Discrete SARS-CoV-2 antibody titers track with functional humoral stability

Nat Commun. 2021 Feb 15;12(1):1018. doi: 10.1038/s41467-021-21336-8.


Antibodies serve as biomarkers of infection, but if sustained can confer long-term immunity. Yet, for most clinically approved vaccines, binding antibody titers only serve as a surrogate of protection. Instead, the ability of vaccine induced antibodies to neutralize or mediate Fc-effector functions is mechanistically linked to protection. While evidence has begun to point to persisting antibody responses among SARS-CoV-2 infected individuals, cases of re-infection have begun to emerge, calling the protective nature of humoral immunity against this highly infectious pathogen into question. Using a community-based surveillance study, we aimed to define the relationship between titers and functional antibody activity to SARS-CoV-2 over time. Here we report significant heterogeneity, but limited decay, across antibody titers amongst 120 identified seroconverters, most of whom had asymptomatic infection. Notably, neutralization, Fc-function, and SARS-CoV-2 specific T cell responses were only observed in subjects that elicited RBD-specific antibody titers above a threshold. The findings point to a switch-like relationship between observed antibody titer and function, where a distinct threshold of activity-defined by the level of antibodies-is required to elicit vigorous humoral and cellular response. This response activity level may be essential for durable protection, potentially explaining why re-infections occur with SARS-CoV-2 and other common coronaviruses.

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.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology*
  • COVID-19 / blood
  • COVID-19 / immunology*
  • Female
  • Humans
  • Immunity, Humoral / immunology
  • Immunoglobulin G / immunology
  • Male
  • Middle Aged
  • SARS-CoV-2 / immunology*
  • Spike Glycoprotein, Coronavirus / immunology
  • T-Lymphocytes / immunology
  • Viral Vaccines / immunology
  • Young Adult


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Immunoglobulin G
  • Spike Glycoprotein, Coronavirus
  • Viral Vaccines
  • spike protein, SARS-CoV-2