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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 7  |  Issue : 2  |  Page : 124-127

Mucormycosis during COVID-19 era: Double whammy in the pandemic


1 Department of Radiation Oncology, State Cancer Institute, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India
2 Department of Surgical Oncology, State Cancer Institute, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India
3 Department of Radiodiagnosis, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India
4 Department of Gynecological Oncology, State Cancer Institute, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India

Date of Submission02-Aug-2021
Date of Decision08-Oct-2021
Date of Acceptance05-Nov-2021
Date of Web Publication17-Aug-2021

Correspondence Address:
Kunal Kishor
Department of Radiation Oncology, State Cancer Institute, Indira Gandhi Institute of Medical Sciences, Patna, Bihar
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jigims.jigims_33_21

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  Abstract 


Backgrounds and Aims: In April − May 2021, India has witnessed a large number of cases of mucormycosis during the second wave of COVID-19 infection both in recovered patients and those in the active phase of disease. Poorly controlled diabetes mellitus, drugs-induced immunosuppression, posttransplantation, and hematological malignancies are the major risk factors for both severe COVID-19 and mucormycosis. This unprecedented rise in COVID-19 infection led to a near collapse of the health-care system with severe shortage of treatment facilities including health-care staff and infrastructure. COVID-19 has highlighted several loopholes in the present health-care system. Most of the existing workforce had to be diverted to treat this disease and its complications. Our aim is to analyze the various clinicopathological characteristics of patients with mucormycosis and COVID-19 by an oncology department in association with the multidisciplinary team of a tertiary care center during the second wave of COVID-19 pandemic.
Materials and Methods: A retrospective observational study was conducted at the oncology ward of a tertiary care center. All biopsy-proven mucormycosis patients were enrolled in the study. A detailed history along with comprehensive clinical examination and imaging studies was done. Surgical intervention and medical management were done by a multidisciplinary coordination team as per the ICMR protocol.
Results: Forty-five patients were enrolled in the study. All cases of mucormycosis occurred in COVID-19 recovered patients. The median age was 52 years. Diabetes mellitus was present in 38 of 45 cases (84%). Periorbital swelling, ocular pain, ptosis, and loss of vision were the main presenting complains. The maxillary sinuses were the most common sinuses affected (45%). Intraorbital extension was seen in five cases (11%). Intracranial extension was seen in nine cases (20%). All patients had received steroids during the COVID-19 treatment.
Conclusion: Poorly controlled diabetes and indiscriminate use of immunosuppressive drugs including steroids have emerged as predisposing factors for causation of mucormycosis in COVID-19 disease. In suspected cases, early initiation of therapy and rapid reversal of underlying predisposing risk factors play a key role.

Keywords: COVID-19, diabetes mellitus, mucormycosis, pandemic, steroids


How to cite this article:
Kishor K, Pawar SS, Kumar M, Raj S, Sinha DK, Kumar D, Kumar A, Kumar A, Anand A, Swati, Nasir Y, Pankaj S, Singh RK. Mucormycosis during COVID-19 era: Double whammy in the pandemic. J Indira Gandhi Inst Med Sci 2021;7:124-7

How to cite this URL:
Kishor K, Pawar SS, Kumar M, Raj S, Sinha DK, Kumar D, Kumar A, Kumar A, Anand A, Swati, Nasir Y, Pankaj S, Singh RK. Mucormycosis during COVID-19 era: Double whammy in the pandemic. J Indira Gandhi Inst Med Sci [serial online] 2021 [cited 2022 Nov 28];7:124-7. Available from: http://www.jigims.co.in/text.asp?2021/7/2/124/331748




  Introduction Top


The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causing COVID-19 is associated with a wide range of disease spectrum. Symptom complex ranges from mild cough and cold to severe pneumonia. The first outbreak began in Wuhan, China in December 2019.[1] COVID-19 is a life-threatening infectious disease. Affected patients have raised the levels of inflammatory mediators and impaired cell-mediated immunity, which leads to more susceptibility to bacterial, viral, and fungal coinfections.[2] Rampant steroid use during COVID management also suppress immunity, thus inviting secondary fungal infections.

