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Table of Contents
Year : 2022  |  Volume : 21  |  Issue : 4  |  Page : 383-389  

A study of rhino-orbito-cerebral mucormycosis with COVID-19: A new challenge in North West of Rajasthan

1 Department of Medicine, S P Medical College, Bikaner, Rajasthan, India
2 Department of Emergency Medicine, S P Medical College, Bikaner, Rajasthan, India

Date of Submission19-Jun-2021
Date of Decision16-Aug-2021
Date of Acceptance12-Sep-2021
Date of Web Publication16-Nov-2022

Correspondence Address:
Harish Kumar
B-3 Shastri Nagar, Bikaner - 334 001, Rajasthan
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aam.aam_129_21

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Background: Mucormycosis is a life-threatening fungal disease in immunocompromised patients. There has been increase in the number of mucormycosis associated with COVID-19 patients in second wave. Now country battle with both COVID-19 and mucormycosis. An invasive mucormycosis infection has been a significant burden in India after COVID-19. It has been recently emerged a notifiable disease by the Rajasthan government. Our aim is to develop awareness regarding the importance of early detection and treatment of mucormycosis with COVID-19 and reduce the morbidity and mortality. Materials and Methods: This is a Prospective longitudinal study including 34 patients diagnosed with acute invasive fungal infection by contrast enhancement magnetic resonance imaging studies of paranasal, orbit and brain or nasal biopsy for KOH/culture. Diagnosis is made through routine blood tests, biopsy, and radiological imaging. The patients taken for the study were COVID-19 reverse transcription-polymerase chain reaction positive or recent post COVID-19 (within 15 days) or symptoms of COVID-19 with bilateral pneumonitis. The study was conducted with 34 patients admitted to the department of medicine with mucormycosis within a month may 2021. Results: A total of 34 patients with a mean age of 50.92 years old and male female ratio 24/10 (70.5/29.41) were included in this study. The most common comorbidity was diabetes mellitus (23 patients 67.64%). Nine patients were newly diagnosed or recent onset of diabetes with or after COVID-19 infection. Twenty-four (70.58%) patients were COVID-19 positive or recent (within 15 days) history of COVID-19 positive. Seven (20.58) patients had the history of steroid as a treatment during COVID-19 and 5 (14.70) patients was on oxygen inhalation. One (2.94%) patient was fully vaccinated, and 5 (14.70) patients had the history of steam inhalation. The most common involvement was naso-orbital mucormycosis found in 28 patients (82.35%) followed by nasal-and orbital 26 (76.47) and 18 (52.94), respectively. Naso-Orbito-Cerebral was seen in 16 (47.05) patients. The more common reported symptoms and signs were headache (76.47), facial numbness (64.70), Nasal discharge (52.94), and ophthalmoplegia (52.94). Cranial nerve involvement was seen in 10 patients (facial palsy in 8 patients and bulbar palsy in 2 patients). Total mortality was 7 (7/34 20.58%). Conclusion: COVID-19 infection associated with the wide range of invasive mucormycosis. Early diagnosis and Clinical suspicion of acute invasive fungal sinusitis among COVID-19 patients is essential for better outcomes and higher survival.

