Late Breaking Abstract - Pulmonary CMV and HSV reactivations in critically ill COVID-19 patients with and without aspergillosis

Pulmonary reactivations of cytomegalovirus (CMV) and herpes simplex virus (HSV) are common in critically ill COVID-19 patients. We assessed the association between viral reactivation and COVID-19-associated pulmonary aspergillosis (CAPA). In a two-centre retrospective study, we included HSV and/or CMV IgG positive mechanically ventilated COVID-19 patients from 03-2020 to 09-2022. All patients underwent bronchoscopy for viral reactivations and CAPA. We used multistate models to estimate time-dependent probabilities of viral reactivation and CAPA occurrence. Time-dependent Cox regression, including age, severe immunosuppression and CAPA as covariates, was used to study the associations of CMV and HSV reactivation with 90-day mortality. 394 patients were included, 93% (367) were IgG positive for HSV and 74% (292) for CMV. CAPA was diagnosed in 35% (138) of patients. HSV reactivation was seen in 43% (103) of COVID-19 vs. 55% (71) of CAPA patients (p=0.03), CMV reactivation in 32% (63) and 57% (60) patients respectively (p<0.001). Highest risk for CAPA was at day 13 post-intubation, for reactivation of HSV at day 17 and CMV at day 27. Median peak pulmonary viral loads (log10 copies/mL) were significantly higher in CAPA compared to COVID-19 patients for HSV (6.83 vs. 5.79, p=0.03). Moreover, HSV reactivation was associated with 90-day mortality (adjusted hazard ratio 2 (CI 1.3 – 3.1), independent from age, severe immunosuppression and CAPA. Pulmonary CMV and HSV reactivations strongly associate with CAPA in critically ill COVID-19 patients. In addition, higher HSV viral loads are seen in CAPA patients and HSV reactivation is an independent risk factor for 90-day mortality.