COVID-19-associated rhino-mucormycosis and pulmonary aspergillosis infection

Jitender Singh; Tarika Sharma

doi:10.4103/jssrp.jssrp_6_22

CASE REPORT

Year : 2022 | Volume : 3 | Issue : 3 | Page : 63-66

COVID-19-associated rhino-mucormycosis and pulmonary aspergillosis infection

Jitender Singh¹, Tarika Sharma²
¹ Department of Interventional Radiology, Shanti Mukand Hospital, New Delhi, India
² Department of College of Nursing, ILBS, New Delhi, India

Date of Submission	22-Apr-2022
Date of Decision	27-May-2022
Date of Acceptance	29-May-2022
Date of Web Publication	19-Dec-2022

Correspondence Address:
Jitender Singh
Department of Interventional Radiology, Shanti Mukand Hospital, New Delhi
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jssrp.jssrp_6_22

Abstract

In the current pandemic, the incidence of fungal infections-associated COVID-19 is surging. Diabetes mellitus, overzealous steroid, and antibiotic use for COVID-19 management may cause or exacerbate the fungal disease. In paranasal sinus (PNS), ethmoids followed by the maxillary sinus are commonly involved with the risk of intra-orbital or/and intracranial involvement is quite common. In lungs, COVID-19 infection has higher mortality rate, if there is an associated fungal infection. Aspergillus fumigates is the most common fungus that cause lung infection and present as discrete lesion different from COVID-19 manifestation. Two cases of COVID-associated fungal infections, i.e., rhino-mucormycosis and pulmonary aspergillosis are described here. In the first case, computed tomography (CT) of PNS was done for the complaints of mild right-sided facial swelling and mild restriction of the eye globe on day 27 of illness. CT showed hyperdense content involving the right-sided nasal sinus with the remodeling of bones with erosion and thinning of the inferior and medial orbital wall with the extension of soft tissue into the extraorbital space. The patient was treated with Amphotericin B and posaconazole oral suspension as the first-line antifungal monotherapy. In the second case, on complaints of cough with expectoration on the 20^th day of illness, X-ray chest and CT chest were done which confirmed a thick-walled cavity in the right lung and other post COVID features. The tracheal aspirate culture was suggestive of Aspergillus fumigatus and Aspergillus antigen galactomannan was found positive in the fluid. The patient was treated for the same with antifungal therapy. Hence it is important to pay attention to the high probability of fungal infections in COVID-19 patients. The association of coronavirus with mucormycosis of the PNSs and aspergillosis of the lung must be given outmost consideration. Noncontrast CT of the PNSs is usually the first investigation of choice for PNS involvement, and CT chest help in the diagnosis of pulmonary fungal infection. Uncontrolled diabetes and use of steroids are two of the main factors for aggravating factors. Both early surgical intervention and anti-fungal treatment should be sought for the management.

Keywords: COVID-19-associated mucormycosis, COVID-19-associated pulmonary aspergillosis, COVID-19, fungal infections

How to cite this article:
Singh J, Sharma T. COVID-19-associated rhino-mucormycosis and pulmonary aspergillosis infection. J Surg Spec Rural Pract 2022;3:63-6

How to cite this URL:
Singh J, Sharma T. COVID-19-associated rhino-mucormycosis and pulmonary aspergillosis infection. J Surg Spec Rural Pract [serial online] 2022 [cited 2023 Feb 2];3:63-6. Available from: http://www.jssrp.org/text.asp?2022/3/3/63/364431

Background

In the current pandemic, the incidence of fungal infections-associated COVID-19 are surging. Diabetes mellitus (DM), overzealous steroid, and antibiotic use for COVID-19 management may cause or exacerbate fungal disease. In paranasal sinus (PNS), ethmoids followed by the maxillary sinus are commonly involved with the risk of intra-orbital or/and intracranial involvement is quite common. In lungs, COVID-19 infection has higher mortality rate, if there is an associated fungal infection. The detection of fungal characteristics on high-resolution computed tomography (CT) thorax is a useful tool in the current pandemic as COVID-19 may lead to an increased incidence of superimposed fungal infection. Several reports related to rhino-nasal-sinus mucormycosis and pulmonary aspergillosis (PA) in COVID patients have been published in recent times; however, most of them are not proven. As the evidence for fungal diseases in covid-19 remains less explored we intend to cover the imaging and clinical spectrum of fungal diseases in covid patients.