   Abstract in French 

Contexte: La mucormycose est une maladie fongique mortelle chez les patients immunodéprimés. Il y a eu une augmentation du nombre de mucormycose associée aux patients Covid - 19 en deuxième vague. Maintenant, le pays se bat contre le Covid-19 et la mucormycose. Une infection invasive en mucormycose a été une charge significative en Inde après Covid - 19. Il a récemment émergé une maladie notifiable du gouvernement du Rajasthan. Notre objectif est de sensibiliser à l'importance de la détection et du traitement précoce de la mucormycose avec Covid-19 et de réduire la morbidité et la mortalité. Matériaux et méthodes: Il s'agit d'une étude longitudinale prospective comprenant 34 patients diagnostiqués avec une infection fongique invasive aiguë par un contraste d'imagerie magnétique des études d'imagerie par résonance magnétique de biopsie paranasale, en orbite et au cerveau ou nasale pour le KOH / la culture. Le diagnostic est posé par des tests sanguins de routine, une biopsie et une imagerie radiologique. Les patients pris pour l'étude ont été la réaction en chaîne de la transcription inverse de Covid-19, la réaction en chaîne de polymérase positive ou le post-COVID-19 récent (dans les 15 jours) ou les symptômes de Covid-19 avec une pneumonite bilatérale. L'étude a été menée avec 34 patients admis au Département de médecine avec mucormycose dans un mois en mai 2021. Résultats: Un total de 34 patients avec un âge moyen de 50,92 ans et un rapport féminine masculin 24/10 (70,5 / 29,41) ont été inclus dans cette étude. La comorbidité la plus courante était le diabète sucré (23 patients 67,64%). Neuf patients ont été récemment diagnostiqués ou un début récent du diabète avec ou après l'infection à Covid - 19. Vingt-quatre (70,58%) patients étaient des antécédents de Covid - 19 positifs ou récents (dans les 15 jours) de Covid - 19 positifs. Sept (20,58) patients avaient des antécédents de stéroïde comme traitement pendant les patients COVID-19 et 5 (14,70) étaient sous inhalation d'oxygène. Un patient (2,94%) a été entièrement vacciné et 5 (14,70) patients avaient des antécédents d'inhalation de vapeur. L'atteinte la plus courante était la mucormycose naso-orbitale trouvée chez 28 patients (82,35%), suivie respectivement par l'orbital nasal et orbital 26 (76,47) et 18 (52,94). Le naso - orbito-cervebral a été observé chez 16 (47,05) patients. Les symptômes et les signes rapportés les plus courants étaient des maux de tête (76,47), un engourdissement facial (64,70), une décharge nasale (52,94) et une ophtalmoplégie (52,94). Une atteinte du nerf crânien a été observée chez 10 patients (paralysie faciale chez 8 patients et paralysie bulbaire chez 2 patients). La mortalité totale était de 7 (7/34 20,58%). Conclusion: Infection Covid - 19 associée à la large gamme de mucormycose invasive. Le diagnostic précoce et la suspicion clinique de sinusite fongique invasive aiguë chez les patients COVID-19 sont essentiels pour de meilleurs résultats et une survie plus élevée.

Mots-clés: Covid - 19, fongique, invasive, nasal, rhinocéros orbital cerebral

Keywords: COVID-19, fungal, invasive, nasal, rhino orbital cerebral

How to cite this article:
Kumar S, Kumar H, Mali M, Meena BL. A study of rhino-orbito-cerebral mucormycosis with COVID-19: A new challenge in North West of Rajasthan. Ann Afr Med 2022;21:383-9

How to cite this URL:
Kumar S, Kumar H, Mali M, Meena BL. A study of rhino-orbito-cerebral mucormycosis with COVID-19: A new challenge in North West of Rajasthan. Ann Afr Med [serial online] 2022 [cited 2023 Mar 25];21:383-9. Available from:

   Introduction Top

Coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected millions worldwide, which cause an emergency global pandemic.[1],[2] It may be associated with a wide range of bacterial and fungal co-infections. Patients infected with SARS-CoV-2 may develop bacterial and fungal secondary infections.[3] Invasive pulmonary aspergillosis coinfection with COVID-19 patients, Many cases being reported worldwide, especially in the intensive care unit.[4] However, there are only a few cases of COVID-19 associated mucormycosis available in the literature.[5] Severe invasive Mucormycosis is a rare, opportunistic fungal infection that typically occurs in individuals with immunocompromised conditions, such as diabetes mellitus (DM), corticosteroid use, neutropenia, solid organ/allogeneic stem cell transplant, HIV/AIDS, malignancies and treatment with immunosuppressants. Mortality is high with invasive mucormycosis by its complication like intracranial involvement, cavernous sinus thrombosis, and osteomyelitis. In extremely rare situation, such infections can be seen in immunocompetent patients.[6] Rhino-orbito-cerebral mucormycosis is considered as the most common manifestation of mucormycosis. The standard protocol for the management of rhinocerebral mucormycosis is primarily reversal of risk factors, surgical debridement as well as intravenous antifungal medication.

   Materials and Methods Top

This is a longitudinal prospective study conducted in 34 patients of mucormycosis admitted within 1 month to the department of medicine in S P Medical College Bikanr Rajasthan. Patients were diagnosed with acute fungal invasive rhinosinusitis, associated with a recent COVID-19 infection or post-COVID b/l pneumonitis. Magnetic resonance imaging (MRI) with contrast enhancement studies of paranasal sinuses, orbit, and brain of all patients revealed invasive fungal sinusitis. Radiological studies of the nose and paranasal sinuses showed variable patterns. Those patterns range from mucosal thickening of the involved sinus mucosa to osteomyelitis of the related bone. Diagnosis of invasive fungal sinusitis was made by histological documented fungal invasion within sinus mucosa, submucosa, or bone. 8 The histopathological diagnosis was determined from the morphology using hematoxylin and eosin, periodic acid-Schiff, and Gomori's methenamine silver staining. Diagnosis is made tthrough routine blood work, biopsy, and radiological imaging.

