Post-Covid Orofacial Mucormycosis: A Clinico-Radiological Classification System and Management Protocol

Abstract

Background

In the wake of the second wave of the COVID-19 pandemic, a substantial number of individuals were afflicted by orofacial mucormycosis post-COVID. The immunocompromised state rendered by the SARS-COV2 (Severe Acute Respiratory Syndrome Corona Virus 2) infection provides a breeding ground for the opportunistic mucor invasion. Corticosteroid and COVID-induced hyperglycemia contribute to the unhindered progress of the mucor infection in these patients. The sino-nasal region serves as the entry point and rapid progress of the disease to the oral cavity, mid-face, orbits, and ultimately the brain proves fatal.

Aim and Objectives

The aim of this study was to present a definitive clinico-radiological staging/classification system for patients of post-covid mid-face mucormycosis based on combined radiographic and clinical features for subsequent convenient staging of maxillofacial mucormycosis. The objectives are being to lay down a comprehensive management protocol for these patients.

Methods

This retrospective study consisted of a cohort of 31 patients presenting to a tertiary care center over a 12-month period and diagnosed as post-covid mucormycosis. Their clinical features at the time of presentation along with radiographic presentation/extent of anatomical destruction were combined to create a clinico-radiological staging system. Further, a comprehensive management protocol including cultures, surgery and chemotherapy has been laid down.

Results

This included 18 males and 13 females. Average age of the patients was 53.5 years. As per the clinico-radiological system formulated by the authors, 2 patients (1 males and 1 females) displayed features of Stage 0, 12 patients (7 males and 5 females) of Stage 1-A, 8 patients (5 males and 3 females) of Stage 1-B, 6 patients (4 males and 2 females) and 3 patients (1 male and 2 females) of Stage 3.

Conclusion

The lacuna of a comprehensive staging/classification system for patients of maxillofacial mucormycosis was felt by the authors while treating those affected by post-covid mucormycosis along with a detailed algorithm for management of the study population. It is to this effect that this clinic–radiological classification system has been suggested by the authors along with a management protocol.

Introduction

The COVID-19 disease caused by SARS-COV2 (Severe Acute Respiratory Syndrome Corona Virus 2) is now associated with a number of secondary infections (both bacterial and fungal) and other associated complications. Certain pathophysiologic features of COVID-19 allow the onset and exacerbation of secondary fungal infections [1]. Further, COVID-19-associated immune dysregulation coupled with the widespread use of steroids and monoclonal antibodies may lead to the development/exacerbation of fungal disease [2]. Among fungal infections, Aspergillosis, Candida and Mucormycosis have been reported as secondary opportunistic infections in patients with/recovering from Covid-19 [3, 4]. Sino-nasal mucormycosis has emerged as an endemic of concern in the shadow of Covid-19, particularly in India. This fulminant spread of mucormycosis is multifactorial. SARS-COV2-induced and steroid-mediated immunosuppression along with a hyperglycemic state is the main factors along with increased ferritin levels and metabolic acidosis/diabetic ketoacidosis responsible for the easy germination and spread of the Mucorales spores in the sino-nasal/orofacial region [5].

Mucormycosis is a mold fungi of genus Rhizopus, Mucor, Rhizomucor, Cunninghamella and Absidia, Order-Mucorales and Class-Zygomycetes [6]. The genus Rhizopus Oryzae is the most common and accounts for roughly 60% of mucormycosis cases in human beings. It further accounts for 90% of the rhino-orbital-cerebral (ROCM) form [7]. Mucormycetes are commonly found in soil and dust and mode of entry of the fungal spores into the upper respiratory system is by inhalation via the nasal route with seeding of the spores in the para nasal sinuses. Entry of the fungal spores can also occur via dental extraction sockets [8].

These two modes of spread account for the mid-face, orofacial or rhino-orbito cerebral mucormycosis (ROCM). Spores also may be inhaled into the lower respiratory tract which causes the pulmonary type of mucormycosis. Other presentations include the gastro-intestinal, cutaneous, bone, renal, cardiac and mediastinal mucormycosis [9, 10].

