Reinfection with new variants of SARS-CoV-2 after natural infection: a prospective observational cohort in 13 care homes in England

Abstract

Background: Understanding the duration of protection and risk of reinfection after natural infection is crucial to planning COVID-19 vaccination for at-risk groups, including care home residents, particularly with the emergence of more transmissible variants. We report on the duration, neutralising activity, and protection against the alpha variant of previous SARS-CoV-2 infection in care home residents and staff infected more than 6 months previously.

Methods: We did this prospective observational cohort surveillance in 13 care homes in Greater London, England. All staff and residents were included. Staff and residents had regular nose and throat screening for SARS-CoV-2 by RT-PCR according to national guidelines, with ad hoc testing of symptomatic individuals. From January, 2021, antigen lateral flow devices were also used, but positive tests still required RT-PCR confirmation. Staff members took the swab samples for themselves and the residents. The primary outcome was SARS-CoV-2 RT-PCR positive primary infection or reinfection in previously infected individuals, as determined by previous serological testing and screening or diagnostic RT-PCR results. Poisson regression and Cox proportional hazards models were used to estimate protective effectiveness of previous exposure. SARS-CoV-2 spike, nucleoprotein, and neutralising antibodies were assessed at multiple timepoints as part of the longitudinal follow-up.

Findings: Between April 10 and Aug 3, 2020, we recruited and tested 1625 individuals (933 staff and 692 residents). 248 participants were lost to follow-up (123 staff and 125 residents) and 1377 participants were included in the follow-up period to Jan 31, 2021 (810 staff and 567 residents). There were 23 reinfections (ten confirmed, eight probable, five possible) in 656 previously infected individuals (366 staff and 290 residents), compared with 165 primary infections in 721 susceptible individuals (444 staff and 277 residents). Those with confirmed reinfections had no or low neutralising antibody concentration before reinfection, with boosting of titres after reinfection. Kinetics of binding and neutralising antibodies were similar in older residents and younger staff.

Interpretation: SARS-CoV-2 reinfections were rare in older residents and younger staff. Protection from SARS-CoV-2 was sustained for longer than 9 months, including against the alpha variant. Reinfection was associated with no or low neutralising antibody before reinfection, but significant boosting occurred on reinfection.

Funding: Public Health England.

Figure 1

Trial profile *Including residents who died or moved from the care home and staff who changed employment.

Figure 2

Numbers of SARS-CoV-2 RT-PCR tests, positive results, and outbreaks in care homes during the study period *Outbreak was defined as two or more people with positive SARS-CoV-2 RT-PCR results within 14 days. The dashed line indicates commencement of vaccination in cohort.

Figure 3

Antibody longevity between T1 and T2 timepoints (A) Seropositive staff and residents by binding assays. (B) Seropositive staff and residents with detectable neutralising antibody titres to live virus (England.2). Timepoint T1 was May, June,or July, 2020, 4 weeks after the first set of testing. Timepoint T2 was September or October, 2020, 4 months after baseline T1 serology. *201 staff and 147 residents, p>0·9999. † 193 staff and 142 residents, p=0·84. ‡180 staff and 136 residents, p=0·026; Fisher's exact p<0·05. §46 staff, loss between T1 and T2 p=0·0063; Fisher's exact p<0·005. ¶86 residents, loss between T1 and T2 p<0·0001; Fisher's exact p<0·0001.

Figure 4

RBD and neutralising antibody titres by previous infection status (A) RBD titre to England.2 strain at T1 and T2 for all individuals with detectable RBD antibodies at T1. (B) Live virus neutralising antibody titre to England.2 virus at T1 and T2 for all individuals with detectable RBD antibodies at T1. Bars indicate geometric mean and 95% CI. Dashed line indicates assay threshold. Timepoint T1 was May, June, or July, 2020, 4 weeks after the first set of testing. Timepoint T2 was September or October, 2020, 4 months after baseline T1 serology. RBD=receptor binding domain assay. Statistical analysis using Wilcoxon matched pairs: *p<0·0001, † p=0·039. ‡p<0·0001, §p<0·0039.

Figure 5

Antibody titres of individuals with reinfection over time (A) Live virus 50% reduction in neutralising antibody measured by Focus reduction (FRNT50) to England.2 virus. (B) Live virus FRNT50 to alpha (B.1.1.7). (C) RBD specific IgG titres over time for the 10 individuals with confirmed reinfection (identification numbers correspond to table 1). (D) Correlation between live virus FRNT50 to England.2 virus and live virus FRNT50 to alpha (B.1.1.7) virus. Statistical analysis using Spearman's rank correlation coefficient (r). X axes refer to timepoints of serological sampling in figures A–C. A minimum of two samples were available for nine individuals with the first sample in May or June, 2020 (at T1), and second sample in September or October (at T2). One individual only had one sample available before reinfection. Samples 1 and 2 represent samples taken from individuals before reinfection (T1 or T2) and samples 3 and 4 represent samples taken after reinfection. Post-reinfection serological samples were available for nine individuals who had a sample within 7–14 days of reinfection RT-PCR (sample 3); an additional five had a further sample (sample 4) taken 4–6 weeks after reinfection RT-PCR. RBD=receptor binding domain assay. FRNT50=focus reduction neutralisation test with 50% reduction of the virus control.