Vaccine-induced correlate of protection against fatal COVID-19 in the old and frail during waves of neutralization resistant variants of concern. (preprint)

Background: To inform future preventive measures including repeated vaccinations, we have searched for a clinically useful immune correlate of protection against fatal Covid-19 among nursing homes residents. Methods: We performed repeated capillary blood sampling with analysis of S-binding IgG in an open cohort study with inclusion of nursing home residents in Sweden. We analyzed immunological and registry data collected from September 2021 with end of follow-up 31 August 2022. The study period included implementation of the 3rd and 4th mRNA monovalent vaccine doses and Omicron virus waves. Findings: A total of 3012 nursing home residents with median age 86 were enrolled. The 3rd mRNA dose elicited a 99-fold relative increase of S-binding IgG among 2606 blood-sampled individuals and corresponding increase of neutralizing antibodies. The 4th mRNA vaccine dose boosted the levels 3.8-fold. Half-life of S-binding IgG was 72 days. A total 528 residents acquired their first SARS-CoV-2 infection after the 3rd or the 4th vaccine dose and the 30-day mortality was 9.1%. We found no indication that antibodies protected against infection with Omicron, but that the risk of death was correlated to levels of S-directed IgG below the 20th percentile. In contrast, the risk plateaued at population average above lower 35th percentile of S-binding IgG. Interpretation: In the absence of neutralizing antibodies that protection from infection, quantification of S-binding IgG post vaccination may be useful to identify the most vulnerable for fatal Covid-19 among the oldest and frailest. This information is of importance for future strategies to protect vulnerable populations against neutralization resistant variants of concern. Funding: Swedish Research Council, SciLife, Knut and Alice Wallenberg Foundation and Vinnova.

Detection of asymptomatic SARS-CoV-2 exposed individuals by a sensitive S-based ELISA. (preprint)

To assess the current coronavirus pandemic, there is a pressing need to determine the exposure and seroconversion to SARS-CoV-2 on a local and global level. Here, we demonstrate a sensitive and specific S-protein based assay that is well suited for detection of weak SARS- CoV-2-directed IgG responses, and that could identify exposed individuals with asymptomatic infection without the requirement of PCR diagnostics. Our results raise the possibility that on- going population-based studies using less sensitive state-of-the-art serological assays may significantly underestimate the frequency of exposure and seroconversion to SARS-CoV-2.