Risk factors associated with cytomegalovirus reactivation and disease in critically-ill COVID-19 and non-COVID-19 patients, concomitantly admitted to intensive care

Critically-ill patients are at increased risk for cytomegalovirus (CMV) reactivation, associated with adverse clinical outcomes. Given the surge in intensive care unit (ICU) admissions during the COVID-19 pandemic and the continued burden of critical illness associated with the ongoing circulation of SARS-CoV-2, we sought to resolve risk factors for CMV reactivation and disease within the broader ICU patient population including those with and without COVID-19, to identify common and potentially distinct contributors to CMV reactivation and disease in this vulnerable setting. This prospective study included 208 adult ICU (85 COVID-19, and 123 concomitant non-COVID-19) patients, monitored weekly for CMV DNAemia. CMV reactivation was categorized as any detectable DNAemia or as clinically-significant reactivation characterized by high-level DNAemia (≥ 1000 IU/mL) and/or CMV disease. Overall, 29.8% of ICU patients experienced CMV reactivation, with 10.6% exhibiting clinically-significant reactivation. COVID-19 ICU patients had significantly higher rates of any CMV reactivation (40% vs. 23%, p = 0.009), high-level DNAemia (18% vs. 2%, p = 0.001), and CMV disease (12% vs. 1%, p = 0.001) compared to concomitant non-COVID-19 patients. Risk factors associated with clinically-significant CMV reactivation in ICU patients included septic shock, lower absolute lymphocyte count, high-dose steroid use, multiple blood transfusions, and COVID-19. CMV reactivation correlated with prolonged ventilation, hospitalization, and ICU stay, and increased in-hospital mortality. The high rates of clinically-significant CMV reactivation in both COVID-19 and non-COVID-19 ICU patients and the identified risk factors, along with the worse clinical outcomes linked to CMV reactivation, highlight the need for vigilant monitoring of CMV reactivation and for consideration of early antiviral treatment in ICU patients at risk, and support future interventional trials.