Kinetics and correlates of the neutralizing antibody response to SARS-CoV-2 infection in humans

Kanika Vanshylla; Veronica Di Cristanziano; Franziska Kleipass; Felix Dewald; Philipp Schommers; Lutz Gieselmann; Henning Gruell; Maike Schlotz; Meryem S Ercanoglu; Ricarda Stumpf; Petra Mayer; Matthias Zehner; Eva Heger; Wibke Johannis; Carola Horn; Isabelle Suárez; Norma Jung; Susanne Salomon; Kirsten Alexandra Eberhardt; Birgit Gathof; Gerd Fätkenheuer; Nico Pfeifer; Ralf Eggeling; Max Augustin; Clara Lehmann; Florian Klein

doi:10.1016/j.chom.2021.04.015

Kinetics and correlates of the neutralizing antibody response to SARS-CoV-2 infection in humans

Cell Host Microbe. 2021 Jun 9;29(6):917-929.e4. doi: 10.1016/j.chom.2021.04.015. Epub 2021 May 3.

Authors

Kanika Vanshylla¹, Veronica Di Cristanziano², Franziska Kleipass¹, Felix Dewald², Philipp Schommers³, Lutz Gieselmann², Henning Gruell², Maike Schlotz¹, Meryem S Ercanoglu¹, Ricarda Stumpf¹, Petra Mayer¹, Matthias Zehner¹, Eva Heger¹, Wibke Johannis⁴, Carola Horn⁵, Isabelle Suárez⁶, Norma Jung⁵, Susanne Salomon¹, Kirsten Alexandra Eberhardt⁷, Birgit Gathof⁸, Gerd Fätkenheuer⁶, Nico Pfeifer⁹, Ralf Eggeling¹⁰, Max Augustin⁵, Clara Lehmann¹¹, Florian Klein¹²

Affiliations

¹ Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
² Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany; German Center for Infection Research, Partner Site Bonn-Cologne, 50931 Cologne, Germany.
³ Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany; German Center for Infection Research, Partner Site Bonn-Cologne, 50931 Cologne, Germany; Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany.
⁴ Institute for Clinical Chemistry, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany.
⁵ Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany.
⁶ German Center for Infection Research, Partner Site Bonn-Cologne, 50931 Cologne, Germany; Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany.
⁷ Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine and Department of Medicine, University Medical Center Hamburg-Eppendorf, 20359 Hamburg, Germany; Institute for Transfusion Medicine, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
⁸ Institute of Transfusion Medicine, Faculty of Medicine and University Hospital Cologne, 50937 Cologne, Germany.
⁹ Methods in Medical Informatics, Department of Computer Science, University of Tübingen, 72076 Tübingen, Germany; Faculty of Medicine, University of Tübingen, 72076 Tübingen, Germany; German Center for Infection Research, Partner Site Tübingen, 72076 Tübingen, Germany.
¹⁰ Methods in Medical Informatics, Department of Computer Science, University of Tübingen, 72076 Tübingen, Germany.
¹¹ German Center for Infection Research, Partner Site Bonn-Cologne, 50931 Cologne, Germany; Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany.
¹² Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany; German Center for Infection Research, Partner Site Bonn-Cologne, 50931 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany. Electronic address: florian.klein@uk-koeln.de.

Abstract

Understanding antibody-based SARS-CoV-2 immunity is critical for overcoming the COVID-19 pandemic and informing vaccination strategies. We evaluated SARS-CoV-2 antibody dynamics over 10 months in 963 individuals who predominantly experienced mild COVID-19. Investigating 2,146 samples, we initially detected SARS-CoV-2 antibodies in 94.4% of individuals, with 82% and 79% exhibiting serum and IgG neutralization, respectively. Approximately 3% of individuals demonstrated exceptional SARS-CoV-2 neutralization, with these "elite neutralizers" also possessing SARS-CoV-1 cross-neutralizing IgG. Multivariate statistical modeling revealed age, symptomatic infection, disease severity, and gender as key factors predicting SARS-CoV-2-neutralizing activity. A loss of reactivity to the virus spike protein was observed in 13% of individuals 10 months after infection. Neutralizing activity had half-lives of 14.7 weeks in serum versus 31.4 weeks in purified IgG, indicating a rather long-term IgG antibody response. Our results demonstrate a broad spectrum in the initial SARS-CoV-2-neutralizing antibody response, with sustained antibodies in most individuals for 10 months after mild COVID-19.

Keywords: COVID-19; IgG; SARS-CoV-2 infection; antibody kinetics; antibody response; correlates of neutralization; longitudinal cohort; neutralizing antibodies; serum.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Antibodies, Neutralizing / immunology*
Antibodies, Viral / immunology*
COVID-19 / immunology*
Cohort Studies
Female
Humans
Immunoglobulin G / immunology
Male
Middle Aged
SARS-CoV-2
Time Factors
Young Adult

Substances

Antibodies, Neutralizing
Antibodies, Viral
Immunoglobulin G