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

Background Long Term Care Facilities (LTCF) have reported high SARS-CoV-2 infection rates and related mortality, but the proportion infected amongst survivors 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 prior infection - in staff and residents from 201 LTCFs. Methods Prospective cohort study of residents aged >65 years and staff of LTCFs in England (11 June 2020-7 May 2021). Serial blood samples were tested for IgG antibodies against SARS-CoV-2 nucleocapsid protein. Prevalence and cumulative incidence of antibody-positivity were weighted to the LTCF population. Cumulative incidence of sero-reversion was estimated from Kaplan-Meier curves. Results 9488 samples were included, 8636 (91%) of which could be individually-linked to 1434 residents or 3288 staff members. The cumulative incidence of nucleocapsid seropositivity was 35% (95% CI: 30-40%) in residents and 26% (95% CI: 23-30%) in staff over 11 months. The incidence rate of loss of antibodies (sero-reversion) was 2.1 per 1000 person-days at risk, and median time to reversion was around 8 months. Interpretation At least one-quarter of staff and one-third of surviving residents were infected during the first two pandemic waves. 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 those with prior infection. Since natural infection may act to boost vaccine responses, better assays to identify natural infection should be developed. Funding UK Government Department of Health and Social Care.

[1]  A. Copas,et al.  Profile of humoral and cellular immune responses to single doses of BNT162b2 or ChAdOx1 nCoV-19 vaccines in residents and staff within residential care homes (VIVALDI): an observational study , 2021, The Lancet Healthy Longevity.

[2]  A. Copas,et al.  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 , 2021, The Lancet Healthy Longevity.

[3]  S. Letovsky,et al.  A population-based analysis of the longevity of SARS-CoV-2 antibody seropositivity in the United States , 2021, EClinicalMedicine.

[4]  B. Ramos,et al.  The Demography and Characteristic of SARS-CoV-2 Sero-positive Residents and Staff of Nursing Homes for Older Adults in the Community of Madrid: the SeroSOS Study , 2021, Age and ageing.

[5]  C. Donnelly,et al.  Prevalence of antibody positivity to SARS-CoV-2 following the first peak of infection in England: Serial cross-sectional studies of 365,000 adults , 2021, The Lancet Regional Health - Europe.

[6]  V. Saliba,et al.  Children develop strong and sustained cross-reactive immune responses against spike protein following SARS-CoV-2 infection , 2021, medRxiv.

[7]  M. Picot,et al.  Spike Antibody Levels of Nursing Home Residents With or Without Prior COVID-19 3 Weeks After a Single BNT162b2 Vaccine Dose. , 2021, JAMA.

[8]  J. V. Van Eyk,et al.  Antibody responses to the BNT162b2 mRNA vaccine in individuals previously infected with SARS-CoV-2 , 2021, Nature Network Boston.

[9]  V. Simon,et al.  Antibody Responses in Seropositive Persons after a Single Dose of SARS-CoV-2 mRNA Vaccine , 2021, The New England journal of medicine.

[10]  M. Van Ranst,et al.  Longitudinal follow-up of IgG anti-nucleocapsid antibodies in SARS-CoV-2 infected patients up to eight months after infection , 2021, Journal of Clinical Virology.

[11]  A. Charlett,et al.  Antibodies to SARS-CoV-2 protect against re-infection during outbreaks in care homes, September and October 2020 , 2021, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[12]  R. Myers,et al.  Infection and transmission of SARS-CoV-2 in London care homes reporting no cases or outbreaks of COVID-19: Prospective observational cohort study, England 2020 , 2021, The Lancet Regional Health - Europe.

[13]  M. Malim,et al.  Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans , 2020, Nature Microbiology.

[14]  J. Farrar,et al.  Study Protocol: Understanding SARS-Cov-2 infection, immunity and its duration in care home residents and staff in England (VIVALDI). , 2020, Wellcome open research.

[15]  B. Guthrie,et al.  Evolution and effects of COVID-19 outbreaks in care homes: a population analysis in 189 care homes in one geographical region of the UK , 2020, The Lancet Healthy Longevity.

[16]  G. Rodger,et al.  Performance characteristics of five immunoassays for SARS-CoV-2: a head-to-head benchmark comparison , 2020, The Lancet Infectious Diseases.

[17]  C. Houlihan,et al.  The complexities of SARS-CoV-2 serology , 2020, The Lancet Infectious Diseases.

[18]  D. Cummings,et al.  A systematic review of antibody mediated immunity to coronaviruses: kinetics, correlates of protection, and association with severity , 2020, Nature Communications.

[19]  A. Casadevall,et al.  Comparative performance of five commercially available serologic assays to detect antibodies to SARS-CoV-2 and identify individuals with high neutralizing titers , 2020, medRxiv.

[20]  A. Comas-Herrera,et al.  COVID-19 mortality and long-term care: a UK comparison , 2020 .

[21]  P. Rochon,et al.  For-profit long-term care homes and the risk of COVID-19 outbreaks and resident deaths , 2020, Canadian Medical Association Journal.

[22]  Otto O. Yang,et al.  Rapid Decay of Anti–SARS-CoV-2 Antibodies in Persons with Mild Covid-19 , 2020, The New England journal of medicine.

[23]  M. Wener,et al.  Performance Characteristics of the Abbott Architect SARS-CoV-2 IgG Assay and Seroprevalence in Boise, Idaho , 2020, Journal of Clinical Microbiology.

[24]  X. Tang,et al.  Antibody responses to SARS-CoV-2 in patients with COVID-19 , 2020, Nature Medicine.

[25]  J. Forder,et al.  Length of stay in care homes , 2011 .

[26]  A. Bebbington,et al.  The length of stay in care , 1989 .