Case Report

Case presentation 1: COVID-associated rhino- mucormycosis

A 60-year-old male with DM and hypertension presented with fever, sore throat, dry cough, and progressive breathlessness of 2 days duration. He was on irregular treatment for DM for the last 15 years. On admission, the respiratory rate was 29 breaths/min, blood pressure was 130/80 mmHg with a heart rate of 100 beats/min. The oxygen saturation improved to 96% with a venturi mask from initial 85% (on room air). CT chest was done the next day which showed features of COVID-19 pneumonitis with a score of 18/25 (severe disease) [Figure 1]. A nasopharyngeal swab was positive for the coronavirus. The glycated hemoglobin at admission was 6.5%. Intravenous dexamethasone and remdesivir along with supportive care, including oxygen supplementation and thromboprophylaxis were started for the patient. Random blood glucose at admission was 160 mg/dL which increased to a maximum of 320 mg/dL during dexamethasone therapy. After 20 days of therapy, he had clinical-radiological improvement. CT of PNS was done as the patient was complaining of mild right-sided facial swelling and mild restriction of the eye globe on day 27 of illness. CT showed hyperdense content involving the right-sided nasal sinus with the remodeling of bones with erosion and thinning of the inferior and medial orbital wall with the extension of soft tissue into the extraorbital space [Figure 2]. Next day biopsy was done by ear, nose, and throat (ENT) specialist which suggested fungal etiology on analysis and on culture Rhizopus microspores were observed. The patient was treated for the same with Amphotericin B (intravenous) and posaconazole (oral suspension) as the first-line antifungal monotherapy (as per the opinion of surgeon). After 1-month follow-up, the patient showed drastic improvement in the symptoms and the clinical examination by ENT specialist showed near complete response.

Figure 1: (a and b) CT chest axial and coronal section shows multiple patchy areas of ground-glass opacities with associated interstitial septal thickening, crazy paving pattern, patchy consolidation and fibrotic opacities in both the lungs (arrow and open arrow). CT: Computed tomography

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Figure 2: (a) CT PNS axial section shows hyperdense content in the ethmoid air cells (arrowhead). (b) CT PNS coronal section shows hyperdense content in the right maxillary sinus (arrowhead). (c) CT PNS sagittal section shows hyperdense content in maxillary sinus with erosion of inferior orbital wall and soft tissue in extraconal space (arrow). (d) Axial section bone window shows bony remodeling of the sinus bony wall with erosion and thinning (arrow). CT: Computed tomography, PNS: Paranasal sinus

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Cass presentation 2: COVID-19-associated pulmonary aspergillosis

A 45-year-old female with long-standing DM (on oral hypoglycemics) was presented with fever and progressive breathlessness of 5 days duration. On admission, her vitals were as following: respiratory rate − 26 breaths/min, blood pressure − 140/80 mmHg, heart rate − 96 beats/min, and oxygen saturation 87% (on room air). X-ray chest at the time of admission showed bilateral diffuse interstitial opacities [Figure 3]a. CT chest was done the next day which showed features of COVID-19 pneumonitis with a score of 17/25 (severe disease) [Figure 3]b and [Figure 3]c. Reverse transcription polymerase chain reaction was found to be positive for SARS-CoV-2. Glycated hemoglobin at admission was found to be 7% for the patient. She was put on intravenous dexamethasone and other supportive care, including oxygen supplementation and thromboprophylaxis. Her random blood plasma glucose was 140 mg/dL at admission and increased to a maximum of 350 mg/dL during dexamethasone therapy. Twenty days later, the patient complained of cough with expectoration. X-ray chest [Figure 4]a and CT chest confirmed a thick-walled cavity in the right lung [Figure 4] and other post COVID features. The tracheal aspirate culture was suggestive of Aspergillus fumigatus and Aspergillus antigen galactomannan was found positive in fluid. The patient was treated for the same with Voriconazole and liposomal amphotericin B antifungal therapy. Follow up of the patient was done based on clinical symptomology and routine investigation, followed which patient showed complete resolution of symptoms after 1 month of treatment.

Figure 3: (a) X-ray chest frontal view shows inhomogeneous opacities in bilateral lung fields (arrow). (b and c) CT chest axial and coronal section shows multiple patchy areas of ground-glass opacities with associated interstitial septal thickening, crazy paving pattern, patchy consolidation and fibrotic opacities seen in both the lungs (arrows). CT: Computed tomography

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Figure 4: (a) X-ray chest frontal view shows inhomogeneous opacities in bilateral lung fields. A cavitatory lesion is seen in right mid zone (arrow). (b and c) CT chest axial and coronal section shows multiple patchy areas of ground-glass opacities with associated interstitial septal thickening, crazy paving pattern, patchy consolidation and fibrotic opacities seen in bilateral lungs. There is an evidence of one cavity measuring 4.7 cm × 3 cm with few hypoattenuating contents in right upper lobe region not seen in previous scan (arrow). CT: Computed tomography

