Risk Factors for Invasive Aspergillosis in Patients Admitted to the Intensive Care Unit With Coronavirus Disease 2019: A Multicenter Retrospective Study

Abstract

Background: Invasive pulmonary aspergillosis (IPA) is a life-threatening complication in coronavirus disease 2019 (COVID-19) patients admitted to intensive care units (ICUs), but risk factors for COVID-19-associated IPA (CAPA) have not been fully characterized. The aim of the current study was to identify factors associated with CAPA, and assess long-term mortality. Methods: A retrospective cohort study of adult COVID-19 patients admitted to ICUs from six hospitals was conducted in Hubei, China. CAPA was diagnosed via composite clinical criteria. Demographic information, clinical variables, and 180-day outcomes after the diagnosis of CAPA were analyzed. Results: Of 335 critically ill patients with COVID-19, 78 (23.3%) developed CAPA within a median of 20.5 days (range 13.0-42.0 days) after symptom onset. Compared to those without CAPA, CAPA patients were more likely to have thrombocytopenia (50 vs. 19.5%, p < 0.001) and secondary bacterial infection prior to being diagnosed with CAPA (15.4 vs. 6.2%, p = 0.013), and to receive vasopressors (37.2 vs. 8.6%, p < 0.001), higher steroid dosages (53.9 vs. 34.2%, p = 0.002), renal replacement therapy (37.2 vs. 13.6%, p < 0.001), and invasive mechanical ventilation (57.7 vs. 35.8%, p < 0.001). In multivariate analysis incorporating hazard ratios (HRs) and confidence intervals (CIs), thrombocytopenia (HR 1.98, 95% CI 1.16-3.37, p = 0.012), vasopressor use (HR 3.57, 95% CI 1.80-7.06, p < 0.001), and methylprednisolone use at a daily dose ≥ 40 mg (HR 1.69, 95% CI 1.02-2.79, p = 1.02-2.79) before CAPA diagnosis were independently associated with CAPA. Patients with CAPA had longer median ICU stays (17 days vs. 12 days, p = 0.007), and higher 180-day mortality (65.4 vs. 33.5%, p < 0.001) than those without CAPA. Conclusions: Thrombocytopenia, vasopressor use, and corticosteroid treatment were significantly associated with increased risk of incident IPA in COVID-19 patients admitted to ICUs. The occurrence of CAPA may increase the likelihood of long-term COVID-19 mortality.

Keywords: CAPA; COVID-19; methylprednisolone; mortality; thrombocytopenia.

Figure 1

Flowchart of the study including patients with CAPA. CAPA, coronavirus disease 2019-associated invasive pulmonary aspergillosis; COVID-19, coronavirus disease 2019.

Figure 2

Survival curves of 335 critically ill patients with or without CAPA. The number of patients with CAPA was 78, and the number without CAPA was 257. CAPA, coronavirus disease 2019-associated invasive pulmonary aspergillosis; COVID-19, coronavirus disease 2019.