Risk factors for SARS-CoV-2 seroprevalence following the first pandemic wave in UK healthcare workers in a large NHS Foundation Trust.

Hayley Colton,Benjamin B Lindsey,David Hodgson,Martin Bayley,Thushan I De Silva,David C James,Steven Wood,Joanne Mckenzie,Hailey Hornsby,Cameron James,Thomas C Darton,Sarah Birch,Louise Marsh,Domen Zafred,Jon R Sayers,Goura Kudesia,Adam J Kucharski ,Martin J.h Nicklin ,Kirsty L Bradley ,Gary W Dickson ,Sarah Rowland‐Jones ,Rebecca L Brown ,Paul Collini

doi:10.12688/wellcomeopenres.17143.1

Abstract

Background: We aimed to measure SARS-CoV-2 seroprevalence in a cohort of healthcare workers (HCWs) during the first UK wave of the COVID-19 pandemic, explore risk factors associated with infection, and investigate the impact of antibody titres on assay sensitivity. Methods: HCWs at Sheffield Teaching Hospitals NHS Foundation Trust were prospectively enrolled and sampled at two time points. SARS-CoV-2 antibodies were tested using an in-house assay for IgG and IgA reactivity against Spike and Nucleoprotein (sensitivity 99·47%, specificity 99·56%). Data were analysed using three statistical models: a seroprevalence model, an antibody kinetics model, and a heterogeneous sensitivity model. Results: As of 12th June 2020, 24·4% (n=311/1275) of HCWs were seropositive. Of these, 39·2% (n=122/311) were asymptomatic. The highest adjusted seroprevalence was measured in HCWs on the Acute Medical Unit (41·1%, 95% CrI 30·0-52·9) and in Physiotherapists and Occupational Therapists (39·2%, 95% CrI 24·4-56·5).Older age groups showed overall higher median antibody titres. Further modelling suggests that, for a serological assay with an overall sensitivity of 80%, antibody titres may be markedly affected by differences in age, with sensitivity estimates of 89% in those over 60 years but 61% in those ≤30 years. Conclusions: HCWs in acute medical units working closely with COVID-19 patients were at highest risk of infection, though whether these are infections acquired from patients or other staff is unknown. Current serological assays may underestimate seroprevalence in younger age groups if validated using sera from older and/or more symptomatic individuals.

Highlights

Healthcare workers (HCWs) are at increased risk of COVID-191,2
Given the IDSA guidance for ensuring a specificity of ≥99·5% in assays used for SARS-CoV-2 seroprevalence studies, specificity was enhanced by defining a SARS-CoV-2 seropositive sample as one where both spike and Nucleocapsid protein (NCP) were reactive[27]
Rapid waning of IgA responses following SARS-CoV-2 infection complicated defining positive and negative samples based on the convalescent sera we used for assay validation

Summary

Introduction

Healthcare workers (HCWs) are at increased risk of COVID-191,2. The true number of HCWs exposed to SARS-CoV-2 to-date is unknown, during the early stages of the pandemic. While antibody levels to some coronaviruses are higher in older individuals, it is unclear whether this results from a higher risk or exposure to the virus, greater antigenic load or boosting of antibodies from previous seasonal coronavirus infections[15,16,17,18,19] This may lead to age-specific differences in antibody assay sensitivity, which could be a significant confounder in population seroprevalence studies. We aimed to measure SARS-CoV-2 seroprevalence in a cohort of healthcare workers (HCWs) during the first UK wave of the COVID-19 pandemic, explore risk factors associated with infection, and investigate the impact of antibody titres on assay sensitivity. Current serological assays may underestimate seroprevalence in younger age groups if validated using sera from older and/or more symptomatic individuals

Objectives

Methods

Results

Conclusion