Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans.
Identifieur interne : 000038 ( Main/Exploration ); précédent : 000037; suivant : 000039Systems 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 :
- Science (New York, N.Y.) [ 1095-9203 ] ; 2020.
Descripteurs français
- KwdFr :
- ADN bactérien (sang), Agranulocytes (immunologie), Agranulocytes (métabolisme), Analyse sur cellule unique (MeSH), Antigènes HLA-DR (analyse), Betacoronavirus (immunologie), Biologie des systèmes (MeSH), Cellules dendritiques (immunologie), Cellules dendritiques (métabolisme), Cellules myéloïdes (immunologie), Cellules myéloïdes (métabolisme), Cytokines (sang), Cytométrie en flux (MeSH), Femelle (MeSH), Humains (MeSH), Immunité (MeSH), Immunité innée (MeSH), Immunoglobulines (immunologie), Immunoglobulines (sang), Infections à coronavirus (immunologie), Interféron de type I (métabolisme), Lipopolysaccharides (sang), Mâle (MeSH), Médiateurs de l'inflammation (sang), Pandémies (MeSH), Pneumopathie virale (immunologie), Sérine-thréonine kinases TOR (métabolisme), Transcription génétique (MeSH), Transcriptome (MeSH), Transduction du signal (MeSH).
- MESH :
- analyse : Antigènes HLA-DR.
- immunologie : Agranulocytes, Betacoronavirus, Cellules dendritiques, Cellules myéloïdes, Immunoglobulines, Infections à coronavirus, Pneumopathie virale.
- métabolisme : Agranulocytes, Cellules dendritiques, Cellules myéloïdes, Interféron de type I, Sérine-thréonine kinases TOR.
- sang : ADN bactérien, Cytokines, Immunoglobulines, Lipopolysaccharides, Médiateurs de l'inflammation.
- Analyse sur cellule unique, Biologie des systèmes, Cytométrie en flux, Femelle, Humains, Immunité, Immunité innée, Mâle, Pandémies, Transcription génétique, Transcriptome, Transduction du signal.
English descriptors
- KwdEn :
- Betacoronavirus (immunology), Coronavirus Infections (immunology), Cytokines (blood), DNA, Bacterial (blood), Dendritic Cells (immunology), Dendritic Cells (metabolism), Female (MeSH), Flow Cytometry (MeSH), HLA-DR Antigens (analysis), Humans (MeSH), Immunity (MeSH), Immunity, Innate (MeSH), Immunoglobulins (blood), Immunoglobulins (immunology), Inflammation Mediators (blood), Interferon Type I (metabolism), Leukocytes, Mononuclear (immunology), Leukocytes, Mononuclear (metabolism), Lipopolysaccharides (blood), Male (MeSH), Myeloid Cells (immunology), Myeloid Cells (metabolism), Pandemics (MeSH), Pneumonia, Viral (immunology), Signal Transduction (MeSH), Single-Cell Analysis (MeSH), Systems Biology (MeSH), TOR Serine-Threonine Kinases (metabolism), Transcription, Genetic (MeSH), Transcriptome (MeSH).
- MESH :
- chemical , analysis : HLA-DR Antigens.
- chemical , blood : Cytokines, DNA, Bacterial, Immunoglobulins, Inflammation Mediators, Lipopolysaccharides.
- immunology : Betacoronavirus, Coronavirus Infections, Dendritic Cells, Immunoglobulins, Leukocytes, Mononuclear, Myeloid Cells, Pneumonia, Viral.
- metabolism : Dendritic Cells, Interferon Type I, Leukocytes, Mononuclear, Myeloid Cells, TOR Serine-Threonine Kinases.
- Female, Flow Cytometry, Humans, Immunity, Immunity, Innate, Male, Pandemics, Signal Transduction, Single-Cell Analysis, Systems Biology, Transcription, Genetic, Transcriptome.
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:
Links toward previous steps (curation, corpus...)