The presentation of patients of post-covid mid-face mucormycosis can be varied with signs and symptoms depending on the region affected. The lacuna of a definitive clinico-radiological classification system as well as management protocol was felt by the workers for comprehensive treatment of these patients.

Aim and Objectives

The aim of this study was to formulate a definitive clinic–radiological classification system for patients of post-covid mid-face mucormycosis. The objectives are being to lay down a comprehensive management protocol consisting of microbiological, histopathological, biochemical (including covid-related pro fungal inflammatory markers) and radiological investigations for carrying out definitive surgical and medical treatment.

Materials and Methods

In total, 31 patients were included in the study, details as shown in Table-1. Both male and female patients were included. Age of the patients ranged from 49 to 63 years, with an average age of 53.5 years. All 31 patients had a history of testing positive for Covid-19 over the previous 3 to 8 weeks. After testing positive for Covid-19, all the patients in the study group had been managed for Covid at other hospitals/nursing homes. In total, 28 out of 31 patients (90.32%) (Table 1) had a history of being treated with injectable corticosteroids with/without oxygen via face mask/nasal prongs along with other recommended medication for Covid as per protocol of the respective treating hospital.

Table 1.

Demographics data of the patient

S no	Age/gender	O2 and steroid therapy	Pre-op diagnosis	CT/MRI	Post-op complication	Duration of hospitalization (days)
1	61/M	O + S	KOH, GMS	CT	Nil	48
2	62/ M	O + S	KOH	CT	Nil	33
3	53/M	N	KOH, GMS	CT	Wound dehiscence	66
4	60/F	O + S	KOH	CT	Nil	60
5	54/M	O + S	KOH, GSM	CT	Nil	46
6	55/F	O + S	KOH	CT	Stitch abscess	32
7	56/F	O + S	KOH, GSM, CG	CT	Nil	48
8	45/F	O + S	KOH, GSM	CT	Nil	51
9	53/F	O + S	KOH	CT, MRI	Nil	60
10	75/M	N	KOH, GSM, CG	Nil	Nil	54
11	66/M	O + S	KOH, GSM	CT	Local infection	42
12	49/M	O + S	KOH, GSM	CT	Nil	38
13	58/F	O + S	KOH	CT	Wound dehiscence	23
14	50/F	O + S	KOH, GSM	CT	Nil	42
15	54/M	N	KOH	CT	Local infection	51
16	65/M	O + S	KOH, GSM	CT	Nil	42
17	69/M	O + S	KOH	CT	Nil	40
18	54/F	O + S	KOH, GSM	CT	Nil	60
19	64/M	O + S	KOH	CT	Stitch abscess	52
20	48/F	O + S	KOH	CT	Nil	38
21	49/M	S	KOH	CT	Nil	41
22	54/M	O + S	KOH	CT	Nil	50
23	59/F	O + S	KOH, GSM	CT	Nil	62
24	60/M	O + S	KOH, GSM	CT	Local infection	42
25	72/F	S	KOH	CT	Nil	52
26	53/M	O + S	KOH, GSM	CT	Nil	40
27	67/M	O	KOH	CT	Nil	49
28	65/M	O + S	KOH, GSM	CT	Nil	50
29	49/F	S	KOH	CT	Nil	41
30	50/M	O + S	KOH, GSM	CT	Nil	55
31	55/F	S	KOH, GSM	CT	Nil	39

The patients reported or were referred to our center on recovery from Covid with various clinical signs and symptoms. These included tooth mobility, boggy swelling over the gingiva and mucosa (Fig. 1), pus discharge over the gingiva and alveolar process (Fig. 2), discoloration of mucosa, ulceration of mucosa, frank discharging sinuses over the oro-facial region, eschar or discoloration of skin/mucosa (Fig. 3), nasal discharge, epiphora, chemosis and proptosis of the globe (Fig. 4), pain over the palate/mid-face/antral/frontal/orbital region and debilitating headaches.

