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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 9  |  Issue : 3  |  Page : 170-174

Analysis of risk factors and clinical trends in post-COVID oral mucormycosis


1 Department of Orthodontics and Dentofacial Orthopedics, University College of Medical Sciences, New Delhi, India
2 Department of Dentistry, University College of Medical Sciences, New Delhi, India

Date of Submission07-Oct-2022
Date of Decision08-Nov-2022
Date of Acceptance09-Nov-2022
Date of Web Publication31-Dec-2022

Correspondence Address:
Dr. Neha Bhutiani
Department of Orthodontics and Dentofacial Orthopedics, University College of Medical Sciences, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/sjoralsci.sjoralsci_44_22

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  Abstract 


Introduction: The COVID-associated surge in mucormycosis cases was seen during the middle and latter of 2021. Mucormycosis is a rapidly destructive opportunistic fungal infection causing severe morbidity and mortality.
Aim: This study aims to identify the risk factors associated with post-COVID oral mucormycosis and analysis of the observed clinical pattern.
Materials and Methods: The current study is a retrospective observational one based on demographics, history, and clinical presentation of 46 patients with dental referrals for mucormycosis admitted at the COVID-19 designated facility during the ferocious second wave of COVID-19 in India.
Results and Discussion: The incidence of post-COVID mucormycosis was found to be higher in males (29) than females (17), with an average age of 54.5 years in males and 50.8 years in females. All patients belonged to poor/lower socioeconomic backgrounds with a history of hypertension (barring four patients), Type 2 diabetes mellitus, poor oral hygiene, and compromised periodontal health. The right maxilla showed the greatest incidence. The median size of the lesion was found to be 2.22 cm2 with an interquartile range of 1.135 cm2 to 3.2 cm2.
Conclusion: The vulnerability of COVID-19 patients to the development of oral mucormycosis was found to be higher for patients with preexisting diabetes mellitus, hypertension, poor socioeconomic background, poor oral hygiene, and periodontal health with greater incidence in maxilla and predilection for the right side.

Keywords: COVID-19, oral mucormycosis, secondary infections


How to cite this article:
Grewal H, Balachandran R, Bhutiani N, Singh K, Bhargava S. Analysis of risk factors and clinical trends in post-COVID oral mucormycosis. Saudi J Oral Sci 2022;9:170-4

How to cite this URL:
Grewal H, Balachandran R, Bhutiani N, Singh K, Bhargava S. Analysis of risk factors and clinical trends in post-COVID oral mucormycosis. Saudi J Oral Sci [serial online] 2022 [cited 2023 Feb 6];9:170-4. Available from: https://www.saudijos.org/text.asp?2022/9/3/170/366528




  Introduction Top


The world has been struggling with the challenges posed by the ongoing COVID-19 pandemic for the past 2 years. It is a severe respiratory syndrome caused by coronavirus-2 (SARS-CoV-2) associated with a multitude of secondary bacterial and fungal infections.[1] The pandemic peaks as waves occur with a spike in the number of cases which then flattens out as the cases decline. In India, the steep rise in COVID-19 cases was seen in May 2021 caused by the Delta variant, wherein over half a million cases were reported (May 6, 2021), whereas more than 6000 (June 9, 2021)[2] were lost their lives. The country was besieged by the acute burden on the country's health infrastructure with a surge in demand for hospital beds, drugs, and oxygen during this particular wave. Another challenge that emerged as a fallout of this episode of the COVID-19 surge was the rise in the number of mucormycosis cases. Mucormycosis is an invasive fungal infection caused by the fungi belonging to the class Zygomycetes and order Mucorales.[3] Human infections are generally associated with 11 genera and ~27 species under Mucorales as causative organisms.[4] They are typical environmental organisms and cause opportunistic infections in immunosuppressed patients. The clinical forms of infection by these fungi can present with pulmonary, gastrointestinal, cutaneous, encephalic, and rhinocerebral mucormycosis.[5]

The otherwise innocuous Mucorales spores germinate upon getting a favorable environment created by hypoxia, diabetes/hyperglycemia, and acidic medium (ketoacidosis) immunosuppression.[6] Mucormycosis is primarily an angioinvasion disease, wherein invasion of blood vessels results in tissue necrosis and subsequent thrombosis that is rapid in progression. The clinical presentation would vary depending on the route of fungal entry and predisposing disease. In the head-and-neck region, it may most commonly present as maxillary and orbital cellulitis in a predisposed individual.[7] The recommended treatment involves the debridement of lesions surgically and medication with antifungals such as amphotericin B and other azoles.

