Prevalence and duration of detectable SARS-CoV-2 nucleocapsid antibodies in staff and residents of long-term care facilities over the first year of the pandemic (VIVALDI study): prospective cohort study in England

Abstract

Background: Long-term care facilities (LTCFs) have reported high SARS-CoV-2 infection rates and related mortality, but the proportion of infected people among those who have survived, and duration of the antibody response to natural infection, is unknown. We determined the prevalence and stability of nucleocapsid antibodies (the standard assay for detection of previous infection) in staff and residents in LTCFs in England.

Methods: This was a prospective cohort study of residents 65 years or older and of staff 65 years or younger in 201 LTCFs in England between March 1, 2020, and May 7, 2021. Participants were linked to a unique pseudo-identifier based on their UK National Health Service identification number. Serial blood samples were tested for IgG antibodies against SARS-CoV-2 nucleocapsid protein using the Abbott ARCHITECT i-system (Abbott, Maidenhead, UK) immunoassay. Primary endpoints were prevalence and cumulative incidence of antibody positivity, which were weighted to the LTCF population. Incidence rate of loss of antibodies (seroreversion) was estimated from Kaplan-Meier curves.

Findings: 9488 samples were included, 8636 (91·0%) of which could be individually linked to 1434 residents and 3288 staff members. The cumulative incidence of nucleocapsid seropositivity was 34·6% (29·6-40·0) in residents and 26·1% (23·0-29·5) in staff over 11 months. 239 (38·6%) residents and 503 women (81·3%) were included in the antibody-waning analysis, and median follow-up was 149 days (IQR 107-169). The incidence rate of seroreversion was 2·1 per 1000 person-days at risk, and median time to reversion was 242·5 days.

Interpretation: At least a quarter of staff and a third of surviving residents were infected with SAR-CoV-2 during the first two waves of the pandemic in England. Nucleocapsid-specific antibodies often become undetectable within the first year following infection, which is likely to lead to marked underestimation of the true proportion of people with previous infection. Given that natural infection might act to boost vaccine responses, better assays to identify natural infection should be developed.

Funding: UK Government Department of Health and Social Care.

Figure 1

Weighted seroprevalence with 95% CIs stratified by staff or resident and interval of testing compared with monthly COVID-19 associated deaths COVID-19 associated deaths are defined as deaths occurring within 28 days of a COVID-19 diagnosis in LTCFs in England according to the Care Quality Commission reporting. In view of limited PCR testing coverage in the first wave of the pandemic, data on COVID-19 deaths were considered a more accurate measure of the disease burden in LTCFs over the pandemic. The red dashed line represents the start date of the UK vaccination programme (Dec 8, 2020). LTCFs=long-term care facilities.

Figure 2

Kaplan-Meier plot of time to antibody loss from estimated date of seroconversion in staff and residents

Figure 3

Quantitative antibody titres on a logarithmic scale over 90 days following nucleocapsid antibody seroreversion for spike antibody (A) and RBD antibody (B) Titres are presented at date of first positive antibody (baseline; n=41), 0–30 days (n=41), and 60–90 days (n=16) after estimated date of seroreversion. Titres are reported from MSD assay according to a logarithmic scale. The red dashed line denotes cutoff for test positivity (spike protein=350 AU/mL, RBD=180 AU/mL). AU=arbitrary units. MSD=Meso Scale Diagnostics. RBD=receptor-binding domain.