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Table of Contents
CASE REPORT
Year : 2022  |  Volume : 11  |  Issue : 5  |  Page : 41-44

COVID-19 to mucormycosis


1 Department of Nephrology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
2 Department of Emergency Medicine, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India

Date of Submission10-Mar-2021
Date of Decision27-Jun-2021
Date of Acceptance06-Jul-2021
Date of Web Publication07-Jul-2022

Correspondence Address:
Rapur Ram
Professor and Head, Department of Nephrology, Sri Venkateswara Institute of Medical Sciences, Tirupati - 517 507, Andhra Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.355151

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  Abstract 


A 54-year-old man with hypertension, end-stage renal disease (ESRD) who was receiving thrice-weekly haemodialysis for the past 3 years, developed breathlessness after a session of haemodialysis. Oxygen saturation by pulse oximetry (SpO2) was 88% and he was admitted for evaluation. Nasopharyngeal swab real time-polymerase chain reaction (RT-PCR) had tested positive for SARS-CoV-2. He was started on intravenous azithromycin, dexamethasone 8 mg, and subcutaneous heparin. On the 8th day after admission, he had painful swelling, redness and watering of the left eye. Within hours, he also complained swelling of the left half of the face, diminished vision and reduced eye movements of the left eye. Magnetic resonance imaging (MRI) and magnetic resonance angiography of the brain revealed left orbital cellulitis. angioinvasive fungal sinusitis. Laboratory testing confirmed the diagnosis. The patient was treated with intravenous ammphotericin B and surgery.

Keywords: Aseptate broad hyphae, COVID-19, orbital cellulitis, rhino-orbital cerebral mucormycosis, sporangiospores


How to cite this article:
Kasinede T, Gaddam S, Lois Ts JB, Kumar K D, Rani J, Soumya A N, Pavuluri LA, Murali M, Ram R, Kumar V S. COVID-19 to mucormycosis. J Clin Sci Res 2022;11, Suppl S1:41-4

How to cite this URL:
Kasinede T, Gaddam S, Lois Ts JB, Kumar K D, Rani J, Soumya A N, Pavuluri LA, Murali M, Ram R, Kumar V S. COVID-19 to mucormycosis. J Clin Sci Res [serial online] 2022 [cited 2022 Dec 7];11, Suppl S1:41-4. Available from: https://www.jcsr.co.in/text.asp?2022/11/5/41/355151




  Introduction Top


Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been sweeping across the globe. We report the case of a patient of COVID-19 with rhino-orbital cerebral mucormycosis.


  Patient Report Top


A 54-year-old male, known to have hypertension for the past 10 years, had been on haemodialysis for end-stage renal disease (ESRD) for the past 3 years. He was not known to have diabetes mellitus. He had left radiocephalic arteriovenous fistula and receiving thrice a week haemodialysis. He received erythropoietin thrice-a-week. He was also receving intravenous iron therapy a year ago. He had never received desferrioxamine. He presented in July 2020 with a history of breathlessness even after a session of haemodialysis. He had no history of fever, cough and haemoptysis. Blood pressure was 130/70 mmHg, pulse rate was 70/min, temperature was 98.4 °F, respirations 28/min and oxygen saturation measured by pulse oximetry (SpO2) was 88%; post-dialysis body weight was 54 Kg. He had neither anaemia nor oedema. Computed tomography (CT) chest had findings of peripheral, bilateral, ground-glass opacities, right mid-zone consolidation and visible intralobular lines ('crazy paving' pattern). Nasopharyngeal swab real time-polymerase chain reaction (RT-PCR) for SARS-CoV-2 had tested positive. Intravenous azithromycin 500 mg once-daily, dexamethasone 8 mg once-daily, subcutaneous heparin 5000 IU four times a day were started. He also received 8L/min oxygen with non-re-breather mask. SpO2 had improved to 96%. The patient also received on regular haemodialysis. On the 8th day after admission, he had painful swelling, redness and watering of the left eye. Within hours, he also complained swelling of the left half of the face, diminished vision and reduced eye movements of the left eye. Central nervous system examination revealed absent perception of light and extra-ocular movements of the left eye, decreased perception on the left side of the face and angle of mouth deviated to the right side and dysdiadochokinesia on the left side and overshooting of the left upper limb while reaching objects. The bulk, tone, power and the deep tendon reflexes were within normal limits. The patient underwent the following investigations [Table 1].
Table 1: Laboratory Investigations

