|Year : 2021 | Volume
| Issue : 1 | Page : 25-28
A case of COVID-19 triggered Rhino-Orbital Pulmonary Mucormycosis in Central India
Chandra Pratap Singh Rathore1, Shirin Ansari2, Trupti Bajpai1
1 Department of Microbiology, Sri Aurobindo Institute of Medical Sciences Medical College and PG Institute, Indore, Madhya Pradesh, India
2 Department of ENT, Sri Aurobindo Institute of Medical Sciences Medical College and PG Institute, Indore, Madhya Pradesh, India
|Date of Submission||08-Apr-2021|
|Date of Decision||29-Apr-2021|
|Date of Acceptance||30-Apr-2021|
|Date of Web Publication||30-Jun-2021|
Dr. Trupti Bajpai
Department of Microbiology, Sri Aurobindo Institute of Medical Sciences Medical College and PG Institute, MR-10, Ujjain-Indore Crossing, Sawner Road, Indore, Madhya Pradesh
Source of Support: None, Conflict of Interest: None
Mucormycosis is a rare but fatal, invasive opportunistic fungal infection generally described among immunocompromised individuals. The ongoing pandemic coronavirus disease-19 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 has severely compromised the immune system of patients thereby making them vulnerable to mucormycosis, especially when they are lined up with associated comorbidities. Here, we present a case of one such 64-year-old male patient being on corticosteroids and a case of long-standing diabetes mellitus and chronic kidney disease. COVID-19 triggered the mucormycosis in this patient thereby leading to a condition we have described as rhino-orbital pulmonary mucormycosis.
Keywords: Coronavirus disease-19, Mucor, opportunistic infection, rhino-orbital mucormycosis, severe acute respiratory syndrome corona virus-2
|How to cite this article:|
Singh Rathore CP, Ansari S, Bajpai T. A case of COVID-19 triggered Rhino-Orbital Pulmonary Mucormycosis in Central India. Biomed Res J 2021;8:25-8
|How to cite this URL:|
Singh Rathore CP, Ansari S, Bajpai T. A case of COVID-19 triggered Rhino-Orbital Pulmonary Mucormycosis in Central India. Biomed Res J [serial online] 2021 [cited 2021 Sep 18];8:25-8. Available from: https://www.brjnmims.org/text.asp?2021/8/1/25/320132
| Introduction|| |
The coronavirus disease-19 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted into wide range of disease patterns ranging from mild to life-threatening conditions. It is known to increase the risk of opportunistic infections among individuals presenting with comorbidities.
Mucormycosis is one such aggressive, fulminant, and opportunistic invasive infection caused by the fungi of class zygomycetes., These soil organisms become highly pathogenic among individuals with diverse precipitating factors such as diabetes mellitus, hematologic malignancies, organ transplantation, immunosuppressive therapy, cirrhosis, acquired immunodeficiency syndrome, burns, and renal failure.,
The inflammatory storm created by the pandemic COVID-19 has compromised the immune system of patients thereby triggering the cases of mucormycosis among them. This alarming affliction although rare is not new. Mucormycosis has been a cause of death among several immunocompromised and immunodeficient individuals in the past. However, its rapid increase among recovering and recovered COVID-19 patients is causing a grave concern. This rare and fatal black fungus infection has been recorded by different health-care centers across India. Based on an anatomic localization, mucormycosis can be classified into six forms such as rhino-orbito-cerebral (ROC), pulmonary, gastrointestinal, disseminated, and uncommon presentations with ROC being common in almost 40% of the cases. The disease usually initiates in the nasal mucosa thereby extending into the paranasal sinuses and retro-orbital regions. Once the fungal hyphae enter into the bloodstream, they may spread into either cerebrum or lungs.,,,,,
Here, we report the case of one such COVID-19 recovering diabetic, chronic kidney disease (CKD) patient who developed rhino-orbital-pulmonary mucormycosis within 10 days of testing COVID-19 negative.
| Case Report|| |
A 64-year-old male patient was admitted to the General Intensive Care Unit of our teaching tertiary care hospital with a history of breathlessness, pyrexia, and malaise. He was a chronic diabetic and a case of CKD. On examination, he was hypoxic with a pulse rate of 88/min, blood pressure was 110/70 mm Hg, and body temperature was 101.5°C with a specific oxygen saturation of 98% with nonrebreather mark. Upon admission, his hematological examination revealed Hb: 12.1 g %, white blood cell: 19,900/cu mm, and platelet count: 1.24 lakhs. Blood chemistry results revealed elevated HBA1C value of 7.93%, creatinine: 7.22 mg/dL, urea: 227 mg/dL, sodium: 138 mEq/L, potassium: 4.87 mEq/L, acid blood gas analysis results: pH: 7.315, and HCO3: 22.4.
