Compromised Humoral Functional Evolution Tracks with SARS-CoV-2 Mortality

Tomer Zohar; Carolin Loos; Stephanie Fischinger; Caroline Atyeo; Chuangqi Wang; Matthew D Slein; John Burke; Jingyou Yu; Jared Feldman; Blake Marie Hauser; Tim Caradonna; Aaron G Schmidt; Yongfei Cai; Hendrik Streeck; Edward T Ryan; Dan H Barouch; Richelle C Charles; Douglas A Lauffenburger; Galit Alter

doi:10.1016/j.cell.2020.10.052

Compromised Humoral Functional Evolution Tracks with SARS-CoV-2 Mortality

Cell. 2020 Dec 10;183(6):1508-1519.e12. doi: 10.1016/j.cell.2020.10.052. Epub 2020 Nov 3.

Authors

Tomer Zohar¹, Carolin Loos¹, Stephanie Fischinger², Caroline Atyeo³, Chuangqi Wang⁴, Matthew D Slein⁵, John Burke⁵, Jingyou Yu⁶, Jared Feldman⁵, Blake Marie Hauser⁵, Tim Caradonna⁵, Aaron G Schmidt⁵, Yongfei Cai⁷, Hendrik Streeck⁸, Edward T Ryan⁹, Dan H Barouch⁶, Richelle C Charles¹⁰, Douglas A Lauffenburger¹¹, Galit Alter¹²

Affiliations

¹ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
² Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; PhD Program in Immunology and Virology, University of Duisburg-Essen, Essen, Germany.
³ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; PhD Program in Virology, Division of Medical Sciences, Harvard University, Boston, MA, USA.
⁴ Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁵ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
⁶ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard, Medical School, Boston, MA 02215, USA.
⁷ Division of Molecular Medicine, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
⁸ Institute of Virology, University Hospital, University of Bonn and German Center for Infection Research (DZIF), Bonn-Cologne, Bonn, Germany.
⁹ Infectious Disease Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
¹⁰ Infectious Disease Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: rcharles@mgh.harvard.edu.
¹¹ Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: lauffen@mit.edu.
¹² Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA. Electronic address: galter@mgh.harvard.edu.

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.

Keywords: COVID-19; Fc receptors; SARS-CoV-2; antibodies; dynamics; innate immunity.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

COVID-19* / immunology
COVID-19* / mortality
Female
HL-60 Cells
Humans
Immunity, Humoral*
Immunoglobulin A / immunology*
Immunoglobulin M / immunology*
Male
Receptors, IgG / immunology*
SARS-CoV-2 / immunology*

Substances

Immunoglobulin A
Immunoglobulin M
Receptors, IgG

Abstract

Publication types

MeSH terms

Substances

Grants and funding