key: cord-1047868-suy6rbyf
authors: Avatef Fazeli, Manouchehr; Rezaei, Leila; Javadirad, Etrat; Iranfar, Khosro; Khosravi, Abbas; Amini Saman, Javad; Poursabbagh, Pardis; Ghadami, Mohammad Rasoul; Parandin, Mohammad Mehdi; Dehghani, Amrollah; Ahmadi Jouybari, Touraj; Mahdavian, Behzad; Eivazi, Nastaran; rezaei, Sohbat; Rezaei, Alireza; Emami, Bashir; Haqgou, Mohadeseh; Bozorgomid, Arezoo; Sayad, Babak
title: Increased incidence of rhino‐orbital mucormycosis in an educational therapeutic hospital during the COVID‐19 pandemic in western Iran: An observational study
date: 2021-07-31
journal: Mycoses
DOI: 10.1111/myc.13351
sha: e9e2516f4c3b7f4c39beabc9e8f173c0004cb2e0
doc_id: 1047868
cord_uid: suy6rbyf

BACKGROUND: COVID‐19 patients, especially the patients requiring hospitalisation, have a high risk of several complications such as opportunistic bacterial and fungal infections. Mucormycosis is a rare and opportunistic fungal infection that mainly affects diabetic and immunocompromised patients. An increase has been observed in the number of rhino‐orbital mucormycosis in patients with COVID‐19 admitted to Imam Khomeini Hospital, Kermanshah, Iran, since October 2020. This is a report of the frequency, risk factors, clinical manifestations, treatment and prognosis of COVID‐19 associated with mucormycosis infection. METHODS: The medical records of COVID‐19 patients with rhino‐orbital mucormycosis who were diagnosed in an educational therapeutic hospital in Kermanshah, west of Iran were surveyed. Several parameters were analysed including demographic, clinical, therapeutic and laboratory characteristics. RESULTS: Twelve patients with COVID‐19–associated rhino‐orbital mucormycosis were identified from 12 October to 18 November 2020. All cases reported as proven mucormycosis had a history of hospitalisation due to COVID‐19. Comorbidities mainly included diabetes mellitus (83.33%) and hypertension (58.33%). Seventy‐five per cent of patients received corticosteroids for COVID‐ 19 treatment. The sites of involvement were rhino‐sino‐orbital (83%) and rhino‐sino (17%). Amphotericin B/liposomal amphotericin B alone or in combination with surgical debridement or orbital exenteration was used as the first‐line therapy. The overall mortality rate was 66.7% (8/12). CONCLUSIONS: We found a high incidence of mucormycosis among COVID‐19 patients. Diabetes mellitus and corticosteroid use were the dominant predisposing factor of mucormycosis. Mucormycosis is a life‐threatening and opportunistic infection; therefore, physicians should know the signs and symptoms of the disease so that a timely diagnosis and therapy can be performed.

A novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, also called COVID- 19) Available guidelines for prevention and control of COVID-19 mainly focus on the prevention and management of disease spread, and little attention is paid to bacterial and fungal infections.

Mucormycosis is a rare but serious infection caused by fungi in the order Mucorales, particularly Rhizopus and Mucor species while another includes Apophysomyces, Rhizomucor, Cunninghamella, Lichtheimia, Cokeromyces and Saksenaea. 5 They release their spores and are easily aerosolised and dispersed in the environment. The predisposing factors for developing mucormycosis include uncontrolled diabetes mellitus, haematologic malignancies, immunosuppression, solid organ and bone marrow transplantation, long-term treatment with corticosteroids, and extensive burns or major trauma. 6 Due to its high mortality and morbidity, early diagnosis and treatment are crucial. 7 However, mucormycosis is rare, even among individuals with the highest risk. Recently, a few studies from different countries have reported COVID-19-associated mucormycosis infection. 8, 9 Since the diagnosis of the first COVID-19 case in Iran on 10

March 2020, the number of confirmed cases has increased to 1.7 million and 61,300 patients have died (as of 15 March 2021) . Iran has experienced one of the worst COVID-19 outbreaks in the world, and the emergence of COVID-19 may be one of the biggest challenges of the century for the society and healthcare system and social in Iran.

Despite promising preventive measures, the third wave of infection occurred in early September 2020 in Iran, which subsided down after four difficult months in the late 2020. During the third wave of the disease, an increase was observed in rhino-orbital mucormycosis cases in Imam Khomeini Hospital, Kermanshah, Iran. This is a report of the frequency and predisposing factors, clinical manifestations, treatment and prognosis of rhino-orbital mucormycosis in COVID-19 patients. 

