Immunosenescence may impact the functionality and breadth of vaccine-elicited humoral immune responses. The ability of sera to neutralize the SARS-CoV-2 spike protein (S) from Beta, Gamma, Delta, and Epsilon variants of concern (VOCs) relative to the ancestral Wuhan-Hu-1 strain was compared in Comirnaty COVID-19-vaccinated elderly nursing home residents, either SARS-CoV-2 naïve (n = 22) or experienced (n = 8), or SARS-CoV-2 naïve younger individuals (n = 18) and non-vaccinated individuals who recovered from severe COVID-19 (n = 19). In all groups, except that including SARS-CoV-2-experienced nursing home residents, some participants lacked NtAb against one or more VOCs, mainly the Beta variant (15–20%). Serum NtAb titers were lowest against the Beta variant followed by Gamma, Delta and Epsilon variants. Overall, fold change reduction in NtAb titers relative to the ancestral strain was greatest for the Beta variant (6.7–19.4) followed by Gamma (4.8–16.0), Epsilon (2.9–13.4), and Delta (3.5–6.5) variants, although subtle differences were observed for Beta, Epsilon and Delta variants across comparison groups. In summary, older age, frailty, and concurrence of co-morbidities had no major impact on the serum NtAb activity profile against SARS-CoV-2 VOCs.

We investigated whether peripheral blood levels of SARS-CoV-2 Spike (S) receptor binding domain antibodies (anti-RBD), neutralizing antibodies (NtAb) targeting Omicron S, and S-reactive-interferon (IFN)-γ-producing CD4 + and CD8 + T cells measured after a homologous booster dose (3D) with the

Studies investigating the cumulative incidence of and immune status against SARS‐CoV‐2 infection provide valuable information for shaping public health decision‐making. A cross‐sectional study on 935 participants, conducted in the Valencian Community (VC), measuring anti‐SARS‐CoV‐2‐receptor binding domain‐RBD‐total antibodies and anti‐Nucleocapsid (N)‐IgGs via electrochemiluminescence assays. Quantitation of neutralizing antibodies (NtAb) against ancestral and Omicron BA.1 and BA.2 variants and enumeration of SARS‐CoV‐2‐S specific‐IFNγ‐producing CD4+ and CD8+ T cells was performed in 100 and 137 participants, respectively. The weighted cumulative incidence was 51.9% (95% confidence interval [CI]: 48.7–55.1) and was inversely related to age. Anti‐RBD total antibodies were detected in 97% of participants; vaccinated and SARS‐CoV‐2‐experienced (VAC‐ex; n = 442) presented higher levels (p < 0.001) than vaccinated/naïve (VAC‐n; n = 472) and nonvaccinated/experienced (UNVAC‐ex; n = 63) subjects. Antibody levels correlated inversely with time elapsed since last vaccine dose in VAC‐n (Rho, −0.52; p < 0.001) but not in VAC‐ex (rho −0.02; p = 0.57). Heterologous booster shots resulted in increased anti‐RBD antibody levels compared with homologous schedules in VAC‐n, but not in VAC‐ex. NtAbs against Omicron BA.1 were detected in 94%, 75%, and 50% of VAC‐ex, VAC‐n and UNVAC‐ex groups, respectively. For Omicron BA.2, the figures were 97%, 84%, and 40%, respectively. SARS‐CoV‐2‐S‐reactive IFN‐γ T cells were detected in 73%, 75%, and 64% of VAC‐ex, VAC‐n and UNVAC‐ex, respectively. Median frequencies for both T‐cell subsets were comparable across groups. In summary, by April 2022, around half of the VC population had been infected with SARS‐CoV‐2 and, due to extensive vaccination, displayed hybrid immunity.

A third Comirnaty® vaccine dose increased SARS-CoV-2-receptor binding domain antibody levels (median of 93-fold) and neutralizing antibody titers against Wuhan-Hu-1 (median, 57-fold), Beta (median, 22-fold), Delta, (median, 43-fold) and Omicron (median, 8-fold) variants, particularly in SARS-CoV-2-naïve individuals, but had a negligible impact on S-reactive T-cell immunity in nursing home residents.

