Correlation of Mucormycosis with Various Clinical Parameters Among COVID-19 Patients: A Cross-Sectional Study

Abstract

Introduction

Coronavirus disease 2019 (COVID-19), during the second wave in early 2021, caused devastating chaos in India. As daily infection rates continue to rise alarmingly, the number of severe cases also increased dramatically. Mucormycosis is an infection caused by filamentous molds, and there was a rise in mucormycosis cases after COVID-19 infection. The aim of the study is to assess various parameters associated with mucormycosis patients who suffered from COVID-19.

Material and Methodology

This study was a cross-sectional questionnaire study. The target population for the study were 70 mucormycosis-infected patients (51 = males, 19 = females). The questionnaire mainly focused on association of various parameters of COVID-19 with mucormycosis.

Results

Result showed that out of 70 cases of mucormycosis the association was found between history of diabetes mellitus 45 (64.2%), type of hospitalization, number of days of hospitalization, oxygen administered, type and maintenance of face mask, i.e., patient who had reused mask by washing 59 (84.3%), and method of oral hygiene practices.

Conclusion

Mucormycosis is extremely rare in population. The study findings emphasize the need to be aware of invasive mucormycosis developing in COVID-19 patients, especially including patients with diabetes mellitus and outside the ICU, patient who had poor oral hygiene during COVID-19, patients receiving oxygen therapy should ensure that the water in the humidifier is clean and is refilled regularly, knowledge and education about the use of the facemask.

Introduction

Mucormycosis has brought down the health system of the world on its knees with millions of people falling prey to this life-threatening pandemic COVID-19. To make the situation worse, India witnessed another epidemic, that of mucormycosis amidst the COVID-19 pandemic [1]. The overall cause mortality rate of mucormycosis is 54% [2]. Mucormycosis is an infection caused by a group of filamentous molds within the order Mucorales. There was a rise in mucormycosis cases during the second wave in May 2021 [3]. More than 31,000 cases have been reported so far across the country, and more than 2100 people have died as a result of mucormycosis [1]. Majority of cases have been reported from the state of Maharashtra followed by Rajasthan, Gujarat, Madhya Pradesh, Haryana, Delhi and Punjab [4]. Mucormycosis cases had increased to double in India in late 2020 compared to the corresponding months of 2019 [1]. There was a direct correlation between COVID-19 and lethal black fungus viral infection which had ravaged in almost each and every state of the country [1]. According to the data, mucormycosis was caused by predominating agent, i.e., Rhizopus arrhizus [5]. As it makes infected tissues turn black, it is described as black fungus [1]. According to the guidelines, steroids are recommended only in moderate to severe cases of COVID-19 when oxygen levels drop [1]. According to an advisory issued by the Indian Council of Medical Research, the following conditions in COVID-19 patients increase the risk of mucormycosis infection: people with uncontrolled diabetes, weakening of immune system due to excessive use of steroids, hospital stay and co-morbidities [6]. In addition to the high mortality rate, mucormycosis is also associated with long hospital stays and substantial costs. Governments and health authorities from around the world had given advisory regarding the use of face mask in the prevention of spread of COVID-19; although there is a significant agreement among the medical community regarding the usefulness of face mask during this pandemic, there are some concerns about possible side effects. Some of these concerns are a false sense of security, inappropriate use, quality and volume of speech and breathing difficulty. So, the aim of the study is to assess various parameters associated with mucormycosis patients who suffered COVID-19.

Material and Methodology

Study Design, Study Population and Study Setting

This study was a cross-sectional questionnaire study. The study was conducted on convenient sample of 70 mucormycosis-infected patients, comprised of 51 males and 19 females. Data were collected from mucormycosis center of tertiary care hospital, A.C.P.M Medical College, Dhule. In this hospital, patients were hospitalized those who were diagnosed with mucormycosis. Ethical approval was obtained from the Institutional Ethics Committee prior to onset of the study and after designing the protocol and questionnaire. Data were collected in hot and humid environment during March 2021 to June 2021.

Questionnaire: A pretested questionnaire was administered through a print from to all the participants. The questionnaire was subjected to content, validity testing in the form of content validity index. Content validity: S-CVI/Ave [scale-level content validity index based on the average method]:0.93;S-CVI/Ave [scale-level content validity index based on proportional relevance] 0.91;& S-CVI/UA [scale-level content validity index based on the universal agreement method] 0.82 [7].

