghina Alaaeddine</name>
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<name sortKey="Leung, Wai Shing" sort="Leung, Wai Shing" uniqKey="Leung W" first="Wai Shing" last="Leung">Wai Shing Leung</name>
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<name sortKey="Paine Mccullough, Michele" sort="Paine Mccullough, Michele" uniqKey="Paine Mccullough M" first="Michele" last="Paine Mccullough">Michele Paine Mccullough</name>
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<name sortKey="Anderson, Evan" sort="Anderson, Evan" uniqKey="Anderson E" first="Evan" last="Anderson">Evan Anderson</name>
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<name sortKey="Upadhyay, Amit A" sort="Upadhyay, Amit A" uniqKey="Upadhyay A" first="Amit A" last="Upadhyay">Amit A. Upadhyay</name>
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<name sortKey="Bosinger, Steve E" sort="Bosinger, Steve E" uniqKey="Bosinger S" first="Steve E" last="Bosinger">Steve E. Bosinger</name>
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<name sortKey="Maecker, Holden Terry" sort="Maecker, Holden Terry" uniqKey="Maecker H" first="Holden Terry" last="Maecker">Holden Terry Maecker</name>
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<name sortKey="Khatri, Purvesh" sort="Khatri, Purvesh" uniqKey="Khatri P" first="Purvesh" last="Khatri">Purvesh Khatri</name>
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<name sortKey="Rouphael, Nadine" sort="Rouphael, Nadine" uniqKey="Rouphael N" first="Nadine" last="Rouphael">Nadine Rouphael</name>
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<name sortKey="Peiris, Malik" sort="Peiris, Malik" uniqKey="Peiris M" first="Malik" last="Peiris">Malik Peiris</name>
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<nlm:affiliation>HKU-Pasteur Research Pole, School of Public Health, HKU Li Ka Shing Faculty of Medicine, The University of Hong Kong (HKU), Hong Kong.</nlm:affiliation>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea>HKU-Pasteur Research Pole, School of Public Health, HKU Li Ka Shing Faculty of Medicine, The University of Hong Kong (HKU)</wicri:regionArea>
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<nlm:affiliation>Centre of Influenza Research, School of Public Health, HKU Li Ka Shing Faculty of Medicine, HKU, Hong Kong.</nlm:affiliation>
<country xml:lang="fr">Hong Kong</country>
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<name sortKey="Pulendran, Bali" sort="Pulendran, Bali" uniqKey="Pulendran B" first="Bali" last="Pulendran">Bali Pulendran</name>
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<nlm:affiliation>Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA. bpulend@stanford.edu.</nlm:affiliation>
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<region type="state">Californie</region>
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<nlm:affiliation>Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.</nlm:affiliation>
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<wicri:regionArea>Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305</wicri:regionArea>
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<region type="state">Californie</region>
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<affiliation wicri:level="2">
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<title xml:lang="en">Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans.</title>
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<name sortKey="Arunachalam, Prabhu S" sort="Arunachalam, Prabhu S" uniqKey="Arunachalam P" first="Prabhu S" last="Arunachalam">Prabhu S. Arunachalam</name>
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<author>
<name sortKey="Mok, Chris Ka Pun" sort="Mok, Chris Ka Pun" uniqKey="Mok C" first="Chris Ka Pun" last="Mok">Chris Ka Pun Mok</name>
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<author>
<name sortKey="Scott, Madeleine" sort="Scott, Madeleine" uniqKey="Scott M" first="Madeleine" last="Scott">Madeleine Scott</name>
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<wicri:regionArea>Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305</wicri:regionArea>
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<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
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<name sortKey="Feng, Yupeng" sort="Feng, Yupeng" uniqKey="Feng Y" first="Yupeng" last="Feng">Yupeng Feng</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305</wicri:regionArea>
<placeName>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Bristow, Laurel" sort="Bristow, Laurel" uniqKey="Bristow L" first="Laurel" last="Bristow">Laurel Bristow</name>
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<country xml:lang="fr">États-Unis</country>