The participant suffered from COVID-19, 48 days before admission. His nasopharyngeal and oropharyngeal specimen already tested reverse transcription-polymerase chain reaction negative 10 days before the present hospitalization. Being in the recovery phase, he developed sudden fever and dyspnea and therefore was admitted urgently. He was immediately started on intravenous (IV) meropenem (500 mg twice daily) and IV clindamycin (600 mg thrice daily), with the local protocol along with supportive care. He was continued with IV methylprednisolone (40 mg once daily), tablets sevelamer (800 mg thrice daily), feburic (40 mg daily), and subcutaneous insulin to manage with his comorbidities.
A high-resolution computed tomography (CT) scan of the chest showed extensive diffuse areas of ground-glass attenuation in both the lung segments involving both the upper lobes and apical segment of left lower lobe with 90%–95% involvement suggestive of acute interstitial pneumonia by COVID-19 with superimposed fungal infection [Figure 1]. Following the 3rd day of admission, his condition started deteriorating. His hematological and biochemical parameters started worsening. Hemoglobin reduced to 8.6 g% and platelet reduced to 29,000 lakhs by the end of the 6th day. His neutrophil count remained 96% and lymphocytes 2% throughout his stay. His creatinine value increased to 8.61 mg/dL and urea increased to 301 mg/dL. However, electrolytes remained within the normal limits. On the 4th day, a bilateral lid edema with right eye prominence was noted. Ophthalmic evaluation revealed bulkiness in the right extraocular muscles with extensive areas of edema in the periorbital region and soft tissue necrosis seen in the upper and lower eyelids. He was prescribed topical moxifloxacin and acetazolamide. The left eye appeared fixed with nondilated pupil [Figure 2]. Detailed ocular movement and vision study could not be done since the patient was not responsive. Simultaneously, black eschar was seen in his nasal passages. ROC was suspected and CT of the paranasal sinuses and orbits revealed gross mucosal thickening in the right maxillary sinus, right ethmoidal air cells, and right frontal sinus with air foci and calcification indicating sinusitis [Figure 3].
|Figure 1: High-resolution computed tomography chest showing extensive|
bilateral lung involvement
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|Figure 2: Image of the patient showing rhino-orbital edema due to|
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|Figure 3: Computed tomography paranasal sinus coronal section|
suggestive of right nasal septum deviation along with chronic sinusitis
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The clinical picture of CT scan reports was strongly suggestive of invasive fungal infection. The patient was continued with antibiotics with the addition of liposomal amphotericin B 0.5 mg/Kg/day. His steroid therapy was ceased immediately. Following nasal biopsy, a piece of tissue was sent to the histopathology laboratory. The section showed fibrin clot with mucinous material and fibrous tissue showing mixed inflammatory cell filtrate, fungal colonies with broad hyphae, and right-angled branching suggestive of mucormycosis. The similar piece of tissue was also received in our microbiology laboratory for microscopy and culture. Microscopically, the tissue revealed ribbon-shaped, branched, filamentous, aseptate fungal hyphae suggestive of mucormycosis. The sample was inoculated on Sabouraud's dextrose agar and incubated at 25°C and 37°C which revealed grayish-brown patchy growth at 25°C within 8 days of inoculation. Microscopy of the fungal growth performed with lactophenol cotton blue showed aseptate hyphae with sporangia containing sporangiospores. The mold was identified as Mucor species based on the phenotypic features [Figure 4]a and [Figure 4]b.
|Figure 4: (a) Mucor growth on Sabouraud's dextrose agar slant. (b) Mucor|
as seen in lactophenol cotton blue mount at ×40 magnification
Click here to view
The condition of the patient continued to deteriorate and he required protective mechanical ventilation. Since the involvement of eyes, nose, and lungs was seen, it was hypothesized as a case of rhino-orbital pulmonary mucormycosis. However, despite all measures, the patient succumbed on the 8th day following admission. The case study has been done with appropriate oral consent from patient's attendant and has been presented in compliance with ethical standards. The written informed consent was obtained from the patient's attendant for the publication of the case report and the accompanying images.
