Impact of age and comorbidities on SARS-CoV-2 vaccine-induced T cell immunity

Lisa Loksø Dietz; Anna Karina Juhl; Ole Schmeltz Søgaard; Joanne Reekie; Henrik Nielsen; Isik Somuncu Johansen; Thomas Benfield; Lothar Wiese; Nina Breinholt Stærke; Tomas Østergaard Jensen; Stine Finne Jakobsen; Rikke Olesen; Kasper Iversen; Kamille Fogh; Jacob Bodilsen; Kristine Toft Petersen; Lykke Larsen; Lone Wulff Madsen; Susan Olaf Lindvig; Inge Kristine Holden; Dorthe Raben; Sidsel Dahl Andersen; Astrid Korning Hvidt; Signe Rode Andreasen; Eva Anna Marianne Baerends; Jens Lundgren; Lars Østergaard; Martin Tolstrup; ENFORCE Study Group

doi:10.1038/s43856-023-00277-x

Impact of age and comorbidities on SARS-CoV-2 vaccine-induced T cell immunity

Lisa Loksø Dietz^*, Anna Karina Juhl^*, Ole Schmeltz Søgaard, Joanne Reekie, Henrik Nielsen, Isik Somuncu Johansen, Thomas Benfield, Lothar Wiese, Nina Breinholt Stærke, Tomas Østergaard Jensen, Stine Finne Jakobsen, Rikke Olesen, Kasper Iversen, Kamille Fogh, Jacob Bodilsen, Kristine Toft Petersen, Lykke Larsen, Lone Wulff Madsen, Susan Olaf Lindvig, Inge Kristine HoldenDorthe Raben, Sidsel Dahl Andersen, Astrid Korning Hvidt, Signe Rode Andreasen, Eva Anna Marianne Baerends, Jens Lundgren, Lars Østergaard, Martin Tolstrup, ENFORCE Study Group

^*Corresponding author for this work

Department of Clinical Medicine - Department of Infectious Diseases

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Abstract

BACKGROUND: Older age and chronic disease are important risk factors for developing severe COVID-19. At population level, vaccine-induced immunity substantially reduces the risk of severe COVID-19 disease and hospitalization. However, the relative impact of humoral and cellular immunity on protection from breakthrough infection and severe disease is not fully understood.

METHODS: In a study cohort of 655 primarily older study participants (median of 63 years (IQR: 51-72)), we determined serum levels of Spike IgG antibodies using a Multiantigen Serological Assay and quantified the frequency of SARS-CoV-2 Spike-specific CD4 + and CD8 + T cells using activation induced marker assay. This enabled characterization of suboptimal vaccine-induced cellular immunity. The risk factors of being a cellular hypo responder were assessed using logistic regression. Further follow-up of study participants allowed for an evaluation of the impact of T cell immunity on breakthrough infections.

RESULTS: We show reduced serological immunity and frequency of CD4 + Spike-specific T cells in the oldest age group (≥75 years) and higher Charlson Comorbidity Index (CCI) categories. Male sex, age group ≥75 years, and CCI > 0 is associated with an increased likelihood of being a cellular hypo-responder while vaccine type is a significant risk factor. Assessing breakthrough infections, no protective effect of T cell immunity is identified.

CONCLUSIONS: SARS-CoV-2 Spike-specific immune responses in both the cellular and serological compartment of the adaptive immune system increase with each vaccine dose and are progressively lower with older age and higher prevalence of comorbidities. The findings contribute to the understanding of the vaccine response in individuals with increased risk of severe COVID-19 disease and hospitalization.

Original language	English
Article number	58
Journal	Communications Medicine
Volume	3
Issue	1
Number of pages	13
ISSN	2730-664X
DOIs	https://doi.org/10.1038/s43856-023-00277-x
Publication status	Published - Apr 2023

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Dietz, L. L., Juhl, A. K., Søgaard, O. S., Reekie, J., Nielsen, H., Johansen, I. S., Benfield, T., Wiese, L., Stærke, N. B., Jensen, T. Ø., Jakobsen, S. F., Olesen, R., Iversen, K., Fogh, K., Bodilsen, J., Petersen, K. T., Larsen, L., Madsen, L. W., Lindvig, S. O., ... ENFORCE Study Group (2023). Impact of age and comorbidities on SARS-CoV-2 vaccine-induced T cell immunity. Communications Medicine, 3(1), Article 58. https://doi.org/10.1038/s43856-023-00277-x

