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

Background: The 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 methods: Serology 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. Results: 2,344 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. Conclusion: All 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.

Previous SARS-CoV-2 Infection, Age, and Frailty Are Associated With 6-Month Vaccine-Induced Anti-Spike Antibody Titer in Nursing Home Residents.

OBJECTIVES: Older nursing home residents make up the population at greatest risk of morbidity and mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. No studies have examined the determinants of long-term antibody responses post vaccination in this group. DESIGN: Longitudinal cohort study. SETTING AND PARTICIPANTS: Residents from 5 nursing homes assessed before vaccination, and 5 weeks and 6 months post vaccination, with the BNT162b2 messenger RNA SARS-CoV-2 vaccine. METHODS: Comprehensive clinical assessment was performed, including assessment for comorbidity, frailty, and SARS-CoV-2 infection history. Serum nucleocapsid and anti-spike receptor binding domain (RBD) antibodies were analyzed at all timepoints. An in vitro angiotensin-converting enzyme (ACE2) receptor-spike RBD neutralization assay assessed serum neutralization capacity. RESULTS: Of 86 participants (81.1 ± 10.8 years; 65% female), just under half (45.4%; 39 of 86) had evidence of previous SARS-CoV-2 infection. All participants demonstrated a significant antibody response to vaccination at 5 weeks and a significant decline in this response by 6 months. SARS-CoV-2 infection history was the strongest predictor of antibody titer (log-transformed) at both 5 weeks [ß: 3.00; 95% confidence interval (CI): 2.32-3.70; P < .001] and 6 months (ß: 3.59; 95% CI: 2.89-4.28; P < .001). Independent of SARS-CoV-2 infection history, both age in years (ß: -0.05; 95% CI: -0.08 to -0.02; P < .001) and frailty (ß: -0.22; 95% CI: -0.33 to -0.11; P < .001) were associated with a significantly lower antibody titer at 6 months. Anti-spike antibody titers at both 5 weeks and 6 months significantly correlated with in vitro neutralization capacity. CONCLUSIONS AND IMPLICATIONS: In older nursing home residents, SARS-CoV-2 infection history was the strongest predictor of anti-spike antibody titers at 6 months, whereas age and frailty were independently associated with lower titers at 6 months. Antibody titers significantly correlated with in vitro neutralization capacity. Although older SARS-CoV-2 naïve nursing home residents may be particularly vulnerable to breakthrough SARS-CoV-2 infection, the relationship between antibody titers, SARS-CoV-2 infection, and clinical outcomes remains to be fully elucidated in this vulnerable population.

Dynamic Assay for Profiling Anti-SARS-CoV-2 Antibodies and Their ACE2/Spike RBD Neutralization Capacity.

Serological assays have been widely employed during the coronavirus disease 2019 (COVID-19) pandemic to measure antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to track seroconversion in populations. However, currently available assays do not allow determination of neutralization capacity within the assay protocol. Furthermore, commercial serology assays have a high buy-in cost that is inaccessible for many research groups. We have replicated the serological enzyme-linked immunosorbent assay for the detection of SARS-CoV-2 antibody isotypes, developed at the Icahn School of Medicine at Mount Sinai, New York. Additionally, we have modified the protocol to include a neutralization assay with only a minor modification to this protocol. We used this assay to screen local COVID-19 patient sera (n = 91) and pre-COVID-19 control sera (n = 103), and obtained approximate parity with approved commercial anti-nucleoprotein-based assays with these sera. Furthermore, data from our neutralization assay closely aligns with that generated using a spike-based pseudovirus infection model when a subset of patient sera was analyzed.