Le document en format XML
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<author><name sortKey="Sigal, Natalia" sort="Sigal, Natalia" uniqKey="Sigal N" first="Natalia" last="Sigal">Natalia Sigal</name>
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<author><name sortKey="Feng, Yupeng" sort="Feng, Yupeng" uniqKey="Feng Y" first="Yupeng" last="Feng">Yupeng Feng</name>
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<author><name sortKey="Bristow, Laurel" sort="Bristow, Laurel" uniqKey="Bristow L" first="Laurel" last="Bristow">Laurel Bristow</name>
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<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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<author><name sortKey="Wagh, Dhananjay" sort="Wagh, Dhananjay" uniqKey="Wagh D" first="Dhananjay" last="Wagh">Dhananjay Wagh</name>
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<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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<author><name sortKey="Alaaeddine, Ghina" sort="Alaaeddine, Ghina" uniqKey="Alaaeddine G" first="Ghina" last="Alaaeddine">Ghina Alaaeddine</name>
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<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>
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<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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<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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<country xml:lang="fr">Hong Kong</country>
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<author><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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<country xml:lang="fr">Hong Kong</country>
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<wicri:noRegion>Hospital Authority of Hong Kong</wicri:noRegion>
</affiliation>
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<author><name sortKey="Huerta, Christopher" sort="Huerta, Christopher" uniqKey="Huerta C" first="Christopher" last="Huerta">Christopher Huerta</name>
<affiliation wicri:level="2"><nlm:affiliation>Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030</wicri:regionArea>
<placeName><region type="state">Géorgie (États-Unis)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Paine Mccullough, Michele" sort="Paine Mccullough, Michele" uniqKey="Paine Mccullough M" first="Michele" last="Paine Mccullough">Michele Paine Mccullough</name>
<affiliation wicri:level="2"><nlm:affiliation>Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030</wicri:regionArea>
<placeName><region type="state">Géorgie (États-Unis)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lv, Huibin" sort="Lv, Huibin" uniqKey="Lv H" first="Huibin" last="Lv">Huibin Lv</name>
<affiliation wicri:level="1"><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>
<wicri:noRegion>The University of Hong Kong (HKU)</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Anderson, Evan" sort="Anderson, Evan" uniqKey="Anderson E" first="Evan" last="Anderson">Evan Anderson</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA 30322, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA 30322</wicri:regionArea>
<placeName><region type="state">Géorgie (États-Unis)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Edupuganti, Srilatha" sort="Edupuganti, Srilatha" uniqKey="Edupuganti S" first="Srilatha" last="Edupuganti">Srilatha Edupuganti</name>
<affiliation wicri:level="2"><nlm:affiliation>Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030</wicri:regionArea>
<placeName><region type="state">Géorgie (États-Unis)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Upadhyay, Amit A" sort="Upadhyay, Amit A" uniqKey="Upadhyay A" first="Amit A" last="Upadhyay">Amit A. Upadhyay</name>
<affiliation wicri:level="2"><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><name sortKey="Bosinger, Steve E" sort="Bosinger, Steve E" uniqKey="Bosinger S" first="Steve E" last="Bosinger">Steve E. Bosinger</name>
<affiliation wicri:level="2"><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>
<affiliation wicri:level="2"><nlm:affiliation>Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30329, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30329</wicri:regionArea>
<placeName><region type="state">Géorgie (États-Unis)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Maecker, Holden Terry" sort="Maecker, Holden Terry" uniqKey="Maecker H" first="Holden Terry" last="Maecker">Holden Terry Maecker</name>
<affiliation wicri:level="2"><nlm:affiliation>Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.</nlm:affiliation>
<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="Khatri, Purvesh" sort="Khatri, Purvesh" uniqKey="Khatri P" first="Purvesh" last="Khatri">Purvesh Khatri</name>
<affiliation wicri:level="2"><nlm:affiliation>Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.</nlm:affiliation>
<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>
<affiliation wicri:level="2"><nlm:affiliation>Center for Biomedical Informatics, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Biomedical Informatics, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Rouphael, Nadine" sort="Rouphael, Nadine" uniqKey="Rouphael N" first="Nadine" last="Rouphael">Nadine Rouphael</name>