India has witnessed the exponential increase in cases during the soaring second wave of COVID-19. Mucormycosis is an angioinvasive fungal infection leading to thrombosis; occur in background of poorly controlled diabetes mellitus, excessive use of corticosteroids for immunosuppression, and prolonged intensive care unit. India has witnessed of approximately 70 times higher prevalence of mucormycosis cases as compared to other countries.[3]

Rhino-orbital cerebral mucormycosis (ROCM) is a fungal infection of the nasal cavity and sinuses, which extends to involve orbit and brain. Rhizopus oryzae and Rhizopus delemar are the most common cause of mucormycosis in Western countries. In highly immunocompromised patient, Cunninghamella species play a major role.[4]

Inhalation of sporangiospores is the most common cause of acquisition of disease. ROCM is a highly invasive and very rapidly progressive disease and needs urgent management to reduce its morbidity and mortality. Early diagnosis by a high index of clinical suspicion facilitates the better outcome. The confirmation of diagnosis by appropriate modalities, initiation of aggressive medical and surgical treatment by a multidisciplinary team yield better results.

Forty-five patients were enrolled in the study. All cases of mucormycosis occurred in COVID-19 recovered patients. We evaluated the various clinicopathological characteristics of patients with mucormycosis and COVID-19 by an oncology team (as entire hospital was converted into a dedicated COVID hospital) of a tertiary care center in association with the multidisciplinary team during the second wave of COVID-19 pandemic.


  Materials and Methods Top


During the second wave of COVID-19 pandemic, our hospital was converted into a “Dedicated COVID Hospital” on May 7, 2021. Our oncology team got an opportunity to treat COVID-19 disease and its complications including mucormycosis. A retrospective observational study was conducted on patients admitted at oncology ward from May to June 2021 for 50 days. All patients with invasive mucormycosis admitted at oncology ward of the paranasal sinuses and who were either COVID positive or had recovered from coronavirus infection were included in the study. The patient's clinical presentation, comorbidities, imaging findings, management details, and follow-up information were obtained, recorded, and analyzed. By the standard mycological techniques, samples from infectious sites were processed in laboratory. All patients underwent surgical treatment and amphotericin B or posaconazole was administered as per the protocol. Complete surgical debridement either by endoscopy or open method was the main aim of treatment with the multidisciplinary coordination.


  Results Top


Of a total 45 postoperative cases of mucormycosis included, 32 were male and 13 were female. The median age of involvement was 52 years. Diabetes mellitus was present in 38 of 45 cases (84%). All 45 patients had recovered from coronavirus infection with prior positive COVID-19 on Reverse Transcriptase-Polymerase Chain Reaction or Rapid Antigen Test report. Steroids and remdesivir were used in 33 and 7 patients, respectively. Two patients required oxygen support to maintain the blood oxygen saturation level above 92%.

Periorbital swelling, ocular pain, ptosis, and loss of vision were the main presenting complaints in 27 (60%) patients. Nasal blockage and epistaxis were present in 18 (40%) patients. Fever and headache observed in 9 (20%) and 8 (17%) patients, respectively. Skin necrosis and pus discharge were present in two patients.

