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ORIGINAL RESEARCH article

Front. Microbiol.
Sec. Virology
Volume 15 - 2024 | doi: 10.3389/fmicb.2024.1508423
This article is part of the Research Topic The interaction of chronic viral infections and SARS-CoV-2 infection and its effect on the COVID-19 pathogenesis View all 6 articles

Can There Be Calm during a Cytokine Storm? Immune Checkpoint Pathways Affecting the Severity of COVID-19 Disease

Provisionally accepted
Matyas Meggyes Matyas Meggyes 1Dávid U. Nagy Dávid U. Nagy 2Ildiko Toth Ildiko Toth 1Timoteus Feik Timoteus Feik 1Agnes Peterfalvi Agnes Peterfalvi 1Polgár Beáta Polgár Beáta 1Dávid Sipos Dávid Sipos 1Agnes Kemeny Agnes Kemeny 1Laszlo Szereday Laszlo Szereday 1*
  • 1 Medical School, University of Pécs, Pécs, Hungary
  • 2 Faculty of Medicine, Martin Luther University of Halle-Wittenberg, Halle/Saale, Germany

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

    The COVID-19 pandemic has become a global health crisis, eliciting varying severity in infected individuals. This study aimed to explore the immune profiles between moderate and severe COVID-19 patients experiencing a cytokine storm and their association with mortality. This study highlights the role of PD-1/PD-L1 and the TIGIT/CD226/CD155/CD112 pathways in COVID-19 patients. Methods: We performed a study using flow cytometry to compare the phenotypic and functional characteristics of peripheral blood mononuclear cells in patients with moderate or severe disease and healthy individuals. Soluble immune checkpoint molecule and ligand levels were measured by Luminex. Results: Severe patients show reduced CD8+ T cell frequency, hyperactivation of CD8+ T, NK and NKT cells with concurrent upregulation of immune checkpoint ligands in monocytes. TIGIT expression by CD8+ T and NK cells and PD-1 by NKT cells suggest a spectrum of immune dysfunction, encompassing both hyperactivation and features of exhaustion. This dual phenomenon likely contributes to the impaired viral clearance and the exacerbation of inflammation characteristic of severe disease. Additionally, the study suggests that increased activation and cytotoxicity of NK cells may be associated with fatal outcomes in severe COVID-19 infection. Conclusion: These findings shed light on the intricate immune response regulation in COVID-19, emphasizing the importance of immune checkpoint pathways and activation signatures in disease severity. A novel aspect of this study is that it includes only COVID-19 patients experiencing cytokine storms, allowing for a focused analysis of immune dysregulation during this critical phase of the disease.

    Keywords: SARS-CoV-2, Cytokine storm, immune checkpoints, COVID-19, immune dysregulation The study reveals that s

    Received: 09 Oct 2024; Accepted: 03 Dec 2024.

    Copyright: © 2024 Meggyes, Nagy, Toth, Feik, Peterfalvi, Beáta, Sipos, Kemeny and Szereday. 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: Laszlo Szereday, Medical School, University of Pécs, Pécs, Hungary

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