Do antibody positive healthcare workers have lower SARS-CoV-2 infection rates than antibody negative healthcare workers? Large multi-centre prospective cohort study (the SIREN study), England: June to November 2020

Abstract

BackgroundThere is an urgent need to better understand whether individuals who have recovered from COVID-19 are protected from future SARS-CoV-2 infection.MethodsA large multi-centre prospective cohort was recruited from publicly funded hospital staff in the UK. Participants attended regular SARS-CoV-2 PCR and antibody testing (every 2-4 weeks) and completed fortnightly questionnaires on symptoms and exposures. At enrolment, participants were assigned to either the positive cohort (antibody positive or prior PCR/antibody test positive) or negative cohort (antibody negative, not previously known to be PCR/antibody positive). Potential reinfections were clinically reviewed and classified according to case definitions (confirmed, probable, possible (subdivided by symptom-status)) depending on hierarchy of evidence. Individuals in the primary infection were excluded from this analysis if infection was confirmed by antibody only. Reinfection rates in the positive cohort were compared against new PCR positives in the negative cohort using a mixed effective multivariable logistic regression analysis.FindingsBetween 18 June and 09 November 2020, 44 reinfections (2 probable, 42 possible) were detected in the baseline positive cohort of 6,614 participants, collectively contributing 1,339,078 days of follow-up. This compares with 318 new PCR positive infections and 94 antibody seroconversions in the negative cohort of 14,173 participants, contributing 1,868,646 days of follow-up. The incidence density per 100,000 person days between June and November 2020 was 3.3 reinfections in the positive cohort, compared with 22.4 new PCR confirmed infections in the negative cohort. The adjusted odds ratio was 0.17 for all reinfections (95% CI 0.13-0.24) compared to PCR confirmed primary infections. The median interval between primary infection and reinfection was over 160 days.InterpretationA prior history of SARS-CoV-2 infection was associated with an 83% lower risk of infection, with median protective effect observed five months following primary infection. This is the minimum likely effect as seroconversions were not included.FundingDepartment of Health and Social Care and Public Health England, with contributions from the Scottish, Welsh and Northern Irish governments.

Changes in symptomatology, re-infection and transmissibility associated with SARS-CoV-2 variant B.1.1.7: an ecological study

“…This rate is consistent with another study of 6614 healthcare workers that had previously tested positive for Covid-19, finding 44 possible reinfections (0.66%). 14 Our reinfection rate did not vary consistently across regions or time, which would be consistent with the hypothesis that reinfection is no more likely in the context of B.1.1.7. This may mean that if adequate immunity is built over the first infection it may be sufficient to protect against reinfection in the presence of B.1.1.7.…”

Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7): an exploratory analysis of a randomised controlled trial

“…least 5 months. 20 However, reinfection with B.1.1.7 and subsequent critical illness has been reported. 21 Amino acid 501 of the SARS-CoV-2 spike protein sits within the receptor binding domain (RBD) of the S1 subunit.…”

An observational cohort study on the incidence of SARS-CoV-2 infection and B.1.1.7 variant infection in healthcare workers by antibody and vaccination status

“…Prior SARS-CoV-2 infection protects against PCR-confirmed symptomatic/asymptomatic SARS-CoV-2 infection by 83-88% up to 5-6 months, with greater reductions in symptomatic infections. [2][3][4] Ongoing longitudinal studies are required to determine the duration of protection conferred by natural immunity; however evaluating this will be more difficult with widespread vaccination. Understanding the interaction between prior infection/serostatus and vaccination on protection from infection is also important.…”