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Earlier this year, hospitals in India were not only dealing with the coronavirus pandemic but also a surge in a potentially lethal fungal infection in patients previously treated for COVID-19. Mucormycosis, also known as black fungus, is typically a rare infection, but India had recorded over 45,000 cases as of July 2021.
Now, a recent report suggests that patients with COVID-19–associated rhino-orbital cerebral mucormycosis (CAM) may have a higher mortality rate than previously estimated. At highest risk, CAM patients with severe COVID-19 or orbital disease are more likely to die within 10 days of admission. The study was published December 9 in JAMA Ophthalmology.
“The mortality indicators we observed, such as assisted ventilation and presence of severe orbital manifestations, can help physicians triage patients for emergency procedures, such as functional endoscopic sinus surgery (FESS), and administer systemic antifungal agents when in short supply,” the study authors write.
Mucormycosis usually infects immunocompromised patients. Previous research has found that poorly controlled diabetes — an epidemic in India — and use of high-dose systemic corticosteroids are two main risk factors for developing CAM. Even before COVID-19, India had a high incidence of mucormycosis compared to other countries, but cases exist around the world. In fact, on December 17, the Centers for Disease Control and Prevention reported 10 isolated cases of COVID-19–associated mucormycosis identified in Arkansas hospitals between July and September 2021.
The disease can cause blurred vision, black lesions on the nose or inside of the mouth, and facial swelling. In rhino-orbital cerebral mucormycosis, extensive infection can necessitate orbital exenteration surgery, a disfiguring surgery that typically involves removal of the entire contents of the bony eye socket, as well as removal of the sinuses. Estimates for the mortality rate for this disease range from 14% to nearly 80%.
To better understand the cumulative morality rates for CAM and to identify additional risk factors, researchers reviewed the medical records of patients diagnosed and treated for CAM at a tertiary care multispecialty government hospital in Maharashtra, a state in the west-central region of India. The analysis included patients who died after admission or who had at minimum 30 days of documented follow-up. All diagnoses occurred between March 1 and May 30, 2021. All patients underwent comprehensive ophthalmic exams and routine blood workups.
Seventy-three patients were included in the study, with the average age of 53.5 years; 66% of patients were male, and 74% of all patients had diabetes. Of the 47 individuals with available COVID-19 vaccination information, 89% had not had either shot of the vaccine, and 11% had the first dose. No patients in the cohort had received both doses of the vaccine; 87% of patients were previously hospitalized for COVID-19, with 43 needing supplemental oxygen, 14 receiving noninvasive ventilation and ventilator support (NIV), and three requiring mechanical ventilation.
Patients developed CAM a median of 28 days after being discharged from the hospital for COVID-19 treatment; 26 patients died, 18 patients underwent FESS, and five underwent orbital exenteration. While 36% of patients died overall, the researchers found the cumulative probability of death from CAM rose from 26% at day 7 to 53% at day 21. They also found that the patients who died had more severe COVID-19, indicated by more days spent on supplemental oxygen (P = .003) and increased need for NIV or mechanical ventilation (P = .02) compared to patients who survived CAM. Those who died also had poorer visual acuity, with 35% of the group having no light perception during examination compared to 6% of surviving CAM patients (P = .02).
These findings are largely “confirmatory to what we previously knew, which is that [CAM] is a very bad disease with high morbidity and high mortality,” Ilan Schwartz, MD, PHD, an infectious disease physician at the University of Alberta, Canada, who researches emerging fungal infections, told Medscape Medical News. He was not involved with the research.
While larger studies looking at similar questions have been published, the new report has longer patient follow-up and is “better positioned to be able to estimate the mortality rate,” Schwartz noted. Even with 30 days of follow-up, “patients can have ongoing problems for many months, and so it’s possible that the true mortality rate is even higher, once you get beyond that period,” he added.
But Santosh Hanovar, MD, the director of medical services at the Centre for Sight Eye Hospital in Hyderabad, India, also unaffiliated with the study, noted that the subset of patients included in the latest report may have had much more severe infection — and subsequently higher mortality rates ― than a more generalized study in a broader patient population.
For example, a study by Mrittika Sen, Hanovar, and their coauthors published in the Indian Journal of Ophthalmology earlier this year found a mortality rate of 14% when examining the records of more than 2800 patients across 102 treatment centers.
Taking that into account, “we believe that the actual mortality may be somewhere between the 14% reported by Sen et al from the large Indian series and the 53% that we report at 3 weeks,” the JAMA Ophthalmology authors write.
Hanovar also noted that the new report of severe infection outcomes identifies subgroups at higher risk of death due to CAM: those with severe COVID-19 infection or orbital disease. These groups “would need higher surveillance for mucormycosis, thus enabling early diagnosis and prompt initiation of amphotericin B upon diagnosis of mucormycosis,” he told Medscape in an email. “These measures can possibly minimize the risk of death.”
Ongoing research on CAM cases will continue to inform knowledge and treatment of the disease, but there are still unanswered questions. “We still have a fairly unsatisfactory understanding of exactly why this [CAM] epidemic occurred and why it was so bad,” Schwartz noted. And while mucormycosis cases have seemed to drop off since the surge earlier this year, “I don’t think we’re out of the woods,” he added. “There’s a lot more awareness in India and around the world about this disease now, but we’re still quite vulnerable to seeing it again.”
Hanovar is the editor-in-chief of the Indian Journal of Ophthalmology. Schwartz reports no relevant financial relationships.