Coronavirus disease-associated mucormycosis (CAM), the so-called black fungus, has emerged as a significant healthcare challenge, with more than 30,000 cases reported until June 2021 in India alone. [1] While previous history of diabetes, unmasking of latent diabetes, and corticosteroid use are commonly understood risk factors, the occurrence of CAM in patients without prediabetes or diabetes is being recognised. In some of our own practices, we have seen cases of young people with no past medical history of diabetes or steroid use, and no history of symptomatic covid-19 infection, presenting with severe proptosis due to mucormycosis. On further testing these patients were found to be seropositive for covid-19. With the extreme short supply of drug treatments in India, these patients have to undergo extensive debridement to save their lives; the long-term consequences for these patients and their families, even if they survive, is likely to be devastating.
A global registry for covid-related mucor cases could help provide timely evidence on the risk factors for CAM and clinical approaches for treating patients. While the diagnostic and treatment pathways for covid-19 patients are not likely to differ between CAM and non-CAM disease, it is the understanding of risk factors that is critical to designing prevention programmes for this deadly disease. This situation warrants timely clinico-epidemiologic studies that can identify novel risk factors, including those that may be specific to different covid-19 variants.
At present there is a paucity of data on the risk factors for mycotic infections in covid-19, so all we have are best guesses and hypotheses. There are multiple untested hypotheses for contributing factors. Iron dysregulation associated with diabetes and covid-19 associated kidney and liver disease is postulated to enhance fungal survival and virulence. [2,3]. Free iron supports fungal growth, and the acidotic state associated with infection can cause dissociation of iron from binding proteins [3]. Ketosis, and the presence of beta-hydroxybutyrate, likely worse during covid-19 associated malnutrition states, are known to increase the expression of host and fungal receptors that contribute to increased tissue invasiveness [4,5]. As yet these are still hypotheses.
Adopting prevention strategies based on lack of evidence will replicate the exact problem that likely got us here in the first place; theory-driven medicine not backed by adequate evidence. This pandemic has underscored the importance of collaborative research and adapting research methodologies while maintaining scientific rigor. Efforts to collect systematic and timely data on clinico-epidemiological risk factors will be hampered by the low rate of adoption of electronic health records (EHR) in most low and middle-income countries, including the ones most affected by the so-called mucor epidemic. A simple, transparent, and effective strategy to overcome this limitation would be to populate a disease registry focused on mycotic infections associated with covid-19 infection. There is ample precedent. Physician reported registries like SECURE IBD have been successful in generating impactful science, relatively fast during the pandemic. [6] Near real-time collection and dissemination of information has been the hallmark of collective global response to covid-19.
Along with colleagues working in various institutions in India and other countries, we have developed an online registry for mucormycosis. MUNCO (Mycotic infections in COVID-19), is an international database to report these cases. The registry aims to rapidly identify the demographic and clinical variables associated with outcomes in this deadly disease. This is likely to be one of several such organic efforts to study the mucormycosis epidemic.
Coronavirus disease-associated mucormycosis is a medical emergency and we must act now. With the collaboration of our entire physician community, we will rapidly be able to define the risk factors associated with development of CAM in covid-19 patients and how factors such as oxygen usage, inflammatory burden, and medication impact outcomes. The principles of evidence-based medicine are even more important now, giving us a rare opportunity to not only study a novel disease as it unfolds, but most importantly, to positively impact our patients.
Shitij Arora is an associate professor in Medicine Albert Einstein College of Medicine, New York and leads the MUNCO registry (@MUNCO5). He tweets at @aroramontefiore.
Charuta Mandke is an associate professor in Ophthalomology at Dr RN Cooper Municipal General Hospital Mumbai. She tweets at @CharutaMandke
Competing interests: none further declared.
The Swasth community science alliance is a partnership of community-based organizations, frontline clinicians, and leading scientists from India and the Indian diaspora that seeks to develop a community of practice committed to advancing evidence-based covid-19 care, contextualized to rural India.
References:
- https://www.bbc.com/news/world-asia-india-57312832
- Oliver A Cornely et al for the Mucormycosis ECMM MSG Global Guideline Writing Group. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. Lancet Infectious disease, Volume 19, Issue 12. E405-E421
- Ayoubkhani D, Khunti K, Nafilyan V, Maddox T, Humberstone B, Diamond I et al. Post-covid syndrome in individuals admitted to hospital with covid-19: retrospective cohort study BMJ 2021; 372 :n693 doi:10.1136/bmj.n693
- Alexander J, Limaye AP, Ko CW, Bronner MP, Kowdley KV. Association of hepatic iron overload with invasive fungal infection in liver transplant recipients. Liver Transplantation 2006;12:1799-1804.
- Ashraf S. Ibrahim, Brad Spellberg, Thomas J. Walsh, Dimitrios P. Kontoyiannis, Pathogenesis of Mucormycosis, Clinical Infectious Diseases, Volume 54, Issue suppl_1, February 2012, Pages S16–S22, https://doi.org/10.1093/cid/cir865].
- https://covidibd.org