Effect of Cytomegalovirus Reactivation on Inflammatory Status and Mortality of Older COVID-19 Patients

Int J Mol Sci. 2023 Apr 6;24(7):6832. doi: 10.3390/ijms24076832.

Abstract

Herpesviridae reactivation such as cytomegalovirus (CMV) has been described in severe COVID-19 (COronaVIrusDisease-2019). This study aimed to understand if CMV reactivation in older COVID-19 patients is associated with increased inflammation and in-hospital mortality. In an observational single-center cohort study, 156 geriatric COVID-19 patients were screened for CMV reactivation by RT-PCR. Participants underwent a comprehensive clinical investigation that included medical history, functional evaluation, laboratory tests and cytokine assays (TNF-α, IFN-α, IL-6, IL-10) at hospital admission. In 19 (12.2%) of 156 COVID-19 patients, CMV reactivation was detected. Multivariate Cox regression models showed that in-hospital mortality significantly increased among CMV positive patients younger than 87 years (HR: 9.94, 95% CI: 1.66-59.50). Other factors associated with in-hospital mortality were C-reactive protein (HR: 1.17, 95% CI: 1.05-1.30), neutrophil count (HR: 1.20, 95% CI: 1.01-1.42) and clinical frailty scale (HR:1.54, 95% CI: 1.04-2.28). In patients older than 87 years, neutrophil count (HR: 1.13, 95% CI: 1.05-1.21) and age (HR: 1.15, 95% CI: 1.01-1.31) were independently associated with in-hospital mortality. CMV reactivation was also correlated with increased IFN-α and TNF-α serum levels, but not with IL-6 and IL-10 serum changes. In conclusion, CMV reactivation was an independent risk factor for in-hospital mortality in COVID-19 patients younger than 87 years old, but not in nonagenarians.

Keywords: COVID-19 patients; aging; cytomegalovirus; inflammation; mortality.

MeSH terms

  • Aged
  • Aged, 80 and over
  • COVID-19* / complications
  • Cohort Studies
  • Cytomegalovirus / physiology
  • Cytomegalovirus Infections* / complications
  • Humans
  • Interleukin-10
  • Interleukin-6
  • Retrospective Studies
  • Tumor Necrosis Factor-alpha
  • Virus Activation

Substances

  • Interleukin-10
  • Interleukin-6
  • Tumor Necrosis Factor-alpha

Grants and funding

This work was supported by the Italian Health Ministry (Ricerca Corrente to IRCCS INRCA) and MARCHE Region.