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<region type="state">Géorgie (États-Unis)</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Tak Yin Tsang, Owen" sort="Tak Yin Tsang, Owen" uniqKey="Tak Yin Tsang O" first="Owen" last="Tak-Yin Tsang">Owen Tak-Yin Tsang</name>
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<nlm:affiliation>Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of Hong Kong, Hong Kong.</nlm:affiliation>
<country xml:lang="fr">Hong Kong</country>
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</author>
<author>
<name sortKey="Wagh, Dhananjay" sort="Wagh, Dhananjay" uniqKey="Wagh D" first="Dhananjay" last="Wagh">Dhananjay Wagh</name>
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<nlm:affiliation>Stanford Functional Genomics Facility, Stanford University School of Medicine, Stanford, CA 94305, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Stanford Functional Genomics Facility, Stanford University School of Medicine, Stanford, CA 94305</wicri:regionArea>
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<region type="state">Californie</region>
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<author>
<name sortKey="Coller, John" sort="Coller, John" uniqKey="Coller J" first="John" last="Coller">John Coller</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Stanford Functional Genomics Facility, Stanford University School of Medicine, Stanford, CA 94305</wicri:regionArea>
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<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Pellegrini, Kathryn L" sort="Pellegrini, Kathryn L" uniqKey="Pellegrini K" first="Kathryn L" last="Pellegrini">Kathryn L. Pellegrini</name>
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<nlm:affiliation>Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329</wicri:regionArea>
<placeName>
<region type="state">Géorgie (États-Unis)</region>
</placeName>
</affiliation>
</author>
<author>
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<region type="state">Californie</region>
</placeName>
</affiliation>
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<author>
<name sortKey="Alaaeddine, Ghina" sort="Alaaeddine, Ghina" uniqKey="Alaaeddine G" first="Ghina" last="Alaaeddine">Ghina Alaaeddine</name>
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<country xml:lang="fr">États-Unis</country>
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<region type="state">Géorgie (États-Unis)</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Leung, Wai Shing" sort="Leung, Wai Shing" uniqKey="Leung W" first="Wai Shing" last="Leung">Wai Shing Leung</name>
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<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea>Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of Hong Kong</wicri:regionArea>
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</author>
<author>
<name sortKey="Chan, Jacky Man Chun" sort="Chan, Jacky Man Chun" uniqKey="Chan J" first="Jacky Man Chun" last="Chan">Jacky Man Chun Chan</name>
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<nlm:affiliation>Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of Hong Kong, Hong Kong.</nlm:affiliation>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea>Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of Hong Kong</wicri:regionArea>
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</author>
<author>
<name sortKey="Chik, Thomas Shiu Hong" sort="Chik, Thomas Shiu Hong" uniqKey="Chik T" first="Thomas Shiu Hong" last="Chik">Thomas Shiu Hong Chik</name>
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<nlm:affiliation>Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of Hong Kong, Hong Kong.</nlm:affiliation>
<country xml:lang="fr">Hong Kong</country>
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<name sortKey="Choi, Chris Yau Chung" sort="Choi, Chris Yau Chung" uniqKey="Choi C" first="Chris Yau Chung" last="Choi">Chris Yau Chung Choi</name>
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<nlm:affiliation>Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of Hong Kong, Hong Kong.</nlm:affiliation>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea>Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of Hong Kong</wicri:regionArea>
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<name sortKey="Huerta, Christopher" sort="Huerta, Christopher" uniqKey="Huerta C" first="Christopher" last="Huerta">Christopher Huerta</name>
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<name sortKey="Paine Mccullough, Michele" sort="Paine Mccullough, Michele" uniqKey="Paine Mccullough M" first="Michele" last="Paine Mccullough">Michele Paine Mccullough</name>
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<nlm:affiliation>HKU-Pasteur Research Pole, School of Public Health, HKU Li Ka Shing Faculty of Medicine, The University of Hong Kong (HKU), Hong Kong.</nlm:affiliation>