@article{79d7b208f25a46b5a2ec6a8d3b1ffd70,

title = "Impact of age and comorbidities on SARS-CoV-2 vaccine-induced T cell immunity",

abstract = "BACKGROUND: Older age and chronic disease are important risk factors for developing severe COVID-19. At population level, vaccine-induced immunity substantially reduces the risk of severe COVID-19 disease and hospitalization. However, the relative impact of humoral and cellular immunity on protection from breakthrough infection and severe disease is not fully understood.METHODS: In a study cohort of 655 primarily older study participants (median of 63 years (IQR: 51-72)), we determined serum levels of Spike IgG antibodies using a Multiantigen Serological Assay and quantified the frequency of SARS-CoV-2 Spike-specific CD4 + and CD8 + T cells using activation induced marker assay. This enabled characterization of suboptimal vaccine-induced cellular immunity. The risk factors of being a cellular hypo responder were assessed using logistic regression. Further follow-up of study participants allowed for an evaluation of the impact of T cell immunity on breakthrough infections.RESULTS: We show reduced serological immunity and frequency of CD4 + Spike-specific T cells in the oldest age group (≥75 years) and higher Charlson Comorbidity Index (CCI) categories. Male sex, age group ≥75 years, and CCI > 0 is associated with an increased likelihood of being a cellular hypo-responder while vaccine type is a significant risk factor. Assessing breakthrough infections, no protective effect of T cell immunity is identified.CONCLUSIONS: SARS-CoV-2 Spike-specific immune responses in both the cellular and serological compartment of the adaptive immune system increase with each vaccine dose and are progressively lower with older age and higher prevalence of comorbidities. The findings contribute to the understanding of the vaccine response in individuals with increased risk of severe COVID-19 disease and hospitalization.",

author = "Dietz, {Lisa Loks{\o}} and Juhl, {Anna Karina} and S{\o}gaard, {Ole Schmeltz} and Joanne Reekie and Henrik Nielsen and Johansen, {Isik Somuncu} and Thomas Benfield and Lothar Wiese and St{\ae}rke, {Nina Breinholt} and Jensen, {Tomas {\O}stergaard} and Jakobsen, {Stine Finne} and Rikke Olesen and Kasper Iversen and Kamille Fogh and Jacob Bodilsen and Petersen, {Kristine Toft} and Lykke Larsen and Madsen, {Lone Wulff} and Lindvig, {Susan Olaf} and Holden, {Inge Kristine} and Dorthe Raben and Andersen, {Sidsel Dahl} and Hvidt, {Astrid Korning} and Andreasen, {Signe Rode} and Baerends, {Eva Anna Marianne} and Jens Lundgren and Lars {\O}stergaard and Martin Tolstrup and {ENFORCE Study Group}",

year = "2023",

month = apr,

doi = "10.1038/s43856-023-00277-x",

language = "English",

volume = "3",

journal = "Communications Medicine",

issn = "2730-664X",

publisher = "Nature Research",

number = "1",

}

Dietz, LL , Juhl, AK , Søgaard, OS, Reekie, J, Nielsen, H, Johansen, IS, Benfield, T, Wiese, L, Stærke, NB, Jensen, TØ, Jakobsen, SF, Olesen, R, Iversen, K, Fogh, K, Bodilsen, J, Petersen, KT, Larsen, L, Madsen, LW, Lindvig, SO, Holden, IK, Raben, D, Andersen, SD, Hvidt, AK, Andreasen, SR , Baerends, EAM, Lundgren, J, Østergaard, L , Tolstrup, M & ENFORCE Study Group 2023, 'Impact of age and comorbidities on SARS-CoV-2 vaccine-induced T cell immunity', Communications Medicine, vol. 3, no. 1, 58. https://doi.org/10.1038/s43856-023-00277-x

TY - JOUR

T1 - Impact of age and comorbidities on SARS-CoV-2 vaccine-induced T cell immunity

