A case control investigation of COVID-19 associated mucormycosis in India
Authors: Anand Tanu , Mukherjee Aparna , Satija Aanchal , Velamuri Poonam Sharma , Singh Kh. Jitenkumar , Das Madhuchhanda , Josten Kripa , Yadav Pragya D. , Sahay Rima R. , Keche Archana Y. , Nagarkar Nitin M. , Gupta Prashant , Himanshu D. , Mistry Sejal N. , Patel Jimy D. , Rao Prajwal , Rohatgi Shalesh , Ghosh Soumitra , Hazra Avijit , Kindo Anupma Jyoti , Annamalai Radha , Rudramurthy Shivaprakash M. , Singh Mini P. , Shameem Mohammad , Fatima Nazish , Khambholja Janakkumar R. , Parikh Sangita , Madkaikar Manisha , Pradhan Vandana D. , Kataria Sushila , Sharma Pooja , Panda Samiran ,   ICMR-Mucormycosis group, Shete Anita M. , Majumdar Triparna , Abraham Priya , Bhargava Anudita , Mehata Rupa , Arora Ripu Daman , Tigga Richa , Banerjee Gopa , Sonkar Vijay , Malhotra H. S. , Kumar Neeraj , Patil Rajashri , Raut Chandrashekhar G. , Bhattacharyya Kumkum , Arthur Preetam , Somu L. , Srikanth Padma , Panda Naresh K. , Sharma Dipti , Hasan Wasil , Ahmed Aftab , Bathla Meeta , Solanki Sunita , Doshi Hiren , Kanani Yash , Patel Nishi , Shah Zincal , Tembhurne Alok Kumar , Rajguru Chhaya , Sankhe Lalitkumar R. , Chavan Shrinivas S. , Yadav Reetika Malik , Deswal Vikas , Kumar Kuldeep 
Published: November 2022

Abstract
Background
Increased occurrence of mucormycosis during the second wave of COVID-19 pandemic in early 2021 in India prompted us to undertake a multi-site case–control investigation. The objectives were to examine the monthly trend of COVID-19 Associated Mucormycosis (CAM) cases among in-patients and to identify factors associated with development of CAM.

Methods
Eleven study sites were involved across India; archived records since 1st January 2021 till 30th September 2021 were used for trend analysis. The cases and controls were enrolled during 15th June 2021 to 30th September 2021. Data were collected using a semi-structured questionnaire. Among 1211 enrolled participants, 336 were CAM cases and 875 were COVID-19 positive non-mucormycosis controls.

Results
CAM-case admissions reached their peak in May 2021 like a satellite epidemic after a month of in-patient admission peak recorded due to COVID-19. The odds of developing CAM increased with the history of working in a dusty environment (adjusted odds ratio; aOR 3.24, 95% CI 1.34, 7.82), diabetes mellitus (aOR: 31.83, 95% CI 13.96, 72.63), longer duration of hospital stay (aOR: 1.06, 95% CI 1.02, 1.11) and use of methylprednisolone (aOR: 2.71, 95% CI 1.37, 5.37) following adjustment for age, gender, occupation, education, type of houses used for living, requirement of ventilatory support and route of steroid administration. Higher proportion of CAM cases required supplemental oxygen compared to the controls; use of non-rebreather mask (NRBM) was associated as a protective factor against mucormycosis compared to face masks (aOR: 0.18, 95% CI 0.08, 0.41). Genomic sequencing of archived respiratory samples revealed similar occurrences of Delta and Delta derivates of SARS-CoV-2 infection in both cases and controls.

Conclusions
Appropriate management of hyperglycemia, judicious use of steroids and use of NRBM during oxygen supplementation among COVID-19 patients have the potential to reduce the risk of occurrence of mucormycosis. Avoiding exposure to dusty environment would add to such prevention efforts.