Post-Covid-19 Rhino-Cerebral Mucormycosis: an Observational Study During the Second Wave

Abstract

Mucormycosis is one of the most lethal and rapidly spreading fungal infection which is caused by fungus of the order Mucorales. The swiftness of spreading and high mortality rate that characterize mucormycosis cases added more burden to the enormous challenge brought by the Covid-19 pandemic globally. The aim of this article is to identify and discuss mucormycosis and review the literature related to its diagnosis and management. A total of 15 mucormycosis cases with a history of Covid-19 infection were identified in the Department of Dentistry of Shri B M Patil Medical College Hospital and Research Centre BLDE (Deemed to be University), Vijayapura, India. The duration of the study was between April 1st and mid-September 2021. Nasal swab and tissue samples from oral and maxillofacial region were collected. Blood investigations, RT-PCR and HbA1c tests and radiography revealed changes in the trabecular pattern and bone loss associated with periodontal inflammation. Mucormycosis is a life-threatening infection. Hence, dental and other clinical professionals must be aware of this possible fatal complication, so as to avoid an unfavorable outcome in clinical practice.

Keywords:Covid- 19 infection, mucormycosis, maxillectomy.

INTRODUCTION

Coronavirus disease is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2), which can progress to severe health problems, including pneumonia, acute respiratory distress syndrome (ARDS), and multiorgan dysfunction (1-4). It is globally accepted that systemic glucocorticoids will help in improving the condition in moderate to severe Covid-19 patients, but if used in excess, it will lead to a serious risk of developing secondary bacterial or fungal infection. Whereas the risk of fungal infection with Candida, Aspergillus and Pneumocystitis jiroveci in Covid-19 settings is well recognized, the unexpected surge in reporting of infection with mucor in these subtypes of cases is a new emerging challenge. The swiftness of spreading and high mortality rate that characterize mucormycosis cases added more burden to the enormous challenge brought by the Covid-19 pandemic globally (5, 6). Mucormycosis is one of the most fatal fungal infections, which is caused by a fungus of the order Mucorales, and also it is the third most common fungal infection apart from candidiasis and aspergillosis (7). These infections facilitate the entry of organisms into the body through the exposed part such as dental extraction site. The nose is the most common entry site and even organisms gain entry by perforation through the skin and mucus membrane (8). Commonly, mucormycosis presents as an acute pulmonary, rhinocerebral or gastrointestinal infection or it can spread through the skin. The diagnosis of mucormycosis is difficult and in most of the cases it is a contributing factor in death or even its cause (9).

This unusual but deadly fungal infection initially occurs in the nasal cavity and paranasal air sinuses, presenting with similar features to those of acute sinusitis but has propensity for rapid spread to orbital and intra cranial sites in an immunosuppressed host, with a subsequent worsening clinical result (3, 4). So, a high index of doubt that would lead to early diagnosis and aggressive management is of uppermost importance in these patients for a successful treatment result (10). We report our experience in the management of mucornycosis in Covid-19 patients admitted to our tertiary care hospital.

METHODS AND MATERIALS

A total of 15 mucormycosis cases with a history of Covid-19 infection were identified in the Department of Dentistry of Shri B M Patil Medical College Hospital and Research Centre BLDE (Deemed to be University), Vijayapura, India. The duration of the study was between April 1st to mid-September 2021. A proper institutional protocol was mentioned in the management of these cases. Nasal swab and tissue samples were collected with all aseptic precaution measures from medial meatal and then sent for tests with potassium hydroxide (KOH) staining for microscopic exam using special stains – periodic acide Schiff and Grocott (or Gomori) methenamine silver – and flourescent brightener. All samples were subjected to fungal culture, bacteriological culture, Gram stain, and all other required blood and biochemical investigations were done. After admission of Covid-19 cases with mucormycosis, all essential investigations such as RT-PCR, HbA1c were done along with computed tomography (CT).

RESULTS

Fifteen mucormycosis cases (total maxillectomy done in nine cases and subtotal maxillectomy done in six cases) of the maxilla were operated in our clinic during a routine check-up for dental infections. Later on, we corelated these patients with Covid-19 infection. There was a history of Covid-19 infection, supported by routine systemic and radiological findings, and also clinical findings such as extrapulmonary manifestations of Covid-19, characterized by necrosis of maxilla with the underlying systemic condition, which may be a post-Covid-19 complication.