Fig. 1.

Mobility of maxillary teeth with swelling of mucosa and discharging sinuses over the Gingiva

Fig. 2.

Pus discharge and draining sinuses over the gingiva

Fig. 3.

Discoloration/eschar of skin over the mid-face

Fig. 4.

Chemosis and proptosis of right eye

After initial clinical examination, on suspicion for fungal osteomyelitis, samples for fungal stains and culture were taken via swabs and incisional biopsy (Fig. 5). Concomitantly, computed tomography (CT) was carried out for all patients to assess extent of osteolysis/bony destruction and also for orbital and intracranial involvement. KOH (potassium hydroxide) mount depicted right-angled branching and ribbon-like folding classical of Rhizopus spp. Grocott Methenamine Silver (GMS) stain and Lactophenol Cotton Blue (LPCB) preparations confirmed the dark colored aseptate hyphae of mucors species.

Fig. 5.

Incisional biopsy to obtain specimens for fungal stains and culture

Based on the clinical presentation and radiographic extent of osteolytic destruction/bony and soft tissue involvement on computed tomography, a clinico-radiological classification system was prepared by the authors (Table 2). All 31 patients were allotted a stage as per the classification system. Stagewise demographics of the study population is given in (Table 3).

Table 2.

Clinico-radiological classification system of post-covid mid-face mucormycosis

Class	Clinical features	Radiologic features (NCCT & MRI)
Stage-0 Unilateral or bilateral	A] Extra oral i) Pain over the midface, maxillary sinus and para nasal region B] Intra oral ii)Pain over the dentoalveolar and palatal region	A] Bony changes i)Change in the bony trabecular pattern of the hard palate and alveolar bone of the maxilla B] Soft tissue i) Polypoidal mucosal thickening confined to the floor and medial wall of the maxillary sinus
Stage-1a (oro sino nasal) unilateral involvement	A] Extra oral i) Swelling & pain over the cheeks & nasal region (Nasal & Para nasal region) ii) Nasal discharge iii) Paresthesia over cheek and infra orbital region B] Intra oral i) Draining sinuses with suppurative discharge over palate & buccal vestibule ii) Boggy, oedematous appearance of palatal & vestibular mucosa iii) Bluish/greyish black discoloration of mucosa iv) Frank ulceration of mucosa ± denudation of underlying bone v) Mobility of teeth vi) Dentoalveolar mobility	A] Bony changes i)Destruction of the hard palate ii) Destruction of alveolar bone of the maxilla iii) Destruction of inferior turbinate ± walls of maxillary sinus B] Soft tissue i)Involvement/Polypoidal mucosal thickening of maxillary sinus and/or ethmoid sinus
Stage-1b (oro sino nasal) bilateral involvement	A] Extra oral i) Swelling & pain over the cheeks & nasal region (Nasal & Para nasal region) ii) Nasal discharge iii) Paresthesia over cheek and infra orbital region B] Intra oral i) Draining sinuses with suppurative discharge over palate & buccal vestibule ii) Boggy, oedematous appearance of palatal & vestibular mucosa iii) Bluish/greyish black discoloration of mucosa iv) Frank ulceration of mucosa ± denudation of underlying bone v) Mobility of teeth vi) Dentoalveolar mobility	A] Bony changes i)Destruction of the hard palate ii) Destruction of alveolar bone of the maxilla iii) Destruction of inferior turbinate ± walls of maxillary sinus B] Soft tissue i)Involvement/Polypoidal mucosal thickening of maxillary sinus and/or ethmoid sinus
Stage-2a (oro sino naso orbital) unilateral involvement	3 or more Clinical Features of Type-1, with:- i)Watering of eye ii) Chemosis of bulbar conjunctiva of eye iii) Proptosis iv) Restricted ocular movements v) Diminished/sluggish pupillary reflex (Direct & Concensual) vi) Pain/tenderness over frontonasal and /or frontal bone region vii) Discoloration/Eschar over skin of mid face region	Radiographic Features of Stage -1, with:- A] Bony changes i)Destruction of lamina papyracea of ethmoid bone ii) Destruction of other bones of medial wall of orbit ± floor of orbit B] Soft tissue i)Invasion of extra conal fat of orbit ii) Involvement of extra ocular muscles of orbit (inferior oblique,inferior rectus,medial rectus) iii) Involvement of frontal sinus and/or sphenoid sinus
Stage-2b (oro sino naso orbital) bilateral Involvement	3 or more Clinical Features of Type-1, with:- i)Watering of eye ii) Chemosis of bulbar conjunctiva of eye iii) Proptosis iv) Restricted ocular movements v) Diminished/sluggish pupillary reflex (Direct & Concensual) vi) Pain/tenderness over frontonasal and /or frontal bone region vii) Discoloration/Eschar over skin of mid face region	Radiographic Features of Stage -1, with:- A] Bony Changes i)Destruction of lamina papyracea of ethmoid bone ii) Destruction of other bones of medial wall of orbit ± floor of orbit B] Soft tissue i)Invasion of extra conal fat of orbit ii) Involvement of extra ocular muscles of orbit (inferior oblique,inferior rectus,medial rectus) iii) Involvement of frontal sinus and/or sphenoid sinus
Stage-3 (Rhino orbito cerebral) [Intra-cranial/Cerebral involvement]	Features of Type-2,with:- i)Ptosis ii) Complete loss of ocular movements iii) Loss of visual acuity (Pupil fixed & unresponsive) iv) Hard, proptosed eyeball v) Pain over parietal and/or frontal region [Features suggestive of cranial nerves 3,4,6; intra cranial involvement]	Radiographic Features of Stage -2, with:- A] Bony changes i)Destruction of frontal bone cortex B] Soft tissue i)Involvement of orbital apex ii) Involvement of Cavernous Sinus iii) Enhancement of dura of brain or underlying neuroparenchyma

