Introduction

The COVID 19 pandemic originated in Wuhan in 2019 and subsequently spread to all corners of the globe leading to widespread morbidity and mortality along with unprecedented economic and societal disruption. The ‘second wave’ of the epidemic in India in the months of April to June 2021 occurred due to the Delta (B.1.617.2) variant and was particularly devastating [1]. It prompted the use of steroids as the first line of management which proved to be a double-edged sword exacerbating diabetes which was previously well controlled or flaring up of latent or previously undiagnosed diabetes. The angio-invasive fungal form of this disease spread by fungal spores in a hyperglycaemic environment causing luminal thrombosis resulting in mucosal infraction and necrosis, bony erosion with its rapid progression advancing into Sino-nasal cavity, orbit and eventually into cranial cavity.[2].

Mucormycosis carries a high fatality rate and the management involves prompt surgical intervention along with liposomal Amphotericin B [3, 4]. It is imperative that all involved sites be thoroughly debrided (as one would expect in a case of malignancy) and no residual disease is left behind. Such large volume excision leaves behind major anatomical defects and the reconstruction in such cases can be equally challenging. In this series we present 6 cases of CAM where resection and immediate flap reconstruction was performed.

Methods

The reported case series was conducted as a retrospective study. Six patients, consisting of four males and two females with a mean age of 46.5 years (range 36–56 years) who presented with signs and symptoms of post covid mucormycosis were evaluated by contrast MRI and CT scan and pre-operative biopsy were sent from the most representative site on radiology. [Table 1] However, Amphotericin B was initiated on high index of clinical suspicion. Diabetes was the predisposing factor in all the cases either diagnosed on admission or uncontrolled previously diagnosed on medication. Three cases had previously undergone endoscopic debridement with post-operative amphotericin B. however they had recurrence of mucormycosis and were then subjected to revision procedure. Three cases had extensive involvement which could not be cleared endoscopically hence were subjected to primary open maxillectomy in one and with orbital exenteration in the other. Reconstruction was done using free flap (five out of six cases) and pedicle (one-sixth). [Table 2]. Institutional ethical committee approval was obtained. The medical charts were reviewed to obtain data on (1) age, (2) sex, (3) Date of surgery, (4) Predisposing factor, (5) Onset after covid, (6) Presenting complaints, (7) Initial medical treatment, [Table:1] (8) Afflicted areas, (9) Surgical procedure and reconstruction (10) Follow-up. [ Table 2]

Table 1 Demography and clinical presentation in individual cases
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Table 2 Excisional defect and reconstructive method in individual cases
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Operative Technique

Diagnosis of post-covid mucormycosis necessitated early intervention with Liposomal Amphotericin B and surgical debridement with reconstruction. The size and volume of a flap for reconstruction were evaluated by assessing the extent of disease on MRI and CT. A two-team approach was used thus reducing the operative time and contamination of wound in the donor area. The skin and soft tissue were resected with a 2-cm macroscopic healthy tissue margin along with affected tissue. Alongside, flap elevation was started by raising one of the flap’s margins to find primary perforator and continued until pedicle dissection of desired length was accomplished.

All resected specimen were sent to pathologist to rule out fungal presence. The samples were evaluated using haematoxylin and eosin staining (20–30 min) for rapid hyphae evaluation. The definitive biopsies were evaluated after staining with Grocott’s methenamine silver. After evaluating intra-operatively with no apparent affected tissue left, we selected the recipient vessels based on the flap location and pedicle length. After dissection, 1 to 2 mm of distal most portion of recipient artery and vein were sent for hyphae analysis in the similar way. On confirmation of fungal hyphae absence and adequate debridement of all the affected tissues, the anastomosis was performed with the pedicle. The purpose of the flap was cavity filling, bulk restoration, provision of oral and nasal lining. The donor site was primarily closed in all the cases (Fig. 1 and 2).

Post-operative care was done in mucormycosis intensive care unit.

figure 1

Fig. 1

figure 2

Fig. 2

Results

Six cases of post-covid mucormycosis with reconstruction are presented. In all these cases we had complete flap survival with mean follow-up of 90 days. All donor sites healed uneventfully. All these patients were given Post-operative L-AmB with a mean of 30 days [range 20–45 days] and then switched to Oral Posaconazole tablets for 3 months. All these cases are asymptomatic and on regular-follow-up.

