Prospective observational study and serosurvey of SARS-CoV-2 infection in asymptomatic healthcare workers at a Canadian tertiary care center

Abstract

Health care workers (HCWs) are at higher risk for SARS-CoV-2 infection and may play a role in transmitting the infection to vulnerable patients and members of the community. This is particularly worrisome in the context of asymptomatic infection. We performed a cross-sectional study looking at asymptomatic SARS-CoV-2 infection in HCWs. We screened asymptomatic HCWs for SARS-CoV-2 via PCR. Complementary viral genome sequencing was performed on positive swab specimens. A seroprevalence analysis was also performed using multiple assays. Asymptomatic health care worker cohorts had a combined swab positivity rate of 29/5776 (0.50%, 95%CI 0.32-0.75) relative to a comparative cohort of symptomatic HCWs, where 54/1597 (3.4%) tested positive for SARS-CoV-2 (ratio of symptomatic to asymptomatic 6.8:1). SARS-CoV-2 seroprevalence among 996 asymptomatic HCWs with no prior known exposure to SARS-CoV-2 was 1.4-3.4%, depending on assay. A novel in-house Coronavirus protein microarray showed differing SARS-CoV-2 protein reactivities and helped define likely true positives vs. suspected false positives. Our study demonstrates the utility of routine screening of asymptomatic HCWs, which may help to identify a significant proportion of infections.

Fig 1. Study flow and outcomes.

Abbreviations: HCW—healthcare workers, NP—nucleoprotein, S—spike.

Fig 2. Heatmap and graph of SARS-CoV-2 reactivity in study samples on antigen microarrays.

A) Heatmap of eight SARS-CoV-2 IgG reactivities in individual anti-NP CMIA+ and anti-S ELISA+ samples. These antigen reactivities represent the eight highest ranked IgG reactivities that are upregulated in COVID+ samples (with mean MFI-B > 1000) as determined by significance analysis of microarrays. Anti-NP and anti-spike reactivity in individual samples on the arrays is indicated above the sample numbers. Positivity on the arrays was determined as described below. The mean reactivity of pre-COVID and COVID+ samples is shown as a comparison. The sample numbers in red indicate dual positive (anti-NP CMIA+ and anti-S ELISA+) samples. Yellow indicates high reactivity, whereas blue indicates low reactivity on the heatmap. B) Graphs of individual antigen IgG reactivity (MFI-B) in pre-COVID, COVID+, anti-NP CMIA+ and anti-S ELISA+ groups. Graphs show mean ± SD for samples in each of the groups. Samples in the anti-NP CMIA+ and anti-S ELISA+ groups were considered positive if the MFI-B was higher than the mean + 3 SD of the pre-COVID samples (dotted line). Abbreviations: MFI-B—median fluorescent intensity minus background; NP—nucleocapsid protein; S—spike; SD—standard deviation.