A review of COVID-19-associated mucormycosis in India

Authors

  • Sumanth Khadke Department of Post Graduate Medical Education, Harvard Medical School, Boston, MA, USA http://orcid.org/0000-0002-7262-6905
  • Vidhatri Khadke Rutgers School of Public Health, Rutgers University, Piscataway, New Jersey, USA
  • Shubham Tomar Department of Post Graduate Medical Education, Harvard Medical School, Boston, MA, USA ICMR-NIRTH, Jabalpur, Madhya Pradesh ICMR-NIRT, Chennai, Tamil Nadu, India
  • Purvi K. Khanuja University of North Carolina, Chapel Hill, North Carolina, USA
  • Surya Suresh Thanjavur Medical College, Thanjavur, Tamil Nadu, India
  • Muhammad R. Sohail Section of Infectious diseases, Department of Internal Medicine, Baylor College of Medicine, Texas, USA
  • Arjun Khanna Department of Pulmonary, Critical Care and Sleep Medicine, Yashoda Super Speciality Hospital, Kaushambi, Ghaziabad, Uttar Pradesh, India

DOI:

https://doi.org/10.18203/2394-6040.ijcmph20221255

Keywords:

COVID-19 associated mucormycosis, Rhinoorbital cerebral mucormycosis, Angioinvasive fungus, Pulmonary mucormycosis, Mucormycosis

Abstract

The resurgence of COVID-19 with the delta variant has accompanied a doubling in the prevalence of COVID-19-associated mucormycosis (CAM) in India. The prevalence grew to 80 times that of the global average. In this review, we describe the epidemiology, the clinical presentation, and treatment of CAM. We conducted a literature search on the PubMed, Google Scholar, Embase, and Harvard Library databases. The cytokine storm with high interleukin-6 (IL-6), hyperglycemia, ketoacidosis culminates into impaired endothelial and immune response, causing improved survival of the fungus. The most common presentation is rhinoorbital cerebral mucormycosis followed by pulmonary mucormycosis in patients with COVID-19. CAM patients have active or prior pulmonary tuberculosis, hyperglycemia, or a prolonged stay in the intensive care unit (ICU). A recent history of steroid medications and a high prevalence of tuberculosis (TB) may have contributed to an increased prevalence of CAM infections. Hypoxemic COVID-19 patients have a substantial improvement with steroid treatment but increases the risk of opportunistic infections. Although radiological signs have been described but the most common presentation is a subtle sign of eye, nasal, oral cavity, or pulmonary symptoms which requires high index of suspicion. Hence, one should not rely on radiological signs alone. Amphotericin B or isavuconazole along with surgical debridement is the treatment of choice for CAM. Early admission, diagnosis, and treatment lead to favorable outcomes.

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References

Jose A, Singh S, Roychoudhury A, Kholakiya Y, Arya S, Roychoudhury S. Current Understanding in the Pathophysiology of SARS-CoV-2-Associated Rhino-Orbito-Cerebral Mucormycosis: A Comprehensive Review. J Maxillofac Oral Surg. 2021;20(3):373-80.

World Health Organization. Mucormycosis Key Facts. 2021. Available at: https://www.who.int/india/ emergencies/coronavirus-disease-(covid-19)/mucor mycosis. Accessed on 24 October 2021.

Rudramurthy SM, Hoenigl M, Meis JF, Cornely OA, Muthu V, Gangneux JP, et al. ECMM and ISHAM. ECMM/ISHAM recommendations for clinical management of COVID-19 associated mucormycosis in low- and middle-income countries. Mycoses. 2021;64(9):1028-37.

Governmentstats.com. Mucormycosis (Black Fungus). 2021. Available at: https://governmentstats. com/mucormycosis/index.html. Accessed on 25 October 2021.

Rocha ICN, Hasan MM, Goyal S, Patel T, Jain S, Ghosh A, et al. COVID-19 and mucormycosis syndemic: double health threat to a collapsing healthcare system in India. Trop Med Int Health. 2021;26(9):1016-8.

John TM, Jacob CN, Kontoyiannis DP. When Uncontrolled Diabetes Mellitus and Severe COVID-19 Converge: The Perfect Storm for Mucormycosis. J Fungi (Basel). 2021;7(4):298.

Sen M, Honavar SG, Bansal R, Sengupta S, Rao R, Kim U, et al. Epidemiology, clinical profile, management, and outcome of COVID-19-associated rhino-orbital-cerebral mucormycosis in 2826 patients in India - Collaborative OPAI-IJO Study on Mucormycosis in COVID-19 (COSMIC), Report 1. Indian J Ophthalmol. 2021;69(7):1670-92.

