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.

Graphical abstract

Fig. 1

Flow diagram describing the study selection process according to the PRISMA guidelines.

Fig. 2

Global distribution of the 958 CAM cases. The number of cases reported from each country is shown on the geographical heatmap with corresponding shades of blue as indicated in the legend. Pie charts show the number of survived and deceased patients for the top 10 countries reporting the most cases.

Fig. 3

Genus distribution of the identified pathogens by continents.

Fig. 4

Mortality rates and distribution of isolated pathogens for each site of mucormycosis. Other sites not shown in the figure are the glottis, mediastinum, breast, lymph node, spleen, vesicle, penis, and musculoskeletal.