CHALLENGES OF TREATMENT

CHALLENGES OF TREATMENT

The possibility of infections caused by the fungus Aspergillus in people with severe COVID-19 is still debated by scientists. In the past, Aspergillosis was reported only from people with severely weakened immune systems. However, nowadays, Aspergillosis is also reported from patients having severe respiratory infections such as influenza, caused by viruses. Several recent reports alsodescribe COVID-19-Associated Pulmonary Aspergillosis (CAPA).

As per available information, CAPA can occur in severe COVID-19 patients who are on ventilators in ICUs. CDC advises physicians to consider the possibility of Aspergillosis in severe COVID-19 patients who have worsening respiratory function or sepsis, even if they are not having the classical risk factors for Aspergillosis. In such situations, testing for CAPA can be done. The test usually involves obtaining specimens from patients’ lower respiratory tract which are tested for Aspergillus galacto-mannan antigen and subjected to fungal culture.

Diagnosis of mucormycosis

CT and MRI scans along with regular examination are very important to detect mucormycosis at an early stage and know its propagation. Scan images of the infected region are very crucial in the early diagnosis of the disease. The images can be useful in identifying the opacifications of involved paranasal sinuses, bone destruction of sinus walls, alterations of intraorbital tissue signal with or without focal mass, cavernous sinus filling defect, intracranial focal mass and alteration of the meningeal signal.

However, mucormycosis is confirmed if blackish necrotic tissues are detected in the infected region and through histopathology. Stains such as Hematoxylin and Eosin, Periodic Acid-Schiff (PAS) and Gomori Methenamine Silver (GMS) can be used to identify the mucor structures. If mucormycosis is the case, histopathologic examinations will be showing relatively broad non-septate hyphae with right angle branches, necrotizing granulomatous inflammation and vasculitis together with the presence of mucor hyphae within the vascular wall and lumen.

Amph B – Drug of choice

Among the different types of mucormycosis, rhino-orbito-cerebral mucormycosis is relatively the most fatal infection and in cases of brain involvement, the mortality can rise up to 50%–85%. For mucormycosis of any kind, systemic Amphotericin B and its liposomal formulation is the first drug of choice. It can significantly improve the survival rate of the patients. The antifungal agent Posaconazole can be used orally as step-down therapy after the initial control of the disease by Amphotericin B.

Surviving mucormycosis will be quite easy if early diagnosis of the disease can be done, says Dr. R. Aravind, Head, Infectious Diseases, Medical College, Thiruvananthapuram, Kerala.

“Regular daily debridement of necrotic tissues from paranasal sinuses is necessary to prevent the propagation of mucormycosis. Also, irrigation of the sinuses and the involved regions with diluted Amphotericin B is recommended. The selection of the most appropriate systemic antifungal agents is also important,” he says.

Diabetes, COVID-19 and mucormycosis

India has the highest burden of mucormycosis in the world with an estimated prevalence of 140 cases per million people. Diabetes mellitus is seen associated with over 50% of cases of mucormycosis in India. So, diabetes mellitus is considered as the single most common risk factor for mucormycosis in India. It is a fact that patients with COVID-19 are predisposed to diabetic ketoacidosis. And in patients with Diabetes mellitus, mucormycosis is associated with increased morbidity and mortality.

Researchers have proved that as with any other serious infection, SARS-CoV-2 induces damage of pancreatic islets resulting in acute diabetes and diabetic ketoacidosis. In a recent paper published in the Journal of Fungi, this is presented as the possible explanation for the ‘diabetogenic state’ in SARS-CoV-2 infection, as there is a high expression of angiotensin-converting enzyme 2 receptors in pancreatic islets, along with increased insulin resistance due to cytokine storm.

In a study conducted in UK, the prevalence of Diabetes mellitus and diabetic ketoacidosis was found to be higher in COVID-19 patients compared to the national prevalence of Diabetes mellitus type 2 and diabetic ketoacidosis in the general population (Goldman, N. et al., 2020). Recently, euglycemic diabetic ketoacidosis is also being reported in COVID-19 patients (Oriot, P. et al., 2020). Researchers propose that the frequent use of corticosteroids can disrupt glucose homeostasis, making patients more susceptible to Mucormycosis (Lionakis, M.S. et al., 2003).

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