European Journal of Cardiovascular Medicine

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) otherwise known as the novel Coronavirus (2019-nCoV) outbreak emerged in Wuhan, Hubei province of China in December 2019 has been dwindling the world since its declaration by the World Health Organization as a pandemic on 11th March 2020 [1].

Mucormycosis is a serious but rare fungal disease caused by fungi belonging to the family of Mucormycetes or Zygomycete[2]. It mostly occurring in immunocompromised patients. It is characterized by extensive angioinvasion that results in vessel thrombosis and subsequent necrosis. Pre-existing diseases such as diabetes mellitus, immunocompromised patients are more prone to mucormycosis. Systemic immune alterations of Covid-19 disease are increasingly being recognized in view of their impact on morbidity and mortality [3,4,5]. Recent case reports indicate an increased prevalence of mucormycosis in severe cases of Covid-19 after recovery [6,7]. Medical procedures and devices, such as contaminated air filters, oxygen tubing, humidifiers, infected wound dressings and tongue depressors have all been linked to nosocomial mucormycosis [8]. Duration of time for infection to occur is couple of days to weeks from covid recovery [9]. Clinical presentation can be diverse. The most commonly reported signs in the literature include nasal obstruction with noisy breathing, blood-stained nasal discharge, headache, facial cellulitis, orbital swelling, palatal ulceration or necrosis, and black necrotic eschar in the nasal cavities, severe pain and loss of vision [10,11,12]. Diagnosis can be done by KOH Mount, Magnetic Resonance Imaging (MRI), Endoscopy and Culture report. Functional Endoscopic Sinus Surgery (FESS), conservative management by antifungal drugs and surgical debridement are the best treatment protocol [13]. Successful treatment of mucormycosis is dependent on four key principles: early diagnosis, treatment of underlying predisposing factors, surgical debridement of necrotic tissue, and administration of systemic Amphotericin B [14].

Aims and objectives:

1. To study the early contact of mucormycosis infection after covid positive test.
2. To study the relation of D-Dimer, C-Reactive protein, Sr. Ferritin, blood group and HbA1c to mucormycosis infection.
3. To study the incidence of death rate in mucormycosis patient.

Study design:

A retrospective cross-sectional observational study was conducted on total 30 patients admitted in a Tertiary care Hospitals, Ahmednagar to treat COVID-19 associated Mucormycosis from 1st May, 2021 to 31st August, 21. All total 30 patients were known cases of previous COVID-19 infection. Institutional ethics committee approval and informed consent from patient is taken.

Data collection:

Routine blood investigations, ECG, chest Xray, CT scan and MRI of the face (including orbits) and brain were done (Fig 5). Sinusitis with mucosal thickening of ethmoidal and maxillary sinuses, facial swelling, sudden dental pain, headache, ophthalmoplegia Fig 8), and orbital cellulitis (Fig.3) etc were few clinical features that the patients presented with in hospital. Ophthalmology reference was taken for those patients having orbital extension. Punch biopsy from the oral cavity especially the necrotic palatal part and/or collection of infected tissue/ nasal discharge is/are sent for (KOH test) (Fig.7), to screen for any fungal hyphae. Once Mucormycosis was confirmed, within 72 hours, surgery was performed as well (Fig 4). Post surgery, Amphotericin B therapy was started. Patient demographic details, COVID status, Co-morbidities, Clinical and treatment details, location of Mucor-mycosis and outcome were collected from case sheets of all patients admitted in Hospitals and the data was subsequently analysed. Standard informed consent to participate and publish were obtained from every patient. Diagnosis of Mucormycosis was based on European Confederation of Medical Mycology guidelines for diagnosing and managing mucormycosis.

Inclusion criteria:

All cases of mucor-mycosis after COVID - 19 infection was admitted in Hospitals for treatment are included in the study.

Exclusion criteria:

Any case of Mucormycosis without COVID - 19 positive was excluded from the study.

Case definitions:

A case of mucormycosis was defined as laboratory identification of Mucorales by histopathology, KOH mount, endoscopy, MRI SCAN and Lab report. Cases were considered COVID-19–associated if the patient received a positive reverse transcription–polymerase chain reaction or antigen test result for SARS-CoV-2(the virus that causesCOVID-19) during the 40 days preceding the mucormycosis diagnosis.

Statistical Analysis:

Data was collected and analysed using SPSS software. Quantitative data with normal distribution were expressed as mean +/- Standard deviation. Nominal data were given as a number(n) and percentage (%). P-value < 0.05 was considered as significant.

