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Observational Study
. 2023 Nov 15;15(11):2260.
doi: 10.3390/v15112260.

Association between Pulmonary Aspergillosis and Cytomegalovirus Reactivation in Critically Ill COVID-19 Patients: A Prospective Observational Cohort Study

Valeria Caciagli  1 , Irene Coloretti  1 , Marta Talamonti  1 , Carlotta Farinelli  1 , Ilenia Gatto  1 , Emanuela Biagioni  1 , Mario Sarti  2 , Erica Franceschini  3 , Marianna Meschiari  3 , Cristina Mussini  3 , Roberto Tonelli  4 , Enrico Clini  4 , Massimo Girardis  1 , Stefano Busani  1 , Modena Covid-Working Group
Affiliations
Observational Study

Association between Pulmonary Aspergillosis and Cytomegalovirus Reactivation in Critically Ill COVID-19 Patients: A Prospective Observational Cohort Study

Valeria Caciagli et al. Viruses. .

Abstract

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 explore the association between CAPA development and the incidence and prognosis of cytomegalovirus (CMV) reactivation in critically ill COVID-19 patients. We included all consecutive critically ill adult patients with confirmed COVID-19 infection who were admitted to three COVID-19 intensive care units (ICUs) in an Italian hospital from 25 February 2020 to 8 May 2022. A standardized procedure was employed for early detection of CAPA. Risk factors associated with CAPA and CMV reactivation and the association between CMV recurrence and mortality were estimated using adjusted Cox proportional hazard regression models. CAPA occurred 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, fewer 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 patients, CMV reactivation is common in those with a previous CAPA diagnosis. Basal immunosuppression 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.

Keywords: COVID-19; ards; critically ill; cytomegalovirus; invasive pulmonary aspergillosis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Kaplan–Meier curve for cumulative 90-day survival in CAPA population developing CMV blood reactivation or not.
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