Get Permission Madhusudhan C N, Raghavendra R, Balakrishna, Prakash, and Satish: Clinical presentations, epidemiology and management of COVID-19 associated Mucor mycosis in a tertiary care hospital in South India


Introduction

The Corona virus caused a global pandemic starting in the early months of January 2020 from the Chinese city of Wuhan.1 Although the first wave did not see a huge number of infective cases requiring hospitalization, the second wave, starting almost a year later in March 2021 was in contrast to the first wave. The newer variant of the older COVID-19 virus, commonly called the Delta variant proved to be highly contagious and infective, especially in the Indian subcontinent where the country reported one of the highest infections and death rates in the world. 2 This unprecedented rise in the number of deaths was also associated with Mucor mycosis, particularly the Rhino-orbito-cerebral type.3, 4 This was due to the innumerable risk factors in the infected cases which comprised of the high usage of steroids, uncontrolled diabetes mellitus, hypoxia which required the usage of inhaled oxygen and immunosuppression which were favorable factors for the growth spread of Mucor mycosis.5, 6, 7

Mucor mycosis is commonly described as “the black fungus” as it turns the infected tissues black due to infarction and necrosis of the hosts tissues.3 It results from the invasion of tissues by the fungal hyphae and implantation of these infectious spores in the mucosal areas of conjunctiva, oral and nasal cavity or by inhalation of spores or ingestion of contaminated food.3

This is a retrospective study conducted in a tertiary care hospital in South India between May 2021 and August 2021 when the Mucor mycosis cases were frequently being diagnosed and treated amongst COVID-19 infected patients. This study is being done to study the statistics of the epidemiology, co-morbidities, clinical presentations, management and prognosis of the study group.

Materials and Methods

This retrospective study was conducted in Krishna Rajendra Hospital and Mysore Medical College and Research Institute, Mysore during May 2021- August 2021.

A total of 100 subjects who fulfil both the inclusion and exclusion criteria were selected for the study conducted at Krishna Rajendra Hospital and Mysore Medical College and Research Institute, Mysore. Followings are inclusion and exclusion criteria.

Patients who were diagnosed with COVID 19 infection after the RT-PCR test and having features of Mucor mycosis and treated were included in the study.

Patients who were COVID-19 negative and Patients who were COVID 19 positive without Mucor mycosis were excluded from study.

Methods

The aim and objectives of the intended study were properly explained to the patients’ attendents and informed consent were obtained from all patients. Detailed information’s were collected for statistical analysis from patients those fulfilling the inclusion and exclusion criteria.

The following parameters and details of the patients will be used for the purpose of the study.

  1. Name of the patient.

  2. Age of the patient.

  3. Gender of the patient.

  4. Date of Admission.

  5. Date of RTPCR positive report.

  6. Patient hospital ID.

  7. SRF ID of patient.

  8. KOH mount findings.

  9. Biopsy or histopathology report of patient confirming mucor myosis.

  10. Co morbidities of the patient.

  11. Presenting complaints.

  12. Vision and color vision of patient.

  13. Extraocular movements.

  14. Anterior segment examination.

  15. Posterior segment examination.

  16. CT scan report of brain, orbit and paranasal sinuses.

  17. MRI scan of brain, orbit and paranasal sinuses.

  18. Treatment given, both medical and surgical for mucor mycosis.

  19. Prognosis of the patient post treatment.

All patients underwent for following investigations.

  1. RTPCR test.

  2. KOH Mount.

  3. CT scan of brain orbit and paranasal sinuses.

  4. MRI scan of brain, orbit and paranasal sinuses.

  5. Biopsy or histopathology report for confirmation of mucor mycosis.

  6. CBC, HIV, HBSAg, FBS, PPBS, Urine routine, LFT, RFT, Coagulation profile, CRP, D Dimer done routinely post COVID-19 diagnosis.

