Plates were washed and were immediately read using a MESO TM QuickPlex SQ 120 system. over time. Antibodies showed stable and equivalent levels Sofosbuvir impurity A of functional inhibition against spike-angiotensin-converting enzyme 2 binding in all age groups with comparable activity against viral variants of concern. SARS-CoV-2 seropositive donors showed high levels of antibodies to other beta-coronaviruses but serostatus did not impact humoral immunity to influenza or other respiratory syncytial viruses. SARS-CoV-2-specific cellular responses were similar across all ages but virus-specific populations showed elevated levels of activation in older donors. Thus, survivors of SARS-CoV-2 infection show a robust and stable immunity against the virus that does not negatively impact responses to other seasonal viruses. Subject terms: SARS-CoV-2, Infection, Ageing This study shows that during the first wave of SARS-CoV-2 infection in England, residents of long-term care facilities who survived infection developed a robust and stable immunity against the virus that did not negatively impact responses to other seasonal viruses. Main A striking feature of the current SARS-CoV-2 pandemic has been the high rates of mortality in older people. The biological basis for this observation is unclear but may relate to relative impairment of innate immune or adaptive responses and increased prevalence of comorbidities. Long-term care facilities (LTCFs) provide residential and/or nursing care support for some of the frailest Sofosbuvir impurity A older adults (>65) in the population and as such have proven vulnerable to the impact of the SARS-CoV-2 pandemic1. Rates of SARS-CoV-2 infection in LTCFs have varied considerably and a range of factors have been determined that may impact susceptibility to infection2. Mortality rates among older adult residents have been estimated at up to 30% (ref. 3) with factors such as cognitive impairment and extreme aging as notable risk factors3C5. Nevertheless, most older people recover from acute SARS-CoV-2 infection and this is dependent on the generation of a functional SARS-CoV-2-specific immune response. This also helps to provide protection against subsequent reinfection and enhances immune responses at the time of coronavirus disease 2019 (COVID-19) vaccination. However, studies of staff and residents in LTCFs are difficult to perform and at the current time there is very limited information regarding the nature of the SARS-CoV-2-specific response after natural infection in this setting. Vaccination against COVID-19 has proven highly Vax2 effective; evidence to date shows that this protective effect is also observed in older adults and frail individuals6,7. As such, LTCF vaccination programs offer the potential to limit the impact of the pandemic in this setting. However, it is also important to determine how the features of natural immunity impact the immune response to vaccination as SARS-CoV-2 serostatus impacts on the response to both single and double vaccination. These studies are required to determine the relative need for booster vaccination, particularly in vulnerable populations where there has been concern about the longevity of vaccine-induced immunity. A further issue of importance relates to the potential impact of SARS-CoV-2 serostatus on heterologous immune responses to other pathogens. Seasonal respiratory viruses such as influenza and respiratory syncytial virus (RSV) are a cause of considerable morbidity Sofosbuvir impurity A and mortality in older adults; it is currently unclear if primary SARS-CoV-2 infection, with its associated acute inflammatory response, might act to suppress memory antibody responses against other pathogens. Competition between plasma cells for space within the immunological niche of the bone marrow and their displacement by subsequent Sofosbuvir impurity A infections has been suggested to be a potential mechanism for loss of some antibody responses with aging8. If so, this could have a considerable impact on policy decisions in relation to the annual influenza vaccination strategy. Furthermore, there is increasing concern about the long-term complications of SARS-CoV-2 infection, which may partly reflect a sustained systemic inflammatory profile. This may be of particular importance Sofosbuvir impurity A in older people since many inflammatory markers increase naturally with age in a process that has been termed inflamm-aging and is particularly marked in those with chronic health conditions9. To date, there is no information on how SARS-CoV-2 serostatus impacts systemic inflammatory markers in older people in the care home setting. We determined virus-specific and general inflammatory profiles in both staff and residents in the LTCF setting over a 4-month period and related these findings to SARS-CoV-2 serostatus. Overall, robust SARS-CoV-2-specific and heterologous immune responses were observed across the life course, which is encouraging for longer-term health outcomes and responsiveness to COVID-19 vaccination. Results SARS-CoV-2-specific antibody responses are higher in residents Blood samples were collected from 276 staff and residents at England LTCFs between June and November 2020, before the introduction of.