Press Information Bureau- Government of India. Stay Safe from Mucormycosis - a Fungal Complication being Detected in COVID-19 Patients Control Diabetes, Use Steroids Judiciously, Keep Good Hygiene, Don’t Self-Medicate. 2021. Available at: https://pib.gov.in/PressReleseDetailm.aspx?PRID=1718501. Accessed on 24 October 2021.

Lamaris GA, Ben-Ami R, Lewis RE, Chamilos G, Samonis G, Kontoyiannis DP. Increased virulence of Zygomycetes organisms following exposure to voriconazole: a study involving fly and murine models of zygomycosis. J Infect Dis. 2009;199(9):1399-406.

Steinbrink JM, Miceli MH. Mucormycosis. Infect Dis Clin North Am. 2021;35(2):435-52.

Cuschieri S, Grech S. COVID-19 and diabetes: The why, the what and the how. J Diabetes Complications. 2020;34(9):107637.

Wu L, Girgis CM, Cheung NW. COVID-19 and diabetes: Insulin requirements parallel illness severity in critically unwell patients. Clin Endocrinol (Oxf). 2020;93(4):390-3.

Gianchandani R, Esfandiari NH, Ang L, Iyengar J, Knotts S, Choksi P, et al. Managing Hyperglycemia in the COVID-19 Inflammatory Storm. Diabetes. 2020;69(10):2048-53.

Yang JK, Lin SS, Ji XJ, Guo LM. Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes. Acta Diabetol. 2010;47(3):193-9.

Hood MI, Skaar EP. Nutritional immunity: transition metals at the pathogen-host interface. Nat Rev Microbiol. 2012;10(8):525-37.

Stanford FA, Matthies N, Cseresnyés Z, Figge MT, Hassan MIA, Voigt K. Expression Patterns in Reductive Iron Assimilation and Functional Consequences during Phagocytosis of Lichtheimia corymbifera, an Emerging Cause of Mucormycosis. J Fungi (Basel). 2021;7(4):272.

Fu Y, Lee H, Collins M, Tsai HF, Spellberg B, Edwards JE, et al. Cloning and functional characterization of the Rhizopus oryzae high affinity iron permease (rFTR1) gene. FEMS Microbiol Lett. 2004;235(1):169-76.

Liu M, Lin L, Gebremariam T, Luo G, Skory CD, French SW, et al. Fob1 and Fob2 Proteins Are Virulence Determinants of Rhizopus oryzae via Facilitating Iron Uptake from Ferrioxamine. PLoS Pathog. 2015;11(5):e1004842.

Ibrahim AS, Spellberg B, Edwards J. Iron acquisition: a novel perspective on mucormycosis pathogenesis and treatment. Curr Opin Infect Dis. 2008;21(6):620-5.

Artis WM, Fountain JA, Delcher HK, Jones HE. A mechanism of susceptibility to mucormycosis in diabetic ketoacidosis: transferrin and iron availability. Diabetes. 1982;31(12):1109-14.

Ribes JA, Vanover-Sams CL, Baker DJ. Zygomycetes in human disease. Clin Microbiol Rev. 2000;13(2):236-301.

Binder U, Maurer E, Lass-Flörl C. Mucormycosis--from the pathogens to the disease. Clin Microbiol Infect. 2014;20:60-6.

Khadke S, Ahmed N, Ahmed N, Ratts R, Raju S, Gallogly M, et al. Harnessing the immune system to overcome cytokine storm and reduce viral load in COVID-19: a review of the phases of illness and therapeutic agents. Virol J. 2020;17(1):154.

Cortese-Krott MM, Koning A, Kuhnle GGC, Nagy P, Bianco CL, Pasch A, et al. The Reactive Species Interactome: Evolutionary Emergence, Biological Significance, and Opportunities for Redox Metabolomics and Personalized Medicine. Antioxid Redox Signal. 2017;27(10):684-712.

Daher R, Manceau H, Karim Z. Iron metabolism and the role of the iron-regulating hormone hepcidin in health and disease. Presse Med. 2017;46(12):272-8.

Spreer A, Rüchel R, Reichard U. Characterization of an extracellular subtilisin protease of Rhizopus microsporus and evidence for its expression during invasive rhinoorbital mycosis. Med Mycol. 2006;44(8):723-31.

Challa S. Mucormycosis: Pathogenesis and Pathology. Curr Fungal Infect Rep. 2019;13:11-20.

Roilides E, Antachopoulos C, Simitsopoulou M. Pathogenesis and host defence against Mucorales: the role of cytokines and interaction with antifungal drugs. Mycoses. 2014;57:40-7.

Liu M, Spellberg B, Phan QT, Fu Y, Fu Y, Lee AS, et al. The endothelial cell receptor GRP78 is required for mucormycosis pathogenesis in diabetic mice. J Clin Invest. 2010;120(6):1914-24.

