Frontiers in Immunology (May 2024)

Exploring the relationship between HCMV serostatus and outcomes in COVID-19 sepsis

  • Dominik Ziehe,
  • Alexander Wolf,
  • Tim Rahmel,
  • Hartmuth Nowak,
  • Helge Haberl,
  • Lars Bergmann,
  • Katharina Rump,
  • Birte Dyck,
  • Lars Palmowski,
  • Britta Marko,
  • Andrea Witowski,
  • Katrin Maria Willemsen,
  • Stephanie Pfaender,
  • Martin Eisenacher,
  • Martin Eisenacher,
  • Moritz Anft,
  • Nina Babel,
  • Thilo Bracht,
  • Thilo Bracht,
  • Barbara Sitek,
  • Barbara Sitek,
  • Malte Bayer,
  • Malte Bayer,
  • Alexander Zarbock,
  • Thilo von Groote,
  • Christian Putensen,
  • Stefan Felix Ehrentraut,
  • Christina Weisheit,
  • Michael Adamzik,
  • Matthias Unterberg,
  • Björn Koos

DOI
https://doi.org/10.3389/fimmu.2024.1386586
Journal volume & issue
Vol. 15

Abstract

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BackgroundSepsis, a life-threatening condition caused by the dysregulated host response to infection, is a major global health concern. Understanding the impact of viral or bacterial pathogens in sepsis is crucial for improving patient outcomes. This study aimed to investigate the human cytomegalovirus (HCMV) seropositivity as a risk factor for development of sepsis in patients with COVID-19.MethodsA multicenter observational study enrolled 95 intensive care patients with COVID-19-induced sepsis and 80 post-surgery individuals as controls. HCMV serostatus was determined using an ELISA test. Comprehensive clinical data, including demographics, comorbidities, and 30-day mortality, were collected. Statistical analyses evaluated the association between HCMV seropositivity and COVID-19 induced sepsis.ResultsThe prevalence of HCMV seropositivity did not significantly differ between COVID-19-induced sepsis patients (78%) and controls (71%, p = 0.382) in the entire cohort. However, among patients aged ≤60 years, HCMV seropositivity was significantly higher in COVID-19 sepsis patients compared to controls (86% vs 61%, respectively; p = 0.030). Nevertheless, HCMV serostatus did not affect 30-day survival.DiscussionThese findings confirm the association between HCMV seropositivity and COVID-19 sepsis in non-geriatric patients. However, the lack of an independent effect on 30-day survival can be explained by the cross-reactivity of HCMV specific CD8+ T-cells towards SARS-CoV-2 peptides, which might confer some protection to HCMV seropositive patients. The inclusion of a post-surgery control group strengthens the generalizability of the findings. Further research is needed to elucidate the underlying mechanisms of this association, explore different patient populations, and identify interventions for optimizing patient management.ConclusionThis study validates the association between HCMV seropositivity and severe COVID-19-induced sepsis in non-geriatric patients, contributing to the growing body of evidence on viral pathogens in sepsis. Although HCMV serostatus did not independently influence 30-day survival, future investigations should focus on unraveling the intricate interplay between HCMV, immune responses, and COVID-19. These insights will aid in risk stratification and the development of targeted interventions for viral sepsis.

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