Background Advanced age is accompanied by a decline of immune functions, which may play a role in increased vulnerability to emerging pathogens and low efficacy of primary vaccinations in elderly people. The capacity to mount immune responses against new antigens is particularly affected in this population. However, its precise determinants are not fully understood. We aimed here at establishing the influence of persistent viral infections on the naive T-cell compartment and primary immune responsiveness in older adults.Methods We assessed immunological parameters, related to CD8 + and CD4 + T-cell responsiveness, according to the serological status for common latent herpesviruses in two independent cohorts: 1) healthy individuals aged 19y to 95y (n = 150) and 2) individuals above 70y old enrolled in a primo-vaccination clinical trial (n = 137).Findings We demonstrate a prevalent effect of age and CMV infection on CD8 + and CD4 + naive T cells, respectively. CMV seropositivity was associated with blunted CD4 + T-cell and antibody responses to primary vaccination.Interpretation These data provide insights on the changes in adaptive immunity over time and the associated decline in vaccine efficacy with ageing. This knowledge is important for the management of emerging infectious diseases in elderly populations.

Background Few data are available on the prognosis of older patients who received corticosteroids for COVID-19. We aimed to compare the in-hospital mortality of geriatric patients hospitalized for COVID-19 who received corticosteroids or not. Methods We conducted a multicentric retrospective cohort study in 15 acute COVID-19 geriatric wards in the Paris area from March to April 2020 and November 2020 to May 2021. We included all consecutive patients aged 70 years and older who were hospitalized with confirmed COVID-19 in these wards. Propensity score and multivariate analyses were used. Results Of the 1579 patients included (535 received corticosteroids), the median age was 86 (interquartile range 81-91)years, 56% of patients were female, the median Charlson Comorbidity Index (CCI) was 2.6 (interquartile range 1-4), and 64% of patients were frail (Clinical Frailty Score 5-9). The propensity score analysis paired 984 patients (492 with and without corticosteroids). The in-hospital mortality was 32.3% in the matched cohort. On multivariate analysis, the probability of in-hospital mortality was increased with corticosteroids use (odds ratio [OR]=2.61 [95% confidence interval (CI) 1.63-4.20]). Other factors associated with in-hospital mortality were age (OR=1.04[1.01-1.07], CCI (OR=1.18[1.07-1.29], activities of daily living (OR=0.85[0.75-0.95], oxygen saturation <90% on room air (OR=2.15[1.45-3.17], C-reactive protein level (OR=2.06[1.69-2.51] and lowest lymphocyte count (OR=0.49[0.38-0.63]). Among the 535 patients who received corticosteroids, 68.3% had at least one corticosteroid side effect, including delirium(32.9%), secondary infections(32.7%) and decompensated diabetes(14.4%). Conclusions In this multicentric matched-cohort study of geriatric patients hospitalized for COVID-19, the use of corticosteroids was significantly associated with in-hospital mortality.