<affiliation wicri:level="2"><nlm:affiliation>Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030</wicri:regionArea>
<placeName><region type="state">Géorgie (États-Unis)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Peiris, Malik" sort="Peiris, Malik" uniqKey="Peiris M" first="Malik" last="Peiris">Malik Peiris</name>
<affiliation wicri:level="1"><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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</affiliation>
<affiliation wicri:level="1"><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>
<wicri:regionArea>Centre of Influenza Research, School of Public Health, HKU Li Ka Shing Faculty of Medicine, HKU</wicri:regionArea>
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<author><name sortKey="Pulendran, Bali" sort="Pulendran, Bali" uniqKey="Pulendran B" first="Bali" last="Pulendran">Bali Pulendran</name>
<affiliation wicri:level="2"><nlm:affiliation>Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA. bpulend@stanford.edu.</nlm:affiliation>
<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>
<affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305</wicri:regionArea>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans.</title>
<author><name sortKey="Arunachalam, Prabhu S" sort="Arunachalam, Prabhu S" uniqKey="Arunachalam P" first="Prabhu S" last="Arunachalam">Prabhu S. Arunachalam</name>
<affiliation wicri:level="2"><nlm:affiliation>Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.</nlm:affiliation>
<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="Wimmers, Florian" sort="Wimmers, Florian" uniqKey="Wimmers F" first="Florian" last="Wimmers">Florian Wimmers</name>
<affiliation wicri:level="2"><nlm:affiliation>Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.</nlm:affiliation>
<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="Mok, Chris Ka Pun" sort="Mok, Chris Ka Pun" uniqKey="Mok C" first="Chris Ka Pun" last="Mok">Chris Ka Pun Mok</name>
<affiliation wicri:level="1"><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>
<wicri:noRegion>The University of Hong Kong (HKU)</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Perera, Ranawaka A P M" sort="Perera, Ranawaka A P M" uniqKey="Perera R" first="Ranawaka A P M" last="Perera">Ranawaka A P M. Perera</name>
<affiliation wicri:level="1"><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>
<wicri:regionArea>Centre of Influenza Research, School of Public Health, HKU Li Ka Shing Faculty of Medicine, HKU</wicri:regionArea>
<wicri:noRegion>HKU</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Scott, Madeleine" sort="Scott, Madeleine" uniqKey="Scott M" first="Madeleine" last="Scott">Madeleine Scott</name>
<affiliation wicri:level="2"><nlm:affiliation>Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.</nlm:affiliation>
<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>
<affiliation wicri:level="2"><nlm:affiliation>Center for Biomedical Informatics, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Biomedical Informatics, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hagan, Thomas" sort="Hagan, Thomas" uniqKey="Hagan T" first="Thomas" last="Hagan">Thomas Hagan</name>
<affiliation wicri:level="2"><nlm:affiliation>Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.</nlm:affiliation>
<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="Sigal, Natalia" sort="Sigal, Natalia" uniqKey="Sigal N" first="Natalia" last="Sigal">Natalia Sigal</name>
<affiliation wicri:level="2"><nlm:affiliation>Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.</nlm:affiliation>
<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="Feng, Yupeng" sort="Feng, Yupeng" uniqKey="Feng Y" first="Yupeng" last="Feng">Yupeng Feng</name>
<affiliation wicri:level="2"><nlm:affiliation>Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.</nlm:affiliation>
<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>
<affiliation wicri:level="2"><nlm:affiliation>Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030</wicri:regionArea>
<placeName><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>
<affiliation wicri:level="1"><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>
<wicri:noRegion>Hospital Authority of Hong Kong</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wagh, Dhananjay" sort="Wagh, Dhananjay" uniqKey="Wagh D" first="Dhananjay" last="Wagh">Dhananjay Wagh</name>
<affiliation wicri:level="2"><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>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Coller, John" sort="Coller, John" uniqKey="Coller J" first="John" last="Coller">John Coller</name>
<affiliation wicri:level="2"><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>
<placeName><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>
<affiliation wicri:level="2"><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><name sortKey="Kazmin, Dmitri" sort="Kazmin, Dmitri" uniqKey="Kazmin D" first="Dmitri" last="Kazmin">Dmitri Kazmin</name>
<affiliation wicri:level="2"><nlm:affiliation>Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.</nlm:affiliation>
<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="Alaaeddine, Ghina" sort="Alaaeddine, Ghina" uniqKey="Alaaeddine G" first="Ghina" last="Alaaeddine">Ghina Alaaeddine</name>
<affiliation wicri:level="2"><nlm:affiliation>Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030</wicri:regionArea>
<placeName><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>