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Magnetic resonance imaging (MRI) and magnetic resonance angiography of the brain revealed left orbital cellulitis [Figure 1] with cavernous sinus thrombus with superior ophthalmic vein thrombosis, acute infarct in the left medial orbital frontal branch territory or focal cerebritis, acute infarct in pons on the left side and left middle cerebellar peduncle, chronic infarct in the left cerebellar hemisphere, left maxillary [Figure 2] and sphenoid sinusitis and age-related cerebral atrophy. It suggested angioinvasive fungal sinusitis.
Figure 1: Magnetic resonance imaging T2-weighted axial image hyperintense mucosal thickening with fluid in the left maxillary sinus

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Figure 2: Magnetic resonance imaging T2-weighted axial image showing ill-defined heterogenous attenuated signal intensity in retrobulbar fat of the left orbit involved intraconal and extraconal space. There was hyperintensity to the muscle. Proptosis noted in the left eye

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Nasal scrapings revealed aseptate broad hyphae on 10% KOH mount and sporangia-containing sporangiospores on lactophenol cotton blue preparation [Figure 3] from cotton-candy-like colonies on Sabouraud dextrose agar at 30 °C [Figure 4]. These suggested the diagnosis of mucormycosis.
Figure 3: Photomicrograph showing Sporangia-containing sporangiospores on lactophenol cotton blue preparation (X 100)

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Figure 4: Cotton-candy-like colonies on Sabouraud dextrose agar

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He was started on injection amphotericin B deoxycholate 50 mg (1 mg/Kg/day) on the first few days; later, the dose increased to 75 mg/day and to 100 mg/day. The precaution measure to minimise risk of nephrotoxicity is the infusion of at least 1 L of 0.9% NaCl before the injection of amphotericin B. This step was skipped as it might precipitate pulmonary oedema in a patient of ESRD on haemodialysis. Pre-medications for fever and chill were, however, given. It included tablet acetaminophen 650 mg PO 30 min before amphotericin B infusion and tablet diphenhydramine 25 mg PO pre-medication 60 min before amphotericin B infusion. The patient also received injection ceftriaxone 1.0 g twice-daily for 2 weeks.

The patient was referred to a facility where surgeries are being done for COVID-19 patients. The patient underwent drainage of the left maxillary and sphenoid sinuses and excision of the left orbital contents. Post-surgery, the patient continued haemodialysis at our unit and had finished total dose of injection amphotericin 3.0 g.


  Discussion Top


Immunocompromising conditions are the main risk factors for mucormycosis. Patients with uncontrolled diabetes mellitus, especially those with ketoacidosis, are at high risk. Other high-risk groups include patients with cancer, especially those who are neutropenic and receiving broad-spectrum antibiotics, and individuals receiving immunosuppressive agents, including oral or intravenous steroids and tumour necrosis factor-alpha blockers. In addition, patients with haematologic cancer who have opportunistic herpetic infections (e.g., cytomegalovirus) and graft versus host disease are at an increased risk. Jeong et al. showed that solid-organ transplantations and neutropenia, commonly reported in patients affected by haematological malignancies, were the only independent risk factors for pulmonary mucormycosis.[1]

Extreme malnutrition is also linked to mucormycosis, especially the gastrointestinal form. Iron is a growth stimulant for Mucorales, and desferrioxamine acts as a siderophore that delivers iron to the fungi.[2] Older iron chelators such as desferrioxamine and all causes of iron overload are additional risk factors for mucormycosis. Trauma and the use of contaminated medical supplies over wounds are associated with cutaneous mucormycosis. In addition, patients with burns and those who use intravenous drugs are at a higher risk. Some patients with mucormycosis have no identifiable risk factors.[3],[4]

Furthermore, SARS-CoV-2 infection itself might trigger an alteration of the immune system.[5] The alterations described in patients of SARS-CoV-2 were significant and sustained decreases in lymphocyte counts but increases in neutrophil counts, significant decreases in the counts of T-cells, especially CD8 + T-cells, as well as increases in interleukin (IL)-6, IL-10, IL-2 and interferon-γ levels in the peripheral blood in the severe patients compared to those in the mild cases.