Before the COVID pandemic, the prevalence of mucormycosis was reported to be nearly 10,000 cases annually by the Leading International Fungal Education portal without the inclusion of Indian data and 9, 10, 000 cases after adding cases in India.[8],[9] However, as the country was hit by the very severe second wave of COVID-19 in early 2021, the country witnessed a very unfortunate rise in hospitalization, rocketing oxygen demand with distressed, and critically ill patients resulting in increased morbidity and mortality.[10] Along with this steep surge in cases, another major challenge that emerged was the rapid increase in cases of COVID-associated mucormycosis. The current retrospective study evaluated the risk factors and clinical patterns observed in the patients with post-COVID oral mucormycosis admitted to the hospital associated with our institute from June 2021 to August 2021.


  Materials and Methods Top


The study was conducted from June 2021 to August 2021. The study group was the patients with post-COVID oral mucormycosis, admitted to the hospital in the vicinity declared as a COVID-19 facility by the government since the beginning of COVID-19, as it is one of the largest medical facilities run by the state government. The hospital recorded more than 100 cases of COVID-associated mucormycosis and out of these dental referrals were made for 46 patients with intraoral manifestations of the disease. The data were obtained from the findings recorded for these patients seeking dental advice and consent for the use of any such data is taken as a policy at the time of dental examination from all the patients. The ethical clearance was obtained from the institutional ethical committee (IECHR-2022-54-4). The current retrospective observational study intends to assess the risk factors and clinical features in these patients. The recorded parameters are given in [Table 1].
Table 1: List of parameters recorded

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As this was a retrospective study, the most relevant data from the available records were extracted. The statistical analysis, however, could not be performed due to the limited data attained. The data were limited since the occurrence of mucormycosis is otherwise rare, especially in COVID-19 cases (prevalence is 0.14/1000 people in India irrespective of COVID incidence).[11]


  Results Top


The incidence of mucormycosis was higher in males (29) than in females (17) with an average age of 54.5 years in males and 50.8 years in females [Table 2].
Table 2: Age/gender distribution and risk factors

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All the patients were found to be from a poor-to-lower-middle socioeconomic background. All the patients presenting with mucormycosis were found to have a history of hypertension and Type 2 diabetes mellitus except four patients who had diabetes mellitus only. All the patients were on antifungal therapy (amphotericin B), whereas five patients were also given additional antibiotics (monocef). The area-wise distribution of intraoral lesion is given in [Table 3] for 22 patients as per available data and the same is represented as a percentage in [Figure 1]. The right maxilla was affected in the majority of patients in both males and females followed by the left maxilla. The anterior mandible and the maxillary vestibule were the least commonly affected sites as lesions in these areas were present in only one female for each site. The area was measured as a product of the maximum length and width of the visible lesion and the median was found to be 2.22 cm2 with an interquartile range of 1.135 cm2–3.2 cm2. Periodontal health was found to be poor in all the patients.
Table 3: Distribution of oral mucormycosis lesions

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Figure 1: Percent-wise distribution of oral mucormycosis lesions with respect to gender and site

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The time of turning COVID positive to negative was found to range from 13 to 25 days and COVID positive to detection of mucormycosis ranged from 26 to 57 days. However, these data were only available for seven patients due to which no correlation could be ascertained.


  Discussion Top


The COVID-19 pandemic has brought with it innumerable challenges and left the entire globe distraught with newer problems. One such aftermath of the second wave of this pandemic in India was the emergence of mucormycosis, also known as, black fungus. The current study was undertaken to understand the factors associated with the occurrence of mucormycosis in COVID-19 patients in India during the second wave of the pandemic and find a correlation, if any, with the oral manifestations of this fungal infection.