<affiliation wicri:level="1"><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>
<wicri:noRegion>Hospital Authority of Hong Kong</wicri:noRegion>
</affiliation>
</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>
<affiliation wicri:level="1"><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>
<wicri:noRegion>Hospital Authority of Hong Kong</wicri:noRegion>
</affiliation>
</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>
<affiliation wicri:level="1"><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>
<wicri:noRegion>Hospital Authority of Hong Kong</wicri:noRegion>
</affiliation>
</author>
<author><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>
<affiliation wicri:level="1"><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>
<wicri:noRegion>Hospital Authority of Hong Kong</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Huerta, Christopher" sort="Huerta, Christopher" uniqKey="Huerta C" first="Christopher" last="Huerta">Christopher Huerta</name>
<affiliation wicri:level="2"><nlm:affiliation>Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030</wicri:regionArea>
<placeName><region type="state">Géorgie (États-Unis)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Paine Mccullough, Michele" sort="Paine Mccullough, Michele" uniqKey="Paine Mccullough M" first="Michele" last="Paine Mccullough">Michele Paine Mccullough</name>
<affiliation wicri:level="2"><nlm:affiliation>Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030</wicri:regionArea>
<placeName><region type="state">Géorgie (États-Unis)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lv, Huibin" sort="Lv, Huibin" uniqKey="Lv H" first="Huibin" last="Lv">Huibin Lv</name>
<affiliation wicri:level="1"><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>
<wicri:noRegion>The University of Hong Kong (HKU)</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Anderson, Evan" sort="Anderson, Evan" uniqKey="Anderson E" first="Evan" last="Anderson">Evan Anderson</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA 30322, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA 30322</wicri:regionArea>
<placeName><region type="state">Géorgie (États-Unis)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Edupuganti, Srilatha" sort="Edupuganti, Srilatha" uniqKey="Edupuganti S" first="Srilatha" last="Edupuganti">Srilatha Edupuganti</name>
<affiliation wicri:level="2"><nlm:affiliation>Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030</wicri:regionArea>
<placeName><region type="state">Géorgie (États-Unis)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Upadhyay, Amit A" sort="Upadhyay, Amit A" uniqKey="Upadhyay A" first="Amit A" last="Upadhyay">Amit A. Upadhyay</name>
<affiliation wicri:level="2"><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><name sortKey="Bosinger, Steve E" sort="Bosinger, Steve E" uniqKey="Bosinger S" first="Steve E" last="Bosinger">Steve E. Bosinger</name>
<affiliation wicri:level="2"><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>
<affiliation wicri:level="2"><nlm:affiliation>Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30329, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30329</wicri:regionArea>
<placeName><region type="state">Géorgie (États-Unis)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Maecker, Holden Terry" sort="Maecker, Holden Terry" uniqKey="Maecker H" first="Holden Terry" last="Maecker">Holden Terry Maecker</name>
<affiliation wicri:level="2"><nlm:affiliation>Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.</nlm:affiliation>
<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="Khatri, Purvesh" sort="Khatri, Purvesh" uniqKey="Khatri P" first="Purvesh" last="Khatri">Purvesh Khatri</name>
<affiliation wicri:level="2"><nlm:affiliation>Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.</nlm:affiliation>
<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>
<affiliation wicri:level="2"><nlm:affiliation>Center for Biomedical Informatics, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Biomedical Informatics, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Rouphael, Nadine" sort="Rouphael, Nadine" uniqKey="Rouphael N" first="Nadine" last="Rouphael">Nadine Rouphael</name>
<affiliation wicri:level="2"><nlm:affiliation>Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030</wicri:regionArea>
<placeName><region type="state">Géorgie (États-Unis)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Peiris, Malik" sort="Peiris, Malik" uniqKey="Peiris M" first="Malik" last="Peiris">Malik Peiris</name>
<affiliation wicri:level="1"><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>
<wicri:noRegion>The University of Hong Kong (HKU)</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><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>
<wicri:regionArea>Centre of Influenza Research, School of Public Health, HKU Li Ka Shing Faculty of Medicine, HKU</wicri:regionArea>
<wicri:noRegion>HKU</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Pulendran, Bali" sort="Pulendran, Bali" uniqKey="Pulendran B" first="Bali" last="Pulendran">Bali Pulendran</name>
<affiliation wicri:level="2"><nlm:affiliation>Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA. bpulend@stanford.edu.</nlm:affiliation>
<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>
<affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
