COVID-19 in Irish Hospital Healthcare Workers; SARS-CoV-2 antibody prevalence, epidemiology of infection and antibody response to vaccination

Abstract

Background Hospital healthcare workers (HCW) are at increased risk of contracting COVID-19 infection. We aimed to determine the seroprevalence of SARS-CoV-2 antibodies in HCW in Ireland in two locations with diverging community and HCW incidence at two points in time during the COVID-19 pandemic, and to determine HCW risk factors for seropositivity. We also aimed to compare commercially available assays for the detection of SARS-CoV-2 antibodies, and to measure serological response to COVID-19 vaccination. Two tertiary referral hospitals in Irish cities with diverging community incidence and seroprevalence were identified; COVID-19 had been diagnosed in 10.2% of staff of St. James?s Hospital, Dublin (SJH) and 1.8% of staff of University Hospital Galway (UHG) respectively by the time of the first study (October 2020 ? PRECISE 1). PRECISE 1 took place prior to the roll-out of COVID-19 vaccination. The second study (PRECISE 2) took place in April 2021, four months after the start of vaccination at both sites. Methods Two cross-sectional studies were performed in October 2020 and April 2021 respectively. All staff of both hospitals (N=9038) were invited to participate in an online questionnaire and blood sampling for SARS-CoV-2 antibody testing in October 2020 and April 2021. In October 2020, all samples were tested on two serological assays (Abbott Architect IgG assay and Roche Elecsys panantibody assay, both detected antibodies to the anti-nucleocapsid (anti-N) protein) and a subset of samples were also tested on the Wantai ELISA total antibody assay, targeting antibodies to the anti-spike (anti-S) protein. In April 2021, all samples were tested via the Roche Elecsys assay for both anti-N and anti-S antibodies. Frequencies and percentages for positive SARS-CoV-2 antibody were calculated and adjusted relative risks (aRR) for participant characteristics were calculated using multivariable regression analysis. The performance of each assay was compared. Results In October 2020 5,788 HCW participated (64% response rate). Seroprevalence of antibodies to SARS-CoV-2 was 15% and 4.1% in SJH and UHG, respectively. Thirty-nine percent of infections were previously undiagnosed. On multivariable analysis, the adjusted relative risk (aRR) for seropositivity was higher for healthcare assistants (aRR: 2.0, 95%CI:1.4?3.0), nurses (aRR: 1.6, 95%CI: 1.1?2.2), daily exposure to patients with COVID-19 (aRR: 1.6, 95%CI: 1.2-2.1), age 18-29 years (aRR: 1.4, 95%CI: 1.1-1.9), living with other HCW (aRR: 1.3, 95%CI: 1.1?1.5), Asian background (aRR: 1.3, 95%CI: 1.0-1.6), and male sex (aRR: 1.2, 95%CI 1.0-1.4). In HCW with prior PCR-confirmed COVID-19 infection (N=367), the Roche assay detected 95% of these infections, and had sustained positivity up to 33 weeks after infection. Only 41% of these participants tested positive on the Abbott assay. The decline in Abbott positivity starting at week 21/day 150 after confirmed infection. In April 2021 5085 HCW participated (56% response rate). Seroprevalence of antibodies to SARS-CoV-2 indicative of past infection rose to 21% and 13% in SJH and UHG respectively. Twenty-six percent of infections had been previously undiagnosed (decreased from 39% in October 2020). Risk of seropositivity was higher for the following characteristics: working in SJH (aRR 1.5, 95% CI 1.3-1.8, p<.001), being a healthcare assistant (aRR 1.8, 95% CI 1.3-2.3, p<.001), being of African or other black background (aRR 1.7, 95% CI 1.3-2.2, p<.001), lower level of education (aRR 1.4 for secondary level education, 95% CI 1.1-1.8, p=0.002), being a nurse (aRR 1.4, 95% CI 1.0-1.8, p=0.022), daily contact with COVID-19 patients (aRR 1.4, 95% CI 1.1-1.7, p=0.002), daily contact with patients without suspected or confirmed COVID-19 (aRR 1.3, 95% CI 1.1-1.5, p=0.013), being 18-29 years of age (aRR 1.3, 95% CI 1.1-1.6, p=0.002), being male (aRR 1.2, 95% CI 1.0-1.4, p=0.016), and living with other HCW (aRR 1.2, 95% CI 1.0-1.4, p=0.007). One hundred percent of fully vaccinated participants had detectable anti-spike antibodies in response to vaccination. Twenty-three of these had had breakthrough COVID-19 infection, representing 0.6% of all fully vaccinated participants. Conclusion The HCW seroprevalence was six times higher than community seroprevalence following the first wave of the pandemic in Ireland and rose further with subsequent waves. Risk was higher in the hospital situated in a higher density area with higher community incidence during the three waves of the pandemic that occurred during this research. Risk was higher for those with close patient contact. The proportion of undiagnosed infections decreased from October 2020 to April 2021 but remained high; this calls for ongoing robust infection control guidance and easy access to testing for HCW. Screening of asymptomatic HCW can help to decrease transmission, inform vaccine efficacy surveillance, and enhance infection prevention and control (IPC) measures, however the role of such screening remains to be clearly defined. The Roche assay performed better than the Abbott assay at detecting past infection and is more appropriate for future population-based studies looking at seroprevalence post natural infection. With emerging evidence of reduction in transmission from vaccinated individuals, the authors strongly endorse rapid vaccination of all HCW. The production of antibodies post-vaccination in all participants fully vaccinated is extremely reassuring; further studies are needed to correlate this serological response with functional immunity. The proportion of breakthrough infections in fully vaccinated participants was in keeping with the published literature; formal vaccine efficiency studies are needed to further characterise breakthrough infections and estimate protection from infection, particularly with the ongoing emergence of variants of concern. The results of this research and the lessons learned from planning and executing the research can inform future pandemic planning as it pertains to hospital practices and risk factors for infection in HCW. This research platform has evolved with the evolution of the pandemic, with further sub-studies providing ongoing contribution to advancing our understanding of the changing epidemiology of COVID-19, and of infection and re-infection as relates to vaccination and serological status among the HCW cohort.