Epidemiology, clinical presentation and management of COVID-19 associated Mucormycosis: A single center experience from Pune, Western India.

Background: The second COVID-19 wave in India, triggered by the Delta variant,has been associated with an unprecedented increase in cases of COVID-19 associated Mucormycosis(CAM), mainly Rhino-orbito-cerebral mucormycosis(ROCM).The primary reason appears to be an unusual alignment of multiple risk factors in patients like prevalence of hypoxia, uncontrolled diabetes mellitus, indiscriminate use of steroids, high iron levels and immune dysfunction. Methods: This retrospective cohort study was conducted at Noble hospital and Research Centre (NHRC), Pune, Western India between 1st April 2020 and 1st August 2021 to identify patients admitted with CAM. The primary endpoint was incidence of all cause mortality due to CAM. Secondary outcomes studied were need for mechanical ventilation and intensive care unit(ICU) admission. Baseline and time dependent risk factors significantly associated with death due to CAM were identified by Relative risk estimation. Results: 59 patients were diagnosed with Mucormycosis at NHRC (58 ROCM, 1 Renal (disseminated) mucormycosis). Median age of the cohort was 52(IQR: 41,61) years and it included 20.3% females. Median duration from first positive COVID-19 RT PCR test to diagnosis of Mucormycosis was 17(IQR: 12,22) days. 90% patients were diabetic with 30% being newly diagnosed at the time of COVID-19 admission and 89% having uncontrolled sugar level (HbA1c > 7%). All patients were prescribed steroids during treatment for COVID-19. 56% patients were prescribed steroids for non-hypoxemic, mild COVID (irrational steroid therapy) while in 9%, steroids were indicated but were prescribed in inappropriately high dose. Majority of the patients were treated with a combination of surgical debridement(94%), intravenous Amphotericin B(91%) and concomitant oral Posoconazole therapy(95.4%). 74.6% patients were discharged after clinical and radiologic recovery while 25.4% (15 patients) died. On Relative risk analysis, CT severity score during COVID-19 admission [≥]18 (p=0.017), presence of orbital symptoms(p=0.002), presence of diabetic ketoacidosis(p=0.011) and cerebral involvement by Mucor(p=0.0004) were associated with increased risk of death. Duration of Amphotericin B therapy of [≥] 21 days was associated with statistically significant reduction in mortality(p=0.002). Conclusions: CAM is an uncommon, rapidly progressive, angioinvasive, opportunistic fungal infection which is fatal if left untreated. Combination of surgical debridement and antifungal therapy leads to clinical and radiologic improvement in majority of cases.