Significance of bold in Table 2 is to highlight relevant headings

Table 3.

Break-up of the study group population as per the clinico-radiologic staging system

Clinico-radiological stage	No. of patients (total)	Male	Female
Stage 0	2	1	1
Stage 1-a	12	7	5
Stage 1-b	8	5	3
Stage 2-a	6	4	2
Stage 2-b	Nil
Stage 3	3	1	2
Total	31	18	13

Systematic management for the study population of post-covid mid-face mucormycosis is as depicted in (Table 4).

Table 4.

Schematic flow chart for management of post-covid mid-face mucormycosis study population

Existing comorbidities like diabetes mellitus were managed with endocrinologist/physician consults. Confirmation of fungal stains and culture validated starting of anti-fungal therapy, liposomal amphotericin B at the rate of 3–5 mg/Kg body weight of the patient. Surgical management however remained the mainstay of treatment to decrease the fungal load, removal of infected hard and soft tissue and prevention of spread of fungal infection to the eye, cranial nerves and brain. Mandatory presurgical clearance was obtained along with high-risk consent for all patients.

All 31 patients were taken up under general anesthesia for surgery which consisted of endoscopic surgical debridement and functional endoscopic sinus surgery (FESS) by the otorhinolaryngology team. The purpose of FESS was to carry out endoscopic clearance of the frontal recess of the frontal sinus and the ethmoid sinus prior to the open surgical debridement. Following that, in the same sitting itself, dental extractions, sequestrectomy and debridement of soft tissue (necrosed antral mucosa, nasal mucosa),unilateral/bilateral subtotal/total maxillectomy, turbinectomy of inferior turbinates (Fig. 6) and orbital exenteration (in cases of evident orbital involvement—Stage 2/3) (Fig. 7) were performed by the maxillofacial team. Where possible, the palatal mucosa was preserved in order to obtain primary closure. Surgical obturators had been prepared preoperatively and fixed over the defect with sutures (Fig. 8). A single surgical team was uniformly involved in the diagnosis, staging and surgical phase of all the patients.

