Uncontrolled diabetes mellitus exacerbated by COVID-19-induced inflammation is the risk factor for COVID-19-associated rhino-orbito-cerebral mucormycosis: A matched pair case-control study

Purpose: Amidst the ongoing coronavirus disease 2019 (COVID-19) pandemic, India experienced an epidemic of COVID-19-associated rhino-orbito-cerebral mucormycosis (ROCM). This study aimed to describe the epidemiology and elucidate the risk factors for developing COVID-19-associated ROCM, comparing the risk factors among COVID-19 patients with and without ROCM. Methods: This case-control study included all COVID-19-associated ROCM patients treated at our hospital from May 1 to July 30, 2021. Controls included age- and sex-matched COVID-19 patients without ROCM, who were treated during the same time (exact matching, in 1:2 ratio). Matched pair analysis using conditional logistic regression was performed to examine the association of various risk factors with the development of ROCM in COVID-19 patients. Results: The study included 69 patients with COVID-19-associated ROCM and 138 age- and gender-matched controls. Epidemiologically, COVID-19-associated ROCM predominantly affected males (59/69, 85%), in their early 50s (mean 52 years), with 48% (33/69) of patients being from medical resource-constrained settings. On multivariate conditional logistic regression, elevated serum glycated hemoglobin (HbA1c) (odds ratio [OR] = 1.36, 95% confidence interval [CI]: 1.03-1.78), blood glucose (OR = 1.008, 95% CI: 1.003-1.013), and C-reactive protein (CRP) (OR = 1.07, 95% CI: 1.02-1.17) were associated with increased odds of developing COVID-19-associated ROCM. Patients with undetected diabetes mellitus with increasing HbA1c (OR = 3.42, 95% CI: 1.30-9.02) and blood glucose (OR = 1.02, 95% CI: 1.005-1.03) (P = 0.02) had a higher probability of developing COVID-19-associated ROCM than patients with established DM. Conclusion: Uncontrolled DM evidenced by elevated HbA1c and blood glucose levels, exacerbated by COVID-19-induced proinflammatory state indicated by elevated CRP, is the principal independent risk factor for COVID-19-associated ROCM. Middle-aged males with undetected DM, from a resource-constraint setting, are particularly at risk.