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Multicenter Epidemiologic Study of Coronavirus Disease-Associated Mucormycosis, India

Our take —

Between September and December 2020, there were 287 mucormycosis cases diagnosed across 16 healthcare centers in India, a two-fold increase compared to the same time period in 2019. Of these cases, 187 were COVID-19 associated mucormycosis (CAM). CAM was extremely rare (<0.3%) among hospitalized COVID-19 patients. Aside from CAM patients having more frequent hypoxia requiring ICU admission, CAM and non-CAM cases had similar clinical manifestations and outcomes. The majority of both CAM and non-CAM cases had uncontrolled diabetes. Most CAM cases were given glucocorticoids as part of their treatment for COVID-19, similar to previous smaller case series from India. It is possible that glucocorticoid treatment contributed to additional CAM cases in certain settings, but more research in larger sample sizes and with additional control for confounding is needed to further evaluate this finding.

Study design

Case Series, Retrospective Cohort

Study population and setting

This multicenter retrospective cohort study evaluated the prevalence, epidemiology, and outcomes of COVID-19 associated mucormycosis (CAM), a fungal disease, in India from September 1, 2020 to December 31, 2020, compared to mucormycosis not associated with COVID-19 (non-CAM) over the same time period. Mucormycosis was defined based on clinical and radiologic findings that showed fungi in tissue or sterile body fluids. COVID-19 diagnosis was based on detection of SARS-CoV-2 on RT-PCR or rapid antigen tests. The data from 16 health centers were used to evaluate predisposing factors and clinical manifestations of CAM and non-CAM patients, and data from 7 of these centers were used to estimate prevalence of CAM. Demographics, medical history, clinical presentation, and outcomes were extracted from patient medical records. Patients were treated for COVID-19 and mucormycosis in accordance with institutional protocols; inappropriate glucocorticoid use was defined as use of any steroid among non-hypoxic patients or when a dexamethasone-equivalent was used for 10 days or more with more than 6 mg/day.

Summary of Main Findings

Across the 16 participating centers, 295 cases of mucormycosis were diagnosed, among whom 287 had complete data and were included in the study population (mean age: 53.4 years, 25% women, 83% diagnosed on direct microscopy). Across the 7 centers with data on all hospitalized COVID-19 patients, the prevalence of CAM was 0.27% (28/10,517) in general wards and 1.6% (25/1579) in the ICU. The total number of mucormycosis cases between September 2020 and December 2020 was over twofold higher than the same time period in 2019, though the number of mucormycosis unrelated to COVID was relatively similar (92 in 2020 vs. 112 in 2019). Of the 187 CAM cases (65% of all mucormycosis cases), 61 (33%) did not have other underlying diseases, compared to only 19 of the 100 non-CAM cases without other underlying diseases. Among CAM and non-CAM cases, uncontrolled diabetes was common (63%) though newly diagnosed diabetes was more common among those with CAM (21% vs. 10%). Both groups experienced similar clinical manifestations and sites of involvement (~85% in each group with rhino-orbital or rhino-orbital-cerebral involvement), and mortality was similarly high (6-week mortality: 38%; 12-week mortality: 46%). However, patients with CAM were more likely to have hypoxia requiring ICU admission than non-CAM patients (31% vs. 9%). CAM patients were classified according to timing of onset (early: <8 days after COVID-19 diagnosis, n=29; late: ≥8 days after COVID-19 diagnosis, n=158), and although demographic, clinical characteristics, and outcomes were similar between early and late CAM groups, hypoxia and inappropriate or non-indicated glucocorticoid use was associated with development of late CAM as compared to early CAM (adjusting for age, sex, and underlying risk factors).

Study Strengths

This was a multisite study with detailed data on clinical characteristics, treatment history, and outcomes of COVID-19 associated mucormycosis, with a comparison group of adults with mucormycosis not associated with COVID-19.

Limitations

Despite its multi-site design, the sample size was still relatively small. Adjusted analyses, especially those among only CAM cases, were likely underpowered to detect associations or overfit. Consequently, many of the estimates had very wide confidence intervals and should be interpreted with caution. The study was retrospective and relied upon data available in the medical record, which may not have fully captured individual disease histories and comorbidities. The study did not report whether there was clustering of cases by healthcare center nor explore facility-level characteristics that might have enabled healthcare-associated sources of mucormycosis during the study period. Given the small sample size, analyses of mucormycosis and CAM outcomes were limited in their ability to fully adjust for treatment practices, which differed between sites.

Value added

This study is among the first and most detailed reports of COVID-19 associated mucormycosis, a rare fungal disease associated with high mortality.

This review was posted on: 27 June 2021