Statistical analyses

Statistical analyses were performed using Statistical Package for the Social Sciences (SPSS) version 18.0 (Released 2009.PASW Statistics for window, Version 18.0. Chicago:SPSS Inc.). Continuous variables are presented as means standard deviation while discrete variables are presented as number and percent. P < 0.05 is considered statistically significant.

   Results Top

This longitudinal prospective study was conducted in 34 patients of acute invasive fungal infection in relation to COVID-19 patients admitted in the department of medicine within 1 month in May 2021. All patients were diagnosed with COVID-19 reverse transcription-polymerase chain reaction (RTPCR) positive or recent COVID-19 b/l pneumonitis (within 15 days). The mean age is 51.94 ± years (range 2–78). The most common comorbidity was DM 23 (67.64) patients and hypertension 5 (14.70) patients. Out of 23 patients, 14 patients had the past history of DM while 9 patients of them had a recent new onset diagnosis during COVID-19 infection. Five of them had a recent onset diagnosis caused by corticosteroid therapy given during COVID-19 treatment. Malignancy was found in 2 patients (5.88) while hypertension, asthma, and CKD were 5 (4.70), 1 (2.94), and 1 (2.94), respectively. Out of 34 patients, 7 patients (20.58) had the history of corticosteroid therapy during treatment. 24 (70.58) patients were COVID-19 RTPCR positive during admission or recent positive (within 15 days). Five (14.70) patients had the history of oxygen inhalation during treatment. And 5 (14.70) patients had recurrent steam inhalation during symptoms. Out of total, only 1 patient was fully vaccinated. Histopathological mucosal biopsies were confirmed in 30 (88.23) patients [Table 1].
Table 1: Demographic data, associated comorbidities, coronavirus disease status of acute invasive mucormycosis patients after coronavirus disease 2019 infection

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In the context of presenting sign and symptoms, [Table 2] and [Graph 1] show that the most common symptom was headache (26,76.47%) followed by facial numbness (22, 64.70%) and nasal discharge (18,52.94). Ophthalmoplegia, Proptosis, Visual loss and Diplopia were present in 18 (52.94%), 16 (47.05), 9 (26.47), and 4 (11.76), respectively. Facial palsy was documented in 8 (23.52) patients while 2 (5.88) patient had bulbar palsy. 5 (14.70) patients was in the state of altered mental status. 8 (23.52) patients were admitted with the respiratory symptoms like fever, cough and dyspnea. 2 (5.88) patient admitted with the symptoms of itching and ulceration.
Figure 1: Invasion of mucormycosis in hard and soft palate

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Figure 2: Facial palsy

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Figure 3: Orbital cellulitis

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Figure 4: Bulbar palsy

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Table 2: Clinical extension with presenting symptoms and signs of acute invasive mucormycosis patients after coronavirus disease 2019 infection [Figure 1],[Figure 2],[Figure 3],[Figure 4]

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Contrast enhancement MRI of paranasal sinus, orbit and brain showed various stages of sinonasal (76.47), orbital (50.94), naso-orbit (82.35), naso-cerebral (23.52), orbito-cerebral (26.47), and naso-orbio-cerebral (47.05) involvement. Isolated intracranial involvement was not seen [Table 2] and [Graph 2].

Interestingly one patient with RTPCR COVID-19 positive immunocompetent nondiabetic without any history of symptoms of COVID-19 was presented with cutaneous right shoulder mucormycosis. Skin biopsy was showing aseptate branched-chain hyphae.

All patients were categorized in moderate to severe illness. Treatment protocol for hospitalized patients generally consisted according to guideline. Regarding acute invasive fungal sinusitis, all patients in the present study were treated with a combined approach of surgical and antifungal drug regimen. In our institute, a team was formed for the management of COVID-19 with mucormycosis.

63.89% (27/34) was survived at the conclusion of the study. Seven patients (20.58) died, 4 from extensive intracranial extension, three cases with continuous severe respiratory failure, and a early cases (thirteen) with limited sinonasal involvement showed early recovery, single surgical debridement procedure, and better results unlike late cases with intracranial extension and venous sinus thrombosis.

   Discussion Top

The COVID-19 infection caused by the novel SARS-CoV-2 has been associated with a mild cough to life-threatening pneumonia,[7]; despite our country battling with COVID-19 s wave, mucor has emerged as a significant problem. Now India fighting with both COVID-19 and post-COVID-19 mucormycosis simultaneously and Post COVID-19 DM with mucormycosis emerge as a disaster.

