Vaccine-induced correlate of protection against fatal COVID-19 in older and frail adults during waves of neutralization-resistant variants of concern: an observational study

作者：Linnea Vikström, Peter Fjällström, Yong-Dae Gwon, Daniel J. Sheward, Julia Wigren-Byström, Magnus Evander, Oscar Bladh, Micael Widerström, Christian Molnár, Gunlög Rasmussen, Louise Bennet, Mikael Åberg, Jonas Björk, Staffan Tevell, Charlotte Thålin, Kim Blom, Jonas Klingström, Ben Murrell, Clas Ahlm, Johan Normark, Anders Johansson, Mattias N.E. Forsell · 发表于：The Lancet Regional Health - Europe · 年份：2023 · DOI：10.1016/j.lanepe.2023.100646 · 被引用次数：28 · 研究领域：SARS-CoV-2 and COVID-19 Research、Immune responses and vaccinations、COVID-19 Clinical Research Studies

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 of nursing home residents in Sweden. We analyzed immunological and registry data from 16 September 2021 to 31 August 2022 with follow-up of deaths to 30 September 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 in blood and corresponding increase of neutralizing antibodies. The 4th mRNA vaccine dose boosted 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 associated 30-day mortality was 9.1%. We found no indication that levels of vaccine-induced antibodies protected against infection with Omicron VOCs. In contrast, the risk of death was inversely correlated to levels of S-directed IgG below the 20th percentile. The death risk plateaued at population average above the lower 35th percentile of S-binding IgG. Interpretation: In the absence of neutralizing antibodies that protect from infection, quantification of S-binding IgG post v...