The maxillary sinuses were the most common paranasal sinuses affected (45%) followed by ethmoids (37%), sphenoid (28%), and frontal sinuses (11%). Six patients had involvement of nasal cavity (13%) [Table 1] and [Figure 1]a, [Figure 1]b, and [Figure 1]d. The left orbit (20%) was involved more than right orbit (11%). Intracranial involvement was seen in nine patients [Figure 1]c. The optic nerve was affected in two patients. The black eschar on the hard palate was observed in two patients. Nasopharynx involved in one patient.Fourteen out of 45 patients had eye involvement at the time of presentation. Seven patients had loss of vision. All 14 patients had simultaneous involvement of maxillary and ethmoid sinuses. Infratemporal fossa and pterygopalatine fossa involvement were seen in six and three patients, respectively. One patient with optic neuritis received retrobulbar amphotericin B treatment. The hard palate was involved in two patients [Table 2].
Figure 1: (a) Magnetic resonance imaging Orbit T2W axial section show fungal involvement of right orbit, right ethmoid and sphenoid sinus (arrow), (b) Magnetic resonance imaging orbit T2W axial section show soft-tissue lesion in intraconal compartment of right orbit, leading to mild proptosis. Right-sided ethmoid sinus also involved, (c) Magnetic resonance imaging contrast and DW1 image show fungal involvement of left maxillary sinus, ethmoid, and sphenoid sinus which extend to left infratemporal fossa (Thick arrow). Left ICA also appear thrombosed (Thin arrow), leading to acute infarct in left cerebral hemisphere, (d) Magnetic resonance imaging T2W coronal image show fungal involvement of bilateral maxillary sinus and frontal sinus (arrow)

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Table 1: Incidence of sinus involvement

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Table 2: Spread of infection to adjacent sites at time of presentation

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Open and endoscopic Functional Endoscopic Sinus Surgery was done in 16 and 15 patients, respectively. Ten patients underwent orbital exenteration. Skull base clearance was done in one patient.

Among 38 patients with diabetes mellitus, 12 had uncontrolled blood sugar levels with HBA1c 12.0. D-dimer, C-reactive protein, lactate dehydrogenase, serum ferritin, and erythrocyte sedimentation rate raised in 17, 16, 15, 14, and 6 patients, respectively. Increased level of total leukocytes count was present in nine patients. Raised neutrophil percentage was seen among 13 patients. Deranged renal function test was present in four patients [Table 3].
Table 3: Raised parameters among mucormycosis patients

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About 38 (84%) out of 45 patients had preexisting diabetes mellitus. Sixteen diabetic patients also had hypertension as comorbidity. Hypothyroidism was present in three patients. Psychiatric disorder and chronic renal disease were present in one patient [Table 4].
Table 4: Associated comorbidities

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  Discussion Top


The COVID-19 infection caused by novel SARS-CoV-2 has a wide spectrum of disease.[5] Paltauf in 1885 described mucormycosis as highly invasive and progressive fungal infection occurring in altered immunological system.[6] COVID-19 patients always have immunosuppression with a decrease in CD4+ T and CD8+ T-cells associated with markedly higher levels of interleukin-2 receptor (IL-2R), IL-6, IL-10, tumor necrosis factor-alpha, and some other inflammatory markers.[7]

During the SARS-CoV-2 infection spread in 2003, the incidence of fungal infection was 14.8–27 percent, and it was the main cause of death for SARS patients, accounting for 25%–73.7%in all causes of death.[8] A UK study by White et al. conducted on 135 adults with COVID-19 infection and reported an incidence of 26.7%for invasive fungal infections.[9],[10] Song et al. in April 2020 shows the association between COVID-19 and invasive fungal sinusitis.

The landmark “RECOVERY” trial in June 2020 advocates the use of corticosteroids in severe to critical COVID-19 cases as a life-saving measure.[11]

Mucorales are ubiquitous environmental fungi. Fungi cause infection in diabetic patients, defect in phagocytic function (neutropenia or glucocorticoid treatment), and elevated level of free iron, supporting fungal growth in serum, and tissue. Pak et al. reported that in 70% patients of ROCM and diabetes mellitus was the most common precipitating factor.[12],[13] ROCM is the most common form of disease presenting with eye or facial pain and facial numbness followed by conjunctival suffusion and blurring of vision. If untreated, infection spread from ethmoid sinus to the orbit. With blood or contiguous spread, goes to frontal lobe and through venous spread to cavernous sinus.

The rate of progression of mucormycosis is variable. It depends on immune status and causative mucorales species. Magnetic resonance imaging is the most sensitive (80%) for detecting orbital and central nervous system (CNS) disease than computed tomography. Definitive diagnosis is done by the positive culture from a sterile site. Biopsy and histopathological examination is the most sensitive and specific modalities for definitive diagnosis.

