Pathogenesis of COVID-19-Associated Mucormycosis: An Updated Evidence-Based Review

Purpose of Review The current review gives a proper understanding of the various dynamics of COVID-associated mucormycosis (CAM). We provide insight into the agent and recent host-related factors that contributed to CAM. Also, we have discussed various environmental-related factors like fungal spore burden that could have contributed to the pathogenesis of CAM. This review also summarizes the main components of pathogenesis under three primary headings: the immunomodulatory effect of the virus, the involvement of underlying comorbidities conditions in the host, and the numerous treatment-related modalities used during COVID-19 treatment. Recent Findings The risk factors for CAM continue to evolve with the development of COVID infection. A sudden rise in CAM cases was observed in countries including India. Along with Rhizopus arrhizus, the rise of other species like Rhizopus homothallicus and Rhizopus microsporus was observed. The virus along with underlying conditions like hyperglycemia, uncontrolled diabetes mellitus, diabetic ketoacidosis, and dysregulated iron metabolism with hyperferritinemia predisposes to CAM. Also, non-judicious and high-dose use of corticosteroids along with interleukins inhibitors (IL-1 and IL-6), and tocilizumab, contributed to a high rise in the cases of CAM. No link was found between the upsurge in CAM cases with the cow dung cake burning in India. Also, the possibility of nosocomial transmission was also raised, which was rejected as the majority of the patients remained at home during COVID-19 infection. Interestingly, in one study, the genetic similarity was observed between the strains isolated from the patient and the environment. Thus, the interplay of various factors like high spore count, uncontrolled diabetes, and the use of inappropriate steroids/IL inhibitors during the management of COVID-19 could have contributed to the alarming rise in cases of CAM. Summary Mucorales are found ubiquitously in the environment. Understanding the pathogenesis and environmental factors like spore count and burden can provide insight into the development of CAM which is critical for optimal patient management. Also, COVID-19 management should include strict glycemic control and avoidance of any unnecessary medication.