Mortality in critically ill COVID‑19 patients with fungal infections: a comprehensive systematic review and meta‑analysis.

Introduction: Patients with COVID‑19 may develop concomitant viral, bacterial, or fungal infections. Such patients are at a higher risk of death, especially from a critical illness. Although much attention has been recently given to fungal infections that may have devastating consequences, data on this issue are scarce.

Objectives: The aim of the study was to assess the impact and prevalence of fungal infections in critically ill patients with COVID 19.

Methods: We systematically searched for studies that focused on critically ill adults diagnosed with COVID‑19 and a fungal coinfection. Mortality was our outcome of interest. The search was conducted within MEDLINE, Web of Science, clinicaltrials.gov, Embase, and Cochrane Library on January 8, 2022.

Results: We reviewed 38 papers covering 17 695 patients, 1182 (6.7%) of whom had an acquired fungal infection. The overall mortality in the papers retrieved for a systematic review (n = 38) varied from 29% to 100% (median [IQR], 56% [40%-77%]). In a meta‑analysis (19 studies), the patients with a fungal infection were more likely to die than the controls (odds ratio [OR], 2.987; 95% CI, 2.369-3.767; P <0.001; I2 = 26.63%). Subgroup analyses showed that COVID‑19-associated pulmonary aspergillosis (CAPA) increased mortality by 3 times (OR, 3.279; 95% CI, 2.692-3.994; P <0.001; I2 = 0%), and that COVID‑19-associated candidiasis (CAC) increased mortality by 2 times (OR, 2.254; 95% CI, 1.322-3.843; I2 = 26.14%).

Conclusions: In critically ill patients with COVID‑ 19, CAPA is rather common and significantly increases mortality. The evidence regarding other fungal infections is weaker, with CAC occurring less frequently but also impacting mortality. Therefore, clinical awareness and screening are needed, followed by personalized antifungal therapy stewardship, which is strongly recommended in order to improve the patients' prognosis.