Kinetics of the Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Response and Serological Estimation of Time Since Infection

J Infect Dis. 2021 Nov 16;224(9):1489-1499. doi: 10.1093/infdis/jiab375.

Abstract

Background: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a complex antibody response that varies by orders of magnitude between individuals and over time.

Methods: We developed a multiplex serological test for measuring antibodies to 5 SARS-CoV-2 antigens and the spike proteins of seasonal coronaviruses. We measured antibody responses in cohorts of hospitalized patients and healthcare workers followed for up to 11 months after symptoms. A mathematical model of antibody kinetics was used to quantify the duration of antibody responses. Antibody response data were used to train algorithms for estimating time since infection.

Results: One year after symptoms, we estimate that 36% (95% range, 11%-94%) of anti-Spike immunoglobulin G (IgG) remains, 31% (95% range, 9%-89%) anti-RBD IgG remains, and 7% (1%-31%) of anti-nucleocapsid IgG remains. The multiplex assay classified previous infections into time intervals of 0-3 months, 3-6 months, and 6-12 months. This method was validated using data from a seroprevalence survey in France, demonstrating that historical SARS-CoV-2 transmission can be reconstructed using samples from a single survey.

Conclusions: In addition to diagnosing previous SARS-CoV-2 infection, multiplex serological assays can estimate the time since infection, which can be used to reconstruct past epidemics.

Keywords: SARS-SoV-2; antibody kinetics; seroprevalence; surveillance; time since infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Viral / blood*
  • Antibody Formation
  • Antibody Specificity
  • COVID-19 / blood*
  • COVID-19 / epidemiology
  • COVID-19 / immunology*
  • Female
  • France / epidemiology
  • Humans
  • Immunoglobulin G / blood
  • Kinetics
  • Male
  • Middle Aged
  • SARS-CoV-2 / immunology
  • Sensitivity and Specificity
  • Seroepidemiologic Studies
  • Serologic Tests / methods*
  • Young Adult

Substances

  • Antibodies, Viral
  • Immunoglobulin G