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

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.