465. A Multifaceted and Multi-Institutional Analysis of the COVID19-Associated Mucormycosis Outbreak in the Delhi Area Indicates the Simultaneous Convergence of Multiple Risk Factors

Abstract

Abstract Background A major outbreak of COVID19-associated mucormycosis (CAM) in India in spring 2021 aggravated the death toll of COVID19. As the causes of that CAM outbreak remain unclear, we performed a multifaceted study of host, pathogen, environmental, and heath care-related factors in adult CAM patients (pts) in the metropolitan New Delhi area. Methods We reviewed the records of all pts diagnosed with culture- or biopsy-proven CAM at 7 hospitals in the New Delhi area (April 1 – June 30, 2021). We used a multivariate logistic regression model to compare clinical characteristics of either all CAM cases (analysis 1, n = 50) or only pts with CAM after moderate or severe COVID19 (analysis 2, n = 31). As controls for both analyses, we used 69 COVID19-hospitalized contemporary pts. Selected hospital fomites were cultured for Mucorales. Additionally, we compared meteorological data and fungal spore concentrations in outdoor air before the CAM outbreak (January-March 2021) and during the outbreak (April-June 2021). Mucorales isolates from CAM pts were identified by MALDI-TOF-MS and ITS sequencing. A subset of 15 isolates underwent whole genome sequencing (WGS). Results Risk factors for CAM in both analyses were newly diagnosed diabetes mellitus (odds ratio [OR] 8.26/5.67) and active cancer (OR 5.98/5.68) (Figure 1). Supplemental oxygen for COVID19 was associated with a lower CAM risk in both analyses (OR 0.13/0.17). Another significant CAM risk predictor identified only in analysis 1 was severe COVID19 (WHO score ≥ 6, OR 4.09), while remdesivir therapy (OR 0.40) and ICU admission for COVID19 were protective (OR 0.41) (Figure 1). No Mucorales were cultured from hospital fomites. The CAM incidence peak coincided with a significant uptick in environmental spore concentrations but was not linked to specific meteorological factors. Rhizopus was the predominant Mucorales genus (64%) identified by MALDI-TOF-MS and ITS sequencing; WGS found no clonal population of isolates but detected 2 cases of the rare pathogen Lichtheimia ornata. Figure 1 Conclusion An intersection of host, environmental, pathogen and healthcare-related factors might have contributed to the emergence of CAM. Surrogates of access to advanced treatment of COVID19 were associated with lower CAM risk. Disclosures Dimiitrios P. Kontoyiannis, MD, ScD, PhD (hon), AbbVie: Advisor/Consultant|Astellas Pharma: Advisor/Consultant|Astellas Pharma: Grant/Research Support|Astellas Pharma: Honoraria|Cidara Therapeutics: Advisor/Consultant|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Merck: Advisor/Consultant.