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<name sortKey="Edupuganti, Srilatha" sort="Edupuganti, Srilatha" uniqKey="Edupuganti S" first="Srilatha" last="Edupuganti">Srilatha Edupuganti</name>
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<region type="state">Géorgie (États-Unis)</region>
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<name sortKey="Upadhyay, Amit A" sort="Upadhyay, Amit A" uniqKey="Upadhyay A" first="Amit A" last="Upadhyay">Amit A. Upadhyay</name>
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<region type="state">Géorgie (États-Unis)</region>
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<author>
<name sortKey="Bosinger, Steve E" sort="Bosinger, Steve E" uniqKey="Bosinger S" first="Steve E" last="Bosinger">Steve E. Bosinger</name>
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<region type="state">Géorgie (États-Unis)</region>
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</affiliation>
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<nlm:affiliation>Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30329, USA.</nlm:affiliation>
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<wicri:regionArea>Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30329</wicri:regionArea>
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<region type="state">Géorgie (États-Unis)</region>
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</affiliation>
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<author>
<name sortKey="Maecker, Holden Terry" sort="Maecker, Holden Terry" uniqKey="Maecker H" first="Holden Terry" last="Maecker">Holden Terry Maecker</name>
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<nlm:affiliation>Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.</nlm:affiliation>
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</author>
<author>
<name sortKey="Khatri, Purvesh" sort="Khatri, Purvesh" uniqKey="Khatri P" first="Purvesh" last="Khatri">Purvesh Khatri</name>
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<nlm:affiliation>Center for Biomedical Informatics, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.</nlm:affiliation>
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<author>
<name sortKey="Rouphael, Nadine" sort="Rouphael, Nadine" uniqKey="Rouphael N" first="Nadine" last="Rouphael">Nadine Rouphael</name>
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<name sortKey="Peiris, Malik" sort="Peiris, Malik" uniqKey="Peiris M" first="Malik" last="Peiris">Malik Peiris</name>
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<name sortKey="Pulendran, Bali" sort="Pulendran, Bali" uniqKey="Pulendran B" first="Bali" last="Pulendran">Bali Pulendran</name>
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<nlm:affiliation>Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.</nlm:affiliation>
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<nlm:affiliation>Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.</nlm:affiliation>
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<title level="j">Science (New York, N.Y.)</title>
<idno type="eISSN">1095-9203</idno>
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<keywords scheme="KwdEn" xml:lang="en">
<term>Betacoronavirus (immunology)</term>
<term>Coronavirus Infections (immunology)</term>
<term>Cytokines (blood)</term>
<term>DNA, Bacterial (blood)</term>
<term>Dendritic Cells (immunology)</term>
<term>Dendritic Cells (metabolism)</term>
<term>Female (MeSH)</term>
<term>Flow Cytometry (MeSH)</term>
<term>HLA-DR Antigens (analysis)</term>
<term>Humans (MeSH)</term>
<term>Immunity (MeSH)</term>
<term>Immunity, Innate (MeSH)</term>
<term>Immunoglobulins (blood)</term>
<term>Immunoglobulins (immunology)</term>
<term>Inflammation Mediators (blood)</term>
<term>Interferon Type I (metabolism)</term>
<term>Leukocytes, Mononuclear (immunology)</term>
<term>Leukocytes, Mononuclear (metabolism)</term>
<term>Lipopolysaccharides (blood)</term>
<term>Male (MeSH)</term>
<term>Myeloid Cells (immunology)</term>
<term>Myeloid Cells (metabolism)</term>
<term>Pandemics (MeSH)</term>
<term>Pneumonia, Viral (immunology)</term>
<term>Signal Transduction (MeSH)</term>
<term>Single-Cell Analysis (MeSH)</term>
<term>Systems Biology (MeSH)</term>
<term>TOR Serine-Threonine Kinases (metabolism)</term>
<term>Transcription, Genetic (MeSH)</term>
<term>Transcriptome (MeSH)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>ADN bactérien (sang)</term>
<term>Agranulocytes (immunologie)</term>
<term>Agranulocytes (métabolisme)</term>
<term>Analyse sur cellule unique (MeSH)</term>
<term>Antigènes HLA-DR (analyse)</term>
<term>Betacoronavirus (immunologie)</term>
<term>Biologie des systèmes (MeSH)</term>
<term>Cellules dendritiques (immunologie)</term>
