Investigating incidence of and factors associated with SARS-CoV-2 infection over a nine-month period in a highly-vaccinated healthcare worker cohort

Background: Healthcare workers (HCWs) are at increased risk of SARS-CoV-2 infection. This risk persists despite the implementation of mitigating factors, including vaccination. The ongoing impact of incident SARS-CoV-2 infection and symptomatic COVID-19 disease in vaccinated HCWs is poorly understood. Aim: We aimed to describe the epidemiology of incident SARS-CoV-2 infections, as well as investigating the serological, clinical and demographic factors associated with developing infection. Design: This was a multi-centre prospective longitudinal study followed a HCW cohort over a nine-month period. Methods: Spike and nucleocapsid SARS-CoV-2 antibodies were measured at enrolment. Vaccination status, demographics and medical history were collated. Incident infection over the study period was recorded. Multivariable regression models investigated factors associated with nucleocapsid antibody status, incident infection and symptomatic infection. Results: About 1260 participants took part, of whom n ¼ 1006 were anti-nucleocapsid antibody positive. Negative anti-nucleocapsid antibody was associated with older age and having a known SARS-CoV-2 acquisition risk. There were n ¼ 274 (22%) incident infections, with n ¼ 225 (87%) diagnosed using antigen tests. Incident infections were associated with lower anti-nucleocapsid titres, increased time since previous SARS-CoV-2 infection, and having a known acquisition risk, but were not associated with vaccination status. Conclusions: This study demonstrates a high rate of incident SARS-CoV-2 infection amongst HCWs, despite broad vaccine coverage. There is a shift in diagnostics, from PCR to antigen testing. We identify at-risk groups for incident infection, and these should continue be targeted as part of risk reduction campaigns. Vaccination status and prior infection status alone are not surrogates for protection.