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, Thea Kølsen Fischer (Member of study group)

*Corresponding author for this work


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 languageEnglish
JournalCommunications medicine
Issue number1
Pages (from-to)58
Publication statusPublished - 24 Apr 2023


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