Invasive fungal disease in COVID-19 patients: a single-center prospective observational study

Invasive fungal diseases (IFDs) are caused by fungal infections that manifest as serious secondary infections in patients with COVID-19. The increased morbidity and mortality rates are most frequently observed in patients with COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated candidiasis (CAC). CAPA is the most frequently encountered infection with an incidence rate of 0.7-7.7%, while CAC is a less common and less studied fungal infection in COVID-19 patients.

The present article is a prospective observational single-center study that was conducted between 1 September 2021 and 24 December 2021, involving 6,335 patients who were admitted to COVID Hospital "Batajnica," University Clinical Center of Serbia, Belgrade.

Of the 6,335 patients hospitalized during the four-month period of the study, 120 patients (1.86%) who had a proven diagnosis of IFD were included in the study. These patients were divided into two groups: CAPA patients (n = 63) and CAC patients (n = 56); however, one of the 120 patients was diagnosed with Cryptoccocus neoformans infection. The mean age of the study population was 65.7 ± 13.9 years, and 78 (65.5%) of them were men. The patients were identified to have the following non-malignant comorbidities: arterial hypertension in 62 (52.1%) patients, diabetes mellitus in 34 (28.65), pre-existing lung damage similar to that observed in COPD and asthma in 20 (16.8%), and chronic renal insufficiency in 13 (10.9%) patients. The hematological malignancies were found to be the most prevalent malignancies and were identified in 20 (16.8%) patients, particularly in CAPA patients [11 (17.5%); p < 0.041]. Fiberoptic bronchoscopy with bronchoalveolar lavage fluid (BALF) and microscopic examination confirmed the presence of fungal infections in 17 (14.3%) patients. Serology testing was also performed in the majority of cases. Antibodies against Aspergillus spp. and Candida spp. were predominantly found in CAPA patients (p < 0.001). The patients were also tested for the presence of (1-3)-β-D glucan (p < 0.019), galactomannan, and mannan in the specimens. Blood cultures were found to be positive in 45 (37.8%) patients, mostly in CAC patients. Mechanical ventilation was applied in 41 (34.5%) patients, while a non-invasive technique, such as continuous positive airway pressure (CPAP) or high-flow nasal cannula (HFNC), was used in 20 (16.8%) patients. The following antifungals were administered: echinocandins in 42 (35.3%), voriconazole in 30 (25.2%), and fluconazole in 27 (22.7%) patients. Most of the patients received systemic corticosteroids (mainly methylprednisolone), while 11 (9.16%) received favipiravir, 32 (26.67%) remdesivir, 8 (6.67%) casirivimab/imdevimab, and 5 (4.16%) sotrovimab. The outcome was lethal in 76 (63.9%) patients, predominantly CAC patients (p < 0.001).

Invasive fungal disease is a severe complication associated with COVID-19 and accounts for increased mortality in these patients. Early identification and appropriate treatment may provide a favorable outcome.