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The Emergence of COVID-19 Associated Mucormycosis: Analysis of Cases From 18 Countries

33 Pages Posted: 12 May 2021

See all articles by Martin Hoenigl

Martin Hoenigl

Medical University of Graz - Department of Infectious Diseases; University of California, San Diego (UCSD) - Division of Infectious Diseases and Global Public Health

Danila Seidel

University of Cologne - Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases (CECAD)

Agostinho Carvalho

University of Minho - Life and Health Sciences Research Institute (ICVS)

Shivaprakash M. Rudramurthy

Sanjay Gandhi Postgraduate Institute of Medical Sciences

Amir Arastehfar

Hackensack Meridian Health - Center for Discovery and Innovation

Jean Pierre Gangneux

University of Rennes 1 - CHU de Rennes

Nosheen Nasir

Aga Khan University

Alexandro Bonifaz

General Hospital of Mexico "Dr. Eduardo Liceaga" - Dermatology Service

Javier Araiza

General Hospital of Mexico "Dr. Eduardo Liceaga" - Dermatology Service

Nikolai Klimko

North-Western State Medical University - Department of Clinical Mycology, Allergy and Immunology

Alexandra Serris

Universite Paris Descartes - Department of Infectious Diseases

Katrien Lagrou

KU Leuven - Department of Microbiology & Immunology

Jacques F. Meis

Canisius-Wilhelmina Ziekenhuis

Oliver A. Cornely

University of Cologne - Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD)

John R. Perfect

Duke University - Medical Center

P. Lewis White

Cardiff and Vale University Health Board - Public Health Wales Microbiology Cardiff

Arunaloke Chakrabarti

Post Graduate Institute of Medical Education & Research (PGIMER) - Department of Microbiology

ECMM and ISHAM Collaborators Group

Independent

More...

Abstract

Coronavirus disease 2019 (COVID-19)–associated mucormycosis (CAM) has recently been increasingly reported, particularly among patients with uncontrolled diabetes. Patients with diabetes and hyperglycemia often display an inflammatory state that may be potentiated by the activation of antiviral immunity to SARS-CoV-2, and thus may favor secondary infections. We analyze 80 published and unpublished cases of CAM, with a predominance (42/80) of cases from India. Uncontrolled diabetes mellitus as well as systemic corticosteroid treatment represented major comorbid predisposing factors and rhino-orbital cerebral mucormycosis was the most frequent presentation of disease. Mortality was high at 49%, driven particularly by those with pulmonary or disseminated mucormycosis and those with cerebral involvement. Furthermore, a significant proportion of surviving patients suffered life-changing morbidities (loss of vision in 46% of survivors). Our review indicates that CAM may be a relevant complication of severe COVID-19, particularly in those with uncontrolled diabetes.

Funding: Martin Hoenigl received funding from Astellas for two investigator initiated studies (ISR005824 and ISR005838), and was supported by the National Institutes of Health, Grant UL1TR001442. Agostinho Carvalho was supported by the Fundação para a Ciência e a Tecnologia (FCT) (UIDB/50026/2020 and UIDP/50026/2020), the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) (NORTE-01-0145-FEDER-000039), the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 847507, and the “la Caixa” Foundation (ID 100010434) and FCT under the agreement LCF/PR/HR17/52190003.

Declaration of Interest: MH received research funding from Gilead, Pfizer, Astellas, Scynexis and NIH. JPG received speaker and expert advice fees from Pfizer and Gilead. NK has received research grants or honoraria as a speaker or advisor from Astellas, Gilead, MSD, and Pfizer, outside the submitted work. KL received consultancy fees from SMB Laboratoires Brussels, MSD and Gilead, travel support from Pfizer, speaker fees from FUJIFILM WAKO, Pfizer and Gilead, a service fee from Thermo fisher Scientific. OAC is supported by the German Federal Ministry of Research and Education, is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy – CECAD, EXC 2030 – 390661388 and has received research grants from, is an advisor to, or received lecture honoraria from Actelion, Allecra Therapeutics, Al-Jazeera Pharmaceuticals, Amplyx, Astellas, Basilea, Biosys, Cidara, Da Volterra, Entasis, F2G, Gilead, Grupo Biotoscana, Immunic, IQVIA, Janssen, Matinas, Medicines Company, MedPace, Melinta Therapeutics, Menarini, Merck/MSD, Mylan, Nabriva, Noxxon, Octapharma, Paratek, Pfizer, PSI, Roche Diagnostics, Scynexis, and Shionogi. PLW performed diagnostic evaluations and received meeting sponsorship from Bruker, Dynamiker, and Launch Diagnostics; Speakers fees, expert advice fees and meeting sponsorship from Gilead; and speaker and expert advice fees 489 from F2G and speaker fees MSD and Pfizer. Is a founding member of the European Aspergillus PCR Initiative. ACh received funding support from educational grant of Pfizer, MSD Pharmaceutical Ltd, and Gilead. All other authors no conflicts.