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</analytic>
<series><title level="j">Science (New York, N.Y.)</title>
<idno type="eISSN">1095-9203</idno>
<imprint><date when="2020" type="published">2020</date>
</imprint>
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<profileDesc><textClass><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>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<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>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><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>
<Article PubModel="Print-Electronic"><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>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y" EqualContrib="Y"><LastName>Arunachalam</LastName>
<ForeName>Prabhu S</ForeName>
<Initials>PS</Initials>
<Identifier Source="ORCID">0000-0003-0090-5689</Identifier>
<AffiliationInfo><Affiliation>Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y" EqualContrib="Y"><LastName>Wimmers</LastName>
<ForeName>Florian</ForeName>
<Initials>F</Initials>
<Identifier Source="ORCID">0000-0002-6482-2228</Identifier>
<AffiliationInfo><Affiliation>Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y" EqualContrib="Y"><LastName>Mok</LastName>
<ForeName>Chris Ka Pun</ForeName>
<Initials>CKP</Initials>
<Identifier Source="ORCID">0000-0002-0525-6772</Identifier>
<AffiliationInfo><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>
</Author>
<Author ValidYN="Y" EqualContrib="Y"><LastName>Perera</LastName>
<ForeName>Ranawaka A P M</ForeName>
<Initials>RAPM</Initials>
<Identifier Source="ORCID">0000-0003-3936-1535</Identifier>
<AffiliationInfo><Affiliation>Centre of Influenza Research, School of Public Health, HKU Li Ka Shing Faculty of Medicine, HKU, Hong Kong.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y" EqualContrib="Y"><LastName>Scott</LastName>
<ForeName>Madeleine</ForeName>
<Initials>M</Initials>
<Identifier Source="ORCID">0000-0001-9350-5451</Identifier>
<AffiliationInfo><Affiliation>Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Center for Biomedical Informatics, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y" EqualContrib="Y"><LastName>Hagan</LastName>
<ForeName>Thomas</ForeName>
<Initials>T</Initials>
<Identifier Source="ORCID">0000-0002-5254-5251</Identifier>
<AffiliationInfo><Affiliation>Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y" EqualContrib="Y"><LastName>Sigal</LastName>
<ForeName>Natalia</ForeName>
<Initials>N</Initials>
<Identifier Source="ORCID">0000-0003-2831-7053</Identifier>
<AffiliationInfo><Affiliation>Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y" EqualContrib="Y"><LastName>Feng</LastName>
<ForeName>Yupeng</ForeName>
<Initials>Y</Initials>
<Identifier Source="ORCID">0000-0001-8550-2787</Identifier>
<AffiliationInfo><Affiliation>Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bristow</LastName>
<ForeName>Laurel</ForeName>
<Initials>L</Initials>
<Identifier Source="ORCID">0000-0001-9050-0057</Identifier>
<AffiliationInfo><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>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Tak-Yin Tsang</LastName>
<ForeName>Owen</ForeName>
<Initials>O</Initials>
<AffiliationInfo><Affiliation>Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of Hong Kong, Hong Kong.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Wagh</LastName>
<ForeName>Dhananjay</ForeName>
<Initials>D</Initials>
<Identifier Source="ORCID">0000-0002-6937-003X</Identifier>
<AffiliationInfo><Affiliation>Stanford Functional Genomics Facility, Stanford University School of Medicine, Stanford, CA 94305, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Coller</LastName>
<ForeName>John</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Stanford Functional Genomics Facility, Stanford University School of Medicine, Stanford, CA 94305, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Pellegrini</LastName>
<ForeName>Kathryn L</ForeName>
<Initials>KL</Initials>
<Identifier Source="ORCID">0000-0002-5089-5477</Identifier>
<AffiliationInfo><Affiliation>Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kazmin</LastName>
<ForeName>Dmitri</ForeName>
<Initials>D</Initials>
<AffiliationInfo><Affiliation>Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Alaaeddine</LastName>
<ForeName>Ghina</ForeName>
<Initials>G</Initials>
<Identifier Source="ORCID">0000-0001-9570-7989</Identifier>
<AffiliationInfo><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>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Leung</LastName>
<ForeName>Wai Shing</ForeName>
<Initials>WS</Initials>
<Identifier Source="ORCID">0000-0001-8377-085X</Identifier>
<AffiliationInfo><Affiliation>Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of Hong Kong, Hong Kong.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Chan</LastName>
<ForeName>Jacky Man Chun</ForeName>
<Initials>JMC</Initials>
<AffiliationInfo><Affiliation>Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of Hong Kong, Hong Kong.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Chik</LastName>
<ForeName>Thomas Shiu Hong</ForeName>
<Initials>TSH</Initials>
<Identifier Source="ORCID">0000-0002-0481-1420</Identifier>
<AffiliationInfo><Affiliation>Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of Hong Kong, Hong Kong.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Choi</LastName>
<ForeName>Chris Yau Chung</ForeName>
