Mass-standardised antibody concentration and affinity immunity endotypes to the spike protein of SARS-CoV-2 variants in a high-exposure cohort

Introduction School staff members are uniquely exposed to asymptomatic infections in children when in enclosed, poorly ventilated environments. Prevalence of SARS-CoV-2 amongst school children in the Omicron wave was high, leading to a constant, high exposure of teachers to the virus. Methods A cohort of staff members (n = 28) was recruited from a UK primary school setting. The prevalent variants in the preceding six months were Omicron BA.1, BA.4/5 and BA.2: 61% of the cohort reported a lateral-flow-confirmed positive test for SARS-CoV-2 infection in late 2021 or 2022. A mass-standardised quantitative antibody spectrum was measured for both antibody concentration and a new measure of antibody quality; the proportion of antibodies still bound to the epitope at pH 3.2 compared with pH 7.4. The antibody spectrum was measured for IgG to the spike protein for variants Wuhan, Alpha, Beta, Gamma, Delta and Omicron BA.1, BA.2.75, BA.2.12.1, BA.4 and BA.5. Results The new antibody quality measure shows a median of 39% with (IQR 24% - 52%). The cohort showed a Universal positive immunity endotype, U(+), with antibodies binding to the spike protein across the variant spectrum having an incidence of 78% (95% CI 60% - 88%) with good antibody concentrations to all ten variants; the U(+) incidence drops to 39% (95% CI 22% - 59%) when the affinity spectrum is measured. Discussion The teachers' cohort shows a significant antibody maturation towards the variants prevalent wave variants with good quality antibodies to Wuhan, Delta and the Omicron variants but not the bet and gamma variants. Teachers and, consequently, parents are a critical perimeter of the pandemic and a high priority for vaccination along with healthcare workers.