In our study, patients were diagnosed with COVID-19 RTPCR positive or recent COVID-19 infection (within 15 days). The mean age was 52.9211.30 years (range 2–78). Out of 23 patients, 14 patients had the past history of DM while 9 patients of them had a recent onset diagnosis during COVID-19 infection.

Sen et al. conducted a retrospective, interventional study on 6 patients COVID-19 patients who developed rhino-orbital mucormycosis and were managed at a tertiary ophthalmic center in India between August 1 and December 15, 2020. All patients were men with mean age of 60.5 ± 12 with type 2 diabetes. All except one patient received systemic corticosteroids treatment for COVID-19. The researchers reported mean duration of 15.6 ± 9.6 days between diagnosis of COVID-19 and development of symptoms of mucor.[8]

In our study, out of total 34 patients of mucormycosis 30 patients were either COVID-19 positive or had symptoms of COVID-19 prior. In our study, DM is most commonly associated with mucormycosis, the cause being either due to previously undiagnosed mucor or due to decrease in the immunity due to COVID-19 infection. Newly diagnosed DM may be due to COVID-19 infections or irrational use of the steroid to treat COVID-19. A higher dose of steroid to treat the COVID-19 infection and monoclonal antibody further exacerbate mucormycosis.[7] Thus, the use of glucocorticoids in mild COVID-19 cases or the utilization of higher doses of glucocorticoids should be avoided. A high degree of clinical suspicion is required to mucormycosis. Early diagnosis and timely management are necessary to improve outcomes in mucormycosis.

Some symptoms of COVID-19 such as fever, cough, and shortness of breath can be similar to those of some fungal diseases. It is necessary to diagnose a person that has a fungal infection or COVID-19. Some have both at the same time. Mucormycosis and COVID-19 co-infection have been reported previously in some healthy young persons.[9],[10] Severe COVID-19 disease leads to cytokine storm by increase in pro-inflammatory markers, such as interleukin-1 (IL-1), IL-6, and tumor necrosis alpha, less CD4 interferon-gamma expression, and fewer CD4 and CD8 cells; this, causes bacterial and fungal infections.[11] Thus it is understood that COVID-19 infection decrease lymphocytes in significant numbers, and persistent lymphopenia[12] is the main cause of opportunistic infection.[13],[14] Most of the patients of severe COVID-19 infection have lymphopenia, this mean low absolute number of T lymphocytes, CD4 and CD8 T[15] cells which play a major role in immune response.[12] Thus the patients with COVID-19 are highly susceptible to fungal co-infections.[16] Some cases have reported of acute invasive fungal rhino-orbital mucormycosis[10] in patients with COVID-19.

Our study has total 34 patients of DM during invasive fungal mucormycosis, out of them 9 patients were not associated with any past history of diabetes. It means these patients was newly diagnosed during or after COVID-19 positive Since diabetes is one of the most common culprit of mucormycosis, it is possible that the patient either had a previous undiagnosed mucor infection or it may have been aggravated with further deregulations of immunity secondary to COVID-19. The use of steroids and monoclonal antibodies to treat COVID-19 may lead to exacerbation of opportunistic infections.[17]

Same result was found by Moorthy et al. completed multi-centric retrospective study in Bangalore, India in 18 patients with DM with positive SARSCoV-2 infections. 15 of 18 patients had confirmed uncontrolled DM and all received corticosteroid for COVID-19 treatment. Surprisingly, 12 of 18 patients had complained of vision loss, 7 of whom then underwent orbital exenteration. The results showed 16 cases of mucormycosis, 1 of aspergillosis and 1 case of mixed fungal infection. Six of these patients died, 11 survived and 1 were lost to follow-up. Researchers confirmed significantly higher incidence of fungal infections (P = 0.03) amongst diabetic patients and suspect a strong association with immunosuppression related to corticosteroid administration.[17]

Infection with mucormycosis is often life threatening[16] due to complications such as cavernous sinus thrombosis, disseminated infection, osteomyelitis, and death. Mucormycosis is a severe fungal infection affects the sinuses, brain or lungs and common in people suffering or recovering from COVID-19. Fever, headache, nasal or sinus congestion, black lesions on nasal bridge or upper inside of mouth and swelling in one side of the face are the common symptoms of mucormycosis.[18]