<term>Cellules dendritiques (métabolisme)</term>
<term>Cellules myéloïdes (immunologie)</term>
<term>Cellules myéloïdes (métabolisme)</term>
<term>Cytokines (sang)</term>
<term>Cytométrie en flux (MeSH)</term>
<term>Femelle (MeSH)</term>
<term>Humains (MeSH)</term>
<term>Immunité (MeSH)</term>
<term>Immunité innée (MeSH)</term>
<term>Immunoglobulines (immunologie)</term>
<term>Immunoglobulines (sang)</term>
<term>Infections à coronavirus (immunologie)</term>
<term>Interféron de type I (métabolisme)</term>
<term>Lipopolysaccharides (sang)</term>
<term>Mâle (MeSH)</term>
<term>Médiateurs de l'inflammation (sang)</term>
<term>Pandémies (MeSH)</term>
<term>Pneumopathie virale (immunologie)</term>
<term>Sérine-thréonine kinases TOR (métabolisme)</term>
<term>Transcription génétique (MeSH)</term>
<term>Transcriptome (MeSH)</term>
<term>Transduction du signal (MeSH)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en">
<term>HLA-DR Antigens</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en">
<term>Cytokines</term>
<term>DNA, Bacterial</term>
<term>Immunoglobulins</term>
<term>Inflammation Mediators</term>
<term>Lipopolysaccharides</term>
</keywords>
<keywords scheme="MESH" qualifier="analyse" xml:lang="fr">
<term>Antigènes HLA-DR</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr">
<term>Agranulocytes</term>
<term>Betacoronavirus</term>
<term>Cellules dendritiques</term>
<term>Cellules myéloïdes</term>
<term>Immunoglobulines</term>
<term>Infections à coronavirus</term>
<term>Pneumopathie virale</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en">
<term>Betacoronavirus</term>
<term>Coronavirus Infections</term>
<term>Dendritic Cells</term>
<term>Immunoglobulins</term>
<term>Leukocytes, Mononuclear</term>
<term>Myeloid Cells</term>
<term>Pneumonia, Viral</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en">
<term>Dendritic Cells</term>
<term>Interferon Type I</term>
<term>Leukocytes, Mononuclear</term>
<term>Myeloid Cells</term>
<term>TOR Serine-Threonine Kinases</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr">
<term>Agranulocytes</term>
<term>Cellules dendritiques</term>
<term>Cellules myéloïdes</term>
<term>Interféron de type I</term>
<term>Sérine-thréonine kinases TOR</term>
</keywords>
<keywords scheme="MESH" qualifier="sang" xml:lang="fr">
<term>ADN bactérien</term>
<term>Cytokines</term>
<term>Immunoglobulines</term>
<term>Lipopolysaccharides</term>
<term>Médiateurs de l'inflammation</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Female</term>
<term>Flow Cytometry</term>
<term>Humans</term>
<term>Immunity</term>
<term>Immunity, Innate</term>
<term>Male</term>
<term>Pandemics</term>
<term>Signal Transduction</term>
<term>Single-Cell Analysis</term>
<term>Systems Biology</term>
<term>Transcription, Genetic</term>
<term>Transcriptome</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Analyse sur cellule unique</term>
<term>Biologie des systèmes</term>
<term>Cytométrie en flux</term>
<term>Femelle</term>
<term>Humains</term>
<term>Immunité</term>
<term>Immunité innée</term>
<term>Mâle</term>
<term>Pandémies</term>
<term>Transcription génétique</term>
<term>Transcriptome</term>
<term>Transduction du signal</term>
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<front>
<div type="abstract" xml:lang="en">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.</div>
</front>
</TEI>
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<PMID Version="1">32788292</PMID>
<DateCompleted>
<Year>2020</Year>
<Month>09</Month>
<Day>18</Day>
</DateCompleted>
<DateRevised>
<Year>2020</Year>
<Month>11</Month>
<Day>18</Day>
</DateRevised>
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<Journal>
<ISSN IssnType="Electronic">1095-9203</ISSN>
<JournalIssue CitedMedium="Internet">
<Volume>369</Volume>
<Issue>6508</Issue>
<PubDate>
<Year>2020</Year>
<Month>09</Month>
<Day>04</Day>
</PubDate>
</JournalIssue>
<Title>Science (New York, N.Y.)</Title>
<ISOAbbreviation>Science</ISOAbbreviation>
</Journal>
<ArticleTitle>Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans.</ArticleTitle>
<Pagination>
<MedlinePgn>1210-1220</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1126/science.abc6261</ELocationID>
<Abstract>
<AbstractText>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.</AbstractText>
<CopyrightInformation>Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.</CopyrightInformation>
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<LastName>Arunachalam</LastName>
<ForeName>Prabhu S</ForeName>
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<AffiliationInfo>
<Affiliation>Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.</Affiliation>
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<LastName>Wimmers</LastName>
<ForeName>Florian</ForeName>