Fig. 6.

Turbinectomy of bilateral diseased inferior turbinates

Fig. 7.

Orbital exenteration with lid sparing approach

Fig. 8.

Surgical obturator in situ

Post-operative care consisted of toileting of the surgical site, removal of scabs, parenteral administration of liposomal amphotericin B and medical management of systemic status of the patient including monitoring for nephrotoxicity and blood sugar levels. Upon achieving a well-healed surgical site and a total cumulative dose of 3–4 Gm Amphotericin, patients were discharged from the hospital on syrup posaconazole and suitable oral hypoglycemic drugs/insulin as advised by the physician. Prior to discharge, all patients underwent an endoscopic check biopsy from the surgical site and KOH mount followed by HPE to rule out residual mucor disease. Further review was done on an outpatient basis for rehabilitation and necessary follow-up.

Results

In total, 31 patients diagnosed with post-covid mid-face mucormycosis were operated under GA for debridement and reduction of fungal load. This included 18 males and 13 females. Average age of the patients was 53.5 years. As per the clinico-radiological system formulated by the authors, 2 patients (1 male and 1 female) displayed features of Stage 0, 12 patients (7 males and 5 females) of Stage 1-A, 8 patients (5 males and 3 females) of Stage 1-B, 6 patients (4 males and 2 females) and 3 patients (1 male and 2 females) of Stage 3. The surgical procedure carried out varied from sequestrectomy and debridement to subtotal maxillectomy with or without orbital exenteration as per the extent of hard and soft tissue involvement.

Two patients expired 2 months and 3 months after discharge from the hospital. Their cause of death whether attributable to a post-covid thromboembolic event or sequelae of intracranial mucormycosis, could not be ascertained.

The remaining 29 patients have been successfully disease free on 6-month follow-up and are currently undergoing prosthetic rehabilitation.

Discussion

COVID-19 has found to be associated with a significant increase in the incidence of secondary infections due to disruption of the immune regulatory mechanism. Added to this, the widespread use of broad-spectrum antibiotics, steroids and monoclonal antibodies during the course of the COVID-19 illness can lead to the development of fungal diseases or the exacerbation of existing fungal diseases [4]. In our study population, we found 28 out of 31 patients (90.32%) had been treated for COVID-19 with steroids.

The inherent affinity of fungal spores for acidic environments with high glucose concentrations has been established by the work of Ismaiel et al., in which they documented 44.4% of their population of post-covid invasive sino-nasal mucormycosis as diabetics [11].

Factors facilitating the germination of Mucorales spores in patients afflicted with Covid-19 are the favourable environment of hypoxia, hyperglycemia (established diabetes, steroid-induced or new onset), acidic medium (metabolic acidosis, diabetic ketoacidosis), high levels of blood iron (increased ferritins) and reduced phagocytic activity of white blood cells (WBC) due to immunosuppression (SARS-CoV-2 mediated, steroid mediated or other comorbidities).

As the route of entry of the mucor spores is via the sino-nasal route, the clinical presentation varies, affecting regions of the mid-face usually in a ‘bottom to up’ manner. ROCM is the commonest variety of clinical presentation of mucormycosis and includes the entire spectrum ranging from limited sino-nasal invasion to rhino-orbital and rhino-orbital cerebral involvement [12, 13].

The clinical signs and symptoms of ROCM are atypical and similar to those of bacterial rhino-sinusitis. These could be headache, facial pain and swelling, nasal discharge [14, 15]. When the disease attains orbital and intracranial involvement, orbital cellulitis, palpebral edema, ptosis, chemosis and ophthalmoplegia [16], cranial nerve involvement is present, specially branches of those passing through the superior orbital fissure [15, 16]. Affected tissue, whether skin or mucosa, may appear normal initially, but gradually progress to an erythematous or violaceous hue to finally developing the characteristic necrotic black eschar due to tissue necrosis and angio invasion [17]. This black eschar found in the palatal or nasal mucosa, although highly suspicious of mucormycosis, may not always be present and has been reported as occurring in a range of 14.8–40% [18, 19]. In our experience, we encountered the black eschar of nasal/oral mucosa in 7 out of 31 patients (22.5%) only.

