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Compromised Humoral Functional Evolution Tracks with SARS-CoV-2 Mortality.
Zohar, Tomer; Loos, Carolin; Fischinger, Stephanie; Atyeo, Caroline; Wang, Chuangqi; Slein, Matthew D; Burke, John; Yu, Jingyou; Feldman, Jared; Hauser, Blake Marie; Caradonna, Tim; Schmidt, Aaron G; Cai, Yongfei; Streeck, Hendrik; Ryan, Edward T; Barouch, Dan H; Charles, Richelle C; Lauffenburger, Douglas A; Alter, Galit.
  • Zohar T; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Loos C; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Fischinger S; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; PhD Program in Immunology and Virology, University of Duisburg-Essen, Essen, Germany.
  • Atyeo C; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; PhD Program in Virology, Division of Medical Sciences, Harvard University, Boston, MA, USA.
  • Wang C; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Slein MD; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Burke J; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Yu J; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard, Medical School, Boston, MA 02215, USA.
  • Feldman J; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Hauser BM; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Caradonna T; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Schmidt AG; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Cai Y; Division of Molecular Medicine, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
  • Streeck H; Institute of Virology, University Hospital, University of Bonn and German Center for Infection Research (DZIF), Bonn-Cologne, Bonn, Germany.
  • Ryan ET; Infectious Disease Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Barouch DH; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard, Medical School, Boston, MA 02215, USA.
  • Charles RC; Infectious Disease Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: rcharles@mgh.harvard.edu.
  • Lauffenburger DA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: lauffen@mit.edu.
  • Alter G; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA. Electronic address: galter@mgh.harvard.edu.
Cell ; 183(6): 1508-1519.e12, 2020 12 10.
Article in English | MEDLINE | ID: covidwho-898562
ABSTRACT
The urgent need for an effective SARS-CoV-2 vaccine has forced development to progress in the absence of well-defined correlates of immunity. While neutralization has been linked to protection against other pathogens, whether neutralization alone will be sufficient to drive protection against SARS-CoV-2 in the broader population remains unclear. Therefore, to fully define protective humoral immunity, we dissected the early evolution of the humoral response in 193 hospitalized individuals ranging from moderate to severe. Although robust IgM and IgA responses evolved in both survivors and non-survivors with severe disease, non-survivors showed attenuated IgG responses, accompanied by compromised Fcɣ receptor binding and Fc effector activity, pointing to deficient humoral development rather than disease-enhancing humoral immunity. In contrast, individuals with moderate disease exhibited delayed responses that ultimately matured. These data highlight distinct humoral trajectories associated with resolution of SARS-CoV-2 infection and the need for early functional humoral immunity.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Immunoglobulin A / Immunoglobulin M / Receptors, IgG / Immunity, Humoral / SARS-CoV-2 / COVID-19 Type of study: Prognostic study Topics: Vaccines Limits: Female / Humans / Male Language: English Journal: Cell Year: 2020 Document Type: Article Affiliation country: J.cell.2020.10.052

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Immunoglobulin A / Immunoglobulin M / Receptors, IgG / Immunity, Humoral / SARS-CoV-2 / COVID-19 Type of study: Prognostic study Topics: Vaccines Limits: Female / Humans / Male Language: English Journal: Cell Year: 2020 Document Type: Article Affiliation country: J.cell.2020.10.052