Immune response in vaccinated healthcare workers with frequent COVID-19 infections is characterised by blunted IFNγ and IL-2 responses to SARS-CoV-2 variants

Clin Immunol. 2024 Nov:268:110371. doi: 10.1016/j.clim.2024.110371. Epub 2024 Sep 27.

Abstract

Healthcare workers (HCWs) are at increased risk of SARS-CoV-2 infection. Despite widespread vaccination, some HCWs develop frequent symptomatic infection. We hypothesised that HCWs with frequent symptomatic COVID-19 have impaired T and B cell mediated immunity to SARS-CoV-2. Vaccinated HCWs with no prior COVID infection (n = 9), asymptomatic recent infection (n = 10), and frequent recent infection (n = 15) were recruited from a longitudinal HCW cohort study. Whole blood stimulation with SARS-CoV-2 variants (Wuhan, B.1.617, BA.2, BA.2.75, BA.4/5, XBB.1.5, BQ.1.1) was performed, with IFNγ and IL-2 responses, total IgG produced, and anti-Spike antibody neutralising capacity measured. Frequent infections had similar IFNγ and IL-2 responses to the never infected group, with significantly higher responses in the asymptomatic group. The frequent cohort had higher IgG responses to Delta and BA.4/5 and higher neutralising capacity against Omicron variants. An immune signature of blunted IL-2 and IFNγ in frequent infections may identify HCWs at increased risk of further infection.

Keywords: COVID-19; Healthcare workers; IFNγ; Immunity; Interleukin-2.

MeSH terms

  • Adult
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral* / blood
  • Antibodies, Viral* / immunology
  • COVID-19 Vaccines / immunology
  • COVID-19* / immunology
  • Cohort Studies
  • Female
  • Health Personnel*
  • Humans
  • Immunoglobulin G* / blood
  • Immunoglobulin G* / immunology
  • Interferon-gamma* / immunology
  • Interleukin-2* / immunology
  • Longitudinal Studies
  • Male
  • Middle Aged
  • SARS-CoV-2* / immunology
  • Spike Glycoprotein, Coronavirus / immunology
  • Vaccination

Substances

  • Interleukin-2
  • Interferon-gamma
  • Antibodies, Viral
  • Immunoglobulin G
  • COVID-19 Vaccines
  • Antibodies, Neutralizing
  • Spike Glycoprotein, Coronavirus

Supplementary concepts

  • SARS-CoV-2 variants