In 1950, Smith and Krichner laid down the following specific clinical features pathognomonic of mucormycosis [14]:-

1. Black, necrotic turbinate’s easily mistaken for dried, crusted blood,

2. Blood-tinged nasal discharge and facial pain, both on the same side,

3. Soft peri-orbital or peri-nasal swelling with discoloration and induration,

4. Ptosis of the eyelid, proptosis of the eyeball and complete ophthalmoplegia and

5. Multiple cranial nerve palsies unrelated to documented lesions.

In addition to these classical features, we came across clinical features such as boggy edema of the palatal mucosa and gingiva/alveolar mucosa, suppurative discharge from the gingiva, draining sinuses over the alveolus/palate and mobility of the dentition.

While diagnosing and working up patients presenting with clinical features suggestive of fungal osteomyelitis of the mid-face region, computed tomography imaging proves an indispensable tool from a diagnostic as well as surgical perspective and is considered as the initial imaging modality of choice [20].

The radiographic appearance of ROCM on computed tomography is characteristically mimicking an osteomyelitis and displays bony erosion with sinus spread. We carried out computed tomography for all our patients to ascertain the extent of spread of the disease and involvement of both bone as well as soft tissue.

Magnetic resonance imaging (MRI) is the imaging modality of choice when identifying the extra sinus soft tissue spread of the disease. It proves invaluable when orbital and cerebral involvement, particularly of the extra ocular muscles, cranial nerves passing through the superior orbital fissure and the cavernous sinus, is suspected.

The lacuna of a classification system combining the region of the face affected clinically and on imaging was felt, which can prove useful when planning the surgical treatment of these affected individuals.

It is to this effect that a clinic–radiological classification system combining clinical and radiological (computed tomography) features that our study population presented with has been proposed (Table 2).

Stage 0 is designated to patients presenting with early stage of the disease. The clinical features comprise of unilateral or bilateral pain over the maxillary dentoalveolar or palatal region intraorally and over the mid-face, maxillary sinus and para nasal region externally.

CT and MRI imaging of these patients depicts a low-level involvement with changes in the bony trabecular pattern of the hard palate and alveolar bone of the maxilla. Soft tissue changes are typically polypoidal mucosal thickening confined to the floor and medial wall of the maxillary sinus.

These patients would require only alveolectomy and sequestrectomy with/without dental extractions or an inferior maxillectomy at most.

Stage 1-A indicates an unilateral oro-sino-nasal clinic–radiological involvement. Extra oral clinical features are swelling & pain over the cheeks & nasal region (nasal & para nasal region), nasal discharge and paresthesia over cheek and infra orbital region. Intraoral signs comprise of draining sinuses with suppurative discharge over palate & buccal vestibule (Fig. 2), boggy edematous appearance of palatal & vestibular mucosa (Fig. 1), bluish/greyish black discoloration of mucosa, frank ulceration of mucosa ± denudation of underlying bone (Fig. 3), mobility of teeth and dentoalveolar mobility.

On imaging, bony changes evident on CT in addition to those of stage 0 were destruction of inferior turbinate ± walls of maxillary sinus. The soft tissue involvement of the ethmoid sinus mucosa was seen in addition to that of the maxillary sinus.

Stage 1-B is a bilateral oro-sino-nasal disease with bilateral clinic–radiological features as described above for Stage 1-A.

Patients of Stage 1-A and 1-B would require a unilateral or bilateral subtotal/partial maxillectomy for adequate surgical clearance.