| Discussion|| |
SARS-CoV-2 infections are known to alter the immune system of host by affecting their T-lymphocytes, which are highly involved in the pathological process of COVID-19. Significant reduction of absolute number of lymphocytes in case of our patient might be responsible for the worst outcome and therefore exposed him with the high risk of developing opportunistic infection such as mucormycosis.,, Therefore, the complex interplay of preexisting comorbidities such as long-standing diabetes mellitus, a case of CKD, corticosteroid therapy, risk of hospital infection, and systemic immune alteration of COVID-19 infection aggravated this lethal, invasive secondary fungal infection. The opportunistic mold which was the cause of infection in our patient was diagnosed to be Mucor both through gold standard methods such as culture and histopathology. The factors such as early diagnosis, surgical debridement, parenteral medical treatment, correction of predisposing factors, and reversal of immune suppression improve the prognosis thereby reducing the mortality rate., Therefore, the patient in our case was also managed through antifungals, debridement of the necrotic tissue, proper insulin dosage, and discontinuation of steroids. In the present case, the surgical intervention could not be done since the patient was considered at the extremely high risk of surgery according to the clinicians. Mucormycosis is known to produce vascular obstructions thereby hindering the penetration of IV amphotericin into the infected tissues. Therefore, the necrotic regions were irrigated with liposomal amphotericin B along with systemic treatment.
In general, pulmonary mucormycosis has been reported among immunocompromised patients with solid organ transplantation and neutropenia, but COVID-19 and extensive steroid therapy must have triggered the opportunistic fungus in our patient inducing pulmonary and rhino-orbital involvement thereby leading to more severe clinical presentations. In spite of the entire therapeutic approach, patient's immune status could not improve and his condition deteriorated on account of multiorgan involvement and comorbidities, steroid therapy, and acute renal failure. The patient was certified following the 8th day of hospitalization. Therefore, the possibilities are that, the SARS-CoV-2 infection by itself is inducing immunosuppression among patients thereby putting them at the risk of developing opportunistic fungal infection.
Another important contributing factor which was responsible for worst patient outcome in our case was the case of chronic diabetes. Such invasive molds find a greater chance of proliferation due to reduced iron-binding capacity of transferrin in such patients. Hyperglycemic condition causes decrease in chemotaxis and phagocytic efficiency which permits the organism to flourish in the tissues. The rhinocerebral form is the most common form of mucormycosis observed among individuals with uncontrolled, long-standing diabetes mellitus. Poor diabetic control and lack of awareness have added to the condition of the patient.
This case has been presented with the aim of highlighting the aggressiveness of opportunistic molds which has revealed with added comorbidities and COVID-19 infection.
Although number of cases has been recorded in different cities of India, only a limited number of studies have been reported and published in the last year.,,,, The authors of the published case reports along with us, therefore, suggest that early identification of coinfection significantly reduces morbidity and mortality.
| Conclusions|| |
The frequency with which we are witnessing the occurrence of COVID-19 triggered mucormycosis with high morbidity and mortality is quite alarming. To conclude, SARS-CoV-2 infection is known to compromise the host response and increase the risk of developing fungal opportunistic infections. Delayed diagnosis may result into worst patient outcomes. Early, clinical suspicions such as swelling in eyes and cheeks and nose obstruction with black dry crusts should immediately prompt for biopsy and antifungal therapy. Furthermore, timely interventions may prevent complications. Furthermore, clinicians should be aware of the possibilities of such secondary infections, especially in patients with associated risk factors, and should follow the multidisciplinary approach in achieving high success rate of survival.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
The authors wish to thank the Chairperson and Dean of the institute for providing laboratory facilities and healthy working atmosphere during the study period. The authors are also thankful to the technical staff of the institute for providing necessary helping hand during the endeavor.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Mehta S, Pandey A. Rhino-orbital mucormycosis associated with COVID-19. Cureus 2020;12:e10726.
Navarro-Perea C, Cañas-Zamarra I, Mencía-Gutiérrez E, Revilla-Sánchez E, Lago-Llinás MD, Pérez-Trigo S, et al.
