Protection of vaccine boosters and prior infection against mild/asymptomatic and moderate COVID-19 infection in the UK SIREN healthcare worker cohort: October 2023 to March 2024

Abstract

Objective To estimate the protection of COVID-19 vaccine boosters against mild/asymptomatic and moderate SARS-CoV-2 infection over a 6-month period of XBB.1.5 and JN.1 variant circulation. Design Multi-state model applied to cohort study, adjusted for vaccination, prior infection, and demographic covariates. Setting National Health Services (NHS) hospitals in the UK. Participants Healthcare worker cohort including 2,867 eligible people with >6 months since a previous booster who tested fortnightly for SARS-CoV-2 between October 2023 and March 2024 and completed symptoms questionnaires. Main outcome measures Vaccine effectiveness (VE) of vaccine boosters received in October 2023 (baseline: booster >6 months prior), and durability of protection from a recent (past 6 months) previous infection (baseline: last infection >2 years prior) against mild/asymptomatic and moderate SARS-CoV-2 infection. Mild symptoms included acute respiratory symptoms for <5 days, moderate symptoms included influenza-like illness, acute respiratory symptoms for 5+ days, or sick-leave. VE and acquired protection were estimated from the multi-state model as: 1 - adjusted hazard ratio. Interventions Receipt of a COVID-19 bivalent original/BA.4-5 or monovalent XBB.1.5 booster during October 2023. Results Half of eligible participants (1,422) received a booster during October 2023 (280 bivalent, 1,142 monovalent) and 536 (19%) had at least one PCR-confirmed infection over the study period. For the monovalent booster, VE against infection was 44.2% (95% confidence interval 21.7 to 60.3%) at 0-2 months, and 24.1% (-0.7 to 42.9%) at 2-4 months post-vaccination, with no evidence of protection by 4-6 months. For the bivalent booster, VE against infection was 15.1% (-55.4 to 53.6%) at 0-2 months and 4.2% (-46.4 to 37.3%) at 2-4 months. VE (monovalent or bivalent) against moderate infection was 39.7% (19.9 to 54.6%), and against mild/asymptomatic infection was 14.0% (-12.1 to 34.0%). Controlling for vaccination, compared to those with an infection >2 years prior, infection within the past 6 months was associated with 58.6% (30.3 to 75.4%) increased protection against moderate infection, and 38.5% (5.8 to 59.8%) increased protection against mild/asymptomatic infection. Conclusions Monovalent XBB.1.5 boosters provided short-term protection against SARS-CoV-2 infection, particularly against moderate symptoms. Vaccine formulations which target the circulating variant may be suitable for inclusion in seasonal vaccination campaigns among healthcare workers.