Risk assessment and antibody responses to SARS-CoV-2 in healthcare workers

Abstract

Background: Preventing infection in healthcare workers (HCWs) is crucial for protecting healthcare systems during the COVID-19 pandemic. Here, we investigated the seroepidemiology of SARS-CoV-2 in HCWs in Norway with low-transmission settings.

Methods: From March 2020, we recruited HCWs at four medical centres. We determined infection by SARS-CoV-2 RT-PCR and serological testing and evaluated the association between infection and exposure variables, comparing our findings with global data in a meta-analysis. Anti-spike IgG antibodies were measured after infection and/or vaccination in a longitudinal cohort until June 2021.

Results: We identified a prevalence of 10.5% (95% confidence interval, CI: 8.8-12.3) in 2020 and an incidence rate of 15.0 cases per 100 person-years (95% CI: 12.5-17.8) among 1,214 HCWs with 848 person-years of follow-up time. Following infection, HCWs (n = 63) mounted durable anti-spike IgG antibodies with a half-life of 4.3 months since their seropositivity. HCWs infected with SARS-CoV-2 in 2020 (n = 46) had higher anti-spike IgG titres than naive HCWs (n = 186) throughout the 5 months after vaccination with BNT162b2 and/or ChAdOx1-S COVID-19 vaccines in 2021. In a meta-analysis including 20 studies, the odds ratio (OR) for SARS-CoV-2 seropositivity was significantly higher with household contact (OR 12.6; 95% CI: 4.5-35.1) and occupational exposure (OR 2.2; 95% CI: 1.4-3.2).

Conclusion: We found high and modest risks of SARS-CoV-2 infection with household and occupational exposure, respectively, in HCWs, suggesting the need to strengthen infection prevention strategies within households and medical centres. Infection generated long-lasting antibodies in most HCWs; therefore, we support delaying COVID-19 vaccination in primed HCWs, prioritising the non-infected high-risk HCWs amid vaccine shortage.

Keywords: COVID-19; SARS-CoV-2; antibodies; healthcare workers; household; occupational; spike protein.

Figure 1

Flow diagram and study procedures. (A) Flowchart of study design and healthcare workers (HCWs) selection. HCWs were recruited from the centralised testing centre (Bergen Municipality Emergency covering 284,000 people), Haukeland University Hospital (a university teaching facility and local hospital for ~500,000 people), Haraldsplass Deaconess Hospital (a local teaching hospital providing acute medical care for 145,000 people), and Stavanger University Hospital (teaching hospital providing medical care for 230,000 people). HCWs were recruited from 6 March 2020 before the first hospitalisations on 9th March and the first death on 23rd March and continued up until December 2020, spanning three SARS-CoV-2 periods: March–May 2020 (n = 1,159; 95.5%), June–September 2020 (n = 583; 48.1%), October–December 2020 (n = 630; 51.9%). HCWs with confirmed SARS-CoV-2 infection in 2020 and vaccinated HCWs were invited for follow-up until June 2021. All HCWs included in the immunological analyses provided baseline and follow-up case report forms and serum samples. We performed a two-step orthogonal ELISA testing algorithm. All samples were tested for SARS-CoV-2 receptor-binding domain (RBD)-specific antibodies. Eligible samples were further tested by SARS-CoV-2 anti-spike IgG ELISA for confirmation. *Eight HCWs (or sera samples) from the infected subgroup were also present in the vaccination subgroup; **46 HCWs (or sera samples) from the infected subgroup were also present in the vaccination subgroup. (B) Community spread of SARS-CoV-2 virus in Western Norway over time. Daily SARS-CoV-2 positive cases (bars) from the Norwegian Surveillance System for Communicable Diseases (MSIS). The pink line is the cumulative number of deaths. During the study period, anyone who tested positive with a rapid antigen test which was available from December 2020 was encouraged to take a confirmatory RT-PCR test. Results from self-tests were not registered in MSIS. Data on reported cases were therefore not directly comparable over time. Data source (29).

Figure 2

SARS-CoV-2 spike-specific IgG antibodies in healthcare workers, HCWs. Each circle/symbol represents one individual HCW. IgG, immunoglobulin G; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. (A, B) Spike-specific IgG endpoint titre transformed on a log₁₀-based scale (y-axis) and month-year format (x-axis), n = 122. A vertical line divides the time prior to vaccines were available and when vaccination was recommended. The horizontal dash line shows the cut-off of the spike IgG ELISA. (B) RT-PCR results are color coded with dark green for negative and firebrick red color for positive test results. (C) The data were collected in 2020 (prior to COVID-19 vaccination), and samples were repeated over time (n = 63). The mixed-effects model with exponential decay was used to analyse antibody waning. The model included population-level fixed effects and individual random effects and fit using the lmer function (lme4 package) in R version 4.2.2. Antibodies were naturally log transformed. The trend line, back-transformed estimated mean (red), is smoothed across the 95% confidence interval values (gray shade). (D) Spike-specific IgG endpoint titre transformed (y-axis) with samples repeated over time and days since the first dose of the COVID-19 vaccine (x-axis). The mixed-effects models were performed with population-level fixed effects and individual random effects and fit using the lmer function (lme4 package) in R version 4.2.2. The trend line, back-transformed estimated mean, is smoothed across the 95% confidence interval values.

Figure 3

Forest plot to evaluate whether SARS-CoV-2 spike-specific IgG seropositivity rates differed with occupational exposure and household exposure among healthcare workers. Data are compiled from a meta-analysis of literature (Supplementary Figure 1) and include our data presented as odds ratios and 95% confidence interval, CI. Subgroups: occupational (–, , , –43) exposure to SARS-CoV-2 cases, no PPE use at work (, , , , –45), and household (–7, 39, 42) exposure to SARS-CoV-2 cases. Meta-analysis of effect estimates was performed using the metabin function (meta package) (46) in R version 4.2.2.

Figure 4

Summary of key findings. Created with BioRender.com (2023).