<Initials>CYC</Initials>
<Identifier Source="ORCID">0000-0002-3695-2770</Identifier>
<AffiliationInfo><Affiliation>Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of Hong Kong, Hong Kong.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Huerta</LastName>
<ForeName>Christopher</ForeName>
<Initials>C</Initials>
<AffiliationInfo><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>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Paine McCullough</LastName>
<ForeName>Michele</ForeName>
<Initials>M</Initials>
<AffiliationInfo><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>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lv</LastName>
<ForeName>Huibin</ForeName>
<Initials>H</Initials>
<AffiliationInfo><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>
</Author>
<Author ValidYN="Y"><LastName>Anderson</LastName>
<ForeName>Evan</ForeName>
<Initials>E</Initials>
<Identifier Source="ORCID">0000-0002-1576-4420</Identifier>
<AffiliationInfo><Affiliation>Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA 30322, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Edupuganti</LastName>
<ForeName>Srilatha</ForeName>
<Initials>S</Initials>
<Identifier Source="ORCID">0000-0001-6566-9969</Identifier>
<AffiliationInfo><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>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Upadhyay</LastName>
<ForeName>Amit A</ForeName>
<Initials>AA</Initials>
<Identifier Source="ORCID">0000-0002-0952-4164</Identifier>
<AffiliationInfo><Affiliation>Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bosinger</LastName>
<ForeName>Steve E</ForeName>
<Initials>SE</Initials>
<Identifier Source="ORCID">0000-0002-2116-5061</Identifier>
<AffiliationInfo><Affiliation>Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30329, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Maecker</LastName>
<ForeName>Holden Terry</ForeName>
<Initials>HT</Initials>
<Identifier Source="ORCID">0000-0003-0795-9946</Identifier>
<AffiliationInfo><Affiliation>Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Khatri</LastName>
<ForeName>Purvesh</ForeName>
<Initials>P</Initials>
<Identifier Source="ORCID">0000-0002-4143-4708</Identifier>
<AffiliationInfo><Affiliation>Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Center for Biomedical Informatics, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Rouphael</LastName>
<ForeName>Nadine</ForeName>
<Initials>N</Initials>
<AffiliationInfo><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>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Peiris</LastName>
<ForeName>Malik</ForeName>
<Initials>M</Initials>
<Identifier Source="ORCID">0000-0001-8217-5995</Identifier>
<AffiliationInfo><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>
<Author ValidYN="Y"><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>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><GrantID>U19 AI090023</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>U19 AI057266</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>U24 AI120134</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>P51 OD011132</GrantID>
<Acronym>OD</Acronym>
<Agency>NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>S10 OD026799</GrantID>
<Acronym>OD</Acronym>
<Agency>NIH HHS</Agency>
<Country>United States</Country>
</Grant>
</GrantList>
<PublicationTypeList><PublicationType UI="D003160">Comparative Study</PublicationType>
<PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2020</Year>
<Month>08</Month>
<Day>11</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>Science</MedlineTA>
<NlmUniqueID>0404511</NlmUniqueID>
<ISSNLinking>0036-8075</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D016207">Cytokines</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D004269">DNA, Bacterial</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D006684">HLA-DR Antigens</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D007136">Immunoglobulins</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D018836">Inflammation Mediators</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D007370">Interferon Type I</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D008070">Lipopolysaccharides</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber>
<NameOfSubstance UI="C546842">MTOR protein, human</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber>
<NameOfSubstance UI="D058570">TOR Serine-Threonine Kinases</NameOfSubstance>
</Chemical>
</ChemicalList>
<SupplMeshList><SupplMeshName Type="Disease" UI="C000657245">COVID-19</SupplMeshName>
<SupplMeshName Type="Organism" UI="C000656484">severe acute respiratory syndrome coronavirus 2</SupplMeshName>
</SupplMeshList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000073640" MajorTopicYN="N">Betacoronavirus</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018352" MajorTopicYN="N">Coronavirus Infections</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D016207" MajorTopicYN="N">Cytokines</DescriptorName>
<QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName>
</MeshHeading>
<MeshHeading><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>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005434" MajorTopicYN="N">Flow Cytometry</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006684" MajorTopicYN="N">HLA-DR Antigens</DescriptorName>
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