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.

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.

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