Mucormycosis, which is a potentially lethal fungal infection, has been increasingly reported in coronavirus disease 2019 (COVID-19) patients, particularly in India. Although COVID-19 itself is associated with several risk factors for mucormycosis, it appears that COVID-19 patients with diabetes are at an even greater risk of acquiring this secondary infection.
Mucor Mold. Image Credit: Kateryna Kon/Shutterstock.com
What is mucormycosis?
Mucormycosis is considered to be the most severe type of Zygomycosis, the latter of which describes infections that are caused by the Mucorales species of the bread mold fungi Zygomycota phylum. Mucormycosis, which is often used interchangeably with Zygomycosis, is a potentially lethal infection that often affects immunocompromised individuals, particularly those with diabetes mellitus, leukemia, lymphoma, neutropenia, a previous stem cell transplant, and systemic corticosteroid use.
Some of the hallmark symptoms of mucormycosis include discoloration or reddening of the nose, blurred or double vision, as well as several respiratory symptoms including chest pain, difficulty breathing, and the coughing up of blood. Mucormycosis is also often associated with myocardial infarctions and the necrosis of host tissues that arise as a result of fungal invasion of the vasculature.
Coinfections and COVID-19
COVID-19, which is caused by infection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected more than 168 million people worldwide, with about 3.5 million people who have died as a result of this disease. The severity of COVID-19 varies significantly across patient populations, with some individuals who are completely asymptomatic or only report mild symptoms, to more severe cases that often involve life-threatening pneumonia that may be accompanied by bacterial or fungal co-infections.
Overall, it is estimated that between 10% and 30% of COVID-19 patients who are severely ill and hospitalized will also experience secondary infections, with fungal infections being 10 times more common than other types of infections. Some of the most common fungal pathogens that have caused co-infections in COVID-19 patients include Aspergillosis and Candida. However, several recent cases of mucormycosis have also been reported in COVID-19 patients worldwide, particularly in India.
COVID-19: the ideal environment for mucormycosis
There are several different factors of COVID-19 that appear to facilitate the increased incidence of these co-infections. For example, COVID-19 patients who also have a history of diabetes, new-onset hyperglycemia, or steroid-induced hyperglycemia have high glucose levels that support the environment needed for Mucorales spores to germinate in.
Similarly, the acidic medium that is often accompanied by metabolic acidosis and diabetic ketoacidosis (DKA), also supports the growth and proliferation of these fungal species.
Other aspects that contribute to this ideal environment for Mucorales spores include low oxygen levels, high iron levels, and a lack of circulating white blood cells (WBCs). Despite the benefits that corticosteroids have in treating serious forms of COVID-19, these pharmaceutical agents can also lead to a state of immunosuppression that can further increase a COVID-19 patient’s risk of mucormycosis. Treatment with mechanical ventilation, antibiotics, and monoclonal antibodies can also contribute to the exposure of COVID-19 patients to co-infections like mucormycosis.
How does mucormycosis infect COVID-19 patients?
Mucoraceae, which are the fungi responsible for mucormycosis, gain entry into hosts through the respiratory tract. With an affinity for the arteries, mucoraceae will pass through the nose and sinuses and enter the blood vessels through vasculature occlusion. The dominant symptoms of mucormycosis at this stage include acute sinusitis, fever, nasal congestion, purulent nasal discharge, and headaches.
As the fungi move past the respiratory tract and into the vasculature, the fungi will begin to grow along the internal elastic lamina, which is a layer of elastic tissue that lines the outermost part of many blood vessels. As the fungi accumulate along these vessels, they can cause thrombosis and infarction. By this point in the infection, tissue necrosis is often a common late sign of angioinvasion and vascular thrombosis.
Treatment
As is the case with COVID-19, the early detection, diagnosis, and intervention of mucormycosis, particularly when affecting COVID-19 patients, is essential for a good prognosis. In fact, it is estimated that even a week delay in the diagnosis of mucormycosis will increase the 30-day mortality rate from 35% to a staggering 66%.
Once a diagnosis of mucormycosis is considered, empiric antifungal treatment must be initiated immediately. Unfortunately, the diagnosis of mucormycosis is often challenging, particularly in COVID-19 patients who are already reporting some similar respiratory and sinus symptoms. Even when early surgical and pharmacological treatment is initiated, the prognosis of mucormycosis remains poor.
Conclusion
There has been a recent increase in the number of case reports/series of mucormycosis in COVID-19 patients around the world, particularly in India. These reports emphasize the need for healthcare professionals to identify possible invasive secondary fungal infections in COVID-19 patients early on to improve their prognoses.
Aside from increased surveillance of possible warning signs of mucormycosis in COVID-19 patients, more research is also needed to better understand how to prevent and manage these co-infections.
References:
- Maini, A., Tomar, G., Khanna, D., et al. (2021). Sino-orbital mucormycosis in a COVID-19 patient: A case report. International Journal of Surgery Case Reports 82. doi:10.1016/j.ijscr.2021.105957.
- Szarpak, L. (2021). Mucormycosis – a serious threat in the COVID-19 pandemic? Journal of Infection. doi:10.1016/j.jinf.2021.05.015.
- Singh, A. K., Singh, R., Joshi, S. R., & Misra, A. (2021). Mucormycosis in COVID-19: A systemic review of cases reported worldwide and in India. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. doi:10.1016/j.dsx.2021.05.019.
- Werthman-Ehrenreich, A. (2021). Mucormycosis with orbital compartment syndrome in a patient with COVID-19. The American Journal of Emergency Medicine 42; 245.e5-264.e8. doi:10.1016/j.ajem.2020.09.032.
Further Reading