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

Author:

Giacconi Robertina1ORCID,Cardelli Maurizio1,Piacenza Francesco1ORCID,Pierpaoli Elisa1ORCID,Farnocchia Elisabetta1,Di Rosa MirKo2ORCID,Bonfigli Anna Rita3ORCID,Casoli Tiziana4,Marchegiani Francesca5ORCID,Marcheselli Fiorella5ORCID,Recchioni Rina5,Stripoli Pierpaolo5,Galeazzi Roberta6,Cherubini Antonio7,Fedecostante Massimiliano7,Sarzani Riccardo89ORCID,Di Pentima Chiara89,Giordano Piero89,Antonicelli Roberto10ORCID,Provinciali Mauro1ORCID,Lattanzio Fabrizia3

Affiliation:

1. Advanced Technology Center for Aging Research, IRCCS INRCA, Via Birarelli 8, 60121 Ancona, Italy

2. Unit of Geriatric Pharmacoepidemiology and Biostatistics, IRCCS INRCA, 60124 Ancona, Italy

3. Scientific Direction, IRCCS INRCA, 60124 Ancona, Italy

4. Center for Neurobiology of Aging, IRCCS INRCA, 60121 Ancona, Italy

5. Center of Clinical Pathology and Innovative Therapy, IRCCS INRCA, 60121 Ancona, Italy

6. Clinical Laboratory and Molecular Diagnostic, Italian National Research Center on Aging, IRCCS INRCA, 60127 Ancona, Italy

7. Geriatria, Accettazione Geriatrica e Centro di Ricerca per L’invecchiamento, IRCCS INRCA, 60127 Ancona, Italy

8. Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, 60126 Ancona, Italy

9. Internal Medicine and Geriatrics, Italian National Research Centre on Aging, Hospital “U. Sestilli”, IRCCS INRCA, 60127 Ancona, Italy

10. Cardiology Unit, IRCCS INRCA, 60129 Ancona, Italy

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.

Funder

Italian Health Ministry

MARCHE Region

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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