COVID-19 Associated Mucormycosis(CAM) in a Tertiary Care Hospital inBangalore: A Case-Series Report

Introduction

While the country is still grappling with the COVID-19 pandemic, it finds itself in, yet another crisis of COVID-19 associated Mucormycosis (CAM). India being the second largest populated country with diabetes mellitus (DM), has the highest cases of mucormycosis in the world.¹

Mucormycosis (previously called zygomycotic) is a serious but rare fungal infection caused by a group of molds called mucoromycetes. It is caused by exposure to mucor mold which is commonly found in soil, plants, manure, decaying fruits and vegetables and hospital ward rooms. Seasonal variance could be related to use of air conditioners.²

Increasing cases of mucormycosis in India amidst the second wave of COVID-19 appears to be mainly because of the presence of diabetes mellitus, increased usage of corticosteroids.3 The Rhizopus Oryzae is most common type and responsible for nearly 60% of mucormycosis cases and for 90% of the Rhino-orbital-cerebral (ROCM) form.³

Further minor causes including the type of oxygen treatment, especially the water used for humidification of oxygen, antibiotic usage, zinc therapy, duration of same mask usage, steam inhalation is said to have some effect in the increased occurrence of mucormycosis in the COVID patients.³

The state has reported more than 1370 cases of mucormycosis so far, of which as many as 51 people have lost their lives to the fungal infection. Bengaluru urban reported 557 cases so far, the maximum in the state. Mucormycosis is declared as an epidemic in Karnataka under section 2 of Epidemic Disease Act, 1897. Victoria hospital in Bangalore Medical College and Research Institute was made the nodal center for Mucormycosis treatment and research.²

It has been understood that mucormycosis is complicating the treatment and recovery of COVID-19 patients. This study was done to help find more specific causes for increased numbers of mucormycosis cases in this second wave compared to first wave, as the same patients with DM or steroid usage were present but mucormycosis was not reported much previously.^4,5

Hence this study was planned as per the instructions of high-level committee and technical advisory committee, Government of Karnataka. This study may help in understanding the causes, precautions to be taken in COVID-19 patients to avoid the incidence of mucormycosis and betterment of the treatment in coming days.

Materials and Methods

The staff from department of Community Medicine and General Medicine, Bangalore Medical College and Research Institute formed a study team. Patients diagnosed with mucormycosis, currently undergoing treatment in Victoria hospital, Bangalore were identified as study subjects.

Study was conducted among active mucormycosis patients admitted in Victoria hospital from 24th May to 4th June 2021 and patients who were cured of mucormycosis and discharged were excluded from the study. Following thorough literature search and discussion with many of the subject experts, a detailed case history data collection tool was prepared.

After taking verbal consent from the subjects and from their attenders, a telephonic interview was conducted. Information was collected about their demographic profile, symptoms, COVID-19 treatment details, comorbidities, risk factors, investigations and treatment details in their understandable language.

Each subject and attenders were called personally during non-clinical rounds time and the relevant data was collected to the best of their knowledge. If the patient was in intensive care unit, or on oxygen therapy, or in post op recovery period or succumbed, then only information from the patient attender was collected.

Every subject was interviewed for a minimum of 30 minutes to 45 minutes. During the interview, history of the initial onset of symptoms, progression, hospital admission details, history of any co-morbidities, personal habits including tobacco smoking, intake of alcohol, use of steam inhalation were also taken. Details about management of COVID-19 and CAM were taken along with detailed history of oxygen therapy, usage of steroids, antibiotics, zinc, and immune-modulators from the patient’s case sheet and from interaction with the treating residents.

A total of 63 subjects were interviewed and the process involved collecting information from subjects and their attenders, assessing case files, and interaction with treating doctors. Initially the information was collected in the form of hard copy case information sheet under the supervision of senior staff from Community Medicine Department. Later the data was exported into MS office excel and analyzed with IBM SPSS V20.0.

Results

Mean age of subjects was 49.4 years (23 years - 76 Years). Forty-five (71.4%) subjects were males, 53 (84.1%) were residents of Bangalore, 50 (79.3%) belonged to Hinduism, 58 (92%) were married and 24 (38.1%) belonged to upper lower socio-economic status as per modified Kuppuswamy classification 2021. Forty-three (68.2%) were living in pucca house, while 33 (52.4%) gave history of overcrowding in the house. Eleven (17.5%) gave history of close contact with animals and 8 (10.2%) gave history of working in humid conditions.