Demographic data included age of the patients, gender, address and since when they are infected with mucormycosis. In the questionnaire, a total of 16 questions were included that focused on medical history, COVID-19 history, details of oral hygiene during & after COVID-19, usage of face mask, oxygen administration during COVID-19, diagnosis of mucormycosis, site of involvement, and outcome of therapy hospitalizations. Drug history was taken from every single patient hospitalized in ACPM Medical College. Participation in this study was voluntary, and the questionnaire was anonymous and self-administered. The participants were informed about the importance of answering the questions correctly and were assured of their confidentiality. Data were collected by personal interview.

The responses were anonymized to keep all the information confidential. The cases were analyzed regarding the site of involvement, underlying disease history of oral hygiene during and after COVID-19 and outcome of therapy hospitalizations. The first sign and symptoms for mucormycosis were collected in case history.

Statistical Analysis: all the data were compiled using Microsoft Excel and analyzed using SPSS version 23 [IBM Corp. Armonk, NY, USA]. Demographic details and clinical characteristics were presented using frequency and percentage. Association between different variable with mucormycosis was tested using Chi-square test. The level of significance kept at 5%.

Result

Table 1 shows the demographic details of the study participants. In 70 cases of mucormycosis, the number of male patients was higher than that of female patients and the mean age of all patients was 49.11 ± 11.78. 27 (38.6%) cases had history of diabetes mellitus, and 18 cases developed diabetes after COVID-19 (25.7%). (Table 1) 59 cases (84.3%) had habit of reusing of mouth mask by washing. 11 cases discarded their mouth mask after use. In overall, 59 patients had history of hospitalization for an average of 9.51±4.40 days (Table 2). We found that mucormycosis was developed after an average mean of 11.51±8.10 days of COVID-19 (Table 3). The first sign and symptoms for mucormycosis were noticed such as tooth pain, numbness in nose region and blurring of vision.

Table 1.

Demographics of the study participants

Variable mean/frequency	Category	Mean/frequency
Age	–	49.11 ± 11.78
Gender	Male	51 (72.9%)
	Female	19 (27.1%)
Place of residence	Urban	48 (68.6%)
	Rural	22 (31.4%)
Past medical history	Yes	35 (50%)
	No	35 (50%)
Details of diabetes	No diabetes	25 (35.7%)
	Past h/o diabetes	27 (38.6%)
	Diabetes developed after COVID-19	18 (25.7%)

Table 2.

COVID-19 features

Variable	Category	Mean/frequency
H/o hospitalization for COVID-19	Yes	59 (84.3%)
	No	11 (15.7%)
Type of hospital	No h/o hospitalization	11 (15.7%)
	Government	14 (20%)
	Private	45 (64.3%)
Oxygen administered	No h/o hospitalization	11 (15.7%)
	Yes	33 (47.1%)
	No	26 (37.2%)
No of days hospitalized	–	9.51 ± 4.40

Chi-square test

Independent t test *indicates significant difference at p ≤ 0.05

Table 3.

Mucormycosis features among all the subjects

Variable mean/frequency	Category	Mean/frequency
First sign of mucormycosis (After no. of days of COVID)	–	Mean: 11.51 ± 8.10 Median: 10
Maintenance of mask	Discard	11 (15.7%)
	Washing	59 (84.3%)
Treatment	Surgical (Complex surgical procedures)	53 (75.7%)
	Minor surgical procedures	17 (24.3%)
Type of mask used	Surgical	14 (20%)
	Cotton	40 (57.1%)
	Other	16 (22.9%)

Chi-square test

Discussion

Mucromycosis is an extremely rare condition seen in immunocompromised patients previously. However during the pandemic it was predominantly seen in patients with history of COVID-19 without any specific underlying immunocompromised condition. Song et al. and Sharma et al. [8] conducted a study which has shown an association between invasive fungal sinusitis (mucormycosis) and coronavirus disease.

In this study, we had correlated the predominance of mucormycosis with various known factors and found that the prevalence of mucormycosis was more; out of 70 cases, male patients (72.9%) were predominant than female patients (27.1%).

Arun Kumar et al. [9] found that mucormycosis cases in Rajasthan urban habitation were exposed to be noticeably linked with death than in rural area, but the majority of the patients (72.7%) came from rural areas with poor literacy levels, but contrary to this we found that most of the cases were from urban area 22(31.4%) than from rural area of Maharashtra; this may be due to industrialisation and pollution in urban areas which may lead to more unhealthy lifestyle, environmental factor which could be favorable for mucormycosis tropical monsoon climate with hot rainy and cold weather season and dry summer.