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Discussion

Fungal infections are rare and carry a high mortality rate, further challenge is to identify through radiologic imaging. There are various types of fungal infections documented; however, common fungus causing infection in COVID-19 patients include aspergillosis, candidiasis, mucormycosis, or cryptococcosis. The infections such as mucormycosis and aspergillosis are age old; however, number of these have been drastically increased during the COVID-19 peak. Incidence of invasive fungal infections among COVID patients is found to be 26.7%.^[1] Impaired immune functioning is considered as the main cause of rise in these cases. Novel SARS-CoV-2 infection is associated with impaired functioning of both cellular and humoral immunity which triggers higher risk of fungal infections. Other risk factor for fungal infections include metabolic syndrome like diabetes, tumors, immunosuppressant intake, long term cancer chemotherapy or/and radiotherapy.^[2] Coronavirus disease is associated to significant and sustained lymphopenia compromising the immune system^[3] Neutropenic patients and elevated serum iron levels are also at increased risk of developing fungal infections.^[4]

The mucor species Rhizopus, absidia, and Cunninghamella are main causative agent for Mucormycosis in human which infects the sinuses, brain, or lungs. Major pathogenesis in fungal infection involves thrombosis and tissue necrosis.^[5] Aspergilloma is most common imaging feature and associated with thickened cavity wall in patients with PA. Presence of focal bony erosions and extrasinus spread on CT PNS are strongly suggestive of the fungal etiology in presumed clinical conditions.^[6]

Aspergillus and mucormycosis have low virulence and are unable to cause pulmonary infection in patients with normal immunity. Altered immunity (both hypersensitivity or immunocompromise state) in COVID-19 patients predisposes them to fungus related lung diseases. First association between viral pneumonia and invasive pulmonary aspergillosis (IPA) was reported in 1950 which was further described in 2009–2011 during the H1N1 influenza seasons.^[7],[8] COVID-19 increases the risk of developing an IPA from 8% to 34% and COVID associated pulmonary aspergillosis (CAPA) is associated with a mortality rate of 36%.^[9] New consensus criteria for CAPA diagnosis in COVID-19 patients was published in late 2020.^[10]

There were few limitations in our study. We included only confirmed cases to reflect radiological manifestation of fungal infection of different organs and it may not reflect the entire spectrum, second, we did not evaluate serial CT findings of follow up cases.

Conclusions

It is important to pay attention to the high probability of fungal infections in COVID-19 patients. Noncontrast CT of the PNSs is usually the first investigation of choice for PNS involvement, and CT chest help in the diagnosis of pulmonary fungal infection. Uncontrolled diabetes and use of steroids are two of the main aggravating factors. A standardized screening, diagnostic and treatment approach should be outlined for the early management of such cases.

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.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	White PL, Dhillon R, Cordey A, Hughes H, Faggian F, Soni S, et al. A national strategy to diagnose COVID-19 associated invasive fungal disease in the ICU. Clin Infect Dis 2021;73:e1634-44.
2.	Chennamchetty VK, Rao MV, Verma MK. An enigma of lower airway mucormycosis infection – Case report. Indian J Clin Pract 2020;31:64-6.
3.	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.
4.	Guarner J, Brandt ME. Histopathologic diagnosis of fungal infections in the 21^st century. Clin Microbiol Rev 2011;24:247-80.
5.	Spellberg B, Edwards J Jr., Ibrahim A. Novel perspectives on mucormycosis: Pathophysiology, presentation, and management. Clin Microbiol Rev 2005;18:556-69.
6.	González Ballester D, González-García R, Moreno García C, Ruiz-Laza L, Monje Gil F. Mucormycosis of the head and neck: Report of five cases with different presentations. J Craniomaxillofac Surg 2012;40:584-91.
7.	Abbott JD, Fernando HV, Gurling K, Meade BW. Pulmonary aspergillosis following post-influenzal bronchopneumonia treated with antibiotics. Br Med J 1952;1:523-5.
8.	Wauters J, Baar I, Meersseman P, Meersseman W, Dams K, De Paep R, et al. Invasive pulmonary aspergillosis is a frequent complication of critically ill H1N1 patients: A retrospective study. Intensive Care Med 2012;38:1761-8.
9.	Bartoletti M, Pascale R, Cricca M, Rinaldi M, Maccaro A, Bussini L, et al. Epidemiology of invasive pulmonary aspergillosis among COVID-19 intubated patients: A prospective study. Clin Infect Dis 2021;73:e3606-14.
10.	Koehler P, Bassetti M, Chakrabarti A, Chen SC, Colombo AL, Hoenigl M, et al. Defining and managing COVID-19-associated pulmonary aspergillosis: The 2020 ECMM/ISHAM consensus criteria for research and clinical guidance. Lancet Infect Dis 2021;21:e149-62.