Results

Table 1

Age distribution in our study

Age in years

Number of cases

%

20-30

8

8.0

31-40

10

10.0

41-50

29

29.0

51-60

34

34.0

61-70

17

17.0

71-80

2

2.0

Total

100

100.0

Table 2

Investigations done in our study formucor mycosis diagnosis

Investigations

Number of cases

%

CT scan

Brain orbit and paranasal sinuses

86

86.0

Not done

14

14.0

Total

100

100.0

MRI scan

Not done

81

81.0

Done

19

19.0

Total

100

100.0

Histopathology

Not done

92

92.0

Done

8

8.0

Total

100

100.0

Table 3

Anterior Segment Examination findings in our study group

Anterior segment

Number of cases

%

Periorbital swelling

67

67.0

Restriction of extraocular movements with lacrimal apparatus blockage

6

6.0

Mild proptosis with non-reactive pupil

3

3.0

Restriction of extraocular movements

2

2.0

Restriction of extraocular movements with non-reactive pupil

20

20.0

Proptosis

2

2.0

Total

100

100.0

Table 4

Posteriorsegment Examination findings in our study group

Posterior segment

Number of cases

%

None

85

85.0

Moderate Non proliferative diabetic retinopathy

1

1.0

Mild non proliferative diabetic retinopathy

2

2.0

Grade 3 hypertensive retinopathy with mild non proliferative diabetic retinopathy

7

7.0

Grade 3 hypertensive retinopathy

4

4.0

Central retinal artery occlusion

1

1.0

Total

100

100.0

Figure 1

Histopathology showing results after KOH mount examination for confirmation of mucor-mycosis

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Figure 2

Co morbidities present in our study group

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Figure 3

Medical treatment given in our study group

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Figure 4

Surgical treatment given to patients in our study group

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Figure 5

Other complications and presentations of the patients in our study group

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Figure 6

Prognosis of the patients in the study group

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The table shows a positive correlation between anterior segment findings and medical management. Tablet Posaconazole was the main mode of treatment with 43(64.2%) patients with periorbital swelling and 11(55.0%) patients with restricted extraocular muscle movements and non-reactive pupil receiving treatment. Amongst Injections, combination of Meropenem, Amphotericin and Fluconazole was given in 22(32.0%) patients with P value <0.001.Table 5

The table shows appositive correlation between surgical management and anterior segment findings with P value=0.79. 44 patients with periorbital (65.7%) received no surgical management while 13 patients (19.4%) underwent partial maxillectomy. 7 patients (35%) patients with restriction of extraocular muscle movements and non-reactive pupil underwent no procedure while 6 patients (30%) underwent partial maxillectomy.Table 6

Table 5

Correlation of Medical treatment withAnterior segment findings

Periorbital swelling

Extraocular muscle restriction with lacrimal sac obstruction

Mild proptosis with non- reactive pupil

Restriction of extraocular muscles movements

Restriction of extraocular movements with non-reactive pupil

Proptosis

Total

Injection Meropenem and

No.

1

2

0

0

1

0

4

%

1.5%

33.3%

5.0%

4%

30mg Tablet

No.

43

3

3

1

11

2

63

%

64.2%

50%

100%

50%

55%

100%

63%

Injection Meropenem, Amphotericin, Linezolid Fluconazole

No.

0

0

0

1

0

0

1

%

50%

1%

Injection Meropenem

No.

22

0

0

0

8

0

30

%

32.8%

40%

30%

Injection and

No.

0

1

0

0

0

0

1

%

16.7%

1%

Injection Ceftriaxone

No.

1

0

0

0

0

0

1

%

1.5%

1%

Total

No.

67

6

3

2

20

2

100

%

100%

100%

100%

100%

100%

100%

100%

[i] X2=85.71, P<0.001, HS

Table 6

Correlation of Surgical treatment withanterior segment findings

Periorbital swelling

Extraocular muscle restriction with lacrimal sac obstruction

Mild proptosis with non- reactive pupil

Restriction of extraocular muscles movements

Restriction of extraocular movements with non-reactive pupil

Proptosis

Total

Orbital exenteration

No.

5

2

0

0

3

0

10

%

7.5%

33.3%

15.0%

10%

No treatment

No.

44

4

1

2

7

2

60

%

65.7%

66.7%

33.3%

100%

35%

100%

60%

Partial Maxillectomy

No.

13

0

2

0

6

0

21

%

19.4%

66.7%

30%

21%

FESS

No.

4

0

0

0

1

0

5

%

6%

5%

5%

Extended radical maxillectomy

No.

0

0

0

0

1

0

1

%

5%

1%

Infrastructural maxillectomy

No.

0

1

%

5%

1%

Supra-structural maxillectomy

No.

1

0

0

0

0

0

1

%

1.5%

1%

Partial debridement

No.

