The double trouble: COVID-19 associated mucormycosis a focused review and future perspectives

Abstract

Mucormycosis, a deadly fungal infection, has affected thousands of COVID-19 patients in India. Mucormycosis, formerly known as zygomycosis, is caused by the many fungi that belong to the family “Mucorales.” These molds are commonly found in soil, air, and damp walls and frequently colonize oral mucosa, nose, paranasal sinuses, and throat. The pathophysiological consequences of diabetes combined with the acute inflammatory surge in COVID-19 and steroid treatment weakens person’s immunity and renders susceptibility to fungal infections. Patients treated for severe COVID-19 have damaged lungs and suppressed immune system, an environment that supports fungal infection. Fungal spores can grow in airways or sinuses, and invade bodies’ tissues, explaining why the nasal cavity and paranasal sinuses are the most common site of mucormycosis infection, the consequential spread to the eyes can cause blindness, or causing headaches or seizures if the infection spreads to the brain. Poorly controlled diabetes often results in acidosis in tissues a suitable environment for Mucorales fungi to grow, exacerbating the risk for mucormycosis. This becomes clinically important, especially in India that has an increased prevalence of undiagnosed and uncontrolled diabetes. Given that a significant increase in the cases of mucormycosis in the diabetic patients treated for COVID-19 is strongly associated with corticosteroid administration, there is a need to evaluate use of dietary nutraceuticals with immune boosting potentials that modulate metabolic abnormalities in the management of COVID-19 associated mucormycosis.

Postoperative clinical nursing care pathway for patients with mucormycosis: An experience from a tertiary care hospital in Rajasthan, India

“…Agnihotri, et al reported that a significant increase in the COVID-19 associated mucormycosis cases is strongly associated with treatment of corticosteroid in the diabetic patients treated for COVID-19. This finding is congruent to our study where 72.2% patients received steroids as a part of treatment for Covid-19 infection during hospitalization [ 13 ].…”

Mucormycosis and COVID-19-Associated Mucormycosis: Insights of a Deadly but Neglected Mycosis

“…To cause such an aggressive and lethal infection, the causative mucormycosis fungi take advantage of the many alterations that SARS-CoV-2 infection generates on the host, such as ( Figure 1 ): Hyperglycemia, caused by the use of corticosteroids to treat COVID-19 [ 143 ] and dysregulation of the host receptor ACE2 (angiotensin-converting enzyme 2) observed during the viral infection [ 144 , 145 ] (explained in vii). Pre-existing diabetes is the main risk factor in most CAM cases [ 12 ] and is also related to an increase in the severity of SARS-CoV-2 infection [ 146 ]; Low pH, caused by diabetic ketoacidosis or metabolic acidosis caused by corticosteroid use [ 147 ], which reduces the leukocytes’ phagocytic activity and impairs bronchoalveolar macrophages migration and functions [ 12 , 148 ]; Immunosuppression, caused by SARS-CoV-2 infection and hypoxia, corticosteroids, and tocilizumab use [ 148 , 149 ] or patients’ previous comorbidities.…”

“…Therapeutic intervention with lactoferrin has been suggested to revert iron availability [ 157 , 158 , 159 ]; Pulmonary changes, including vascular endothielitis, thrombosis, and angiogenesis, caused by SARS-CoV-2 infection, which provides a focal point for fungal growth and dissemination [ 103 , 160 ]. The damage to alveolar cells can also promote anaerobic glycolysis, which causes lactic acidosis [ 145 ]; Overexpression of endothelial cells GRP-78, caused by hyperglycemia, acidosis, and iron availability, which enables angioinvasion, hematogenous dissemination, and tissue necrosis [ 58 ]; Dysregulation of ACE2 by SARS-CoV-2. By being present in many organs and tissues, the alteration of the receptor ACE2 expression causes a suitable environment for the development of mucormycosis.…”

“…During COVID-19, a downregulation of ACE2 has been observed in the lungs [ 161 ], which causes inflammation, leukocytes exudation, and altered pulmonary function and therefore poor oxygenation [ 144 ]. Additionally, the effect of the virus on ACE2 in the pancreatic beta cells causes hyperglycemia, while dysregulation of the receptor in the vascular endothelium causes endothelial damage and vascular thrombosis, leading to vascular endothelial injury and venous stasis, causing an increase in serum iron due to hemolysis [ 144 , 145 ]; Prolonged hospital stays and mechanical ventilation in severe COVID-19 cases expose the patient to fungal coinfections [ 15 , 103 ]. …”

“…Hyperglycemia, caused by the use of corticosteroids to treat COVID-19 [ 143 ] and dysregulation of the host receptor ACE2 (angiotensin-converting enzyme 2) observed during the viral infection [ 144 , 145 ] (explained in vii). Pre-existing diabetes is the main risk factor in most CAM cases [ 12 ] and is also related to an increase in the severity of SARS-CoV-2 infection [ 146 ];…”