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SARS-CoV-2 Infection Severity Is Linked to Superior Humoral Immunity against the Spike.
Guthmiller, Jenna J; Stovicek, Olivia; Wang, Jiaolong; Changrob, Siriruk; Li, Lei; Halfmann, Peter; Zheng, Nai-Ying; Utset, Henry; Stamper, Christopher T; Dugan, Haley L; Miller, William D; Huang, Min; Dai, Ya-Nan; Nelson, Christopher A; Hall, Paige D; Jansen, Maud; Shanmugarajah, Kumaran; Donington, Jessica S; Krammer, Florian; Fremont, Daved H; Joachimiak, Andrzej; Kawaoka, Yoshihiro; Tesic, Vera; Madariaga, Maria Lucia; Wilson, Patrick C.
  • Guthmiller JJ; Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, Illinois, USA jguthmiller@uchicago.edu wilsonp@uchicago.edu.
  • Stovicek O; Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, Illinois, USA.
  • Wang J; Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, Illinois, USA.
  • Changrob S; Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, Illinois, USA.
  • Li L; Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, Illinois, USA.
  • Halfmann P; Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
  • Zheng NY; Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, Illinois, USA.
  • Utset H; Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, Illinois, USA.
  • Stamper CT; Committee on Immunology, University of Chicago, Chicago, Illinois, USA.
  • Dugan HL; Committee on Immunology, University of Chicago, Chicago, Illinois, USA.
  • Miller WD; Department of Medicine, Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, Illinois, USA.
  • Huang M; Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, Illinois, USA.
  • Dai YN; Department of Pathology and Immunology and Center for Structural Genomics of Infectious Diseases, Consortium for Advanced Science and Engineering, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Nelson CA; Department of Pathology and Immunology and Center for Structural Genomics of Infectious Diseases, Consortium for Advanced Science and Engineering, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Hall PD; Department of Pathology and Immunology and Center for Structural Genomics of Infectious Diseases, Consortium for Advanced Science and Engineering, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Jansen M; Department of Medicine, University of Chicago, Chicago, Illinois, USA.
  • Shanmugarajah K; Department of Surgery, University of Chicago, Chicago, Illinois, USA.
  • Donington JS; Department of Surgery, University of Chicago, Chicago, Illinois, USA.
  • Krammer F; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Fremont DH; Department of Pathology and Immunology and Center for Structural Genomics of Infectious Diseases, Consortium for Advanced Science and Engineering, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Joachimiak A; Center for Structural Genomics of Infectious Diseases, Consortium for Advanced Science and Engineering, University of Chicago, Chicago, Illinois, USA.
  • Kawaoka Y; Structural Biology Center, X-ray Science Division, Argonne National Laboratory, Argonne, Illinois, USA.
  • Tesic V; Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
  • Madariaga ML; Department of Pathology, University of Chicago, Chicago, Illinois, USA.
  • Wilson PC; Department of Surgery, University of Chicago, Chicago, Illinois, USA.
mBio ; 12(1)2021 01 19.
Article in English | MEDLINE | ID: covidwho-1038406
Preprint
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ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently causing a global pandemic. The antigen specificity of the antibody response mounted against this novel virus is not understood in detail. Here, we report that subjects with a more severe SARS-CoV-2 infection exhibit a larger antibody response against the spike and nucleocapsid protein and epitope spreading to subdominant viral antigens, such as open reading frame 8 and nonstructural proteins. Subjects with a greater antibody response mounted a larger memory B cell response against the spike, but not the nucleocapsid protein. Additionally, we revealed that antibodies against the spike are still capable of binding the D614G spike mutant and cross-react with the SARS-CoV-1 receptor binding domain. Together, this study reveals that subjects with a more severe SARS-CoV-2 infection exhibit a greater overall antibody response to the spike and nucleocapsid protein and a larger memory B cell response against the spike.IMPORTANCE With the ongoing pandemic, it is critical to understand how natural immunity against SARS-CoV-2 and COVID-19 develops. We have identified that subjects with more severe COVID-19 disease mount a more robust and neutralizing antibody response against SARS-CoV-2 spike protein. Subjects who mounted a larger response against the spike also mounted antibody responses against other viral antigens, including the nucleocapsid protein and ORF8. Additionally, this study reveals that subjects with more severe disease mount a larger memory B cell response against the spike. These data suggest that subjects with more severe COVID-19 disease are likely better protected from reinfection with SARS-CoV-2.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 Type of study: Prognostic study / Randomized controlled trials Limits: Adult / Female / Humans / Male / Middle aged Language: English Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 Type of study: Prognostic study / Randomized controlled trials Limits: Adult / Female / Humans / Male / Middle aged Language: English Year: 2021 Document Type: Article