# Risk Factors and Clinical Outcomes of Invasive Fungal Infections in Patients with Severe COVID-19: A Case–Control Study

## TL;DR

This study finds that invasive fungal infections in severe COVID-19 patients lead to higher death rates and longer hospital stays, with mechanical ventilation being a key risk factor.

## Contribution

The study identifies mechanical ventilation as an independent risk factor for invasive fungal infections in severe COVID-19 patients.

## Key findings

- Invasive fungal infections were found in 11.8% of severe COVID-19 patients.
- Patients with IFIs had a 2.19 times higher risk of in-hospital death compared to those without IFIs.
- Mechanical ventilation was independently associated with IFIs (OR: 2.5).

## Abstract

Background: Invasive fungal infections (IFIs) in patients with COVID-19 contribute to significant morbidity and mortality, with reported incidence between 5% and 26.7%. COVID-19-associated pulmonary aspergillosis (CAPA), candidiasis (CAC), mucormycosis (CAM), and Pneumocystis jirovecii pneumonia (PJP) are the most common IFIs in this population. Methodology: We conducted a case–control study in the ratio of 1:2 between March 2020 and April 2022 using institutional COVID-19 registry data. The cases were severe COVID-19 patients with IFIs, and the controls were severe COVID-19 patients without IFIs. Multivariate logistic regression was used to identify independent risk factors, with adjusted odds ratios (aOR) and 95% confidence intervals (CIs). The outcomes for the study were to assess the clinical outcomes, i.e., in-hospital mortality and length of hospitalization in a subgroup of severe COVID-19 patients who had IFIs. A p-value < 0.05 was considered significant. Results: Among 5368 COVID-19 patients admitted to hospital during the study period, 1333 had a severe infection. Of these, 158/1333 (11.8%) met the criteria for IFIs, with a median age of 65 years and 71% male predominance. Diabetes (53.8%) and hypertension (57.6%) were the most common comorbid conditions. Acute respiratory distress syndrome (ARDS) developed in 55% of patients. Overall mortality was 48%. For the case control analysis, 119 patients with IFIs were selected as cases and 240 patients without IFIs were selected as controls. On univariate analysis ARDS was significantly associated with IFIs (OR: 1.91; 95% CI: 1.23–2.99, p-value = 0.004). Patients with IFIs had higher odds of being on hemodialysis compared to those without IFIs (OR: 2.17; 95% CI: 1.18–3.99; p-value = 0.013). Mechanical ventilation was found to be independently associated with IFIs in multivariate logistic regression analysis (OR: 2.5, 95% CI: 1.58–3.96, p-value < 0.001). The odds for in-hospital death in patients with IFIs were 2.19 (95% CI: 1.35–3.56; p-value < 0.001) compared to patients without IFIs. The median hospital stay for patients with IFIs was markedly longer (14 days) compared to 8 days in patients without IFIs. Conclusions: IFIs significantly worsened outcomes in severe COVID-19 patients, leading to increased mortality and prolonged hospital stays. Mechanical ventilation was an independent risk factor for IFIs.