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

Linnea Vikström; Peter Fjällström; Yong-Dae Gwon; Daniel J Sheward; Julia Wigren-Byström; Magnus Evander; Oscar Bladh; Micael Widerström; Christian Molnar; Gunlög Rasmussen; Louise Bennet; Mikael Åberg; Jonas Björk; Staffan Tevell; Charlotte Thålin; Kim Blom; Jonas Klingström; Ben Murrell; Clas Ahlm; Johan Normark; Anders F Johansson; Mattias N E Forsell

doi:10.1016/j.lanepe.2023.100646

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

Lancet Reg Health Eur. 2023 May 6:30:100646. doi: 10.1016/j.lanepe.2023.100646. Online ahead of print.

Authors

Linnea Vikström¹, Peter Fjällström¹, Yong-Dae Gwon¹, Daniel J Sheward², Julia Wigren-Byström¹, Magnus Evander¹, Oscar Bladh³, Micael Widerström¹, Christian Molnar⁴, Gunlög Rasmussen⁵, Louise Bennet⁶, Mikael Åberg⁷, Jonas Björk⁸, Staffan Tevell⁹, Charlotte Thålin³, Kim Blom¹⁰, Jonas Klingström¹¹, Ben Murrell², Clas Ahlm¹, Johan Normark¹, Anders F Johansson¹, Mattias N E Forsell¹

Affiliations

¹ The Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
² The Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden.
³ The Department of Clinical Sciences, Karolinska Institutet Danderyd Hospital, Stockholm, Sweden.
⁴ Familjeläkarna, Stockholm, Sweden.
⁵ School of Medical Sciences, Örebro University, Örebro, Sweden.
⁶ Department of Clinical Sciences, Clinical Studies Sweden, Forum South, Skåne University Hospital, Lund University, Lund, Sweden.
⁷ The Department of Medical Sciences, Clinical Chemistry and SciLifeLab, Uppsala University, Uppsala, Sweden.
⁸ The Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
⁹ Faculty of Medicine and Health, The Department of Infectious Diseases, Karlstad Hospital and Centre for Clinical Research and Education, Region Värmland, Örebro University, Örebro, Sweden.
¹⁰ The Swedish Public Health Agency, Stockholm, Sweden.
¹¹ The Department of Biomedical Clinical Sciences, Linköpings University, Linköping, Sweden.

Abstract

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 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, SciLifeLab via Knut and Alice Wallenberg Foundation, VINNOVA. Swedish Healthcare Regions, and Erling Persson Foundation.

Keywords: COVID-19; Correlate of protection; Immune monitoring of vulnerable populations; Longevity of vaccination; Open cohort study; Vaccination; Vulnerable population.