0

0

0

0

1

0

1

%

5.0%

1%

Total

No.

67

6

3

2

20

2

100

%

100%

100%

100%

100%

100%

100%

100%

[i] X2=28.01, P=0.79, NS

Table 7

Correlation ofmedical treatment with posterior segment findings

None

Moderate non proliferative diabetic retinopathy

Mild non proliferative diabetic retinopathy

Grade 3 hypertensive retinopathy with mild non proliferative diabetic retinopathy

Grade 3 hypertensive retinopathy

Central retinal artery occlusion

Total

Injection Meropenem and Amphotericin B

No.

1

1

0

1

1

0

4

%

1.2%

100%

14.3%

25.0%

4%

30mg Tablet Posaconazole

No.

58

0

2

1

2

0

63

%

68.2%

100%

14.3%

50%

63%

Injection Meropenem, Amphotericin, Linezolid Fluconazole

No.

1

0

0

0

0

0

1

%

1.20%

1%

Injection Meropenem Amphotericin and Fluconazole

No.

24

0

0

4

1

1

30

%

28.2%

57.1%

25%

100%

30%

Injection and tablet Meropenem and Amphotericin

No.

0

0

0

1

0

0

1

%

14.3%

1%

Injection Ceftriaxone

No.

1

0

0

0

0

0

1

%

1.2%

1%

Total

No.

85

1

2

7

4

1

100

%

100%

100%

100%

100%

100%

100%

100%

[i] X2=53.94, P<0.001, HS

Table 8

Correlation of Surgical treatment with posterior segment findings

None

Moderate non proliferative diabetic retinopathy

Mild non proliferative diabetic retinopathy

Grade 3 hypertensive retinopathy with mild non proliferative diabetic retinopathy

Grade 3 hypertensive retinopathy

Central retinal artery occlusion

Total

Orbital exenteration

No.

7

1

1

1

0

0

10

%

81.2%

100%

50%

14.3%

10%

No treatment

No.

52

0

1

4

3

0

60

%

61.2%

50%

57.1%

75%

60%

Partial maxillectomy

No.

19

0

0

1

0

1

21

%

22.4%

14.3%

100%

21%

FESS

No.

4

0

0

0

1

0

5

%

4.7%

25%

5%

Extended radical maxillectomy

No.

1

0

0

0

0

0

1

%

1.2%

1%

Infra-structural maxillectomy

No.

1

0

0

0

0

0

1

%

1.2%

1%

Supra-structural maxillectomy

No.

1

0

0

0

0

0

1

%

1.2%

1%

Partial debridement

No.

0

0

0

1

0

0

1

%

14.3%

1%

Total

No.

85

1

2

7

4

1

100

%

100%

100%

100%

100%

100%

100%

100%

[i] X2=35.85, P=0.43, NS

Table 9

Shows the correlation between co-morbidities and prognosis of the patients in the study group

Co-morbidities

Discharge

Death

Total

Diabetes

No.

31

1

32

%

96.9%

3.1%

100%

Diabetes and Hypertension

No.

11

0

11

%

100%

100%

Diabetes, Hypertension and Ischemic heart disease

No.

2

0

2

%

100%

100%

Diabetes and pneumonia with long term steroid usage

No.

1

0

1

%

100%

100%

Hypertension

No.

2

0

2

%

100%

100%

Pneumonia with long term steroid usage

No.

0

1

1

%

100%

100%

Pneumonia with steroid use and acute kidney injury with long term hospitalization

No.

0

1

1

%

100%

100%

None

No.

49

0

49

%

100%

100%

Chronic kidney disease with long term hospitalization

No.

1

0

1

%

100%

100%

Hypertension with chronic kidney disease and long-term hospitalization

No.

97

3

100

%

97%

3%

100%

[i] X2=66.71, P<0.001, HS

There was a positive correlation between medical management and posterior segment findings with P value<0.001.58 patients (68.2%) with normal posterior segment had no treatment while 24 patients (28.2%) received Injection Meropenem, Fluconazole and Amphotericin. 4 patients (57.1%) with grade 3 hypertension and mild non proliferative diabetic retinopathy received Injection Meropenem, Amphotericin and Fluconazole.Table 7

There was a positive correlation between posterior segment findings and surgical management with P value=0.43. 7 patients (81.2%) with normal posterior segment underwent orbital exenteration and 52 (61.2%) had no treatment.Table 8