According to various guidelines & advisories for oral hygiene, during the pandemic, regular brushing at least twice daily along with flossing, mouthwash with 1% povidone iodine was advised for ambulatory COVID-19 patients whereas oral hygiene using toothbrush and gauze piece for soft tissue hygiene was advised for intubated patients [2]. Also, it is recommended to change the toothbrush of patients who recovered from COVID-19. In this study, it was found that 33 patients had not used any oral hygiene aid during the period of hospitalization, 14 cases had used toothbrush and toothpaste, 8 patients had used mouthwash, and 11 patients had used both toothbrush, toothpaste and mouthwash. There is a favorable environment for fungal growth during oxygen administration because of humid environment, and it is difficult to maintain oral hygiene practices.

All patients had a history of steroid use during their coronavirus treatment. A recent study has been conducted by John et al. [10] in which 93% of cases had history of diabetes mellitus, while 88% cases were receiving corticosteroids which was compared with this study that has shown similar results and this study found that 25.7% cases had developed diabetes mellitus after COVID-19. Diabetes mellitus was present in 64.2%, and diabetes developed after COVID-19 in 25.7%.

According to the WHO guidelines, medical-use oxygen differs from industrial-use oxygen with regards to impurities and the quality [11]. According to a study by Ramreddy Bhogireddy et al. unhygienic delivery of oxygen may result in contamination [12] they stated that the unhygienic delivery of oxygen. In this study, mucormycosis is more in patient who were administered oxygen (n=33, 47.1%) than those who were not administered oxygen (n=26, 37.2%); this is may be due to low-quality tubing system at hospital ICUs with unclean mask or contaminated tap water in humidifier and prolonged usage of same mask for more than two patients [12] (Table 4).

Table 4.

Association of method of oral hygiene with mortality

Variable	Oral hygiene practices	Alive	Dead	p value
Method of oral hygiene	None	33	3	0.703
	Toothpaste and brush	13	1
	Mouthwash	8	0
	Both	9	2
	Other	1	0

Chi-square test

The results of the present study showed a higher prevalence of mucormycosis in patients who were using cotton masks rather than surgical or the recommended N-95 mouth masks. These findings were similar to the study conducted by Kuljit Singh et al. [13] as well as the findings of the study of Dr. S.N. Chandan et al. [14] which also stated a higher prevalence in patients using the same mouth mask without changing or washing. The moisture exposure of unchanged mask or oxygen therapy of COVID-19 patients in hospitals could be prone to fungal infection like mucormycosis. This study showed that mucormycosis was seen more in patients repeating the use of same masks after washing [59 (84.3%)] compared to those who discarded the single use mask after every use [11 (15.7%)]. This may be attributed to reduced awareness, impaired knowledge regarding the use and prohibited re-use of single use surgical mouth masks.

In this, the patients were managed by major surgical treatment (n=53, 75.7%), such as maxillectomy, open sinus debridement and other complex surgical procedures, while 17 (24.3%) patients were managed by nonsurgical treatment who had undergone tooth extraction, alveolectomy and if needed necrotic tissue debridement performed under local anesthesia. Intravenous liposomal amphotericin was initiated after confirmation of mucormycosis. All patients with limited sinonasal mucormycosis were administered liposomal amphotericin at 5 mg/kg/body weight, based on clinical findings and investigations [15]. Patients underwent emergency endoscopic debridement, orbital decompression, orbital exenteration and maxillectomy, based on the extent of disease.

Despite the increasing number of mucormycosis cases, there was a need for more specialists in the field of maxillofacial prosthodontics worldwide to treat the increasing number of patients requiring treatment for maxillofacial defects, due to COVID-19-associated mucormycosis [16]. From the total number of mucormycosis cases, rehabilitation was done for 41 cases. Out of 71 mucormycosis cases, 3 were deceased.

Based on this study we came across correlation between mucormycosis and various variable.

Limitation

This study has imitation such as small sample size.

Conclusion

Mucormycosis is a life-threatening fungal infection characterized by host tissue infarction and necrosis that occurs mostly in immunocompromised patients. The study findings emphasize the need to be aware of effect of invasive mucormycosis developing in COVID-19 patients, especially among patients with diabetes mellitus and patients with poor oral hygiene. Also, for the patients receiving oxygen therapy, water used in the humidifier should be clean and refilled regularly. Patients should be educated about the use of the facemask and method of oral hygiene during the period of hospitalization.  There is a need to spread an awareness in paramedical staff in prevention of mucormycosis. Due to the rarity of mucormycosis, particularly the indolent presentation, knowledge and awareness of the disease, further research is needed for the disease.

Declarations

Conflict of interest

The authors declare no conflict of interest.