The alleged primary risk factors for mucormycosis are diabetic ketoacidosis, immunosuppression, corticosteroids, and mucocutaneous barriers disruption with consequent exposure to these infectious fungi.[3],[4] As seen in the current study, all patients with oral manifestations of post-COVID mucormycosis had a history of diabetes mellitus Type 2. The reason cited for such predilection is the persistence of an inflammatory state in such patients with hyperglycemia that triggers constant recruitment and local activation of immune cells.[12] Hyperglycemia and acidosis reduce phagocytic mobility, jeopardizing their ability to kill the organisms by both oxidative and nonoxidative mechanisms.[13] The SARS-CoV-2 infection activates antiviral immunity that possibly potentiates this inflammatory phenotype, favoring secondary infections. The presence of diabetes mellitus has been observed in cases of mucormycosis affecting various parts of the body such as the eye, cerebral, lungs, gastrointestinal, etc.[9],[14],[15],[16],[17]

Another most commonly observed comorbidity in patients with secondary mucormycosis was the presence of hypertension which was seen in 42 out of 46 patients. Such association has also been reported by Shakir et al., Asdaq et al., Alloush et al., and various other authors.[18],[19],[20] the greater predilection for males as seen in the current study is similar to that reported by Sarvestani et al.,[21] wherein the male-to-female ratio was 2.39:1 in a sample of 95 patients. Walia et al. reported similar observations of male preponderance with a commonly affected age group of 41–50 years similar to the average age of 50–55 years as seen in our study.[22]

The poor socioeconomic background may be related to a lack of awareness and attention toward maintenance of hygienic practices culminating in poor oral hygiene as seen in the current study. Goel et al. reported a case of rhinomaxillary mucormycosis with cerebral extension with oral mucosal denudation on the right side of the maxilla, swelling on the palate, and poor oral hygiene.[23] The flag marks of poor oral hygiene with severe halitosis have also been suggested by Sadasivam and Geeta in COVID patients with oral mucormycosis.[24]

The intraoral lesions in oral mucormycosis are most commonly observed on the palate.[25] Many a time, the patient seeks treatment after the progression of the lesion to a larger extent and hence the site of origin may not be discerned. However, in our study, as the patients were already admitted due to COVID-19, the initiation of the lesion could be recorded with the greatest incidence being observed on the right side of the maxilla in both males and females. The palatal lesion was seen in eight patients (five males and three females) similar to observations by Ahmed et al.[25] The mandibular involvement was most infrequent with only one female showing lesions in the anterior mandibular region. Mucormycosis has been observed more frequently in the rhino-orbital-cerebral region and this may account for greater involvement of the maxilla than the mandible due to regional proximity.[26]

In a study by Muley et al., 76% of the patients with mucormycosis had a history of hospitalization due to COVID-19 with existing risk factors such as diabetes mellitus (esp. uncontrolled), other comorbid and immunocompromised states and use of corticosteroids.[26] Amphotericin B was given to all patients in this study similar to the regimen observed in ours. With the increased vaccination and the mutations of the fatal virus with the passage of time, no doubt the fear of the disease has reduced considerably. However, the observations and the lessons gained from the past experiences of 2 years should be closely studied and the vital information and conclusions may be drawn as a guard against any such unfortunate incidence in the future.

The limitations of the study include the limited data available as it was performed in a retrospective manner which limited the parameters that could be analyzed related to the incidence of mucormycosis in a viral infection like COVID. However, the data are derived from the maximum number of such cases reported from a single center and hence can provide a reliable estimate of the risk factors and clinical presentation of mucormycosis in patients with COVID-19.


  Conclusion Top


The incidence of mucormycosis in post-COVID patients can be attributed to preexisting risk factors such as diabetes mellitus (Type II), hypertension, lower socioeconomic background, and poor oral hygiene. The lesions were more commonly observed in males, the average age group of 50–55 years with a greater incidence of lesion on the right maxilla. The study highlights the need for elaborate routine recording protocols for such incidences to enhance the understanding of risk factors associated with life-threatening diseases such as COVID-19 and mucormycosis. The factors and clinical trends associated with post-COVID mucormycosis that have emerged from this study serve as a caution for the population at risk in case of any similar future pandemic.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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