T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses

Nat Commun. 2021 Apr 6;12(1):2055. doi: 10.1038/s41467-021-21856-3.

Abstract

Identification of protective T cell responses against SARS-CoV-2 requires distinguishing people infected with SARS-CoV-2 from those with cross-reactive immunity to other coronaviruses. Here we show a range of T cell assays that differentially capture immune function to characterise SARS-CoV-2 responses. Strong ex vivo ELISpot and proliferation responses to multiple antigens (including M, NP and ORF3) are found in 168 PCR-confirmed SARS-CoV-2 infected volunteers, but are rare in 119 uninfected volunteers. Highly exposed seronegative healthcare workers with recent COVID-19-compatible illness show T cell response patterns characteristic of infection. By contrast, >90% of convalescent or unexposed people show proliferation and cellular lactate responses to spike subunits S1/S2, indicating pre-existing cross-reactive T cell populations. The detection of T cell responses to SARS-CoV-2 is therefore critically dependent on assay and antigen selection. Memory responses to specific non-spike proteins provide a method to distinguish recent infection from pre-existing immunity in exposed populations.

Publication types

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

MeSH terms

  • Antiviral Agents / pharmacology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • COVID-19 / epidemiology
  • COVID-19 / immunology*
  • COVID-19 / virology*
  • Cell Proliferation
  • Cross Reactions / immunology*
  • Cytokines / metabolism
  • HEK293 Cells
  • Health Personnel
  • Humans
  • Immunoassay / methods*
  • Immunoglobulin G / immunology
  • Immunologic Memory
  • Interferon-gamma / metabolism
  • Pandemics
  • Peptides / metabolism
  • SARS-CoV-2 / drug effects
  • SARS-CoV-2 / physiology*
  • T-Lymphocytes / immunology*

Substances

  • Antiviral Agents
  • Cytokines
  • Immunoglobulin G
  • Peptides
  • Interferon-gamma