Secondary Cutaneous Mucormycosis Post-COVID-19: Case Series from a Tertiary Center.

Background: Mucormycosis is an angioinvasive mucorales fungal infection. Cutaneous type formed 10.5% of cases in India in precovid-19 era. Glucocorticoid-induced immunosuppression and hyperglycemia, reusable oxygen humidifiers in COVID-19 therapy, and preexisting uncontrolled diabetes mellitus contribute to post-COVID-19 mucormycosis. However, for post-COVID-19 cutaneous mucormycosis, sufficient data is not available. Aim: To study factors related to post-COVID-19 cutaneous mucormycosis. Methodology: Clinical and investigation details of six patients admitted in tertiary center with post-COVID-19 cutaneous mucormycosis.
Results: Among six patients, three were males and three females; all in 45-60 years age group from districts under tertiary center. Site of eschar was face (four) and lips (two). All six were positive for COVID-19 10-12 days prior to admission for mucormycosis. All had intravenous steroids and supportive humidified oxygen therapy for minimum 1 week under COVID-19 treatment. They presented to emergency with ophthalmic/ENT complaints; subsequently, they developed cutaneous manifestations within 2-3 days. All six had diabetes mellitus, with above 400 mg/dL sugar levels at admission.
Conclusion: This study's findings correlated with various studies across the country and elsewhere. Preexisting diabetes mellitus and steroid therapy for COVID-19 increase the risk of mucormycosis. Caution for early diagnosis, maintaining blood glucose levels, and judicious use of steroids for treatment of COVID-19 are indicated. Copyright:

Introduction

Mucormycosis among COVID-19 and post-COVID-19 patients is reported in second wave from March 2021.[1] Seven thousand mucormycosis were reported so far in India. However, there are very few reports on post-COVID-19 cutaneous mucormycosis. This paper reports occurrence and possible factors related to post-COVID-19 cutaneous mucormycosis in a tertiary hospital.

Aims and objectives

To study factors related to post-COVID-19 cutaneous mucormycosis.

Materials and Methods

A case series of six patients with post-COVID-19 cutaneous mucormycosis admitted in a tertiary center (31/05/2021 to 06/06/2021 – posting time of the first investigator in COVID duty) is described with microbiological confirmation for one patient.

Results

Informant was either the patient or attendant.

Summary of clinical details of all six patients [Figures 1-6] is in Table 1.

Figure 1

Fifty-five-year-old female with eschar on the face

Figure 6

Forty-six-year-old female with eschar on the face

Table 1

Details of the six patients with post-COVID-19 cutaneous mucormycosis

Age/Sex	COVID-19 positive/negative	Days of Injectable steroids for COVID-19	Days of humidified oxygen for COVID-19	COVID-19 Severity	ICU care for COVID-19
55/F	07/05/21 21/05/21	10	10	Moderate	Yes
56/M	10/05/21 22/05/21	07	07	Moderate	No
54/M	08/05/21 20/05/21	08	08	Moderate	No
58/F	16/05/21 28/05/21	10	10	Moderate	No
48/M	03/05/21 29/05/21	12	12	Severe	Yes
46/F	12/05/21 30/05/21	12	12	Moderate	Yes
Comorbidities	Readmission for mucormycosis	Mucormycosis features	Mucormycosis types	Radiological confirmation
DM	24/05/21	Right orbital swelling with pain and discharge	Rhino-orbital	NA
DM + HT	25/05/21	Intermittent headache, right sided facial pain and swelling, right orbital swelling	Rhino-orbital	MRI Brain/Orbit/PNS –Sino-orbital mucormycosis
DM	23/05/21	Intermittent headache, right sided facial pain, nasal stuffiness	Rhino-cerebral	HRCT PNS - Features of fungal sinusitis
DM	31/05/21	Right orbital swelling with pain	Rhino-orbital	CECT Orbit/PNS - Sino-orbital mucormycosis
DM	31/05/21	Right orbital swelling with pain and discharge	Rhino-orbital	NA
DM	02/06/21	Left orbital swelling with pain and discharge	Rhino-orbital	CECT PNS – Maxillary and ethmoid sinus obliteration
(DM – diabetes mellitus, HT – hypertension)
RBS at admission (mg/dL)	Cutaneous mucormycosis post readmission (in days)		Management	Sequelae
429	3		IV Amphotericin-B, 7 days	Succumbed to DKA
350	2		IV Amphotericin-B, 14 days	Palatal perforation
354	2		IV Amphotericin-B,10 days	Discharged on patient request
405	2		IV Amphotericin-B, 21 days + Partial Maxillectomy	Loss of vision (right eye)
425	2		IV Amphotericin-B, 7 days	Palatal perforation Succumbed to DKA
402	3		IV Amphotericin-B, 21 days+Total Maxillectomy	Loss of vision (left eye) Hemiparesis Cavernous sinus thrombosis Succumbed to surgical complications

(DKA – diabetic ketoacidosis)

Fifty-six-year-old male with eschar on the lower lip

Fifty-four-year-old male with eschar on the lower lip

Fifty-eight-year-old female with eschar on the face

Forty-eight-year-old male with eschar on the face

In all cases, face was site of cutaneous manifestation. Four patients developed eschar over skin adjacent to upper half of nose and below affected eye. Two had eschar on lower lip. Though mucormycosis was rapidly progressive, cutaneous mucormycosis was asymptomatic and slowly progressive in size, as per history by the patient's attender.

