COVID-19-associated mucormycosis: a systematic review and meta-analysis of 958 cases

Abstract

Background: Mucormycosis, a rare fungal infection, has shown an increase in the number of reported cases during the COVID-19 pandemic.

Objectives: To provide a comprehensive insight into the characteristics of COVID-19-associated mucormycosis, through a systematic review and meta-analysis.

Methods of data synthesis: Demographic information and clinical features were documented for each patient. Logistic regression analysis was used to predict the risk of mortality.

Data sources: PubMed, Scopus, Web of Science, Cochrane, CINAHL, Ovid MEDLINE, and FungiSCOPE.

Study eligibility criteria: Studies reporting individual-level information in patients with adult COVID-19-associated mucormycosis (CAM) between 1 January 2020 and 28 December 2022.

Participants: Adults who developed mucormycosis during or after COVID-19.

Interventions: Patients with and without individual clinical variables were compared.

Assessment of risk of bias: Quality assessment was performed based on the National Institutes of Health quality assessment tool for case series studies.

Results: Nine hundred fifty-eight individual cases reported from 45 countries were eligible. 88.1% (844/958) were reported from low- or middle-income countries. Corticosteroid use for COVID-19 (78.5%, 619/789) and diabetes (77.9%, 738/948) were common. Diabetic ketoacidosis (p < 0.001), history of malignancy (p < 0.001), underlying pulmonary (p 0.017), or renal disease (p < 0.001), obesity (p < 0.001), hypertension (p 0.040), age (>65 years) (p 0.001), Aspergillus coinfection (p 0.037), and tocilizumab use during COVID-19 (p 0.018) increased the mortality. CAM occurred on an average of 22 days after COVID-19 and 8 days after hospitalization. Diagnosis of mucormycosis in patients with Aspergillus coinfection and pulmonary mucormycosis was made on average 15.4 days (range, 0-35 days) and 14.0 days (range, 0-53 days) after hospitalization, respectively. Cutaneous mucormycosis accounted for <1% of the cases. The overall mortality rate was 38.9% (303/780).

Conclusion: Mortality of CAM was high, and most reports were from low- or middle-income countries. We detected novel risk factors for CAM, such as older age, specific comorbidities, Aspergillus coinfection, and tocilizumab use, in addition to the previously identified factors.

Keywords: COVID-19; Corticosteroids; Fungal infections; Mucormycosis; Opportunistic infections.