# Cytomegalovirus reactivation in mechanically ventilated patients with or without SARS-CoV-2 infection: A retrospective cohort study

## TL;DR

This study found that CMV reactivation was not significantly linked to SARS-CoV-2 infection in ventilated ICU patients, but was strongly associated with steroid use and increased mortality when combined with the virus.

## Contribution

The study clarifies the relationship between CMV reactivation and SARS-CoV-2 in ventilated ICU patients, identifying methylprednisolone as a key risk factor.

## Key findings

- CMV reactivation occurred in 34.7% of SARS-CoV-2 negative and 45.4% of positive patients, but the difference was not statistically significant.
- Methylprednisolone treatment was strongly associated with CMV reactivation in both unadjusted and adjusted analyses.
- Patients with both SARS-CoV-2 infection and CMV reactivation had higher mortality, while ganciclovir reduced day-60 mortality in those with CMV reactivation.

## Abstract

Data comparing the incidence, risk factors and outcomes of cytomegalovirus (CMV) reactivation in SARS-CoV-2 positive and negative patients remain controversial.

A retrospective cohort study in a tertiary center.

Patients admitted to the intensive care unit between December 2019 and May 2021, under invasive mechanical ventilation for 4 days or more and screened for CMV reactivation were included.

The primary outcome was the incidence of CMV reactivation in SARS-CoV-2 negative and positive patients. Secondary outcomes included risk factors for CMV reactivation in both populations and survival analysis according to CMV reactivation in SARS-CoV-2 negative and positive patients.

CMV reactivation occurred in 34.7% (n = 51/147) of SARS-CoV-2 negative patients and in 45.4% (83/183) of SARS-CoV-2 positive patients (p = 0.08). When considering competing factors, SARS-CoV-2 infection was not associated with CMV reactivation (sub-hazard ratio (SHR) = 1.01 [0.68–1.49], p = 0.98). Treatment with methylprednisolone was significantly associated with CMV reactivation in the unadjusted and adjusted analysis (SHR 2.81 [2.01–3.93] p < 0.001; SHR 2.84 [1.94–4.15] p < 0.001 respectively). Patients combining SARS-CoV-2 infection and CMV reactivation had a significantly higher all-cause mortality. Among patients presenting a CMV reactivation, the administration of ganciclovir was a protective factor for day-60 mortality (HR = 0.4; [0.22–0.74] p = 0.004).

In this large retrospective cohort, CMV reactivation was not significantly associated with SARS-CoV-2 infection in patients undergoing invasive mechanical ventilation for at least 4 days. The major risk factor for CMV reactivation was treatment with methylprednisolone. The combination of CMV reactivation with SARS-CoV-2 infection was associated with a higher mortality whereas ganciclovir treatment reduced mortality.