Biopsy from eschar of the first patient showed fungal hyphae on KOH mount [Figure 7] and black colonies of Rhizopus oryzae on Sabouraud agar [Figure 8] confirming cutaneous mucormycosis.

Figure 7

KOH mount showing fungal hyphae

Figure 8

Black colonies of Rhizopus oryzae in Sabouraud agar

All six patients were above 45 years (range 45–60 years), three males and three females from referral area of this tertiary center. They had tested positive for COVID-19 previously (hospital records) and recovered from illness from various nongovernment hospitals in the state. Their COVID-19 illness occurred –10–12 days prior to symptoms of mucormycosis.

Initial symptoms involved ophthalmic/ENT complaints which started 1/2 days after the patient tested negative for COVID-19. Skin manifestations occurred –2–3 days after initial symptoms among all six patients.

All received injectable dexamethasone 8 mg twice daily for at least 1 week followed by oral tapering steroids for another week and humidified oxygen for minimum 1 week during hospitalization for COVID-19. They had coexisting diabetes mellitus with fasting sugar between 250 and 300 mg/dL and post prandial sugar between 350 and 500 mg/dL following steroid administration during COVID-19. Their RBS at admission were above 350 mg/dL.

Of the six patients, one had received both doses of covishield vaccine.

Discussion

All six patients developed cutaneous mucormycosis as necrotic eschar with surrounding erythema and induration.[23] Face, the classically affected site,[34] was site of cutaneous mucormycosis in all cases. Cutaneous lesions developed either after rhino-cerebral or rhino-orbital mucormycosis without preexisting history of trauma; hence, they classified as secondary cutaneous mucormycosis.[345]

Punch skin biopsy for KOH mount and Sabouraud dextrose agar culture for fungal elements are approved methods for confirming diagnosis.[36]

All six patients were in 45–-60 years age group as also reported by KR Kumar et al.[7] There were three males and three females. However, Singh AK et al.[1] and Nurettin Bayram et al.[8] reported post-COVID-19 mucormycosis predominantly among males.

All of them tested positive and received treatment under COVID-19 protocol. They developed mucormycosis 10–12 days after COVID-19, which agrees with Nurettin Bayram et al.[8] and Deepak Garg et al.[9]

Patients in this study received injectable steroids twice daily for minimum 1 week; then oral tapering steroids for another week for COVID-19 and subsequently developed mucormycosis as comparable to reports by Singh AK et al.,[1] Asri S et al.,[5] Bayram et al.,[8] Garg et al.,[9] Khatri et al.,[10] S Sharma et al.,[11] and Mainak Banerjee et al.[12] RECOVERY trial[13] observed injectable dexamethasone 6 mg once daily for 10 days as optimum dose for COVID-19. They had received humidified oxygen during COVID-19 treatment and developed cutaneous mucormycosis thereafter. La Fauci V et al.[14] reported reusable oxygen humidifiers play a role in transmission of nosocomial pathogens through aerosol. Asri S et al.[5] reported increase in mucormycosis infection following use of low-quality industrial-grade oxygen cylinders and tap water in humidifiers.

They had diabetes mellitus and uncontrolled sugar profile at admission and developed clinical manifestations of mucormycosis subsequently as with Singh et al.,[1] Bonifaz A,[4] Bayram et al.,[8] Garg et al.,[9] Akshay Khatri et al.,[10] S Sharma et al.,[11] and Mainak Banerjee et al.[12]

One had received both doses of covishield vaccine. Shah KM et al.[15] reported cutaneous mucormycosis at injection site following COVID-19 vaccination (Moderna).

Thus, factors related to post-COVID-19 cutaneous mucormycosis could be the same as post-COVID-19 mucormycosis; however, study on larger sample will help comment on the same.

Limitations

Detailed comment on post-COVID-19 cutaneous mucormycosis in this tertiary center is not possible as study includes only patients seen during first investigator's COVID-19 posting.

Conclusion

This study reports post-COVID-19 cutaneous mucormycosis during the second wave of COVID-19 from this tertiary center. Preexisting diabetes mellitus and uncontrolled sugar levels, excessive use of steroids, and use of humidified oxygen for COVID-19 are main factors in the development of rhino-orbital/rhino-cerebral mucormycosis and subsequently cutaneous mucormycosis.

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

There are no conflicts of interest.