Introduction

Coronavirus disease 2019 (Covid-19) is an infection caused by severe acute respiratory syndrome (SARS-CoV-2). The Covid-19 symptom have increased since the initial days of the disease's presentation, to begin with it included only dry cough and high grade fever, however it now includes varied multisystemic problems as well. It has also been associated with a wide range of opportunistic bacterial and fungal infections.1

Several cases of Covid related mucormycosis have been emerging world-wide, particularly from India. The primary reason thought to be facilitating Mucorales spores to germinate in covid patients is an ideal environment of high glucose (diabetes, new-onset hyperglycaemia, steroid-induced hyperglycaemia), low oxygen, increased levels of ferritin, acidic medium (metabolic acidosis, diabetic ketoacidosis),and decreased phagocytic activity of white blood cells due to immunosuppression combined with considerable other shared risk factors including prolonged hospitalization with or without mechanical ventilators.2

Mucormycosis is a rare yet fatal fungal infection affecting patients with weakened immunity. Patients include those with uncontrolled diabetes mellitus, acquired immunodeficiency syndrome, iatrogenic immunosuppression and haematological malignancies, and those who have undergone organ transplantation.3

Rhizopus Oryzae, a filamentous microfungus, belonging to the family Mucoraceac, is known to be the most common type, accountable for approximately 60.0% of mucormycosis cases in humans and is also responsible for 90.0% of the Rhino-orbital-cerebral (ROCM) form. 4 Here the mode of contamination occurs through inhalation of fungal spores.

The characteristic features of mucormycosis includes the presence of hyphal invasion of sinus tissue and a duration of less than four weeks.5, 6 Clinically, it can present with few atypical signs and symptoms like complicated sinusitis with crusting and nasal blockade, proptosis, ptosis,facial pain and oedema, ophthalmoplegia with fever, headache and other neurological signs and symptoms if intracranial extension is present.7, 8 A black eschar may be seen in the nasal cavity or over the hard palate region, but is not characteristic. 9

A rapid progression of the disease is seen without prompt intervention. Sometimes, even after swift diagnosis, treatment, aggressive medical and surgical intervention, management is often ineffective, resulting in an extension of the infection and ultimately death. 10 Here, we present our recent experience of 50 cases of mucormycosis seen over a time period of just six months in Covid-19 positive cases.

Materials and Methods

A retrospective observational study was undertaken at Jawaharlal Nehru Medical College, AMU, Aligarh, India, over a period of six months, from May to November 2021 in 50 clinically suspected cases of rhino-orbital mucormycosis received in the Department of Pathology.

The samples were received in normal saline and crush/imprint smears were prepared and stained with H&E, PAP and PAS stains for rapid evaluation. The patient’s presentation details, imaging findings, co-morbidities, management details and follow-up information were obtained, recorded and analysed.

Results

Our study included a total of 50 cases of Mucormycosis. The most common age group of presentation was bimodal between 31-40 and 51-60 years, with 15 cases (30.0%) in each decade. Males comprised 28 cases (56.0%) and 22 cases (44.0%) were females (Table 1, Table 2).

Nose seemed to be the most common site for the development of Mucormycosis, comprising of 36 cases (72.0%), followed by maxilla with 06 cases (12.0%). Within the Nose, Nasal cavity showed the maximum number of cases with 24 (48.0%), while the anterior turbinate was least favourable with only 06 cases (12.0%) (Table 3, Table 4).

On Cytology, of all the patients showing positivity, 36 cases (72.0%) were positive exclusively for Mucormycosis, with thick broad aseptate hyphae and spores (Figure 1).

Figure 1

Tissue section shows Mucormycosis, with thick broad aseptate hyphae and spores. Haematoxylin and Eosin x40X.

Candida was seen in 03 cases (6.0%) and aspergillosis in 02 cases (4.0%), with acute angle septate thin hyphae (Figure 2).

Figure 2

Section shows aspergillosis infection, with acute angle branching septate thin hyphae. PAS x40X.

Three (6.0%) cases showed association with a superadded bacterial infection (Figure 3).

Figure 3

Smear shows mucor with hyphae and spores with superadded bacterial infection. PAS x40X.

There were also 6.0% cases which were associated with chronic osteomyelitis (Table 5).

Discussion

The Covid-19 infection has been associated with a wide range of disease patterns, ranging from mild cough to life-threatening pneumonia.11 Although, the chances of healthy individuals contracting mucormycosis is extremely rare, a complex interplay of factors such as as diabetes mellitus, use of immunosuppressive therapy, previous respiratory disorders risk of hospital-acquired infection can lead to secondary infections. 12

The sites favoured by mucormycosis may includes nose, sinuses, orbit, CNS, GIT, lung, jaw, heart and mediastinum, however ROCM is considered to be the most common variety seen world-wide. 13 Here, ROCM refers to the entire spectrum ranging from limited sino-nasal disease (tissue invasion), limited rhino-orbital disease (progression to orbits) to rhino-orbital-cerebral disease (CNS involvement). 13

On microbiological examination, mucormycosis hyphae can be differentiated from other fungal infections based on the diameter, branching angle (right or acute branching), presence or absence of septa and pigmentation. Smith and Krichner 14 in 1950 laid out the criteria for clinical diagnosis of mucormycosis including: (i) Blood-tinged nasal discharge and facial pain, both on the same side, (ii) Black, necrotic turbinate's easily mistaken for dried, crusted blood, (iii) Ptosis of the eyelid, proptosis of the eyeball and complete ophthalmoplegia (iv) Soft peri-orbital or peri-nasal swelling with discoloration and induration and (v) Multiple cranial nerve palsies unrelated to documented lesions.

Patel et al conducted a study in June 2021 with 465 cases of Mucormycosis without covid-19 and showed that rhino-orbital presentation was most commonly seen (67.7%), followed by pulmonary presentation (13.3%) and cutaneous type (10.5%). Among Indians, diabetes mellitus (73.5%), malignancy (9.0%) and organ transplantation (7.7%) were the most common predisposing factors for the development of disease. 15

Song et al. conducted a study in April 2020 where the association between Covid-19 and invasive fungal sinusitis was examined which led to the conclusion that a large number of patients affected by or recovered from Covid-19 are at an increased risk of developing invasive fungal diseases.16 Another study conducted by White et al. comprising of 135 adults with Covid-19 infection, reported an incidence of 26.7% for invasive fungal infections. 17 In a recent review, 8.0% of coronavirus-positive or recovered patients had secondary bacterial or fungal infections during hospital admission, with widespread use of broad-spectrum antibiotics and steroids.18, 19

Ideally, surgical debridement of the infected area should be performed as soon as possible once the diagnosis is confirmed. Although surgery alone is reported not to be curative,an aggressive surgical approach has been shown to improve survival.20  Amphotericin-B deoxycholate remains the anti-fungal treatment of choice to start, with its liposomal preparations preferred because of decreased nephrotoxicity. Prognosis remains poor even with aggressive surgery and intravenous anti-fungal therapy, with reported mortality rates of 33.3–80 per cent, going up to 100 per cent in disseminated infections.21

Conclusions

Covid-19 is associated with a significant incidence of secondary infections both bacterial and fungal due to weakened/altered immunity. Additionally, the rampant use of corticosteroids and high prevalence of diabetes in India are two of the main factors aggravating the illness. If infected, early surgical intervention and intravenous anti-fungal treatment is the current mainstay for management, with a good prognosis and less severe disease course in cases of post-coronavirus mucormycosis.

Conflict of Interest

The authors declare that there is no conflict of interest.

Source of Funding

None.