Abstract
Introduction: Cytomegalovirus (CMV) infection is a well-known factor associated with invasive aspergillosis in immunocompromised hosts. However, its association with COVID-19-associated pulmonary aspergillosis (CAPA) has not been described. We aimed to examine the possible link between CMV replication and CAPA occurrence. Methods: A single-center, retrospective case–control study was conducted. A case was defined as a patient diagnosed with CAPA according to 2020 ECMM/ISHAM consensus criteria. Two controls were selected for each case among critically ill COVID-19 patients. Results: In total, 24 CAPA cases were included, comprising 14 possible CAPA and 10 probable CAPA. Additionally, 48 matched controls were selected. CMV replication was detected more frequently in CAPA than in controls (75.0% vs. 35.4%, p = 0.002). Probable CMV end-organ disease was more prevalent in CAPA (20.8% vs. 4.2%, p = 0.037). After adjusting for possible confounding factors, CMV replication persisted strongly associated with CAPA (OR 8.28 95% CI 1.90–36.13, p = 0.005). Among 11 CAPA cases with CMV PCR available prior to CAPA, in 9 (81.8%) cases, CMV replication was observed prior to CAPA diagnosis. Conclusions: Among critically ill COVID-19 patients, CMV replication was associated with CAPA and could potentially be considered a harbinger of CAPA. Further studies are needed to confirm this association.
Highlights
Cytomegalovirus (CMV) infection is a well-known factor associated with invasive aspergillosis in immunocompromised hosts
Between March 2020 and August 2021, 28 COVID-19associated pulmonary aspergillosis (CAPA) patients were identified in our center, including 22 ICU admitted patients, representing 6.04% (22/364) of the patients admitted to ICU with severe acute respiratory distress syndrome (ARDS) due to COVID-19
After excluding patients with no concomitant plasma CMV PCR available, 24 CAPA patients were included as cases
Summary
Cytomegalovirus (CMV) infection is a well-known factor associated with invasive aspergillosis in immunocompromised hosts. Two controls were selected for each case among critically ill COVID-19 patients. Conclusions: Among critically ill COVID-19 patients, CMV replication was associated with CAPA and could potentially be considered a harbinger of CAPA. COVID-19-associated pulmonary aspergillosis (CAPA) has recently been recognized as a major complication of critically ill COVID-19 patients [1]. In contrast with influenza-associated pulmonary aspergillosis, in which angioinvasion would be facilitated by extensive respiratory mucosal damage, dysregulation in T-cell response and antigen presentation would be the main mechanisms that facilitate Aspergillus infection in COVID19 patients [7,8]. In a single-center, retrospective study [12], this association has been described in critically ill patients, including patients with influenza. A causal role is still to be demonstrated, several factors could influence the higher risk of fungal infection in patients with CMV infection, including T-cell response dysregulation induced by CMV replication itself [13,14]
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