AU - Dietz, Lisa Loksø

AU - Juhl, Anna Karina

AU - Søgaard, Ole Schmeltz

AU - Reekie, Joanne

AU - Nielsen, Henrik

AU - Johansen, Isik Somuncu

AU - Benfield, Thomas

AU - Wiese, Lothar

AU - Stærke, Nina Breinholt

AU - Jensen, Tomas Østergaard

AU - Jakobsen, Stine Finne

AU - Olesen, Rikke

AU - Iversen, Kasper

AU - Fogh, Kamille

AU - Bodilsen, Jacob

AU - Petersen, Kristine Toft

AU - Larsen, Lykke

AU - Madsen, Lone Wulff

AU - Lindvig, Susan Olaf

AU - Holden, Inge Kristine

AU - Raben, Dorthe

AU - Andersen, Sidsel Dahl

AU - Hvidt, Astrid Korning

AU - Andreasen, Signe Rode

AU - Baerends, Eva Anna Marianne

AU - Lundgren, Jens

AU - Østergaard, Lars

AU - Tolstrup, Martin

AU - ENFORCE Study Group

PY - 2023/4

Y1 - 2023/4

N2 - BACKGROUND: Older age and chronic disease are important risk factors for developing severe COVID-19. At population level, vaccine-induced immunity substantially reduces the risk of severe COVID-19 disease and hospitalization. However, the relative impact of humoral and cellular immunity on protection from breakthrough infection and severe disease is not fully understood.METHODS: In a study cohort of 655 primarily older study participants (median of 63 years (IQR: 51-72)), we determined serum levels of Spike IgG antibodies using a Multiantigen Serological Assay and quantified the frequency of SARS-CoV-2 Spike-specific CD4 + and CD8 + T cells using activation induced marker assay. This enabled characterization of suboptimal vaccine-induced cellular immunity. The risk factors of being a cellular hypo responder were assessed using logistic regression. Further follow-up of study participants allowed for an evaluation of the impact of T cell immunity on breakthrough infections.RESULTS: We show reduced serological immunity and frequency of CD4 + Spike-specific T cells in the oldest age group (≥75 years) and higher Charlson Comorbidity Index (CCI) categories. Male sex, age group ≥75 years, and CCI > 0 is associated with an increased likelihood of being a cellular hypo-responder while vaccine type is a significant risk factor. Assessing breakthrough infections, no protective effect of T cell immunity is identified.CONCLUSIONS: SARS-CoV-2 Spike-specific immune responses in both the cellular and serological compartment of the adaptive immune system increase with each vaccine dose and are progressively lower with older age and higher prevalence of comorbidities. The findings contribute to the understanding of the vaccine response in individuals with increased risk of severe COVID-19 disease and hospitalization.

AB - BACKGROUND: Older age and chronic disease are important risk factors for developing severe COVID-19. At population level, vaccine-induced immunity substantially reduces the risk of severe COVID-19 disease and hospitalization. However, the relative impact of humoral and cellular immunity on protection from breakthrough infection and severe disease is not fully understood.METHODS: In a study cohort of 655 primarily older study participants (median of 63 years (IQR: 51-72)), we determined serum levels of Spike IgG antibodies using a Multiantigen Serological Assay and quantified the frequency of SARS-CoV-2 Spike-specific CD4 + and CD8 + T cells using activation induced marker assay. This enabled characterization of suboptimal vaccine-induced cellular immunity. The risk factors of being a cellular hypo responder were assessed using logistic regression. Further follow-up of study participants allowed for an evaluation of the impact of T cell immunity on breakthrough infections.RESULTS: We show reduced serological immunity and frequency of CD4 + Spike-specific T cells in the oldest age group (≥75 years) and higher Charlson Comorbidity Index (CCI) categories. Male sex, age group ≥75 years, and CCI > 0 is associated with an increased likelihood of being a cellular hypo-responder while vaccine type is a significant risk factor. Assessing breakthrough infections, no protective effect of T cell immunity is identified.CONCLUSIONS: SARS-CoV-2 Spike-specific immune responses in both the cellular and serological compartment of the adaptive immune system increase with each vaccine dose and are progressively lower with older age and higher prevalence of comorbidities. The findings contribute to the understanding of the vaccine response in individuals with increased risk of severe COVID-19 disease and hospitalization.

U2 - 10.1038/s43856-023-00277-x

DO - 10.1038/s43856-023-00277-x

M3 - Journal article

C2 - 37095240

SN - 2730-664X

VL - 3

JO - Communications Medicine

JF - Communications Medicine

IS - 1

M1 - 58

ER -

Impact of age and comorbidities on SARS-CoV-2 vaccine-induced T cell immunity

Abstract

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