Rhino-orbito-cerebral mucormycosis: Two cases with amaurosis as presentation, medical surgical management and follow-up. Case Rep 2019;2019: 4215989. 1-7.
Pasero D, Sanna S, Liperi C, Piredda D, Branca GP, Casadio L, et al
challenging complication following SARS-CoV-2 infection: A case of pulmonary mucormycosis. Infection 2020;1-6. doi.org/10.1007/s15010-020-01561-x.
Pana ZD, Seidel D, Skiada A, Groll AH, Petrikkos G, Cornely OA, et al.
Invasive mucormycosis in children: An epidemiologic study in European and non-European countries based on two registries. BMC Infect Dis 2016;16:667.
Tutak AS, Findikh HA, Aslan S, Turk BA, Sirik M, Bekfilavioglu G. Severe rhino-orbital mucormycosis infection of an intensive care unit patient: A case report. Arch Clin Med Case Rep 2017;1:84-8.
Kawahara Y, Wada S, Nijima H, Hayase T, Furukawa R, Ashizawa K, et al.
Rhinocerebral mucormycosis with temporal artery thrombosis in an adolescent following HLA-haploidentical stem cell transplantation. J Pediatr Hematol Oncol 2018;40:e461-3.
McNulty JS. Rhinocerebral mucormycosis: Predisposing factors. Laryngoscope 1982;92:1140-3.
Kim J, Fortson JK, Cook HE. A fatal outcome from rhinocerebral mucormycosis after dental extractions: A case report. J Oral Maxillofac Surg 2001;59:693-7.
Salisbury PL 3rd
, Caloss R Jr, Cruz JM, Powell BL, Cole R, Kohut RI. Mucormycosis of the mandible after dental extractions in a patient with acute myelogenous leukemia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997;83:340-4.
Peng M, Meng H, Sun Y, Xiao Y, Zhang H, Lv K, et al.
Clinical features of pulmonary mucormycosis in patients with different immune status. J Thorac Dis 2019;11:5042-52.
Liu J, Li S, Liu J, Liang B, Wang X, Wang H, et al.
Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. EBioMedicine 2020;55:102763. 1-10.
Pagano L, Ricci P, Tonso A, Nosari A, Cudillo L, Montillo M, et al.
Mucormycosis in patients with haematological malignancies: A retrospective clinical study of 37 cases. GIMEMA Infection Program (Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto). Br J Haematol 1997;99:331-6.
Danion F, Aguilar C, Catherinot E, Alanio A, DeWolf S, Lortholary O, et al.
Mucormycosis: New developments into a persistently devastating infection. Semin Respir Crit Care Med 2015;36:692-705.
Saydam L, Erpek G, Kizilay A. Calcified mucor fungas ball of sphenoid sinus: An unusual presentation of sinoorbital mucormycosis. Ann Otol Rhinol Laryngol 1997;106:875-77.
Jeong W, Keighley C, Wolfe R, Lee WL, Slavin MA, Kong DC, et al.
The epidemiology and clinical manifestations of mucormycosis: A systematic review and meta-analysis of case reports. Clin Microbiol Infect 2019;25:26-34.
Buchta V, Palaskar S, Shetty VP, Bhushan A. Rhinomaxillary mucormycosis with cerebral extension. J Oral Maxillofacial Pathol 2003;31:57-9.
Spellberg B, Edwards J Jr, Ibrahim A. Novel perspectives on mucormycosis: Pathophysiology, presentation, and management. Clin Microbiol Rev 2005;18:556-69.
Hanley B, Naresh KN, Roufosse C, Nicholson AG, Weir J, Cooke GS, et al.
Histopathological findings and viral tropism in UK patients with severe fatal COVID-19: A post-mortem study. Lancet Microbe 2020;1:e245-53.
White PL, Dhillon R, Cordey A, Hughes H, Faggian F, Soni S, et al
national strategy to diagnose COVID-19 associated invasive fungal disease in the ICU. Clin Infect Dis 2020; doi. 10.1093/cid/ciaa1298 , 1-11 .
Werthman-Ehrenreich A. Mucormycosis with orbital compartment syndrome in a patient with COVID-19. Am J Emerg Med 2021;42:264.e5-8.
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