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Observational Study
. 2024 May 8:15:1386586.
doi: 10.3389/fimmu.2024.1386586. eCollection 2024.

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

Dominik Ziehe #  1 , Alexander Wolf #  1 , Tim Rahmel  1 , Hartmuth Nowak  1 , Helge Haberl  1 , Lars Bergmann  1 , Katharina Rump  1 , Birte Dyck  1 , Lars Palmowski  1 , Britta Marko  1 , Andrea Witowski  1 , Katrin Maria Willemsen  1 , Stephanie Pfaender  2 , Martin Eisenacher  3   4 , Moritz Anft  5 , Nina Babel  5 , Thilo Bracht  1   3 , Barbara Sitek  1   3 , Malte Bayer  1   3 , Alexander Zarbock  6 , Thilo von Groote  6 , Christian Putensen  7 , Stefan Felix Ehrentraut  7 , Christina Weisheit  7 , Michael Adamzik  1 , Matthias Unterberg #  1 , Björn Koos #  1
Affiliations
Observational Study

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

Dominik Ziehe et al. Front Immunol. .

Abstract

Background: Sepsis, 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.

Methods: A 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.

Results: The 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.

Discussion: These 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.

Conclusion: This 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.

Keywords: COVID-19 risk stratification; COVID-19 survival; cross-reactive CD8+ T-cells; human cytomegalovirus; viral sepsis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Grouping of patients with COVID-19 induced sepsis (left) and control subjects without infection (right) according to their CMV serostatus on day 1 and subsequently according to age (<= vs >60 years).
Figure 2
Figure 2
Proportion of CMV-seropositive (red) versus -seronegative (blue) patients in the (A) total cohorts (COVID-19 versus controls) and (B) in the subgroup of non-geriatric patients (COVID-19 versus controls).
Figure 3
Figure 3
30-day survival (Kaplan-Meier curve) based on HCMV serostatus in (A) the overall cohort and (B) in the subgroup of non-geriatric patients.
See this image and copyright information in PMC

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