The present patient received neither immunosuppressant therapy nor intravenous iron therapy or desferrioxamine. The patient did not have diabetes mellitus. He received dexamethasone for 8 days. However, the patient showed a severe form of COVID-19 with multiple deranged parameters that suggested cytokine storm syndrome. A significant and sustained lymphopenia with neutrophil lymphocyte ratio alteration had been described to be highly associated with the most severe clinical presentation and the worst outcome.[5] The significant reduction of the absolute number of lymphocytes and specifically of T-cells as described in the most severe COVID-19 patients might expose patients to a higher risk of developing opportunistic infections.[6]

In addition to this patient in the early phase of the SARS-CoV-2 infection pandemic, we had two more patients of rhino-orbital mucormycosis. These two were aged 61 and 85 years. Both were not diabetics. One had painful restriction of the extra-ocular movements, redness, watering, ptosis and proptosis of the right eye and the other left eye. Both had nasopharyngeal swab RT-PCR for SARS-CoV-2 positive.

In a study[7] six patients of mucormycosis concurrent with COVID-19 were reported. All patients were male. The mean age was 60.5 ± 12 (46.2–73.9) years. All had type 2 diabetes mellitus with mean blood glucose level of 222.5 (range 86–404) mg/dL. Except for one patient, all patients received systemic corticosteroids for the treatment of COVID-19. The mean duration between diagnosis of COVID-19 and development of symptoms of mucormycosis was 15.6 (range 3–42) days. All patients underwent endoscopic sinus debridement, and two patients required orbital exenteration. At the last follow-up, all six patients were alive, on antifungal therapy.

In a report[8] a 60-year-old male patient, with a longstanding history of diabetes mellitus, with a positive RT-PCR for SARS-CoV-2 was documented. He had received parenteral meropenem and oral oseltamivir with parenteral methylprednisolone. Over the course of the admission, he developed signs of orbital cellulitis. MRI of the brain, orbits and paranasal sinuses revealed soft tissue swelling in the right preseptal, malar, premaxillary and retrobulbar regions with paranasal sinusitis. Nasal biopsy revealed broad aseptate filamentous fungal hyphae suggestive of mucormycosis, which was confirmed on culture. The patient had eventually succumbed.

A case report[9] documented a 41-year-old man with type 1 diabetes mellitus with RT-PCR–positive COVID-19 pneumonia, who also had diabetes ketoacidosis and rhinocerebral mucormycosis. He underwent surgical debridement and received amphotericin B lipid complex.

Another report[10] reported death of a 56-year-old female patient type 2 diabetes, COVID-positive pneumonia and rhinocerebral mucormycosis as it was an invasive fungal infection that was not suitable for debridement due to the risk of fungal sepsis.

In conclusion, SARS-CoV-2 infection could be regarded as a cause of severe immunosuppression that might compromise the host response and increase the risk to develop opportunistic infections, including those caused by moulds, leading to higher risk of negative outcomes.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

The authors are faculty members/Postgraduate students/ residents of Sri Venkateswara Institute of Medical Sciences, Tirupati, of which Journal of Clinical and Scientific Research is the official Publication. The article was subject to the journal's standard procedures, with peer review handled independently of these faculty and their research groups.



 
  References Top

1.
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.  Back to cited text no. 1
    
2.
Boelaert JR, Fenves AZ, Coburn JW. Deferoxamine therapy and mucormycosis in dialysis patients: Report of an international registry. Am J Kidney Dis 1991;18:660-7.  Back to cited text no. 2
    
3.
Mohindra S, Mohindra S, Gupta R, Bakshi J, Gupta SK. Rhinocerebral mucormycosis: The disease spectrum in 27 patients. Mycoses 2007;50:290-6.  Back to cited text no. 3
    
4.
Rahman A, Akter K, Hossain S, Rashid HU. Rhino-orbital mucourmycosis in a non-immunocompromised patient. BMJ Case Rep 2013;2013:bcr2012007863.  Back to cited text no. 4
    
5.
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.  Back to cited text no. 5
    
6.
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.  Back to cited text no. 6
    
7.
Sen M, Lahane S, Lahane TP, Parekh R, Honavar SG. Mucor in a viral land: A tale of two pathogens. Indian J Ophthalmol 2021;69:244-52.  Back to cited text no. 7
[PUBMED]  [Full text]  
8.
Mehta S, Pandey A. Rhino-orbital mucormycosis associated with COVID-19. Cureus 2020;12:e10726.  Back to cited text no. 8
    
9.
Alekseyev K, Didenko L, Chaudhry B. Rhinocerebral mucormycosis and COVID-19 pneumonia. J Med Cases 2021;12:85-9.  Back to cited text no. 9
    
10.
Sargin F, Akbulut M, Karaduman S, Sungurtekin H. Severe rhinocerebral mucormycosis case developed after COVID 19. J Bacteriol Parasitol 2021;12:386.  Back to cited text no. 10
    


    Figures

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

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