Schmidt S, Tramsen L, Perkhofer S, Lass-Flörl C, Hanisch M, Röger F, et al. Rhizopus oryzae hyphae are damaged by human natural killer (NK) cells, but suppress NK cell mediated immunity. Immunobiology. 2013;218(7):939-44.

Bruserud O. Bidirectional crosstalk between platelets and monocytes initiated by Toll-like receptor: An important step in the early defense against fungal infections? Platelets. 2013;24(2):85-97.

Semple JW, Italiano JE, Freedman J. Platelets and the immune continuum. Nature Rev Immunol. 2011;11(4):264-74.

Speth C, Rambach G, Lass-Flörl C. Platelet immunology in fungal infections. Thromb Haemost. 2014;112(4):632-9.

Alastruey-Izquierdo A, Hoffmann K, de Hoog GS, Rodriguez-Tudela JL, Voigt K, Bibashi E, et al. Species recognition and clinical relevance of the zygomycetous genus Lichtheimia (syn. Absidia pro parte, Mycocladus). J Clin Microbiol. 2010;48(6):2154-70.

Morace G, Borghi E. Invasive mold infections: virulence and pathogenesis of mucorales. Int J Microbiol. 2012;349278.

Lionakis MS, Kontoyiannis DP. Glucocorticoids and invasive fungal infections. Lancet. 2003;362(9398):1828-38.

Cornely OA, Alastruey-Izquierdo A, Arenz D, Chen SCA, Dannaoui E, Hochhegger B, et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. Lancet Infect Dis. 2019;19(12):405-21.

Honavar SG. Code Mucor: Guidelines for the Diagnosis, Staging and Management of Rhino-Orbito-Cerebral Mucormycosis in the Setting of COVID-19. Indian J Ophthalmol. 2021;69(6):1361-5.

Kashyap S, Bernstein, Ghanchi JH, Bowen I, Cortez V. Diagnosis of Rhinocerebral Mucormycosis by Treatment of Cavernous Right Internal Carotid Artery Occlusion With Mechanical Thrombectomy: Special Case Presentation and Literature Review. Front Neurol. 2019;10.

Mempin R, Kamangar N. Pulmonary Artery Pseudoaneurysm due to Mucormycosis: Case Report and Literature Review. J Clin Imaging Sci. 2020;10:55.

Agrawal R, Yeldandi A, Savas H, Parekh ND, Lombardi PJ, Hart EM. Pulmonary Mucormycosis: Risk Factors, Radiologic Findings, and Pathologic Correlation. Radiographics. 2020;40(3):656-66.

Seifert S, Wiley J, Kirkham J, Lena S, Schiers K. Pulmonary mucormycosis with extensive bronchial necrosis and bronchomediastinal fistula: A case report and review. Respir Med Case Rep. 2020;30:101082.

Peng M, Meng H, Sun Y, Xiao Y, Zhang H, Lv K, et al. Clinical features of pulmonary mucormycosis in patients with different immune status. J Thorac Dis. 2019;11(12):5042-52.

Georgiadou SP, Sipsas NV, Marom EM, Kontoyiannis DP. The diagnostic value of halo and reversed halo signs for invasive mold infections in compromised hosts. Clin Infect Dis. 2011;52(9):1144-55.

National Centre for Disease Control. 2021. Available at: https://www.ncdc.gov.in/WriteReadData/l892s/ 22911839231625743853.pdf. Accessed on 24 October 2021.

Fungal Infection Study Forum Recommentation, “COVID-19-associated mucormycosis (CAM). 2021. Available at: http://www.fisftrust.org/covid-19/Asscoiated-Mucormycosis/. Accessed on 24 October 2021.

Shrinivasan R, Rane S, Pai M. India's syndemic of tuberculosis and COVID-19. BMJ Glob Health. 2020;5(11):e003979.

Unnikrishnan R, Misra A. Infections and diabetes: Risks and mitigation with reference to India. Diabetes Metab Syndr. 2020;14(6):1889-94.

Prakash H, Chakrabarti A. Epidemiology of Mucormycosis in India. Microorganisms. 2021;9(3):523.

Drug Information Bulletin, Regulatory Affairs Division (RAD), IPA. 2020. Available at: https://ipapharma.org/wp-content/uploads/2020/03/ Drug-Information-Bulletin-13_25_.pdf. Accessed on 24 October 2021.

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Published

2022-04-27

How to Cite

Khadke, S., Khadke, V., Tomar, S., Khanuja, P. K., Suresh, S., Sohail, M. R., & Khanna, A. (2022). A review of COVID-19-associated mucormycosis in India. International Journal Of Community Medicine And Public Health, 9(5), 2297–2304. https://doi.org/10.18203/2394-6040.ijcmph20221255

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Review Articles