SARS-CoV-2 epidemiology, antibody dynamics, and neutralisation capacity in Irish healthcare workers in the era of booster COVID-19 vaccinations

Abstract

BackgroundThe PRECISE Study, a multi-phase cross-sectional seroprevalence study of anti-SARS-CoV-2 antibodies in Irish healthcare workers (HCW) investigated: (1) risk factors for SARS-CoV-2 seropositivity, (2) the durability of antibody responses in a highly vaccinated HCW cohort, and (3) the neutralisation capacity of detected antibodies, prior to booster COVID-19 vaccination.Materials and methodsSerology samples were collected across two hospital sites in November 2021 and analysed using the Roche Elecsys Anti-SARS-CoV-2/Elecsys-S Anti-SARS-CoV-2 assays to detect anti-nucleocapsid (N) and anti-spike (S) antibodies respectively. Paired serology results from prior study phases were used to analyse changes in individual HCW serostatus over time. Risk-factors for SARS-CoV-2 infection were assessed for demographic and work-related factors. Antibody neutralisation capacity was assessed in a subset of samples via an in vitro ACE2 binding enzyme-linked immunosorbent assay.Results2,344 HCW samples were analysed. Median age was 43 years (IQR 33–50) with 80.5% (n = 1,886) female participants. Irish (78.9%, n = 1,850) and Asian (12.3%, n = 288) were the most commonly reported ethnicities. Nursing/midwifery (39.3%, n = 922) was the most common job role. 97.7% of participants were fully vaccinated, with Pfizer (81.1%, n = 1,902) and AstraZeneca (16.1%, n = 377) the most common vaccines received. Seroprevalence for anti-SARS-CoV-2 antibodies indicating prior infection was 23.4%, of these 33.6% represented previously undiagnosed infections. All vaccinated participants demonstrated positive anti-S antibodies and in those with paired serology, no individual demonstrated loss of previously positive anti-S status below assay threshold for positivity. Interval loss of anti-N antibody positivity was demonstrated in 8.8% of previously positive participants with paired results. Risk factors for SARS-CoV-2 seropositivity suggestive of previous infection included age 18–29 years (aRR 1.50, 95% CI 1.19–1.90, p < 0.001), India as country of birth (aRR 1.35, 95% CI 1.01–1.73, p = 0.036), lower education level (aRR 1.35, 95% CI 1.11–1.66, p = 0.004) and HCA job role (aRR 2.12, 95% CI 1.51–2.95, p < 0.001). Antibody neutralisation varied significantly by anti-SARS-CoV-2 antibody status, with highest levels noted in those anti-N positive, in particular those with vaccination plus previous SARS-CoV-2 infection.ConclusionAll vaccinated HCWs maintained anti-S positivity prior to COVID-19 booster vaccination, however anti-N positivity was more dynamic over time. Antibody neutralisation capacity was highest in participants with COVID-19 vaccination plus prior SARS-CoV-2 infection.

Point of care detection of SARS-CoV-2 antibodies and neutralisation capacity—lateral flow immunoassay evaluation compared to commercial assay to inform potential role in therapeutic and surveillance practices

“…A statistically significant difference in ACE2-RBD binding inhibition was also demonstrated when stratified by the anti-S titre sub-groups “high” vs. “low.” A significant difference was not demonstrated between the anti-S titre sub-groups “negative” and “low” or “high” likely due to the small numbers of participants proving anti-S negative ( n = 3), and thus, robust conclusions from this result are difficult to draw. The PRECISE group has previously demonstrated that ACE2-RBD binding inhibition is highest in anti-S plus anti-N positive individuals ( 28 ), and this is again demonstrated here via the statistical correlation between anti-N titres and ACE2-RBD binding inhibition when assessed via Spearman rank correlation or anti-N titre sub-group assessment via a Kruskal–Wallis test with Dunn's multiple comparison test. Multiple other factors influence antibody neutralisation capacity, including COVID-19 vaccination/infection history ( 28 ) and other SARS-CoV-2 neutralising antibody targets, such as the N-terminal domain (NTD) ( 6 ).…”

“…The PRECISE group has previously demonstrated that ACE2-RBD binding inhibition is highest in anti-S plus anti-N positive individuals ( 28 ), and this is again demonstrated here via the statistical correlation between anti-N titres and ACE2-RBD binding inhibition when assessed via Spearman rank correlation or anti-N titre sub-group assessment via a Kruskal–Wallis test with Dunn's multiple comparison test. Multiple other factors influence antibody neutralisation capacity, including COVID-19 vaccination/infection history ( 28 ) and other SARS-CoV-2 neutralising antibody targets, such as the N-terminal domain (NTD) ( 6 ). It appears that this LFA POC cannot be relied upon solely to determine the neutralisation capacity of detected antibodies for a given individual.…”

“…This surrogate neutralisation assay demonstrates the extent to which biotinylated ACE2 interaction with spike-RBD is inhibited by antibodies in participant sera and has demonstrated a close correlation with spike-based pseudo-virus infection assays for the assessment of ACE2-RBD binding neutralisation. Full details of this assay including comparator results to other assays are published elsewhere ( 28 , 35 ) and in Supplementary material A . The sample selection process for the pseudo-neutralisation assay is detailed in Supplementary material A .…”

“…The initial phases of the PRECISE study assessed HCW SARS-CoV-2 epidemiology and seroprevalence prior to the availability of COVID-19 vaccines (October 2020) ( 33 ) and subsequent serological responses to primary COVID-19 vaccination (April 2021) ( 29 ). A November 2021 study phase (PRECISE 4) was undertaken immediately prior to the roll-out of booster COVID-19 vaccination for HCWs, assessing the durability of SARS-CoV-2 antibody responses and the changing SARS-CoV-2 serological status of HCWs in the era of booster vaccinations ( 28 ). The use of a lateral flow POCT for identifying the presence of anti-S-RBD antibodies compared to a widely used commercial assay and a surrogate neutralisation assay was investigated in this study.…”

Healthcare Worker Characteristics Associated with SARS-CoV-2 Vaccine Uptake in Ireland; a Multicentre Cross-Sectional Study

“…The Prevalence of Antibodies to SARS-CoV-2 in Irish HCWs (PRECISE) study is a multicentre cross-sectional study of COVID-19 vaccine uptake and antibody response in HCWs [22][23][24]. Here, we investigate the demographic and epidemiological factors associated with primary vaccine uptake and receipt of additional booster vaccines in this population.…”