Association of COVID-19-Associated Pulmonary Aspergillosis with Cytomegalovirus Replication: A Case–Control Study

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. Conclusion: 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.

COVID‐19‐associated pulmonary aspergillosis (CAPA): Risk factors and development of a predictive score for critically ill COVID‐19 patients

“…Additionally, other risk factors outside the score should be taken into account, such as CMV replication. 37 …”

“…Nevertheless, the CAPA score needs external validation in other populations and further evaluation in order to assess the efficacy of the targeted approach based on the stratification in reducing CAPA cases and improving survival in critically ill COVID‐19 patients. Additionally, other risk factors outside the score should be taken into account, such as CMV replication 37 …”

Tocilizumab and Corticosteroids Increase Risk of COVID-19–Associated Pulmonary Aspergillosis Development Among Critically Ill Patients

“…Systemic corticosteroids use during ICU admission was evaluated in 5 studies as a risk factor for developing CAPA in 1423 patients. 13,14,16,19,20 Meta-analysis showed a significantly increased risk of developing CAPA in patients who were on steroids (OR = 2; 95% CI, 1.14–3.51) (Figure 1F).…”

“…[11][12][13][14][15][16][17][18][19][20] There was one study by Calderón-Parra (2022) that was published twice with the same cohort but with additional studied risk factors. 12,13 Table 1 summarizes the study and participants' characteristics. Most of the studies originated in Europe.…”

“…A total of 9 studies were included in our meta-analysis, which were published between January 2020 and April 2022. [11][12][13][14][15][16][17][18][19][20] There was one study by Calderón-Parra (2022) that was published twice with the same cohort but with additional studied risk factors. 12,13 Table 1 summarizes the study and participants' characteristics.…”