Unusually, a rising number of invasive fungal infection has been reported recently in COVID-19 patients in the second wave in North West part of Rajasthan. We have reported approximately 34 patients within 15 days so, it has been marked as a notifiable disease by Rajasthan government. The incidence of invasive fungal sinusitis in COVID-19 patients is still unknown. Only isolated case has been published earlier.[7],[9] According to Standardized definition of acute invasive fungal infection presence of tissue invasion by fungus is done in <4 weeks[19] with vascular invasion and thrombosis.[20] Usually, it presents with acute onset of headache, nasal discharge, facial numbness, facial pain, fever, and nasal congestion with frequent involvement of adjacent structures, including the paranasal soft tissues, orbit, and cranial vault. Orbital involvement can result attenuation of vision, while sinus or intracranial extension can be associated with proptosis or neurological impairments, respectively.[20],[21]

Mucormycosis is classified into pulmonary, gastrointestinal, rhino-cerebral, cutaneous, and disseminated mucormycosis.[19] This is the deadly result of opportunistic co infection with the COVID-19 disease.

In the present study, contrast enhancement MRI of paranasal sinus, orbit and brain showed various stages of sinonasal (76.47), orbital (52.94), naso-orbit (82.35), nasocerebral (23.52), orbito-cerebral (26.47), and naso-orbio-cerebral (47.05) involvement. Isolated intracranial involvement was not presented. Several other Rhino-orbital mucormycosis cases have been reported. Waizel-Haiat et al.[22] reported a case of a 24-year-old female in Mexico City with the past medical history of obesity, which tested positive for COVID-19.

In the context of present study, sign and symptoms showing that the most common symptom was headache (26, 76.47%) followed by facial numbness (22, 64.70) and nasal discharge (18, 52.94). Ophthalmoplegia, Proptosis, Visual loss, and Diplopia were present in 18 (52.94), 16 (47.05), 9 (26.47) and 4 (11.76), respectively. Facial palsy was documented in 8 (23.52) patients while 2 (5.88) had bulbar palsy. 5 (14.70) patients were in altered mental status. While 8 (23.52) patients were admitted with fever, cough and dyspnea and 2 (5.88) patients with itching and ulceration. Abu El-Naaj et al., mentioned symptoms as pain resembling sinusitis, facial swelling, and fever in his case series.[23] Kursun et al. listed fever (79%), periorbital cellulitis (75%), and periorbital edema (70%) as the most common manifestations among their cases[24] while Ketenci et al.[25] reported fever, facial edema, facial pain, and nasal obstruction as the most frequent symptoms. In the same study, nine (64%) patients had skin and/or palatal involvement in comparison to 14 cases in the present study. In addition, Ketenci et al., had five cases (35%) of ophthalmoplegia and blindness in comparison to 23 (63.9%) cases in the current study.[25] This disease and its aggressive orbital and intracranial extension should be given close scrutiny. A single most important element for successful attenuation of this infection is early diagnosis followed by aggressive medical care, surgical debridement, and control of associated diseases.

This disease has lethal prognosis, so close scrutiny is much essential. Early diagnosis and aggressive treatment with medical as well as surgical intervention is the most important step in our study. There is a team of Anaesthesia, Medicine, ENT, Ophthalmologist and Dental surgeon for successful attenuation of this infection, early diagnosis followed by aggressive medical care, surgical debridement, and control of associated diseases.

It was observed in our study that early diagnosis and aggressive treatment have the best outcome with minimal mortality and morbidity. The survival rate in studies ranges from 20% to 80%.[24],[25],[26],[27],[28] Studies showed that immune system, play an important role to clear this infection.[29] In our study, better survival rate may be due to early diagnosis, aggressive surgical debridement, and early use of antifungal medications.

Limitations of this study include relatively limited patient number, single tertiary referral center experience, and short-term follow-up. Future research studies are planned to update this experience with long-term follow-up and to target a larger group of patients on a comparative basis with evaluation of risk factor association between AIFR and COVID-19 infection.

   Conclusion Top

This study raises the awareness for early detection and treatment of various fungal infections to reduce mortality by mucormycosis in COVID-19 patients. Due to very high mortality rate, early diagnosis, and rapid initiation of antifungal therapy, and immediate management with surgical intervention could improve the prognosis of the patients and improve survival rates. Additional investigation is needed to understand the role of opportunistic infections in COVID-19 patients. Clinical suspicion and early diagnosis of AIFR in COVID-19 patients are essential for better treatment outcomes.

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Conflicts of interest

There are no conflicts of interest.

   References Top

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1], [Table 2]


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