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. 2021 Sep;64(9):1028-1037.
doi: 10.1111/myc.13335. Epub 2021 Jul 26.

ECMM/ISHAM recommendations for clinical management of COVID-19 associated mucormycosis in low- and middle-income countries

Shivaprakash M Rudramurthy  1 , Martin Hoenigl  2   3 , Jacques F Meis  4 , Oliver A Cornely  5   6   7 , Valliappan Muthu  8 , Jean Pierre Gangneux  9 , John Perfect  10 , Arunaloke Chakrabarti  1 ; ECMM and ISHAM
Affiliations

ECMM/ISHAM recommendations for clinical management of COVID-19 associated mucormycosis in low- and middle-income countries

Shivaprakash M Rudramurthy et al. Mycoses. 2021 Sep.

Abstract

Reports are increasing on the emergence of COVID-19-associated mucormycosis (CAM) globally, driven particularly by low- and middle-income countries. The recent unprecedented surge of CAM in India has drawn worldwide attention. More than 28,252 mucormycosis cases are counted and India is the first country where mucormycosis has been declared a notifiable disease. However, misconception of management, diagnosing and treating this infection continue to occur. Thus, European Confederation of Medical Mycology (ECMM) and the International Society for Human and Animal Mycology (ISHAM) felt the need to address clinical management of CAM in low- and middle-income countries. This article provides a comprehensive document to help clinicians in managing this infection. Uncontrolled diabetes mellitus and inappropriate (high dose or not indicated) corticosteroid use are the major predisposing factors for this surge. High counts of Mucorales spores in both the indoor and outdoor environments, and the immunosuppressive impact of COVID-19 patients as well as immunotherapy are possible additional factors. Furthermore, a hyperglycaemic state leads to an increased expression of glucose regulated protein (GRP- 78) in endothelial cells that may help the entry of Mucorales into tissues. Rhino-orbital mucormycosis is the most common presentation followed by pulmonary mucormycosis. Recommendations are focused on the early suspicion of the disease and confirmation of diagnosis. Regarding management, glycaemic control, elimination of corticosteroid therapy, extensive surgical debridement and antifungal therapy are the standards for proper care. Due to limited availability of amphotericin B formulations during the present epidemic, alternative antifungal therapies are also discussed.

Keywords: Mucorales; COVID-19; SARS-CoV-2; corticosteroids; diabetes; infection; mucormycosis.

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Conflict of interest statement

MH received research funding from Pfizer, Astellas, Gilead, Scynexis, MSD and NIH. OAC reports grants and personal fees from Actelion, Amplyx, Astellas, Basilea, Cidara, Da Volterra, F2G, Gilead, MedPace, Merck/MSD, Pfizer, Scynexis; grants from DFG (German Research Foundation), German Federal Ministry of Research and Education, Immunic, Janssen, Medicines Company, Melinta Therapeutics; personal fees from Allecra Therapeutics, Al‐Jazeera Pharmaceuticals, Biocon, Biosys, CoRe Consulting, Entasis, Grupo Biotoscana, IQVIA, Matinas, Menarini, Molecular Partners, MSG‐ERC, Mylan, Nabriva, Noxxon, Octapharma, Paratek, PSI, Roche Diagnostics, Seres, Shionogi; others from Wiley (Blackwell); outside the submitted work. JPG received research fundings from Gilead and Pfizer. Other authors expressed no conflict of interest in preparation of the manuscript.

Figures

FIGURE 1
FIGURE 1
Schematic representation of pathogenesis of COVID‐19–associated mucormycosis. This illustration was prepared using BioRender software
FIGURE 2
FIGURE 2
Left facial and orbital swelling with chemosis in a case of rhino‐orbital mucormycosis (A), and a large necrotic ulcer on the left half of palate in a patient with left maxillary mucormycosis (B). Coronal view of magnetic resonance imaging of paranasal sinuses showing bilateral maxillary and ethmoidal sinusitis (C), more involvement on right side, contrast study showed post‐contrast enhancement (D)
FIGURE 3
FIGURE 3
Computed Tomography (CT) thorax with CT pulmonary angiography showing reverse halo in left upper lobe (A), CT pulmonary angiography showed vessel occlusion sign (B & C)
FIGURE 4
FIGURE 4
Broad aseptate hyphae on potassium hydroxide wet mount (A), classical cottony appearance of Rhizopus arrhizus colony (B) Microscopic picture of Rhizopus arrhizus (C)
FIGURE 5
FIGURE 5
Treatment algorithm for CAM prepared by the Fungal Infections Study Forum (modified) [CVC, central venous catheter; PICC, peripherally inserted central catheter; TDM, therapeutic drug monitoring]
FIGURE 6
FIGURE 6
Figure depicting prevention and misconception regarding COVID‐19–associated mucormycosis
See this image and copyright information in PMC

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