Ethical Approval: MISSING

Keywords: COVID-19, fungal, mould, Mucorales, diabetes, corticosteroids, infection, SARS-CoV2

Suggested Citation

Hoenigl, Martin and Seidel, Danila and Carvalho, Agostinho and Rudramurthy, Shivaprakash M. and Arastehfar, Amir and Gangneux, Jean Pierre and Nasir, Nosheen and Bonifaz, Alexandro and Araiza, Javier and Klimko, Nikolai and Serris, Alexandra and Lagrou, Katrien and Meis, Jacques F. and Cornely, Oliver A. and Perfect, John R. and White, P. Lewis and Chakrabarti, Arunaloke and Group, ECMM and ISHAM Collaborators, The Emergence of COVID-19 Associated Mucormycosis: Analysis of Cases From 18 Countries (May 12, 2021). Available at SSRN: https://ssrn.com/abstract=3844587 or http://dx.doi.org/10.2139/ssrn.3844587

Martin Hoenigl (Contact Author)

Medical University of Graz - Department of Infectious Diseases ( email )

Graz
Austria

University of California, San Diego (UCSD) - Division of Infectious Diseases and Global Public Health ( email )

9500 Gilman Drive
Mail Code 0502
La Jolla, CA 92093-0112
United States

Danila Seidel

University of Cologne - Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases (CECAD)

Albertus-Magnus-Platz
Cologne, 50923
Germany

Agostinho Carvalho

University of Minho - Life and Health Sciences Research Institute (ICVS)

Campus de Gualtar
Braga
Portugal

Shivaprakash M. Rudramurthy

Sanjay Gandhi Postgraduate Institute of Medical Sciences

India

Amir Arastehfar

Hackensack Meridian Health - Center for Discovery and Innovation

Nutley
United States

Jean Pierre Gangneux

University of Rennes 1 - CHU de Rennes ( email )

Service de Parasitologie-Mycologie
Rennes
France

Nosheen Nasir

Aga Khan University

Stadium Road, P.O. Box 3500
Karachi, 74800
Pakistan

Alexandro Bonifaz

General Hospital of Mexico "Dr. Eduardo Liceaga" - Dermatology Service

Mexico

Javier Araiza

General Hospital of Mexico "Dr. Eduardo Liceaga" - Dermatology Service

Mexico

Nikolai Klimko

North-Western State Medical University - Department of Clinical Mycology, Allergy and Immunology

St. Petersburg
Russia

Alexandra Serris

Universite Paris Descartes - Department of Infectious Diseases

Paris
France

Katrien Lagrou

KU Leuven - Department of Microbiology & Immunology

Belgium

Jacques F. Meis

Canisius-Wilhelmina Ziekenhuis

Nijmegen
Netherlands

Oliver A. Cornely

University of Cologne - Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) ( email )

Albertus Magnus Platz
Cologne, GA NRW 50923
Germany

John R. Perfect

Duke University - Medical Center

100 Fuqua Drive
Durham, NC 27715
United States

P. Lewis White

Cardiff and Vale University Health Board - Public Health Wales Microbiology Cardiff

Cardiff
United Kingdom

Arunaloke Chakrabarti

Post Graduate Institute of Medical Education & Research (PGIMER) - Department of Microbiology ( email )

Department of Community Medicine and Schoo
PGIMER, Sec. 12
Chandigarh, 160012
India

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