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

BackgroundThe aetiology of the major outbreak of COVID-19-associated mucormycosis (CAM) in India in spring 2021 remains incompletely understood. Herein, we provide a multifaceted and multi-institutional analysis of clinical, pathogen-related, environmental and healthcare-related factors during CAM outbreak in the metropolitan New Delhi area. MethodsWe reviewed medical records of all patients diagnosed with biopsy-proven CAM (n = 50) at 7 hospitals in the New Delhi, and NCR area in April-June 2021. Two multivariate logistic regression models were used to compare clinical characteristics of CAM cases with COVID-19-hospitalised contemporary patients as controls (n = 69). Additionally, meteorological parameters and mould spore concentrations in outdoor air were analysed. Selected hospital fomites were cultured. Mucorales isolates from CAM patients were analysed by ITS sequencing and whole-genome sequencing (WGS). ResultsIndependent risk factors for CAM identified by multivariate analysis were previously or newly diagnosed diabetes mellitus, active cancer and severe COVID-19 infection. Supplemental oxygen, remdesivir therapy and ICU admission for COVID-19 were associated with reduced CAM risk. The CAM incidence peak was preceded by an uptick in environmental spore concentrations in the preceding 3-4 weeks that correlated with increasing temperature, high evaporation and decreasing relative humidity. Rhizopus was the most common genus isolated, but we also identified two cases of the uncommon Mucorales, Lichtheimia ornata. WGS found no clonal population of patient isolates. No Mucorales were cultured from hospital fomites. ConclusionsAn intersection of host and environmental factors contributed to the emergence of CAM. Surrogates of access to advanced COVID-19 treatment were associated with lower CAM risk.

Automated summary

This study provides a multifaceted analysis of the major outbreak of COVID-19-associated mucormycosis (CAM) in the metropolitan New Delhi area. It identifies independent risk factors for CAM, including diabetes mellitus, active cancer, and severe COVID-19 infection. Environmental factors, such as increasing spore concentrations and temperature, are also associated with CAM incidence.