The table shows correlation of co-morbidities and prognosis. 31 (96.9%) diabetics were discharged while 1 patient amongst 3 deaths was a diabetic which is significant. 100% of patients with Pneumonia and Acute kidney injury with long term hospitalization and long term steroid usage experienced mortality while remaining patients were discharged with vast morbidities.Table 9

Discussion

Mucor mycosis is more commonly seen in patients with immunological suppression, like chronic uncontrolled steroids, chronic kidney disease on dialysis, long term inhalational steroids for pneumonia, malignancies, post organ transplantation and malnutrition. Although it can involve most organs in the body, rhino-orbito-cerebral type is the most common. Thrombosis with inflammation and necrosis of the underlying tissue with infiltration of cells like eosinophils and giant cells is the pathology. It can be differentiated from other fungi by its hyphae diameter, branching angle, black pigmentation and classical clinical signs like periorbital edema, pain, loss of vision, necrosis with black eschar, facial pain, cranial nerve palsies and blood-tinged discharge. 8

A multicentric study conducted by Prakash et al in 2019 in 388 patients who were confirmed or suspects of COVID 19, showed that 18% had diabetic ketoacidosis and 57% patients had uncontrolled diabetes.9 Patel et al, in India showed in their study that rhino-orbital type was most common, 67.7% with diabetics and patients with malignancies comprising 73.5% and 9% totally.10 Diabetes increases risk of mucor mycosis by 7.5-fold (Odd ratio 7.55. P=0.001).11 In the study conducted by John et al, 93% had diabetes and 88% on long term usage of corticosteroids. Precipitation of ketoacidosis and acidic Ph is fertile for spore germination.12 Steroids suppress phagocytic activity of white blood cells and suppress defense mechanisms. Expression of glucose regulator proteins and availability of free iron for chelation damages endothelium of cells and causes thrombosis, Angio invasion and tissue necrosis. 13

Conclusion

The rising cases of mucor in India can be due to high genetic predisposition of patients to diabetes and hypertension which remain undiagnosed for a long time due to vast majority belonging to low socio-economic strata which could be the reason for delayed diagnosis and treatment. Moreover, patients belonging to the working class cannot afford expensive investigations and treatment. Chronic kidney disease is indirectly related to metabolic syndrome. Long term steroid usage amongst asthma, pneumonia due to pollution, organ transplant patients and genetic predisposition of patients to these diseases can also cause immune suppression. In order to contain symptomatology and grave prognosis amongst patients, early diagnosis, affordable treatment and follow-up including patient education about the etiology and pathogenesis of the disease must be available.

Source of Funding

None.

Conflict of Interest

None.

References

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Pan American Health Organization/ World Health Organization. Epidemiological Alert: COVID-19 associated Mucor mycosis. 11 June, Washington D.C.: PAHO/WHO2021

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J Chakravarti M Gupta R Tilak R Kumar RP Maurya K Nilesh COVID-19-associated Mucormycosis: A clinic-epidemiological studyJ Diabetes Complications202236910828410.1016/j.jdiacomp.2022.108284

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RP Maurya Indications for orbital exenteration in COVID-19 associated Rhino-orbito-cerebral MucormycosisIP Int J Ocul Oncol Oculoplast202172105810.18231/j.ijooo.2021.023

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SK Aggrwal RP Maurya Invasive Sino-orbito-cerebral Mycosis: An overviewInd J Clin Exp Ophthalmol20151314955

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AM Sugar MucormycosisClin Infect Dis199214Suppl 1126910.1093/clinids/14.supplement_1.s126

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A Patel H Kaur I Xess A multicentric observational study on the epidemiology, risk factors, management and outcomes of mucor mycosis in IndiaClin Microbiol Infect2020267944.e9e15

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K Bala J Chander U Handa A prospective study of mucor mycosis in north India: experience from a tertiary care hospitalMed Mycol201553324857

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TM John CN Jacob DP Kontoyiannis When uncontrolled diabetes mellitus and severe COVID 19 converge: the perfect storm for mucor mycosisJ Fungi202174298

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C Baldin A S Ibrahim Molecular mechanisms of mucor mycosis-The bitter and sweetpLoS Pathog20171381006408



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Received : 05-04-2023

Accepted : 25-04-2023


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https://doi.org/10.18231/j.ijooo.2023.002


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