Introduction
As a human-to-human transmitted disease, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was an emergency amidst global public health events. Besides, the diffuse alveolar damage with severe inflammatory exudation, COVID-19 patients have immunosuppression. Critically ill patients, especially those admitted to the intensive care unit (ICU) and required mechanical ventilation, or those that had a longer duration of hospital stays, even as long as 50 days, were more likely to develop fungal co-infections. COVID-19 patients with trauma, diabetes mellitus, corticosteroid use, prolonged neutropenia, also-hematopoietic stem cell implant, and organ transplant were more likely to develop mucormycosis. 1
The occurrence of mucormycosis, a rare disease, in the general population was previously cited as 0.005 to 1.7 per million population. However, the incidence of mucormycosis in India was reported to be 0.14 per 1000 diabetic patients which are 80 times higher than that reported in other parts of the world. There are multiple case reports describing mucormycosis in COVID-19 and most of these case reports were from India, especially in diabetic COVID-19 patients and those in whom corticosteroids were administered injudiciously for controlling the severity of COVID-19, leading to a higher fatality and complicated the pandemic scenario. 2
Early diagnosis and accurate classification of fungal rhinosinusitis helped in deciding the treatment protocol and preventing multiple surgical procedures, and leading to effective treatment. 3
In this case series, we elaborated on the KOH (potassium hydroxide) and histopathological report which helped us to treat mucormycosis patients in our clinical setup.
Case Series
As the world is experiencing COVID-19 and India had a huge surge of COVID cases with an added fear striking the Indian population – the black fungus. Mucormycosis is a normally occurring commensal and in normal times it was a rare case but during the COVID pandemic, it became an endemic of its own. In this study, we observed 30 patients who presented to our hospital with sinusitis-like features post-COVID infection. In this series, we explain the intraoperative endoscopic features which helped us to differentiate mucormycosis from sinusitis, and the importance of tools that helped us substantiate the diagnosis such as KOH and histopathological report.
In the majority of the patients, the common feature that we encountered was that 90-95% of the patients were COVID positive and had associated co-morbidities like diabetes mellitus, cardiac complications, etc. Patients presented with symptoms similar to fungal sinusitis and were initially subjected to Diagnostic Nasal Endoscopy. They were then assessed with MRI & CT PNS to look for the involvement of sinuses and plan the operation accordingly.
Intraoperatively majority of the patients had middle and inferior turbinate necrosis with sinus involvement, and mucopurulent discharge, two-thirds of patients had septal involvement and a third of the patients had hard palate involvement like necrosis and granulomatous lesions of the hard palate. Amongst sinus involvement most common to least are maxillary, anterior & posterior ethmoids, and sphenoids.
After debridement, the samples were sent for KOH, histopathological report (HPR), and fungal culture. KOH was positive for all the samples and HPR showed features of sinusitis and fungal filaments under a microscope. The number of patients involved in the study and their KOH & histopathological reports are displayed in a table. (Table 1), (Figure 3) according to our observation mucormycosis is more predominantly present in males who were COVID positive or recovered with associated co-morbidities which made them immunosuppressed.
For a rapid presumptive diagnosis of mucormycosis, KOH wet mounts can be used for direct microscopy. It is used as a primary screening tool; it detects fungal elements present but may not necessarily identify the species of the fungi. Mucormycosis in KOH presents with features of aseptate hyphae. (Figure 1)
All the samples sent to histopathological examination tissue sections were fixed and stained with hematoxylin and eosin (H&E) or specialized fungal stains and appeared as ribbon-like, non-septate hyphae with wide-angle branching (approximately 90°). Tissue histopathology was dominated by inflammation which may be neutrophilic or granulomatous; inflammation seemed to be absent in a few cases, particularly in immunosuppressed patients. Invasive disease is characterized by prominent infarcts and angioinvasion. (Figure 2)
Patients were initially treated with medical management like Amphotericin B, Posaconazole, Isavuconaole, etc. Patients needed repeated debridement and after 2 negative KOH patients were discharged and followed up regularly.
Table 1
The number of patients involved in the study and their KOH & histopathological reports
Discussion
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with a wide range of opportunistic bacterial and fungal infections. Recently, several cases of mucormycosis in people with COVID-19 have been increasingly reported worldwide, in particular in India. Mucormycosis is extremely rare in healthy individuals, but immunocompromised conditions predispose it. This includes uncontrolled DM with or without DKA, hematological and other malignancies, organ transplantation, prolonged neutropenia, immunosuppressive and corticosteroid therapy, iron overload or hemochromatosis, and deferoxamine therapy, severe burns, and acquired immunodeficiency syndrome (AIDS), intravenous drug abusers, malnutrition and open wound following trauma. Mucormycosis can involve the nose, sinuses, orbit, central nervous system (CNS), lung (pulmonary), gastrointestinal tract (GIT), skin, jawbones, joints, heart, kidney, and mediastinum (invasive type), but ROCM (rhino-orbit-cerebral mucormycosis) is the commonest variety seen in clinical practice worldwide.
The diagnosis and treatment of mucormycosis are challenging Clinical approach to diagnosis lacks sensitivity and specificity as it can mimic sinusitis microscopic examination of the specimens either KOH or HPR aids in confirming the diagnosis to start the patient on appropriate antifungal medication and also help to follow up. 4