Discussion

Covid associated mucormycosis [CAM] may involve the nose, paranasal sinuses, orbit, cranium and palate which is challenging in terms of management. The most critical aspect in having a favourable outcome is prompt diagnosis. It is known that diplopia, ophthalmoplegia, proptosis, periocular cellulitis, ocular pain, acute vision loss, nasoantral or cutaneous eschar in a predisposed host carry a potentially high predictive value.[5] Along with L-AmB, radical surgical debridement must be expeditious to eradicate the fungal reservoir by acting aggressively until bleeding tissue, bone, and periosteum is well perfused with the antifungal agent.

It is vital to provide these patients with a good outcome in terms of survival, quality of life, speech, feeding and aesthetics [7]. The appropriate technique for reconstruction depends primarily on the type of anatomical defect. There are several classification systems for maxillary defects [8], although the Brown classification system has been widely adopted. [9] Although these are more pertinent for maxillary tumours, similar principles may be extrapolated for cases of CAM as well. The reconstruction may be done by the use of prosthesis or flap reconstruction.

Historically, maxillectomy defects were reconstructed with a skin graft to revive a mucosal barrier followed by use of an obturator. [6] Obturator can be used when the defect is limited, patients are poor surgical candidates with an advantage that it is a cheaper reconstructive option, causing less surgical morbidity but with a disadvantage of giving persistent crusting and pain, subjective to wear and tear over time, require daily maintenance and may require frequent visits for adjustments. It may demand a level of manual dexterity for insertion, removal and cleaning which can be challenging for elderly and people with failing dexterity. [10]

Depending of the size and volume of defect, either free flaps or pedicled flaps may be employed. With free flap reconstruction, there are several options like fasciocutaneous flap from anterolateral thigh, radial forearm, myocutaneous flaps from latissimus dorsi or rectus abdominis, or osseocutaneous flaps - fibular free flap, scapular flaps with either thoracodorsal artery or circumflex scapular artery, radial forearm osseocutaneous flap and iliac crest free flap. All types of flaps have their pros and cons and the ultimate decision rests with the reconstructive surgeon based on the type and size of the defect along with convenience and expertise. [11] The algorithms proposed by Cordeiro and Chen serve as valuable guides in decision making [12].

Perforator free flaps allow surgeons to reap large areas of skin and subcutaneous tissue, supplied by vessels perforating the underlying muscle, without harvesting denervated muscle. In so doing, surgeons can minimize postoperative pain, muscle weakness, and therefore the risk of hernia formation after muscle harvest. Surgeons can also better predict flap bulk by not including denervated muscle during a flap which will significantly atrophy over time. [13] The anterolateral thigh (ALT) flap for example, can be harvested as a perforator flap for midface reconstruction. It provides significant tissue bulk and an extended pedicle (10–15 cm), allows for primary closure of the donor [13]. site, and can be sensate. Further, when two separate perforators are harvested, then the ALT can provide two separate skin flaps allowing for intraoral and skin reconstruction. Other perforator flaps include the deep inferior epigastric perforator flap, the anteromedial thigh perforator flap, the arteria glutes perforator flap, the thoracodorsal artery perforator flap, peroneal artery perforator flap, submental perforator flap, and others [13].

Previous studies have demonstrated the feasibility of flap reconstruction in maxilla defects. [14] The reconstruction may also be either immediate or delayed. A large proportion of cases from older series underwent delayed reconstruction. [14] The apprehension with immediate reconstruction is that of recurrence of local disease and failure of the flap which may render the whole surgery futile and lead to tremendous patient morbidity. However, it has been demonstrated that if the margins are clear of the disease, then simultaneous flap reconstruction is also a valid option. [14, 15]

The management of CAM during the deadly second wave of COVID 19 was a challenge not just in terms of medical and surgical management but also in terms of logistics. The volume of cases was unprecedented. Health facilities and intensive care were completely saturated with COVID cases. There were also issues with availability of Liposomal Amphotericin. This series highlights that despite these mitigating factors it was still possible to provide satisfactory patient outcome with single-stage surgical debridement and autologous flap reconstruction.

Conclusions

Stepping up on the reconstruction ladder to provide a single stage management in patients of covid associated mucormycosis by adequate surgical debridement, intra-operative negative margins on histopathology and subsequent reconstruction using autologous flaps is the need of the hour to provide within a shorter duration, favourable overall outcome in terms of survival, quality of life, speech, deglutition and aesthetics.