Association Between Pulmonary Aspergillosis And Cytomegalovirus Reactivation In Critically Ill Covid-19 Patients: A Prospective Observational Cohort Study.

COVID-19-associated invasive pulmonary aspergillosis (CAPA) is common and is associated with poor outcomes in critically ill patients. This prospective observational study aimed to ex-plore the association between CAPA development and the incidence and prognosis of cytomegalo-virus (CMV) reactivation in critically ill COVID-19 patients. We included all consecutive criti-cally ill adult patients with confirmed COVID-19 infection who were admitted to three COVID-19 intensive care units (ICUs) in an Italian hospital from February 25, 2020, to May 8, 2022. A standardized procedure was employed for early detection of CAPA. Risk factors associ-ated with CAPA and CMV reactivation and the association between CMV recurrence and mor-tality were estimated using adjusted Cox proportional hazard regression models. CAPA oc-curred in 96 patients (16,6%) of the 579 patients analyzed. Among the CAPA population, 40 (41,7%) patients developed CMV blood reactivation with a median time of 18 days (IQR 7-27). The CAPA+CMV group did not exhibit a significantly higher 90-day mortality rate (62.5% vs. 48.2%) than the CAPA alone group (p=0.166). The CAPA+CMV group had a longer ICU stay, few-er ventilation-free days, and a higher rate of secondary bacterial infections than the control group of CAPA alone. In the CAPA population, prior immunosuppression was the only independent risk factor for CMV reactivation (HR 2.33, 95% C.I. 1.21-4.48, p=0.011). In critically ill COVID-19 pa-tients, CMV reactivation is common in those with a previous CAPA diagnosis. Basal immuno-suppression before COVID-19 appeared to be the primary independent variable affecting CMV reactivation in patients with CAPA. Furthermore, the association of CAPA+CMV versus CAPA alone appears to impact ICU length of stay and secondary bacterial infections but not mortality.