COVID-19 Associated Rhino-Orbital-Cerebral Mucormycosis: Clinical Features, Antifungal Susceptibility, Management and Outcome in a Tertiary Hospital in Iran

Mycopathologia. 2023 Oct;188(5):783-792. doi: 10.1007/s11046-023-00785-3. Epub 2023 Sep 6.


Background: Despite the unprecedented surge in the incidence of mucormycosis in the COVID-19 era, the antifungal susceptibility patterns (ASPs) of COVID-19 associated mucormycosis (CAM) isolates have not been investigated so far and it is unclear if the high mortality rate associated with CAM is driven by decreased susceptibility of Mucorales to antifungal drugs.

Objectives: To describe the clinical, mycological, outcome and in vitro ASPs of CAM cases and their etiologies from Iran.

Patients/methods: A prospective study from January 2020 to January 2022 at a referral tertiary hospital in Tehran, Iran was conducted for screening mucormycosis through histopathology and mycological methods. The identity of Mucorales isolates was revealed with ITS-panfungal PCR& sequencing and MALDI-TOF. The AS for amphotericin B, itraconazole, isavuconazole and posaconazole was cleared according to the EUCAST antifungal susceptibility testing protocol.

Result: A total of 150 individuals were diagnosed with CAM. Males constituted 60.7% of the population. The mean age was 54.9 years. Diabetes was the leading risk factor (74.7%). The median interval between diagnosis of COVID-19 and CAM was 31 days. The recovery rate of culture was as low as 41.3% with Rhizopus arrhizus being identified as the dominant (60; 96.7%) agent. Amphotericin B (MIC50 = 0.5 µg/ml) demonstrated the highest potency against Mucorales.

Conclusion: Majority of the cases had either diabetes, history of corticosteroid therapy or simultaneously both conditions. Accordingly, close monitoring of blood glucose should be considered. The indications for corticosteroids therapy are recommended to be optimized. Also, an anti Mucorales prophylaxis may be necessitated to be administrated in high risk individuals. Although amphotericin B was the most active agent, a higher rate of resistance to this antifungal was noted here in comparison with earlier studies on mucormycetes from non-CAM cases.

Keywords: COVID-19; Diabetes; Rhino-orbital-cerebral mucormycosis.

MeSH terms

  • Amphotericin B / pharmacology
  • Amphotericin B / therapeutic use
  • Antifungal Agents / pharmacology
  • Antifungal Agents / therapeutic use
  • COVID-19*
  • Diabetes Mellitus* / drug therapy
  • Humans
  • Iran / epidemiology
  • Male
  • Middle Aged
  • Mucorales*
  • Mucormycosis* / diagnosis
  • Mucormycosis* / drug therapy
  • Mucormycosis* / epidemiology
  • Prospective Studies
  • Tertiary Care Centers


  • Antifungal Agents
  • Amphotericin B