These findings are in keeping with findings from huge cohort research of medical center staff broadly, and extend the data of substantial safety to frail the elderly, who are vunerable to severe outcomes of SARS-CoV-2 infection due to age-related changes in immunity (immune-senescence) and high levels of comorbidity. in staff (aged 65 years) and occupants (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 weeks thereafter and tested for IgG antibodies to SARS-CoV-2 nucleocapsid and spike proteins. PCR screening for SARS-CoV-2 was carried out weekly in staff and regular monthly in occupants. Cox regression was used to estimate risk ratios (HRs) of a PCR-positive test by baseline antibody status, modified for age and sex, and stratified by LTCF. Findings 682 occupants from 86 LCTFs and 1429 staff members from 97 LTCFs met study inclusion criteria. At baseline, IgG antibodies to nucleocapsid were recognized in 226 (33%) of 682 occupants and 408 Oxi 4503 (29%) of 1429 staff members. 93 (20%) of 456 occupants who have been antibody-negative at baseline experienced a PCR-positive test (infection rate 0054 per month at risk) compared with four (2%) of 226 occupants who have been antibody-positive at baseline (0007 per month at risk). 111 (11%) Oxi 4503 of 1021 staff members who have been antibody-negative at baseline experienced PCR-positive checks (0042 per month at risk) compared with ten (2%) of 408 staff members who have been antibody-positive staff at baseline (0009 per month at risk). The risk of PCR-positive illness was higher for occupants who have been antibody-negative at baseline than occupants who have been antibody-positive at baseline (modified HR [aHR] 015, 95% CI 005C044, p=00006), and the risk of a PCR-positive illness was also higher for staff who have been antibody-negative at baseline compared with staff who have been antibody-positive at baseline (aHR 039, 019C082; p=0012). 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 similar in PCR-positive and PCR-negative instances. Interpretation The presence of IgG antibodies to nucleocapsid protein was associated with considerably reduced risk of reinfection in staff and occupants for up to 10 weeks after primary illness. Funding UK Authorities Division of Health and Sociable Care. Introduction Occupants of long-term care facilities (LTCFs) that Foxo1 provide residential or nursing care to older people have had the highest burden of COVID-19 related mortality of any human population group. Older adults might have less powerful immune reactions to illness due to age-related immune-senescence and underlying comorbidities, and although growing data suggest that most LTCF occupants possess a detectable immune response following natural illness with SARS-CoV-2,1, 2, 3, 4 the degree to which this protects against a second infection is definitely unclear. Understanding the degree of safety afforded by earlier infection, period of illness, and whether main illness and reinfection differ with regard to disease severity and clinical demonstration has major implications for vaccination and for policy decisions concerning the ongoing need for non-pharmaceutical interventions in LTCFs to prevent transmission. Most folks who are infected with SARS-CoV-2 develop antibodies against the spike and nucleocapsid proteins of the disease 1C2 weeks after sign onset;5 however, data from residents of LTCFs are limited by small sample sizes.3, 4 The magnitude of neutralising antibodies against the spike protein receptor-binding domain have been shown to correlate with post-infection immunity, to be dependent on disease severity,6 and to decline over time,7 but understanding of the immune correlates of safety against reinfection in all age groups remains poor. Study in context Evidence before this study We did a systematic search of MEDLINE (Ovid) and the medRxiv preprint server on Jan 18, 2021, for studies done in long-term care facilities (LTCFs) that explained the risk of illness in individuals who were antibody-positive for SARS-CoV-2 compared with individuals who were antibody-negative using the search terms SARS-CoV-2 OR COVID-19 OR coronavirus AND care home OR nursing home OR long term care facility, without day or language restrictions. We did not identify any Oxi 4503 publications that focused on risk of reinfection in seropositive individuals; however, since our systematic search, one study has been published using data from two LTCFs in London, UK. This study reported a 96% reduction in the odds of reinfection in individuals who were seropositive compared with those who were seronegative centered at 4-month follow-up in 161 participants. We found ten studies that included seroprevalence studies of staff or of staff and occupants in LTCFs in eight cohorts. Five of these surveys were carried out in response to SARS-CoV-2 outbreaks within the care homes, as part of the subsequent investigation or as post-infection monitoring. The largest of these studies, which enrolled both staff and occupants, was carried out in six LTCFs and included longitudinal antibody screening. Added value.