Maintaining a high risk of suspicion for mucormycosis is important. Rapidly reverse the underlying defects by stopping or reducing the immunesuppressive medication, restoring euglycemia, and normal acid − base status. Debridement of all necrotic tissue is critical for eradication of disease. Liposomal amphotericin B is preferred to ABLC for the management of CNS infection. Isavuconazole and posaconazole reserved for oral step-down therapy.

We found that all the 45 cases of mucormycosis of paranasal sinuses had been infected with coronavirus previously.


  Conclusion Top


We are in the learning curve of new and long-term manifestations of the COVID-19 infection. There must be the high index of suspicion of rhino-orbital mucormycosis in COVID-19 era in all patients who present with signs and symptoms having a history of concurrent uncontrolled diabetes mellitus. In the high index of suspicion, early initiation of therapy, rapid reversal of underlying predisposing risk factors, and surgical debridement, when possible, should be done. More studies need to be done to document the management modality and risk factors.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Covid-19 as on 2020. Available from: https://www.mohfw.gov.in. [Last accessed on 2020 May 10].  Back to cited text no. 1
    
2.
Song G, Liang G, Liu W. Fungal co-infections associated with global COVID-19 pandemic: A clinical and diagnostic perspective from China. Mycopathologia 2020;185:599-606.  Back to cited text no. 2
    
3.
Prakash H, Chakrabarti A. Global epidemiology of mucormycosis. J Fungi (Basel) 2019;5:26.  Back to cited text no. 3
    
4.
Spellberg B, Ibrahim AS. University of California, Los Angeles (UCLA); Harrison's manual of medicine. 20th ed. Vol. 1. p. 1537.  Back to cited text no. 4
    
5.
Petrikkos G, Skiada A, Lortholary O, Roilides E, Walsh TJ, Kontoyiannis DP. Epidemiology and clinical manifestations of mucormycosis. Clin Infect Dis 2012;54:S23-34.  Back to cited text no. 5
    
6.
Mehta S, Pandey A. Rhino-orbital mucormycosis associated with COVID-19. Cureus 2020;12:e10726.  Back to cited text no. 6
    
7.
Paltauf A. Mycosis mucorina. Virchows Arch Pathol Anat Physiol Klin Med 1885;102:543-64.  Back to cited text no. 7
    
8.
Yang W, Cao Q, Qin L, Wang X, Cheng Z, Pan A, et al. Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19): A multi-center study in Wenzhou city, Zhejiang, China. J Infect 2020;80:388-93.  Back to cited text no. 8
    
9.
Zhang Y, Li WX, Huang KW, Cao ZX, Hao JY. Hospital acquired pneumonia occurring after acute stage of the serious SARS and its treating strategies. Chin J Nosocomiol 2003;11:1081-7.  Back to cited text no. 9
    
10.
White L, Dhillon R, Cordey A, Hughes H, Faggian F, Soni S, et al. A national strategy to diagnose coronavirus disease 2019 – associated invasive fungal disease in the intensive care unit. Clin Infectious Dis 2021;73:e1634-e1644.  Back to cited text no. 10
    
11.
RECOVERY Collaborative Group; Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, et al. Dexamethasone in hospitalized patients with COVID-19 – Preliminary report. N Engl J Med 2021;384:693-704.  Back to cited text no. 11
    
12.
Pak J, Tucci VT, Vincent AL, Sandin RL, Greene JN. Mucormycosis in immunochallenged patients. J Emerg Trauma Shock 2008;1:106-13.  Back to cited text no. 12
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13.
Amalanathan S, Colbert KR, Chockalingam SK, Sinhasan SP, Jadhav C. Mucormycosis complicating diabetes mellitus and COVID-19: A diagnostic and therapeutic threat. Int J Otorhinolaryngol Head Neck Surg 2021;7:679-82.  Back to cited text no. 13
    


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