Risk factors and outcomes of fungal superinfections in patients with severe COVID-19: an observational study from Pisa academic hospital.

Background: Superinfections acquired during the hospital course represent common complications in COVID-19 patients. Several studies reported an increasing incidence of COVID-19 associated pulmonary aspergillosis (CAPA) and candidaemia. The aim of this study is to describe fungal superinfections in a large cohort of hospitalized patients with COVID-19 and identify factors independently associated with the risk of fungal superinfections. Methods: Observational study including patients with COVID-19 admitted to the tertiary-care, University Hospital of Pisa, Italy from April 2020 to May 2021. Patients with pneumonia and laboratory confirmed SARS-CoV-2 infection with a RT-PCR test on a nasopharyngeal swab, were eligible for the study. Patients who died within 24 hours from admission and those with missing data were excluded. Data about fungal superinfections were collected. To identify factors independently associated with the development of fungal superinfections, a multivariate regression analysis was performed. Results: Among 983 patients with COVID-19, 52 (5.3%) fungal superinfections were detected. Fungal superinfections included: 24/52 (46%) CAPA, 27/52 (51.9%) episodes of candidaemia and 1 case of pulmonary pneumocystosis in a haematological patient. All patients with CAPA were cared for in intensive care unit (ICU). The majority of patients received liposomal amphotericin B as antifungal treatment (83.3%). In-hospital mortality was 41.7%. Among 27 episodes of candidaemia, 16 (59.3%) occurred in ICU while 11 (40.7%) in medical wards. In-hospital mortality was 14.8%. Overall, patients with fungal superinfections had a median age of 73 (IQRs 59-77) years and a median length of ICU stay of 40 (17-50) days. In-hospital mortality among all patients with superinfections was 28.8%. On multivariable analysis, ICU stay (OR 17.63, 95% CI 8.3-37.41, p<0.001), high-dose steroids (OR 13.48, 95% CI 6.68-27.26, p<0.001), and diabetes mellitus (OR 2.14, 95% CI 1.09-4.17, p=0.026) were factors independently associated with the risk of developing a fungal superinfection. Conclusions: Fungal superinfections may complicate the hospital course of COVID-19 patients, especially of those admitted to ICU. Surveillance with detection of galactomannan on bronchoalveolar lavage in patients with clinical deterioration should be performed. A rational use of steroids is essential to avoid the risk of developing a fungal superinfection.