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

Abstract

Background: COVID-19-associated pulmonary aspergillosis (CAPA) is a major complication of critically ill COVID-19 patients, with a high mortality rate and potentially preventable. Thus, identifying patients at high risk of CAPA would be of great interest. We intended to develop a clinical prediction score capable of stratifying patients according to the risk for CAPA at ICU admission.

Methods: Single centre retrospective case-control study. A case was defined as a patient diagnosed with CAPA according to 2020 ECMM/ISHAM consensus criteria. 2 controls were selected for each case among critically ill COVID-19 patients.

Results: 28 CAPA patients and 56-matched controls were included. Factors associated with CAPA included old age (68 years vs. 62, p = .033), active smoking (17.9% vs. 1.8%, p = .014), chronic respiratory diseases (48.1% vs. 26.3%, p = .043), chronic renal failure (25.0% vs. 3.6%, p = .005), chronic corticosteroid treatment (28.6% vs. 1.8%, p < .001), tocilizumab therapy (92.9% vs. 66.1%, p = .008) and high APACHE II at ICU admission (median 13 vs. 10 points, p = .026). A score was created including these variables, which showed an area under the receiver operator curve of 0.854 (95% CI 0.77-0.92). A punctuation below 6 had a negative predictive value of 99.6%. A punctuation of 10 or higher had a positive predictive value of 27.9%.

Conclusion: We present a clinical prediction score that allowed to stratify critically ill COVID-19 patients according to the risk for developing CAPA. This CAPA score would allow to target preventive measures. Further evaluation of the score, as well as the utility of these targeted preventive measures, is needed.

Keywords: CAPA; COVID-19; critically ill; score.

FIGURE 1

CAPA risk score receiver operator curve. The AUC was 0.861 (95% CI 0.78–0.93, p < .001)

FIGURE 2

Histogram of distribution of area under the receiver operator curve (AUC) of 1000 bootstrapped samples. The optimism estimated was 0.047, with a corrected AUC of 0.854 (95% CI 0.77–0.92)

FIGURE 3

Kaplan–Meier survival curves of 180‐day mortality among different population of COVID‐associated pulmonary aspergillosis (CAPA) and controls. Survival analysis was made by means of Cox regression. Hazards ratios (HR) with their 95% confidence interval (CI) are presented. Figure 1A represents survival curve among patients with CAPA and ICU controls. Adjusted HR (aHR) was obtained after adjusting for age, smoking, chronic respiratory disease, immunocompromised status, prior chronic corticoid treatment, chronic renal failure, renal replacement therapy, APACHE II at ICU admission and blood component transfusion. Figure 1B represents survival curve according to 2020 ECMM/ISHAM consensus criteria CAPA classification and Figure 1C survival curve according to 2020 ECMM/ISHAM consensus criteria plus serum galactomannan (GM). Only patients with probable CAPA had positive serum GM