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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Inflammation
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1459593

Impact of COVID-19, Lockdowns and Vaccination on Immune Responses in a HIV cohort in the Netherlands

Provisionally accepted
Twan Otten Twan Otten 1,2*Xun Jiang Xun Jiang 3Manoj Kumar Gupta Manoj Kumar Gupta 3Nadira Vadaq Nadira Vadaq 1Maartje Cleophas Maartje Cleophas 1Jéssica C. dos Santos Jéssica C. dos Santos 1Albert L. Groenendijk Albert L. Groenendijk 4Wilhelm Vos Wilhelm Vos 5Louise Van Eekeren Louise Van Eekeren 1Marc Blaauw Marc Blaauw 1Elise M. Meeder Elise M. Meeder 6Olivier Richel Olivier Richel 1Vasiliki Matzaraki Vasiliki Matzaraki 1Jan Van Lunzen Jan Van Lunzen 1Leo A. Joosten Leo A. Joosten 1Yang Li Yang Li 3Cheng-Jian Xu Cheng-Jian Xu 3Andre Van Der Ven Andre Van Der Ven 1Mihai Netea Mihai Netea 1*
  • 1 Radboud University Medical Centre, Nijmegen, Netherlands
  • 2 Elisabeth Tweesteden Hospital (ETZ), Tilburg, Netherlands
  • 3 Centre for Individualised Infection Medicine, Helmholtz Center for Infection Research, Helmholtz Association of German Research Centers (HZ), Hannover, Germany
  • 4 Erasmus Medical Center, Rotterdam, Netherlands
  • 5 Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam, Netherlands
  • 6 Donders Centre for Neuroscience, Radboud University, Nijmegen, Gelderland, Netherlands

The final, formatted version of the article will be published soon.

    During the COVID-19 pandemic, major events with immune-modulating effects at populationlevel included COVID-19 infection, lockdowns, and mass vaccinations campaigns. As immune responses influence many immune-mediated diseases, population scale immunological changes may have broad consequences. We investigated the impact of lockdowns, COVID-19 infection and vaccinations on immune responses in the 2000HIV study including 1895 asymptomatic virally-suppressed people living with HIV recruited between October 2019 and October 2021. Their inflammatory profile was assessed by targeted plasma proteomics, immune responsiveness by cytokine production capacity of circulating immune cells, and epigenetic profile by genome-wide DNA methylation of immune cells. Past mild COVID-19 infection had limited long-term immune effects. In contrast, COVID-19 vaccines and especially lockdowns significantly altered both the epigenetic profile in immune cells at DNA methylation level and immune responses. Lockdowns resulted in a strong overall exaggerated immune responsiveness, while COVID-19 vaccines moderately dampened immune responses. Lockdown-associated immune responsiveness alterations were confirmed in 30 healthy volunteers from the 200FG cohort that, like the 2000HIV study, is part of the Human Functional Genomics Project. Our data suggest that lockdowns have unforeseen immunological effects. Furthermore, COVID-19 vaccines have immunological effects beyond anti-SARS-CoV-2 activity, and studies of their impact on non-COVID-19 immune-mediated pathology are warranted.

    Keywords: COVID-19, Lockdowns, Vaccination, Inflammation, Hygiene Hypothesis

    Received: 04 Jul 2024; Accepted: 26 Aug 2024.

    Copyright: © 2024 Otten, Jiang, Gupta, Vadaq, Cleophas, dos Santos, Groenendijk, Vos, Van Eekeren, Blaauw, Meeder, Richel, Matzaraki, Van Lunzen, Joosten, Li, Xu, Van Der Ven and Netea. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Twan Otten, Radboud University Medical Centre, Nijmegen, Netherlands
    Mihai Netea, Radboud University Medical Centre, Nijmegen, Netherlands

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.