The information provided by SARS‐CoV‐2 spike (S)‐targeting immunoassays can be instrumental in clinical‐decision making. We compared the performance of the Elecsys® Anti‐SARS‐CoV‐2 S assay (Roche Diagnostics) and the LIAISON® SARS‐CoV‐2 TrimericS IgG assay (DiaSorin) using a total of 1176 sera from 797 individuals, of which 286 were from vaccinated‐SARS‐CoV‐2/experienced (Vac‐Ex), 581 from vaccinated/naïve (Vac‐N), 147 from unvaccinated/experienced (Unvac‐Ex), and 162 from unvaccinated/naïve (Unvac‐N) individuals. The Roche assay returned a higher number of positive results (907 vs. 790; p = 0.45; overall sensitivity: 89.3% vs. 77.6%). The concordance between results provided by the two immunoassays was higher for sera from Vac‐N (ϰ: 0.58; interquartile ranges [IQR]: 0.50−0.65) than for sera from Vac‐Ex (ϰ: 0.19; IQR: −0.14 to 0.52) or Unvac‐Ex (ϰ: 0.18; IQR: 0.06−0.30). Discordant results occurred more frequently among sera from Unvac‐Ex (34.7%) followed by Vac‐N (14.6%) and Vac‐Ex (2.7%). Antibody levels quantified by both immunoassays were not significantly different when <250 (p = 0.87) or <1000 BAU/ml (p = 0.13); in contrast, for sera ≥1000 BAU/ml, the Roche assay returned significantly higher values than the DiaSorin assay (p < 0.008). Neutralizing antibody titers (NtAb) were measured in 127 sera from Vac‐Ex or Vac‐N using a S‐pseudotyped virus neutralization assay of Wuhan‐Hu‐1, Omicron BA.1, and Omicron BA.2. The correlation between antibody levels and NtAb titers was higher for sera from Vac‐N than those from Vac‐Ex, irrespective of the (sub)variant considered. In conclusion, neither qualitative nor quantitative results returned by both immunoassays are interchangeable. The performance of both assays was found to be greatly influenced by the vaccination and SARS‐CoV‐2 infection status of individuals.

The effect of a third vaccine dose (3D) of homologous mRNA vaccine on blood levels of SARS-CoV-2-receptor binding domain (RBD)-total antibodies was assessed in 40 hemodialysis patients (HD) and 21 kidney transplant recipients (KTR) at a median of 46 days after 3D. Anti-RBD antibodies were detected in 39/40 HD and 19/21 KTR. Overall, 3D boosted anti-RBD antibody levels (median: 58-fold increase). Neutralizing antibodies (NtAb) against the Wuhan-Hu-1, Delta, and Omicron variants were detected in 14, 13, and 11 out of 14 HD patients, and in 5, 5, and 4 out of 8 KTR patients, respectively. The median fold increase in NtAb titers in HD patients was 77, 28, and 5 and 56, 37, and 9 in KTR patients for each respective variant. SARS-CoV-2-S S-IFN-γ-producing CD8+ and CD4+ T-cell responses were detected in the majority of HD (35 and 36/37, respectively) and all KTR (16/16) patients at 3D. Overall, the administration of 3D boosted T-cell levels in both population groups. In conclusion, a homologous mRNA COVID-19 vaccine 3D exerts a booster effect on anti-RBD antibodies, NtAb binding to Wuhan-Hu-1, Delta, and Omicron variants, and SARS-CoV-2-S-IFN-γ-producing T cells in both HD and KTR patients. The magnitude of the effect was more marked in HD than KTR patients.

No abstract

Supervised machine learning (ML) methods have been used to predict antibody responses elicited by COVID-19 vaccines in a variety of clinical settings. Here, we explored the reliability of a ML approach to predict the presence of detectable neutralizing antibody responses (NtAb) against Omicron BA.2 and BA.4/5 sublineages in the general population. Anti-SARS-CoV-2 receptor-binding domain (RBD) total antibodies were measured by the Elecsys ® Anti-SARS-CoV-2 S assay (Roche Diagnostics) in all participants. NtAbs against Omicron BA.2 and BA4/5 were measured using a SARS-CoV-2 S pseudotyped neutralization assay in 100 randomly selected sera. A ML model was built using the variables of age, vaccination (number of doses) and SARS-CoV-2 infection status. The model was trained in a cohort (TC) comprising 931 participants and validated in an external cohort (VC) including 787 individuals. Receiver operating characteristics analysis indicated that an anti-SARS-CoV-2 RBD total antibody threshold of 2300 BAU/mL best discriminated between participants either exhibiting or not detectable Omicron BA.2 and Omicron BA.4/5-Spike targeted NtAb responses (87% and 84% precision, respectively). The ML model correctly classified 88% (793/901) of participants in the TC: 717/749 (95.7%) of those displaying ≥2300 BAU/mL and 76/152 (50%) of those exhibiting antibody levels <2300 BAU/mL. The model performed better in vaccinated participants, either with or without prior SARS-CoV-2 infection. The overall accuracy of the ML model in the VC was comparable. Our ML model, based upon a few easily collected parameters for predicting neutralizing activity against Omicron BA.2 and BA.4/5 (sub)variants circumvents the need to perform not only neutralization assays, but also anti-S serological tests, thus potentially saving costs in the setting of large seroprevalence studies.