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

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 NormarkAnders F Johansson, Mattias N E Forsell

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	100646
Journal	The Lancet regional health. Europe
Volume	30
Early online date	2023 May 6
DOIs	https://doi.org/10.1016/j.lanepe.2023.100646
Publication status	Published - 2023

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Subject classification (UKÄ)

Infectious Medicine

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.lanepe.2023.100646Licence: CC BY

PREPARE: Improved preparedness for future pandemics and other health crises through large-scale disease surveillance
Björk, J. (Researcher), Inghammar, M. (Researcher), Litins'ka, Y. (Researcher), Forsell, M. (Researcher), Ohlsson, M. (Researcher), Lingman, M. (Researcher), Wigren Byström, J. (Researcher), Almgren, M. (Researcher), Kahn, F. (Researcher), Rasmussen, M. (Researcher), Malmqvist, U. (Researcher), Mitchell, A. (Researcher), Neumann, A. (Researcher), Dietler, D. (Researcher), Bennet, L. (Researcher), Bonander, C. (Researcher), Eriksson, T. (Researcher), Björkelund, A. (Researcher), Vilhelmsson, A. (Researcher), Nilsson, A. (Researcher), Wetterberg, H. (Researcher), Hassan, M. (Research student) & Hashemi, A. S. (Researcher)
Swedish Research Council
2021/01/01 → 2025/12/31
Project: Research

Cite this

Vikström, L., Fjällström, P., Gwon, Y.-D., Sheward, D. J., Wigren-Byström, J., Evander, M., Bladh, O., Widerström, M., Molnar, C., Rasmussen, G., Bennet, L., Åberg, M., Björk, J., Tevell, S., Thålin, C., Blom, K., Klingström, J., Murrell, B., Ahlm, C., ... Forsell, M. N. E. (2023). 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. The Lancet regional health. Europe, 30, Article 100646. https://doi.org/10.1016/j.lanepe.2023.100646

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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.",

author = "Linnea Vikstr{\"o}m and Peter Fj{\"a}llstr{\"o}m and Yong-Dae Gwon and Sheward, {Daniel J} and Julia Wigren-Bystr{\"o}m and Magnus Evander and Oscar Bladh and Micael Widerstr{\"o}m and Christian Molnar and Gunl{\"o}g Rasmussen and Louise Bennet and Mikael {\AA}berg and Jonas Bj{\"o}rk and Staffan Tevell and Charlotte Th{\aa}lin and Kim Blom and Jonas Klingstr{\"o}m and Ben Murrell and Clas Ahlm and Johan Normark and Johansson, {Anders F} and Forsell, {Mattias N E}",

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year = "2023",

doi = "10.1016/j.lanepe.2023.100646",

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Vikström, L, Fjällström, P, Gwon, Y-D, Sheward, DJ, Wigren-Byström, J, Evander, M, Bladh, O, Widerström, M, Molnar, C, Rasmussen, G, Bennet, L, Åberg, M, Björk, J, Tevell, S, Thålin, C, Blom, K, Klingström, J, Murrell, B, Ahlm, C, Normark, J, Johansson, AF & Forsell, MNE 2023, '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', The Lancet regional health. Europe, vol. 30, 100646. https://doi.org/10.1016/j.lanepe.2023.100646

TY - JOUR

T1 - Vaccine-induced correlate of protection against fatal COVID-19 in older and frail adults during waves of neutralization-resistant variants of concern

T2 - an observational study

AU - Vikström, Linnea

AU - Fjällström, Peter

AU - Gwon, Yong-Dae

AU - Sheward, Daniel J

AU - Wigren-Byström, Julia

AU - Evander, Magnus

AU - Bladh, Oscar

AU - Widerström, Micael

AU - Molnar, Christian

AU - Rasmussen, Gunlög

AU - Bennet, Louise

AU - Åberg, Mikael

AU - Björk, Jonas

AU - Tevell, Staffan

AU - Thålin, Charlotte

AU - Blom, Kim

AU - Klingström, Jonas

AU - Murrell, Ben

AU - Ahlm, Clas

AU - Normark, Johan

AU - Johansson, Anders F

AU - Forsell, Mattias N E

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

U2 - 10.1016/j.lanepe.2023.100646

DO - 10.1016/j.lanepe.2023.100646

M3 - Article

C2 - 37363799

SN - 2666-7762

VL - 30

JO - The Lancet regional health. Europe

JF - The Lancet regional health. Europe

M1 - 100646

ER -

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

Abstract

Bibliographical note

Subject classification (UKÄ)

UN SDGs

Access to Document

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PREPARE: Improved preparedness for future pandemics and other health crises through large-scale disease surveillance

Cite this