Hyperglycemia and steroid use increase the risk of rhino-orbito-cerebral mucormycosis regardless of COVID-19 hospitalization: Case-control study, India

Abstract

Background In the ongoing COVID-19 pandemic, an increased incidence of ROCM was noted in India among those infected with COVID. We determined risk factors for rhino-orbito-cerebral mucormycosis (ROCM) post Coronavirus disease 2019 (COVID-19) among those never and ever hospitalized for COVID-19 separately through a multicentric, hospital-based, unmatched case-control study across India. Methods We defined cases and controls as those with and without post-COVID ROCM, respectively. We compared their socio-demographics, co-morbidities, steroid use, glycaemic status, and practices. We calculated crude and adjusted odds ratio (AOR) with 95% confidence intervals (CI) through logistic regression. The covariates with a p-value for crude OR of less than 0·20 were considered for the regression model. Results Among hospitalised, we recruited 267 cases and 256 controls and 116 cases and 231 controls among never hospitalised. Risk factors (AOR; 95% CI) for post-COVID ROCM among the hospitalised were age 45–59 years (2·1; 1·4 to 3·1), having diabetes mellitus (4·9; 3·4 to 7·1), elevated plasma glucose (6·4; 2·4 to 17·2), steroid use (3·2; 2 to 5·2) and frequent nasal washing (4·8; 1·4 to 17). Among those never hospitalised, age ≥ 60 years (6·6; 3·3 to 13·3), having diabetes mellitus (6·7; 3·8 to 11·6), elevated plasma glucose (13·7; 2·2 to 84), steroid use (9·8; 5·8 to 16·6), and cloth facemask use (2·6; 1·5 to 4·5) were associated with increased risk of post-COVID ROCM. Conclusions Hyperglycemia, irrespective of having diabetes mellitus and steroid use, was associated with an increased risk of ROCM independent of COVID-19 hospitalisation. Rational steroid usage and glucose monitoring may reduce the risk of post-COVID.

Multicenter Case–Control Study of COVID-19–Associated Mucormycosis Outbreak, India

“…Diabetes mellitus and glucocorticoid therapy were shown to be the major contributors for CAM in the case–control studies and large case series ( 2 , 3 , 6 , 21 , 35 , 37 ). Further, in addition to zinc and elevated inflammatory markers (C-reactive protein), which were also associated with CAM in this study, the use of cloth masks, nasal washing during COVID-19, and elevated serum glucose-regulated protein 78 were other possible associations described in smaller case–control studies ( 29 , 30 , 33 ). In our study, mean glycated hemoglobin values were significantly higher in the CAM cases.…”

“…However, a recent experimental aeromycological study found no evidence for this theory (25). Several case-control studies (n = 13) have assessed the risk factors associated with CAM (Appendix Table 8) (6,7,20,21,(28)(29)(30)(31)(32)(33)(34)(35)(36). In 8 studies (sample sizes ranging from 46 to 870), risk factors for CAM were assessed using multivariate analysis (6,7,(29)(30)(31)(32)(33)35).…”

“…Several case-control studies (n = 13) have assessed the risk factors associated with CAM (Appendix Table 8) (6,7,20,21,(28)(29)(30)(31)(32)(33)(34)(35)(36). In 8 studies (sample sizes ranging from 46 to 870), risk factors for CAM were assessed using multivariate analysis (6,7,(29)(30)(31)(32)(33)35). Diabetes mellitus and glucocorticoid therapy were shown to be the major contributors for CAM in the case-control studies and large case series (2,3,6,21,35,37).…”

Multimodal analysis of the COVID‐19‐associated mucormycosis outbreak in Delhi, India indicates the convergence of clinical and environmental risk factors

“…Although more common in patients with prior severe COVID-19, CAM cases were seen even in patients with mild COVID-19, consistent with prior reports. 16,17 The overuse of GCS, even in non-hypoxemic patients, was suggested by the fact that 80% of our CAM cohort received GCS, while only 60% of patients required supplemental oxygen. Several studies from India and elsewhere, have documented the inappropriately frequent use of GCS, even at high doses, in patients with COVID-19.…”

Mucormycosis in a Patient with Severe COVID-19 Disease—The First Case Report in Romania and a Literature Review

“…In the study conducted by Ponnaiah et al, it was shown that the use of steroids and diabetes were risk factors for the onset of CAM, with diabetic patients having a 5-times higher risk of developing CAM and those receiving steroid treatment having a 3-times higher risk [ 14 ]. In our case, the patient received steroid treatment and also had a high glycemic level, including diabetic acidosis.…”