During the study period, rhino-orbital mucormycosis was clinically diagnosed in 14 patients, of whom two were excluded from the study due to their critical condition that made it impossible to

No financial support was provided relevant to this article. therefore, physicians should know the signs and symptoms of the disease so that a timely diagnosis and therapy can be performed.

co-infection, COVID-19, Iran, mucormycosis, SARS-CoV-2 perform an imaging or a tissue biopsy for histopathological confirmation of mucormycosis. The patients presented with following signs and symptoms: headache, facial cellulitis, maxillary sinusitis, rhinorrhea, periorbital and retro-orbital pain, proptosis, restriction of eye movements, loss of vision, etc ( Table 1 . The mean age of the patients with COVID-19-associated rhino-orbital mucormycosis was 62.08 ± 11.75 years (median age: 60, IQR: 12, range: 46-87), and the majority of the patients were female (58.33%). The most common underlying condition was diabetes (83.33%) followed by hypertension (58.33%), ischaemic heart disease (33.33%) and chronic kidney disease (16.66%).

Our four patients developed acute-onset diabetes during SARS-CoV-2 infection. The sites of involvement were rhino-sino-orbital (83%) and rhino-sino (17%). All cases reported as proven mucormycosis had a history of hospitalisation due to COVID-19. Seventy-five per cent of patients received corticosteroids for COVID-19 treatment (detailed information on COVID-19 care was not available for 

Although the prevalence of bacterial or fungal co-infections in The patients in the present study were slightly older (mean age ± SD: 62.08 ± 11.75 years) compared to COVID-19 patients with mucormycosis in a systematic review of the literature. 9 The mean age 61.6 years, 51.7 years and 45 years reported in different studies. [12] [13] [14] Our findings are not surprising since older individuals are more susceptible to SARS-CoV-2 and have a higher risk of hospitalisation. 15 The majority of the cases in this study were female, which was consistent with a study by Dolatabadi et al 16 In this study, the sites of involvement were rhino-sino-orbital (83%) and rhino-sino (17%). A literature review of COVID-19associated mucormycosis found that rhino-orbito-cerebral mucormycosis was the most common presentation. 11 The involvement of sinuses seems to be mainly documented in diabetic patients. 30 Although we found an increase in LDH level (6 out of 12 cases), we think it is a non-specific finding in COVID-19 patients with rhinoorbital mucormycosis. We know that the increase in LDH indicates damage to a number of different tissues; therefore, it can be considered as the effect of the inflammatory response on tissue damage associated with mucormycosis . 32 Serum LDH also has been identified as a potential biomarker for the activity and severity of This study had several limitations including lack of culture for mucor due to insufficient laboratory biosafety conditions and the potential risk SARS-CoV-2 spread and a short follow-up period. In addition, some patients were referred to our hospital for diagnosing the cause of the disease and detailed information on COVID-19 care was not available.

We found a high incidence of mucormycosis among COVID-19 patients in our province. We also hypothesise that the actual number of the cases of COVID-19-associated mucormycosis is higher than the published cases and this disease may be underestimated due to the difficulties in diagnosis and non-specific symptoms as two of the 

Investigation (equal)

Resources (equal)

Supervision (equal)

Validation (equal)

Leila Rezaeia: Conceptualization (equal); Data curation (equal)

Investigation (equal)

Resources (equal)

Supervision (equal)

Validation (equal)

Visualization (equal)

Mohamadmehdi Parandin: Data curation (equal)

Amrollah Dehghani: Data curation (equal)

Pardis Poursabbagh: Data curation (equal)

Mohammad Rasool Ghadami: Data curation (equal)

Behzad Mahdavian: Data curation (equal)

Nastaran Eivazi: Data curation (equal)

Sohbat Rezaei: Data curation (equal)

Alireza Rezaei: Data curation (equal)

Arezoo Bozorgomid: Data curation (equal)

Writingoriginal draft (equal)

Babak Sayad: Investigation (equal)

Supervision (equal)

Writing-review & editing (equal)

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How to cite this article

Increased incidence of rhino-orbital mucormycosis in an educational therapeutic hospital during the COVID-19 pandemic in western Iran: An observational study

AB, AK, PP and R. G. contributed to acquisition of data, draft the article and agree to be accountable for all aspects of the work related to its accuracy or integrity. MAF, L. R., E. J., K. I., MMP, AD, JAS, TAJ, BM, NE, SR, MH, BS and B. E. contributed to acquisition of clinical data, agreed to be accountable for all aspects of the work related to its accuracy or integrity and reviewed the manuscript critically for important intellectual content. AB, BS, MAF and L. R. contributed to analysis and interpretation of data and agreed to be accountable for all aspects of the work related to its accuracy or integrity. MAF, L.R and B. S. made substantial contributions to conception and design of the study, given final approval of the version to be published and agreed to be accountable for all aspects of the work related to its accuracy or integrity.

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