Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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

Vikström, Linnea ; Fjällström, Peter LU ; Gwon, Yong-Dae ; Sheward, Daniel J ; Wigren-Byström, Julia ; Evander, Magnus ; Bladh, Oscar ; Widerström, Micael ; Molnar, Christian and Rasmussen, Gunlög , et al. (2023) In The Lancet regional health. Europe 30.
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
The Lancet regional health. Europe
volume
30
article number
100646
publisher
Elsevier
external identifiers
  • scopus:85156247971
  • pmid:37363799
ISSN
2666-7762
DOI
10.1016/j.lanepe.2023.100646
project
Improved preparedness for future pandemics and other health crises through large-scale disease surveillance
language
English
LU publication?
yes
additional info
© 2023 The Author(s).
id
5c97927b-5707-4d43-8bb2-ed872dffaa1b
date added to LUP
2023-08-15 13:26:20
date last changed
2024-04-20 00:40:21
@article{5c97927b-5707-4d43-8bb2-ed872dffaa1b,
  abstract     = {{<p>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.</p><p>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.</p><p>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.</p><p>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.</p><p>FUNDING: Swedish Research Council, SciLifeLab via Knut and Alice Wallenberg Foundation, VINNOVA. Swedish Healthcare Regions, and Erling Persson Foundation.</p>}},
  author       = {{Vikström, Linnea and Fjällström, Peter and Gwon, Yong-Dae and Sheward, Daniel J and Wigren-Byström, Julia and Evander, Magnus and Bladh, Oscar and Widerström, Micael and Molnar, Christian and Rasmussen, Gunlög and Bennet, Louise and Åberg, Mikael and Björk, Jonas and Tevell, Staffan and Thålin, Charlotte and Blom, Kim and Klingström, Jonas and Murrell, Ben and Ahlm, Clas and Normark, Johan and Johansson, Anders F and Forsell, Mattias N E}},
  issn         = {{2666-7762}},
  language     = {{eng}},
  month        = {{05}},
  publisher    = {{Elsevier}},
  series       = {{The Lancet regional health. Europe}},
  title        = {{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}},
  url          = {{http://dx.doi.org/10.1016/j.lanepe.2023.100646}},
  doi          = {{10.1016/j.lanepe.2023.100646}},
  volume       = {{30}},
  year         = {{2023}},
}