Covid-19-associated rhino-orbito-cerebral mucormycosis (CAROM) in Delhi: Demographics and risk factors in a single-centre consecutive cohort of 200 inpatients.

Background There was a dramatic rise in the incidence of rhino-orbito-cerebral mucormycosis associated with the 2021 Covid-19 wave in India. We aim to document the demographic characteristics and risk factors of a consecutive cohort of inpatients with Covid-19-associated rhino-orbito-cerebral mucormycosis (CAROM) during the surge of April-June 2021. Methods We included all patients of CAROM treated at our tertiary referral facility from 1 April to 14 June 2021. We prospectively gathered details with regard to Covid-19 illness and treatment, CAROM presentation, comorbid conditions and risk factors. Results Our prospective cohort consisted of 200 consecutive patients, of which 146 (73%) patients tested positive on the Covid-19 RT-PCR test at presentation. CAROM occurred concurrent with the Covid-19 infection in 86%, and delayed CAROM after seeming recovery from Covid-19 was seen in 14%. Covid-19 was classified as mild, moderate and severe in 54%, 33% and 13%. The surge of CAROM followed the population peak of Covid-19 infections by about 3 weeks. Advanced disease at presentation was frequent with ocular involvement in 56.6% (111/196) and central nervous system involvement in 20% (40/199). One or more comorbid conditions were identified in 191/200 (95.5%) patients. The dominant associations were with diabetes (189/200; 94.5%) and uncontrolled hyper-glycaemia (122/133; 91.7%), recent steroid use (114/ 200; 57%), which was often considered as inappropriate in dosage or duration, lymphopenia (142/176; 80.7%), and increased ferritin levels (140/160; 87.5%). No evidence supported the role of previous oxygen therapy or previous nasal swab testing as risk factors for CAROM. Conclusion The inpatient volumes of CAROM were noted to parallel the Covid-19 incidence curve by about 3 weeks. Covid-19 infection may directly predispose to CAROM by way of lymphopenia and increased ferritin levels. Uncontrolled hyperglycaemia is identified as a near-invariable association. Recent steroid use is noted as very frequent and was often received in excess of treatment advisories.

Experience on rhino-orbital mucormycosis from a tertiary care hospital in the first wave of COVID-19: An Indian perspective.

Background: To highlight the clinical presentations and management outcomes of rhino-orbital mucormycosis during first wave of COVID-19 pandemic in North India. Methods: A retrospective observational study. 15 patients with mucormycosis (orbital disease) who presented during short span of 3 months (October-December 2020) in a tertiary-care referral institution were analysed. Results: At presentation, 13 of 15 patients had uncontrolled diabetes. Four had history of COVID-19 infection. All patients had advanced orbital disease with sinusitis; cavernous sinus involvement was in nine and intracranial spread in three patients. Liposomal amphotericin-B was started and prompt orbital exenteration with sinus surgery was performed in 12 patients. All 12 patients survived with an average follow-up of 4.8 months. Conclusion: In the present series, cases with orbital spread of mucormycosis were mostly found in non-COVID uncontrolled diabetics. Exenteration was done in 80% of cases with advanced orbital disease. Prevention and early detection of infection at the stage of sino-nasal involvement might help to prevent spread and/or halt the orbital disease.

Risk factors for Coronavirus disease-associated mucormycosis.

BACKGROUND: The epidemiology of the Coronavirus-disease associated mucormycosis (CAM) syndemic is poorly elucidated. We aimed to identify risk factors that may explain the burden of cases and help develop preventive strategies. METHODS: We performed a case-control study comparing cases diagnosed with CAM and taking controls as recovered COVID 19 patients who did not develop mucormycosis. Information on comorbidities, glycemic control, and practices related to COVID-19 prevention and treatment was recorded. Multivariate regression analysis was used to identify independent predictors. RESULTS: A total of 352 patients (152 cases and 200 controls) diagnosed with COVID-19 during April-May 2021 were included. In the CAM group, symptoms of mucormycosis began a mean of 18.9 (SD 9.1) days after onset of COVID-19, and predominantly rhino-sinus and orbital involvement was present. All, but one, CAM cases had conventional risk factors of diabetes and steroid use. On multivariable regression, increased odds of CAM were associated with the presence of diabetes (adjusted OR 3.5, 95% CI 1.1-11), use of systemic steroids (aOR 7.7, 95% CI 2.4-24.7), prolonged use of cloth and surgical masks (vs. no mask, aOR 6.9, 95%CI 1.5-33.1), and repeated nasopharyngeal swab testing during the COVID-19 illness (aOR 1.6, 95% CI 1.2-2.2). Zinc therapy was found to be protective (aOR 0.05, 95%CI 0.01-0.19). Notably, the requirement of oxygen supplementation or hospitalization did not affect the risk of CAM. CONCLUSION: Judicious use of steroids and stringent glycemic control are vital to preventing mucormycosis. Use of clean masks, preference for N95 masks if available, and minimizing swab testing after the diagnosis of COVID-19 may further reduce the incidence of CAM.

COVID-19-associated subacute invasive pulmonary aspergillosis.

BACKGROUND: Though invasive pulmonary aspergillosis is a well known complication of COVID-19 pneumonia, indolent forms of aspergillosis have been rarely described. METHODS: We prospectively collected the clinico-radio-microbiological data of 10 patients of subacute invasive pulmonary aspergillosis (SAIA), who presented to our hospital with recent history of COVID-19 pneumonia along with cavitary lung disease, positive IgG (against Aspergillus) with or without positive respiratory samples for Aspergillus spp. RESULT: The mean age of presentation of SAIA was 50.7 ± 11.8 years. All the patients had recently recovered from severe COVID-19 illness with a mean duration of 29.2 ± 12 days from COVID-19 positivity. Cough was the predominant symptom seen in 8/10 (80%) patients followed by haemoptysis. 7/10 (70%) patients were known diabetic. While serum galactomannan was positive in 5/9 patients (55.5%), fungal culture was positive in 2/7 patients (28.5%) and polymerase chain reaction (PCR) for Aspergillus was positive in three patients. Eight (80%) patients presented with a single cavitary lesion; pseudoaneurysm of pulmonary artery was seen in two patients and post-COVID-19 changes were seen in all patients. All patients were treated with voriconazole, out of which four (40%) patients died during the follow-up period. CONCLUSION: SAIA should be considered in the differential diagnosis of cavitating lung lesions in patients with recent history of COVID-19 in the background of steroid use with or without pre-existing diabetes.

Multicenter Epidemiologic Study of Coronavirus Disease-Associated Mucormycosis, India.

During September-December 2020, we conducted a multicenter retrospective study across India to evaluate epidemiology and outcomes among cases of coronavirus disease (COVID-19)-associated mucormycosis (CAM). Among 287 mucormycosis patients, 187 (65.2%) had CAM; CAM prevalence was 0.27% among hospitalized COVID-19 patients. We noted a 2.1-fold rise in mucormycosis during the study period compared with September-December 2019. Uncontrolled diabetes mellitus was the most common underlying disease among CAM and non-CAM patients. COVID-19 was the only underlying disease in 32.6% of CAM patients. COVID-19-related hypoxemia and improper glucocorticoid use independently were associated with CAM. The mucormycosis case-fatality rate at 12 weeks was 45.7% but was similar for CAM and non-CAM patients. Age, rhino-orbital-cerebral involvement, and intensive care unit admission were associated with increased mortality rates; sequential antifungal drug treatment improved mucormycosis survival. The COVID-19 pandemic has led to increases in mucormycosis in India, partly from inappropriate glucocorticoid use.