COVID-19-associated rhino-orbital-cerebral mucormycosis: A systematic review, meta-analysis, and meta-regression analysis

Indian J Pharmacol. 2021 Nov-Dec;53(6):499-510. doi: 10.4103/ijp.ijp_839_21.


Background: Till now, no meta-analysis is available to address the clinical profile, risk factors, different interventions, and outcomes among COVID-19-associated rhino-orbito-cerebral mucormycosis (C-ROCM) cases.

Materials and methods: Eight literature databases were screened using appropriate keywords from November 1, 2019, to June 30, 2021. The objectives were to analyze the clinical and microbiological profile, risk factor/comorbidity, intervention, and outcome. "R-metafor package" was used for analysis.

Results: A total of 23 studies were included. The mean age of presentation of C-ROCM was 54.6 years. The most common presentation was ptosis (72.7%), lid edema (60.6%), proptosis (60.6%), ophthalmoplegia (57.3%), loss of vision (53.7%), facial edema (34.7%), and nasal-blockage (11.8%). Evidence of intracranial spread was seen in 42.8% of cases. Rhizopus was the most common fungus (57.1%) isolated in fungal culture. Among C-ROCM patients, diabetes was the commonest comorbid condition, and the use of corticosteroids related to COVID-19 treatment was the most common risk factor (85.75%). Compared to controlled diabetics, C-ROCM was significantly higher among uncontrolled diabetics (odds ratio [OR] 0.15, 95% confidence interval [C.I.] 0.041-0.544, P = 0.0010). However, no significant association was seen between C-ROCM and COVID-19 severity (OR 0.930, 95% C.I. 0.212-4.087, P = 0.923). For treatment, amphotericin-B was the most common antifungal drug used which was followed by surgical options. However, mortality was high (prevalence 0.344, 95% C.I. 0.205-0.403) despite treatment.

Conclusion: Although local rhino-orbito symptoms were the first to appear, rapid intracranial extension was seen in a significant number of C-ROCM cases. Uncontrolled diabetes and excessive use of corticosteroid were the most common risk factors present among the C-ROCM cases. High index clinical suspicion is imperative (specifically among COVID-19 patients with diabetes), and routine screening may be helpful.

Keywords: COVID-19; COVID-19–associated mucormycosis; SARS CoV-2; cerebral; mucormycosis; orbital; rhino; rhino-orbito-cerebral mucormycosis.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Amphotericin B / therapeutic use
  • Antifungal Agents / therapeutic use
  • Brain Diseases / complications*
  • Brain Diseases / drug therapy
  • COVID-19 / complications*
  • COVID-19 / virology
  • Humans
  • Mucormycosis / complications*
  • Mucormycosis / drug therapy
  • Nose Diseases / complications*
  • Nose Diseases / drug therapy
  • Orbital Diseases / complications*
  • Orbital Diseases / drug therapy
  • Regression Analysis
  • Risk Factors
  • SARS-CoV-2 / isolation & purification


  • Antifungal Agents
  • Amphotericin B