Stage 2 is referred to as orbital involvement. Stage 2-A indicates an unilateral oro-sino-naso-orbital involvement. Clinical criteria would include atleast three of those of Stage 1 plus signs of orbital involvement like watering of the eye, chemosis of bulbar conjunctiva of eye, proptosis (Fig. 5), restricted ocular movements, diminished/sluggish pupillary reflex (Direct & Consensual), pain/tenderness over frontonasal and/or frontal bone region and discoloration/eschar over skin of mid-face region (Fig. 4).

On imaging, destruction of lamina papyracea of ethmoid bone and destruction of other bones of medial wall of orbit ± floor of orbit is seen in addition to the bony destruction seen in Stage 1. Classical soft tissue features on MRI are invasion of extra conal fat of orbit, involvement of extra ocular muscles of orbit (inferior oblique, inferior rectus, medial rectus) with or without involvement of frontal sinus and/or sphenoid sinus.

Stage 2-B is bilateral clinic–radiographic features as described above for Stage 2-A.

These individuals of Stage 2-A and 2-B required ophthalmological intervention as well. Parenteral administration of liposomal amphotericin B would help arrest the disease process, allowing a total maxillectomy as the surgical modality of choice. If orbital signs did not improve or further deteriorate, the orbit was then viewed as a potential nidus of fungal infection for the brain and an orbital exenteration was then carried out for these individuals. A lid sparing orbital exenteration technique was the modality of choice to achieve satisfactory cosmesis and soft tissue lining of the orbit on healing.

Stage 3 indicates intracranial/cerebral involvement referred to as the classical rhino-orbital cerebral mucormycosis or ROCM. Clinical features include those of Stage 2 along with ptosis, complete loss of ocular movements, loss of visual acuity (pupil fixed & unresponsive), hard and proptosed eyeball and/or pain over the parietal and/or frontal region. These clinical features are suggestive of involvement of cranial nerves 3,4,6 and intracranial involvement. CT depicts destruction of bone as seen in Stage 2 plus destruction of frontal bone cortex. MRI revealed involvement of orbital apex and the cavernous sinus. In severe cases, enhancement of dura of brain or underlying neuroparenchyma could be visualized by the radiologist.

Surgical intervention in these cases would combine aggressive debridement in the form of total maxillectomy with orbital exenteration along with parenteral antifungal medication, liposomal amphotericin B and posaconazole.

All patients receiving amphotericin were monitored closely for signs of nephrotoxicity and acute kidney injury by serum creatinine and liver function indices. When needed, drug holidays were exercised as deemed fit by the physician.

Fungal cultures prove extremely useful in identifying the fungal etiology [21], and fungal cultures, namely KOH, GMS and LPCB, were carried out in our study. A stepwise algorithm is outlined in Table 4 for a rational and definitive approach to a patient suspicious of post-covid mucormycosis. Definitive diagnosis is achieved by histopathology of the biopsy specimen, identifying the characteristic branching pattern and aseptate hyphae of the Mucor Sp.

Other methods documented to help in the diagnosis of mucormycosis are fine needle aspiration and nasal scraping [21], calcofluor fluorescence [22] and quantitative polymerase chain reaction system [15].

Management of mucormycosis is multi-pronged, combining aggressive surgical debridement, parenteral antifungal therapy (amphotericin B or posaconazole), addressing the underlying systemic status of hyperglycemia and immunosuppression, monitoring nutritional status and nephrotoxicity. In spite of the best of efforts and systematic approach, ROCM is lethal and is associated with a fairly high fatality rate.

Conclusion

Post-covid ROCM wreaked havoc during the second wave of Covid-19 in the Indian subcontinent. A streamlined approach to management of these cases was the need of the hour. The authors have proposed a clinic–radiological classification system which can be applied to cases of cranio-facial mucormycosis, both post-covid and otherwise. An algorithm/ladder approach has also been submitted to help manage these cases in a comprehensive manner.

Funding

Nil.

Declarations

Conflict of interest

There are no conflict of interest.

Ethical Approval

Institutional ethical committee clearance obtained.