Table 2 shows that 60 (95.2%) were tested positive for COVID-19 and among them, 6 (10%) were diagnosed with severe COVID disease. Fifty-one (85%) gave history of admission for COVID management. Fortythree (68.2%) had concomitant mucormycosis and only 2 (3.4%) were fully vaccinated and 8 (13.6%) received one dose of vaccination.

Table 3 shows 44 (69.8%) patients had a history of steroid use for management, and among them 42 (95.4%) received IV steroids, mainly Dexamethasone [39(88.6%)]. Forty-seven (74.6%) gave history of Zinc therapy, 59 (93.7%) gave history of antibiotic treatment and 12 (19%) were under immunomodulator treatment.

Table 4 shows 49 (77.7%) were on oxygen therapy and 40 (63.4%) were on face mask, 8 (12.7%) were on nasal cannula and 1 (1.6%) was on High flow nasal oxygen (HFNO). Thirty-four (59.6%) were put on oxygen therapy before reaching the hospital, 91.2% of the set up used medical oxygen.

Table 5 shows symptoms associated with mucormycosis. Mean duration of symptoms was 8 days (2-16 days). Most of them presented with headache (86.4%), pain around the eyeballs (81.4%), swelling of eyeballs (81.4%), facial swelling (66.1%), blurring of vision (59.3%), pain on cheek bone (57.6%) and other associated symptoms.

Table 6 shows that 56 (88.8%) has Diabetes mellitus. Fourteen (22.3%) of them were in euglycemic state, 22 (40%) were only on oral hypoglycemics and 1 (1.92%) had DKA before admission. Other comorbidities were Osteo arthritis (3), Liver disease (2), Heart problem (2). Thyroid problem (2), Skin disease (1). Twelve (20.3%) gave history of addiction, 7 (11%) gave history of consumption of alcohol and tobacco. Forty-seven (79.7%) were using cloth mask, 32 (54.2%) among them were not cleaning mask regularly. Thirty-five (59.3%) gave history of steam inhalation in last 3 months, 13 (37.1%) of them used essential oil and 32 (91.4%) of them changed water regularly.

Table 7 shows among 63 study subjects, 60 (94.9%) cases presented with rhino-orbital involvement and 3 (5.1%) cases presented with brain involvement. 77.7% had deranged HbA1c levels, 65.1% had deranged ferritin levels and 55.5% had neutropenia at the time of diagnosis. Thirty-five (55.5%) were diagnosed with KOH swab and others were diagnosed with clinical suspect and imaging of PNS, mainly MRI. Fifty (79.3%) were managed medically and others required surgical intervention along with medical management. Sixty-one (96.8%) received Amphotericin B and 2 (3.2%) received Posaconazole as medical line of treatment.

Discussion

Mucormycosis is a life-threatening invasive fungal infection that arises particularly in diabetic patients with or without other underlying conditions such as haematological malignancies or the need for solid-organ transplantation.6 Pathogen can be found ubiquitously in fruits, soil, and feces and can also be cultured from the oral cavity, nasal passages, and throat of healthy diseasefree individuals. Mucorales is a subtype of Zygomycetes, which produces a distinct pattern of clinical infection. The fungi are usually avirulent; they become pathogenic only when the host resistance is exceptionally low.

The CAM incidence was higher among males than females, and this difference was consistently found in the previous case series (71.4%) and the reviewed literature (74.4%). Moreover, this finding is comparable to the previously published epidemiologic studies during the pre-COVID-19 era.⁷

A study conducted by Afroze et al in 2017 showed that the common form of mucormycosis infection is seen in the rhinomaxillary region and in patients with immunocompromised state such as diabetes which was similar to the present study.⁸

Rhino-orbito-cerebral involvement is the primary site of mucormycosis, but the paucity of signs may be a cause of delayed diagnosis. In the study conducted, we have seen that 56 (88.8%) had diabetes mellitus; 14 (22.3%) of them were in euglycemic state, 22 (40%) were only on oral hypoglycemics and 1 (1.92%) had DKA before admission. Other comorbidities were Osteo arthritis (3), Liver disease (2), Heart problem (2), Thyroid problem (2), Skin disease (1). This was similar to the results reported in the study by Riad A et al which showed diabetes mellitus (79.1%), chronic hypertension (30%), and renal disease/failure (13.6%) to be the most common medical comorbidities, while steroids (64.5%) were the most frequently prescribed medication for COVID-19, followed by Remdesivir (18.2%), antibiotics (12.7%), and Tocilizumab (5.5%) associated with CAM.⁹

Among 63 subjects, 60 (94.9%) cases presented with rhino-orbital involvement and 3 (5.1%) cases presented with brain involvement. 77.7% had deranged HbA1c levels, 65.1% had deranged ferritin levels and 55.5% had neutropenia at the time of diagnosis.

