Incidence of SARS-CoV-2 infection according to baseline antibody status in staff and residents of 100 long-term care facilities (VIVALDI): a prospective cohort study

Abstract

Background: SARS-CoV-2 infection represents a major challenge for long-term care facilities (LTCFs) and many residents and staff are seropositive following persistent outbreaks. We aimed to investigate the association between the SARS-CoV-2 antibody status at baseline and subsequent infection in this population.

Methods: We did a prospective cohort study of SARS-CoV-2 infection in staff (aged <65 years) and residents (aged >65 years) at 100 LTCFs in England between Oct 1, 2020, and Feb 1, 2021. Blood samples were collected between June and November, 2020, at baseline, and 2 and 4 months thereafter and tested for IgG antibodies to SARS-CoV-2 nucleocapsid and spike proteins. PCR testing for SARS-CoV-2 was done weekly in staff and monthly in residents. Cox regression was used to estimate hazard ratios (HRs) of a PCR-positive test by baseline antibody status, adjusted for age and sex, and stratified by LTCF.

Findings: 682 residents from 86 LCTFs and 1429 staff members from 97 LTCFs met study inclusion criteria. At baseline, IgG antibodies to nucleocapsid were detected in 226 (33%) of 682 residents and 408 (29%) of 1429 staff members. 93 (20%) of 456 residents who were antibody-negative at baseline had a PCR-positive test (infection rate 0·054 per month at risk) compared with four (2%) of 226 residents who were antibody-positive at baseline (0·007 per month at risk). 111 (11%) of 1021 staff members who were antibody-negative at baseline had PCR-positive tests (0·042 per month at risk) compared with ten (2%) of 408 staff members who were antibody-positive staff at baseline (0·009 per month at risk). The risk of PCR-positive infection was higher for residents who were antibody-negative at baseline than residents who were antibody-positive at baseline (adjusted HR [aHR] 0·15, 95% CI 0·05-0·44, p=0·0006), and the risk of a PCR-positive infection was also higher for staff who were antibody-negative at baseline compared with staff who were antibody-positive at baseline (aHR 0·39, 0·19-0·82; p=0·012). 12 of 14 reinfected participants had available data on symptoms, and 11 of these participants were symptomatic. Antibody titres to spike and nucleocapsid proteins were comparable in PCR-positive and PCR-negative cases.

Interpretation: The presence of IgG antibodies to nucleocapsid protein was associated with substantially reduced risk of reinfection in staff and residents for up to 10 months after primary infection.

Funding: UK Government Department of Health and Social Care.

Figure 1

Study flow diagram LCTFs=long-term care facilities. NHS=National Health Service.

Figure 2

Cumulative new PCR-confirmed infections by baseline antibody status Late entrants to the analysis (n=165) were excluded from Kaplan-Meier estimates to allow presentation on a calendar timescale starting from Oct 1, 2020. Shaded areas show 95% CIs.

Figure 3

Quantitative SARS-CoV-2-spike and nucleocapsid IgG titres by reinfection status at the first testing round and last testing round SARS-CoV-2 spike antibody values at the first round of testing (A) and last round of testing, stratified by duration between the last antibody test and last relevant PCR test (B). SARS-CoV-2 nucleocapsid antibody values at the first round of testing (C) and last round of testing, stratified by duration between the last antibody test and last relevant PCR test (D). The last relevant PCR test was defined as the first positive PCR test following antibody testing for reinfected cases and the last negative PCR test for controls. The median duration between the last antibody test and last relevant PCR result (first positive for cases, last negative for controls) was 62 days (28–88) among reinfected cases and 68 days (48–75) among control cases; on the basis of this testing gap, participants were categorised into three categories (0–50 days between tests, 50–75 days, and 75–180 days). Horizontal lines represent median values, boxes show the IQR, whiskers show data points within 1·5 × the IQR (upper and lower quartile; missing whiskers indicate that there were no data points within this range), and dots show outliers. AU=arbitrary units.