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<Affiliation>Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.</Affiliation>
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<ForeName>Chris Ka Pun</ForeName>
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<Affiliation>HKU-Pasteur Research Pole, School of Public Health, HKU Li Ka Shing Faculty of Medicine, The University of Hong Kong (HKU), Hong Kong.</Affiliation>
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<ForeName>Ranawaka A P M</ForeName>
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<Affiliation>Centre of Influenza Research, School of Public Health, HKU Li Ka Shing Faculty of Medicine, HKU, Hong Kong.</Affiliation>
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<Affiliation>Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA.</Affiliation>
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<LastName>Tak-Yin Tsang</LastName>
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<Affiliation>Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA.</Affiliation>
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<Affiliation>Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of Hong Kong, Hong Kong.</Affiliation>
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<LastName>Chan</LastName>
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<ForeName>Evan</ForeName>
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<Affiliation>Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA 30322, USA.</Affiliation>
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<LastName>Edupuganti</LastName>
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<LastName>Bosinger</LastName>
<ForeName>Steve E</ForeName>
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<Affiliation>Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA.</Affiliation>
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<ForeName>Holden Terry</ForeName>
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<Affiliation>Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.</Affiliation>
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<Affiliation>Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.</Affiliation>
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<LastName>Rouphael</LastName>
<ForeName>Nadine</ForeName>
<Initials>N</Initials>
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</AffiliationInfo>
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<LastName>Peiris</LastName>
<ForeName>Malik</ForeName>
<Initials>M</Initials>
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<Affiliation>HKU-Pasteur Research Pole, School of Public Health, HKU Li Ka Shing Faculty of Medicine, The University of Hong Kong (HKU), Hong Kong.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Centre of Influenza Research, School of Public Health, HKU Li Ka Shing Faculty of Medicine, HKU, Hong Kong.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Pulendran</LastName>
<ForeName>Bali</ForeName>
<Initials>B</Initials>
<Identifier Source="ORCID">0000-0001-6517-4333</Identifier>
<AffiliationInfo>
<Affiliation>Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA. bpulend@stanford.edu.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.</Affiliation>
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<Language>eng</Language>
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<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
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<Grant>
<GrantID>U19 AI057266</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
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<Country>United States</Country>
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<Agency>NIH HHS</Agency>
<Country>United States</Country>
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<Month>08</Month>
<Day>11</Day>
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</Chemical>
<Chemical>
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<Chemical>
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</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
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<Chemical>
<RegistryNumber>EC 2.7.1.1</RegistryNumber>
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<RegistryNumber>EC 2.7.1.1</RegistryNumber>
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</MeshHeading>
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</MeshHeading>
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<DescriptorName UI="D004269" MajorTopicYN="N">DNA, Bacterial</DescriptorName>
<QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D003713" MajorTopicYN="N">Dendritic Cells</DescriptorName>
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<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
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