Clinical symptoms manifested as toothache of non-odontogenic cause with radiating pain with altered sensation. Radiologically (CT scan) there was an unexplained erosion of the alveolar process (Figures 1 and 3). In some cases, an erosion of the inferior wall of the orbital bone (Figure 2) and an erosion of the anterior and lateral wall and floor of both maxillary sinuses were noted (Figure 4). The biopsy report helped in diagnosing these ases and mucormycosis. In all mucormycosis cases, maxillectomy was planned with debridement and curettage with possible tissue preservation.

DISCUSSION

Mucormycosis is caused by fungi pertaining to the order Mucorales. Rhizopus oryzae is a typical organism seen in infected patients and is accountable for the majority of mucormycosis cases (around 70 to 80% of patients) (11). Uncontrolled diabetes mellitus in ketoacidosis, other types of metabolic acidosis, management of patients with corticosteroids, neutropenia, malignant hematologic disorders and also patients who are receiving deferoxamine therapy and undergoing hemodialysis are at high risk of getting mucormycosis. Usually, in Covid-19 positive cases diabetes mellitus, prolonged hospitalization and use of immunosuppressive medication will lead to more risk in such cases (12). This disease generally spreads mainly through inhalation of spores from one person to another through environment (13).

The main symptoms of Covid-19 create perfect homeostasis for the growth and development of Mucorales inside the human body (14). Hosts susceptible to mucormycosis include persons with diabetes, those on systemic corticosteroid treatment, patients with neutropenia and hematologic malignancies, stem cell transplant patients and immunocompromised individuals. According to the current literature, diabetic patients are more prone to acquire Covid-19 accompanied by mucormycosis infection (15). For the detection of mucormycosis, CT is the generally selected initial imaging method. However, CT finding scan be non-specific in the early stages of disease; even if a patient has an invasive mucormycosis, he/she can present a normal sinus on a CT scan. Bone erosion and extra sinus spread are distinct features of mucormycosis and therefore comprise strong evidence for its diagnosis (16). Tissue necrosis is the distinguished feature of mucormycosis and is seen due to angioinvasion and successive vascular thrombosis. Clinically, bone exposure and necrosis are seen in the oral and maxillofacial region, and for diagnostic confirmation histopathological investigation are done. The feature is quite similar to osteomyelitis, trauma and iatrogenic infections. The main feature of pathogenesis and also a peculiarity of this disease is the substantial angioinvasion leading to vessel thrombosis and tissue necrosis (17). This angioinvasion is incorporated with the capability of the organism to spread through the blood stream from the primary site of infection to cause sepsis (18). Curiously, even Rhizopus oryzae is destroyed by antifungal treatment but interestingly, these dead Rhizopus will cause substantial damage to endothelial calls. This is the likely reason for which solely antifungal treatment will not be helpful in controlling this disease, so further systematic debridement is required to clean the dead fungi or tissue to prevent further tissue destruction leading to necrosis. Amongst all these types, rhinocerebral mucormycosis is a very common disease which accounts for 1/3 –1/2 of all reported cases (19, 20). Usually, rhino-orbital-cerebral and rhinomaxillary mucormycosis (21) are used similarly in the literature, but we feel they are different from each other, even though the phrase used for them are mutual in published studies. Given the closeness to the base of the skull, there are often more chances of cerebral involvement, and thus, rhinoorbital mucormycosis needs to be considered more fatal than others.

CONCLUSIONS

Mucormycosis is a fine drawn, destructive infection of fungal origin. It is a very difficult and crucial task to recognize or detect this infection in an early stage. In patients with mucormycosis, dentists and/or maxillofacial surgeons play a vital role due to the appearance of oral manifestations at the very early stage mainly in immunocompromised cases. For a clear and better diagnosis, histopathologic studies will be very useful. Intermodal remedies, which include both medical and surgical procedures, are of great use in bringing down patients’ morbidity and death rates. Mucormycosis is challenging to detect, diagnose, and treat by clinicians who are not so familiar with its clinical findings. It is considered as life-threatening disease associated with poor prognosis. Therefore, proper diagnosis of this infection in a very early stage is essential to reduce death rates among infected patients.

Conflict of interests: none declared

Financial support: none declared.

FIGURE 1.

Computed tomography scan showing erosion of the maxilla

FIGURE 2.

Erosion of the inferior wall of the orbital bone

FIGURE 3.

Erosion of the alveolar process of the maxilla

FIGURE 4.

Erosion of the anterior and lateral wall and floor of both maxillary sinuses