Table 1: Age & Gender distribution:

There were 24 males (80%) and 6 females (20%). Out of 30, 14 were from age group 41-60 years (46.67%), 13 were from age group 61-80 years (43.33%) and rest 3 were less than 40 years (10%). Age range was 30-80 years with mean age of 57.40 ± 12.45 years.

Table 2: Descriptive statistics of the study parameters:

Table 3: Blood groups of the participants:

We had majority of the patients with blood group O+ 13 cases (43.33%), followed by A+ 9 cases (30%) and B+ 6 cases (20%).

Fig1: Blood group of the participants

KOH mount showed Zygomycetes fungus in all specimens. Debridement was done in 22 patients (73.33%). There were 10 deaths in our study participants (33.33%).

Table4: Difference between different study parameters in patients who Died:

We observed a significant difference in Serum ferritin levels (p = 0.048) and HbA1c levels (p = 0.017) in patients who had died of Mucormycosis as compared to those who survived. There was no any significant difference in number of days after Covid-positive, D-Dimer levels and C reactive protein levels (p>0.05). The Serum ferritin levels in patients who died were 641.90 ± 168.75 ng/ml as compared to those who survived with levels of 370.80 ± 193.69 ng/ml. The Glycosylated Hb was 9.73 ± 0.93 in patients who died as compared to 8.36 ± 1.57 in patients who survived. All 10 patients who died had undergone debridement (100%) and there was no any significant association between the deaths and blood group of the patients (p>0.05). 

Mucormycosis is an aggressive and lethal infection caused by Zygomycetes [15,16]. The fungus has a likeliness to affect the nasal mucosa and mostly seen in immunosuppressive conditions like diabetes. Germination is seen in the nasal and paranasal sinuses ultimately involving the palate, orbit and brain causing death [17].

The prognosis is poor with about 33.33% being the overall mortality rate [18,19]. MRI scan is usually the first diagnostic tool to check the status of sinuses and to detect extra sinus spread [15]. A definitive diagnosis of mucormycosis as the causative species is achieved only by histological examination of the biopsy specimen and KOH mount. Due to the high mortality rate, need of early intervention by aggressive surgical debridement, systemic antifungal medications and management of underlying illness are much essential for a better rate of survival. A standard protocol of steroid.

administration for COVID-19 infection may need to be evaluated again and an emphasis on strict blood sugar control during and after COVID-19 infection should be

done. Orbital exenteration can be done to reduce the disease burden and prevent the intracranial spread in cases where blindness is delayed even if having a clear radiological picture of involvement of the orbital cavity. In India, Rhino-orbital cerebral mucormycosis is more common compared to the Pulmonary form. It occurs more frequently in outside the ICU setting [20]. Ferritin, a key mediator contributor of cytokine storm and predictor of COVID severity [21,22]. Very high level of serum ferritin was found in almost all the patients as ferritin feeds and thrives the fungus, mucormycosis. Clinical findings along with MRI, lab tests, nasal endoscopy (FESS) has assessed the disease extension and an invasion pattern in an individual. Surgical debridement [23] is dependent on extension of an infection to get successful outcome from maxillary necrosis, orbital involvement, nasal crusting and intracranial involvement. debridement of necrotic tissue, enucleation and infra-temporal curettage were performed as a surgical procedure under prescribed necessary medications with time.

Limitations of our Study:

In this retrospective observational study, we could not compare various risk factors among COVID-associated Mucormycosis with Non- COVID patients to establish a causal association.

This clinical observational study includes few points to be considered in priority are Antifungal medications, surveillance of immuno-compromised status of diabetes mellitus in all patients, screening of COVID-19, early diagnosis of fungal co-infection,

focus on triggering contributor factors and timely required treatment are a valuable means to control disease and its severe outcome. Potentials of developing rhino-orbito-cerebral mucormycosis in patients having diabetes mellitus are more.  A careful management plan for COVID-19 Disease can prevent rhino-orbital cerebral disease. Combined Medical and surgical management exhibited better outcomes.

Funding:

This work did not receive any grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflict of interest

There are no conflicts of interest to declare by any of the authors of this study.

Acknowledgements

We want to acknowledge Dr.Gautam Kale (Nerophysian), Dr.Gajanan Kashid (ENT Surgeon), Dr.Rane (Ophthalmologist), Dr.Gawali (Physician) for constant support and guidance.

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