Mucormycosis is an uncommon but serious infection that complicates the course of severe COVID-19. Subjects with diabetes mellitus and multiple risk factors may be at a higher risk for developing mucormycosis. Concurrent glucocorticoid therapy probably heightens the risk of mucormycosis. A high index of suspicion and aggressive management is required to improve outcomes.¹⁰

Successful management of this fatal infection requires early identification of the disease and aggressive and prompt medical and surgical interventions to prevent the high morbidity and mortality associated with this disease process.¹¹

Conclusion

A total of 63 individuals were diagnosed with mucormycosis during the study period. The proportion of male subjects were higher than females and the mean age of subjects was 49.43 years.

Twenty-four (38.1%) of them belonged to upper lower socio-economic status. Nearly half of the subjects gave history of use of only cloth masks and steam inhalation with essential oil in the past three months.

Sixty (95.2%) of the subjects were tested positive for COVID-19. Preponderance of them showed previous history of hospital admission, oxygen therapy for hypoxia, antibiotic therapy and IV steroid usage. Complete vaccination for COVID-19 was limited to <5% among the study subjects.

Diabetes mellitus [56(88.8%)] was the dominant predisposing factor; 49 (77.7%) of them had poor glycemic control and among 23 (44%) of them hyperglycemia was diagnosed during the evaluation of mucormycosis.

Positive for KOH swab was seen in 55.9% of the subjects and others were diagnosed with the aid of imagining, mainly MRI. More than half of the subjects had deranged ferritin and neutropenia at the time of admission.

96.6% of the patients were treated with Amphotericin, combined medical and surgical management was performed in 22.1% of the subjects.

The main causes that appear to be aiding mucormycosis to infect the patients with COVID-19 are hyperglycemia, hypoxia, antibiotic and steroid use, not being vaccinated for COVID-19, neutropenia, deranged ferritin levels along with social factors like poor hygiene, overcrowding and lower socio-economic status among the study subjects.

Recommendations

It is important to do whole genomic sequencing of SARS-COV2 virus to explore any possible causative role of it in these patients. Judicious use of steroids only when necessary and when prescribed. Strict control of blood glucose in COVID-19 patients who are known diabetics and pre-diabetics. Periodic monitoring of infection prevention and control practices in high-risk units.

To address the delay in seeking health care and to emphasize regular complete evaluation for mucormycosis among high-risk individuals. Vaccination of all vulnerable population will decrease the occurrence of COVID-19 and mucormycosis in future. The present study emphasizes the need for further analytical studies to know more about the risk factors and its association with CAM.

Limitations

Although an epidemiological study, we were unable to assess the exact incidence or prevalence of mucormycosis with respect to time, place, and person of occurrence.

Although we have described the predisposing factors, we were not able to assess the strength of association of these risk factors, because of the absence of a control group. We were able to fetch only limited information from the attenders of four death cases among the study subjects. Similarly, the study results may not be generalizable to centers where other risk factors are dominant. 

Acknowledgments

We are very much thankful to our Director cum Dean for all the support to conduct this study. We are thankful to the Technical advisory committee, Govt of Karnataka for giving opportunity to conduct this study. Our special thanks to Medical Superintendent of Victoria Hospital for all the support.

We thank the faculty, Department of General Medicine, Minto hospital, Department of ENT, Department of Pathology, Microbiology and Department of Radiology, BMCRI who assisted us in the clinical diagnosis of mucormycosis. Our sincere gratitude to the patients suffering from mucormycosis and their family members who supported us with their consent to carry out this study.

We thank the faculty, postgraduates from the Department of Community Medicine and General Medicine for executing this study in a short span of time. We thank our House surgeons who actively helped us in this study from data collection to report writing.

Conflict of Interest

None.