Elderly are an understudied, high-risk group vulnerable to severe COVID-19. We comprehensively analyzed the durability of humoral and cellular immune responses after BNT162b2 vaccination and SARS-CoV-2 infection in elderly and younger adults. Home-dwelling old (n = 100, median 86 years) and younger adults (n = 449, median 38 years) were vaccinated with two doses of BNT162b2 vaccine at 3-week intervals and followed for 9-months. Vaccine-induced responses were compared to home-isolated COVID-19 patients (n = 183, median 47 years). Our analysis included neutralizing antibodies, spike-specific IgG, memory B-cells, IFN-γ and IL-2 secreting T-cells and sequencing of the T-cell receptor (TCR) repertoire. Spike-specific breadth and depth of the CD4⁺ and CD8⁺ TCR repertoires were significantly lower in the elderly after one and two vaccinations. Both vaccinations boosted IFN-γ and IL-2 secreting spike-specific T-cells responses, with 96 % of the elderly and 100 % of the younger adults responding after the second dose, although responses were not maintained at 9-months. In contrast, T-cell responses persisted up to 12-months in infected patients. Spike-specific memory B-cells were induced after the first dose in 87 % of the younger adults compared to 38 % of the elderly, which increased to 83 % after the second dose. Memory B-cells were maintained at 9-months post-vaccination in both vaccination groups. Neutralizing antibody titers were estimated to last for 1-year in younger adults but only 6-months in the older vaccinees. Interestingly, infected older patients (n = 15, median 75 years) had more durable neutralizing titers estimated to last 14-months, 8-months longer than the older vaccinees. Vaccine-induced spike-specific IgG and neutralizing antibodies were consistently lower in the older than younger vaccinees. Overall, our data provide valuable insights into the kinetics of the humoral and cellular immune response in the elderly after SARS-CoV-2 vaccination or infection, highlighting the need for two doses, which can guide future vaccine design.Clinical trials.gov; NCT04706390.

Background: Evaluation of susceptibility to emerging SARS-CoV-2 variants of concern (VOC) requires rapid screening tests for neutralising antibodies which provide protection. Methods: Firstly, we developed a receptor-binding domain-specific haemagglutination test (HAT) to Wuhan and VOC (alpha, beta, gamma and delta) and compared to pseudotype, microneutralisation and virus neutralisation assays in 835 convalescent sera. Secondly, we investigated the antibody response using the HAT after two doses of mRNA (BNT162b2) vaccination. Sera were collected at baseline, three weeks after the first and second vaccinations from older (80–99 years, n = 89) and younger adults (23–77 years, n = 310) and compared to convalescent sera from naturally infected individuals (1–89 years, n = 307). Results: Here we show that HAT antibodies highly correlated with neutralising antibodies (R = 0.72–0.88) in convalescent sera. Home-dwelling older individuals have significantly lower antibodies to the Wuhan strain after one and two doses of BNT162b2 vaccine than younger adult vaccinees and naturally infected individuals. Moverover, a second vaccine dose boosts and broadens the antibody repertoire to VOC in naïve, not previously infected older and younger adults. Most (72–76%) older adults respond after two vaccinations to alpha and delta, but only 58–62% to beta and gamma, compared to 96–97% of younger vaccinees and 68–76% of infected individuals. Previously infected older individuals have, similarly to younger adults, high antibody titres after one vaccination. Conclusions: Overall, HAT provides a surrogate marker for neutralising antibodies, which can be used as a simple inexpensive, rapid test. HAT can be rapidly adaptable to emerging VOC for large-scale evaluation of potentially decreasing vaccine effectiveness.

The aim of this study was to evaluate the performances of three commercially available antibody assays for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies at different time points following SARS-CoV-2 infection. Sera from 536 cases, including 207 SARS-CoV-2 PCR positive, were tested for SARS-CoV-2 antibodies with the Wantai receptor binding domain (RBD) total antibody assay, Liaison S1/S2 IgG assay and Alinity i nucleocapsid IgG assay and compared to a two-step reference ELISA (SARS-CoV-2 RBD IgG and SARS-CoV-2 spike IgG). Diagnostic sensitivity, specificity, predictive values and Cohen’s kappa were calculated for the commercial assays. The assay’s sensitivities varied greatly, from 68.7% to 95.3%, but the specificities remained high (96.9–99.1%). The three tests showed good performances in sera sampled 31 to 60 days after PCR positivity compared to the reference ELISA. The total antibody test performed better than the IgG tests the first 30 days and the nucleocapsid IgG test showed reduced sensitivity two months or more after PCR positivity. Hence, the test performances at different time points should be taken into consideration in clinical practice and epidemiological studies. Spike or RBD IgG tests are preferable in sera sampled more than two months following SARS-CoV-2 infection.

Evaluation of susceptibility to emerging SARS-CoV-2 variants of concern (VOC) requires rapid screening tests for neutralising antibodies which provide protection. We developed a receptor-binding domain specific hemagglutination test (HAT) which correlated with neutralising antibodies (R=0.74-0.82) in two independent cohorts from 798 convalescents. Home-dwelling older individuals (80-99 years, n=89) had significantly lower antibodies after one dose of BNT162b2 vaccine than younger adult vaccinees (n=310) and naturally infected individuals (n=307). The second vaccine dose boosted and broadened the antibody repertoire to VOC in naïve but not previously infected, older and younger adults. >75% of older adults responded after two vaccinations to alpha and delta, but only 59-62% to beta and gamma, compared to 96-97% of younger vaccinees and 68-76% of infected individuals. Overall, the HAT provides a surrogate marker for neutralising antibodies, could be used as a simple inexpensive, rapid test, rapidly adaptable to emerging VOC for large-scale evaluation of potentially diminishing vaccine effectiveness.

Background: Comparative data on COVID-19 among health care workers (HCWs) in different health care settings are scarce. This study investigated the rates of previous COVID-19 among HCWs in nursing homes, hospitals and a municipal emergency room (ER). Methods: We prospectively included 747 HCWs: 313 from nursing homes, 394 from hospitals and 40 from the ER. The diagnosis of COVID-19 was based on serological evidence of SARS-CoV-2 antibody positivity and self-reported RT-PCR positivity prior to inclusion. Information regarding age, sex and exposure to SARS-CoV-2 infection was collected. Results: A total of 4% (11/313) of nursing home HCWs and 6% (28/434) of HCWs in hospitals/the ER tested positive by serology and/or RT-PCR (p = 0.095). Fewer HCWs in nursing homes had occupational exposure to SARS-CoV-2 compared to those in hospitals/the ER (16% vs. 48%, p < 0, 001), but nursing homes had a higher proportion of HCWs with occupational exposure using partial/no PPE (56% vs. 19%, p < 0.001). Nevertheless, no significant differences in the risk for COVID-19 were found in relation to the rate of occupational exposure (p = 0.755) or use of inadequate PPE (p = 0.631). Conclusions: Despite a small sample size, the risk for COVID-19 among HCWs did not appear to be related to the type of health care facility, rates of occupational exposure or use of PPE.