Hyperglycemia and steroid use increase the risk of rhino-orbito-cerebral mucormycosis regardless of COVID-19 hospitalization: Case-control study, India
Authors: Ponnaiah Manickam , Ganesan Sivaraman , Bhatnagar Tarun , Thulasingam Mahalakshmy , Majella Marie Gilbert , Karuppiah Mathan , Rizwan S. A. , Alexander Arun , Sarkar Sonali , Kar Sitanshu Sekhar , Kadhiravan Tamilarasu , Bhatnagar Aparna , S. Prasanna Kumar , Pillai Vivekanandan M. , Nair Pradeep Pankajakshan , Dhodapkar Rahul , Ch Toi Pampa , Singh Rakesh , Kasthuri Nirupama , Kumar Girish C. P. , Jaisankar Saranya , Saini Vaibhav , Kankaria Ankita , Raj Anuradha , Goyal Amit , Sharma Vidhu , Khichar Satyendra , Soni Kapil , Garg Mahendra Kumar , Selvaraj Kalaiselvi , B. H. ShriKrishna , Bhavana Kranti , Bharti Bhartendu , Singh C. M. , Chaudhary Neha , R. Vijayaravindh , K. Gopinath , Palaninathan Karthikeyan , Dube Simmi , Saxena Rita Singh , Gupta Nikhil , Rathinavel A. , Priya S. , Arulsundareshkumar  , Bellad Shama A. , Kavi Avinash , Harugop Anilkumar S. , Pujary Kailesh , Ballala Kirthinath , Mallya Sneha Deepak , Prasad Hanumanth M. , Ravi D. , Balaji N. K. , Hegde Raghuraj , Mishra Neha , Ray Shalina , Karthikeyan S. , Ramalingam Sudha , Murali A. , Vaidya Sudhakar , Samadhiya Mohit , Bhojani Dhaval , Lakshmanan Somu , Singh Sudagar R. B. , Pillai Nataraj , Deepthi P. , Banumathi K. , Sumathi V. , Ramesh D. , Nissar Sonam Poonam , Sheikh Khushnood M. , Patel Manisha N. , Shristava Vipul , Kumar Suresh S. , Shantaraman K. , Pandian Rajkamal D. , Murhekar Manoj , Aggarwal Rakesh 
Published: August 2022

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.