An Observational Cohort Study on the Incidence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection and B.1.1.7 Variant Infection in Healthcare Workers by Antibody and Vaccination Status

Abstract

Background: Natural and vaccine-induced immunity will play a key role in controlling the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. SARS-CoV-2 variants have the potential to evade natural and vaccine-induced immunity.

Methods: In a longitudinal cohort study of healthcare workers (HCWs) in Oxfordshire, United Kingdom, we investigated the protection from symptomatic and asymptomatic polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection conferred by vaccination (Pfizer-BioNTech BNT162b2, Oxford-AstraZeneca ChAdOx1 nCOV-19) and prior infection (determined using anti-spike antibody status), using Poisson regression adjusted for age, sex, temporal changes in incidence and role. We estimated protection conferred after 1 versus 2 vaccinations and from infections with the B.1.1.7 variant identified using whole genome sequencing.

Results: In total, 13 109 HCWs participated; 8285 received the Pfizer-BioNTech vaccine (1407 two doses), and 2738 the Oxford-AstraZeneca vaccine (49 two doses). Compared to unvaccinated seronegative HCWs, natural immunity and 2 vaccination doses provided similar protection against symptomatic infection: no HCW vaccinated twice had symptomatic infection, and incidence was 98% lower in seropositive HCWs (adjusted incidence rate ratio 0.02 [95% confidence interval {CI} < .01-.18]). Two vaccine doses or seropositivity reduced the incidence of any PCR-positive result with or without symptoms by 90% (0.10 [95% CI .02-.38]) and 85% (0.15 [95% CI .08-.26]), respectively. Single-dose vaccination reduced the incidence of symptomatic infection by 67% (0.33 [95% CI .21-.52]) and any PCR-positive result by 64% (0.36 [95% CI .26-.50]). There was no evidence of differences in immunity induced by natural infection and vaccination for infections with S-gene target failure and B.1.1.7.

Conclusions: Natural infection resulting in detectable anti-spike antibodies and 2 vaccine doses both provide robust protection against SARS-CoV-2 infection, including against the B.1.1.7 variant.

Keywords: SARS-CoV-2; antibody; healthcare worker; immunity; vaccine.

Figure 1.

Vaccination timings (A) and observed incidence of symptomatic PCR-confirmed SARS-CoV-2 infection (B) and any PCR-positive result (C) by antibody and vaccine status. Some staff members received the Oxford-AstraZeneca vaccine in clinical trials beginning 23 April 2020 and were included following unblinding if in the active arm. Number of days at risk per month for each follow-up group is shown at the bottom of panel (C). Due to small numbers, rates are not plotted for vaccinated individuals prior to August 2020. Abbreviations: PCR, polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 2.

Protection from infection by antibody and vaccination status, compared with unvaccinated seronegative individuals. Number of HCWs in each follow-up group is shown; 95% confidence intervals are plotted, except for previously seronegative HCWs vaccinated twice who had no symptomatic PCR confirmed infections. Abbreviations: HCW, healthcare worker; PCR, polymerase chain reaction.

Figure 3.

PCR-positive results following first vaccination. A, Observed rates of symptomatic and asymptomatic PCR-positive results; counts and days at risk plotted under each bar. B, Relative incidence of PCR-positive results by vaccine and days since first vaccine compared to rates in unvaccinated seronegative HCWs. For both plots follow-up is censored if a second vaccination was given. Abbreviations: HCW, healthcare worker; PCR, polymerase chain reaction.

Figure 4.

Relationship between SARS-CoV-2 PCR cycle threshold (Ct) values and symptoms (A), antibody and vaccine status (B). Ct values were available for HCWs tested using the Thermo-Fisher TaqPath assay from 16 November 2020 onwards, n = 423. Mean per sample Ct value across all detected targets is shown. For panel A, Kruskal-Wallis P < .001; for panel B, Kruskal-Wallis P = .06, Wilcoxon rank sum test P values are shown between categories. Abbreviations: HCW, healthcare worker; IgG, immunoglobulin G; PCR, polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 5.

Incidence of SGTF (A) and B.1.1.7 (B) infection by week of testing. From 16 November 2020 onward samples from HCWs were routinely processed using the Thermo-Fisher TaqPath assay allowing SGTF to be identified, shown in panel A. Sequencing was undertaken of samples processed on other assays as well, hence the larger total in panel B. Abbreviations: HCW, healthcare worker; PCR, polymerase chain reaction; SGTF, S gene target failure.