Discussion:
Up to now, there are limited data about the impact of COVID-19 on mucormycosis or other fungal infections. On the one hand, the robust inflammatory immune response following COVID-19 and usage of immunosuppressive drugs afterwards, provides a favorable condition for development of fungal co-infections. On the other hand, it is suggested that venous thromboembolism (VTE) caused by COVID-19 infection leads to mechanical ventilation, central venous catheterization, and surgeries, all of which could damage elastic lamina of blood vessels and eventually trigger the propagation of mucorales (3). Furthermore, comorbidities such as diabetes mellitus and diabetic nephropathy are risk factors for both COVID-19 and mucormycosis (8).
This case report is consistent with other case reports in which diabetes mellitus was a predisposing condition regarding SARS-CoV-2 and mucormycosis co-infection. Besides, this case had multiple underlying health conditions including diabetic ketoacidosis, diabetic nephropathy, hypertension and history of CABG surgery. All of these conditions, increase COVID-19 severity and the risk of co-infection or superinfection with other microorganisms (9). Unfortunately, this case had a poor prognosis due to extensive involvement of rhino-orbital mucormycosis and ARDS and passed away after one month of hospitalization.
Based on a broad literature search, the presented case had some unique features compared to the similar reported cases. First of all, Diabetic nephropathy followed by hemodialysis has not been reported in concurrent infection of COVID-19 and mucormycosis. Secondly, limited cases of diabetic ketoacidosis as a comorbidity in SARS-CoV-2 co-infected with mucormycosis have been reported previously (10, 11). The presented case was the only case with uncontrolled diabetes mellitus, diabetic ketoacidosis, diabetic nephropathy under hemodialysis and hypertension who was suffering from rhino-orbital mucormycosis following severe COVID-19 infection. It should be noted that in reports from different countries other underlying health conditions have also been associated with mucormycosis following COVID-19 such as; Hematological malignancies, Hypothyroidism, Asthma and obesity with median age of 53.4 and male sex comprising the majority of the cases (12-19).
Up to July 4, four cases of rhino-orbital–cerebral mucormycosis following COVID-19 have been reported in Iran. The median age of the patients was 51.2 years. Besides, 3 out of 4 were women. Diabetes mellitus was the most historical condition (3 of 4). Of these four cases, one death was reported. Amphotericin B was prescribed for all of them as the first line treatment for mucormycosis infection(20-22).
Mucormycosis is a serious opportunistic fungal infection that could lead to rhino-orbital, gastrointestinal, pulmonary, renal, cutaneous and disseminated infections. The infection enters the host via respiratory tract. Since it has a noticeable affinity for arteries it grows in internal elastic lamina, which triggers thrombosis and infarction (23). The disease can progress from nose and sinuses directly or through vascular occlusion. Invasion through superior orbital fissure, ophthalmic vessels, cribriform plate, carotid artery or possibly via a perineural route can involve intracranial part (24).
Necrotic tissue surgical debridement, treatment with liposomal amphotericin B as an antifungal therapy and risk factors control were suggested to improve survival (25).
Since COVID-19 pandemic is continuing in Iran and mass vaccination has not been started yet, co-infection of SARS-CoV-2 and other microorganisms should be taken under consideration. Prescribing immuno-suppressants for COVID-19 patients with underlying health conditions should be done more cautiously along with continuous monitoring. In spite of massive researches on COVID-19 management performing all around the world, extensive researches are needed regarding better prevention and management of opportunistic infections among COVID-19 patients, yet.