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

ABSTRACT

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 12 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.