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Saberi-Hasanabadi P, Esmaeilzadeh Farmad M, Ataee R. Mucormycosis: An Emerging Fungal Infection in the COVID-19 Pandemic. JoMMID 2024; 12 (2) :84-99
URL: http://jommid.pasteur.ac.ir/article-1-558-en.html
Mucormycosis: An Emerging Fungal Infection in the COVID-19 Pandemic
Parisa Saberi-Hasanabadi , Milad Esmaeilzadeh Farmad , Ramin Ataee
Medicinal Plants Research Center, Mazandaran University of Medical Sciences, Sari, Iran
Abstract:   (117 Views)
During the COVID-19 pandemic, there has been a resurgence of mucormycosis, a rare and opportunistic fungal infection, with India reporting a particularly notable increase in incidence. Mucormycosis is a life-threatening condition that requires prompt diagnosis and treatment to prevent high mortality rates and severe sequelae. It is caused by the inhalation of spores from ubiquitous filamentous fungi belonging to the order Mucorales. Individuals with compromised immune systems or underlying conditions, such as diabetes, ketoacidosis, and neutropenia, are particularly vulnerable to infection. The risk and severity of mucormycosis are exacerbated by several factors, including corticosteroid therapy, prolonged intensive care stay, and the use of ventilators. Additionally, contaminated oxygen humidifiers pose a significant risk. Effective management of mucormycosis in critically ill COVID-19 patients relies on early diagnosis, optimization of predisposing factors, timely antifungal treatment, surgical debridement, and adjuvant therapies. Imaging modalities such as contrast-enhanced CT scans and MRI are crucial for guiding surgical debridement and assessing disease extent. This review article provides a comprehensive overview of the clinical pathogenesis, risk factors, diagnosis, treatment, and challenges associated with mucormycosis in COVID-19 patients, summarizing the latest findings in this field.


 
Keywords: COVID-19 infections, Mucormycetes, Organ damage, Risk factors and linkages
Full-Text [PDF 1519 kb]   (36 Downloads)    
Type of Study: Review article | Subject: Infectious diseases and public health
Received: 2023/05/31 | Accepted: 2024/09/20 | Published: 2024/09/18
References
1. Petrikkos G, Skiada A, Lortholary O, Roilides E, Walsh TJ, Kontoyiannis DP. Epidemiology and clinical manifestations of mucormycosis. Clin Infect Dis. 2012; 54 (1): 23-34. [DOI:10.1093/cid/cir866]
2. Singh A., Singh R, Joshi SR, Misra, A. Mucormycosis in COVID-19: a systematic review of cases reported worldwide and in India. Diabetes Metab Syndr. 2021; 15 (4): 102146. [DOI:10.1016/j.dsx.2021.05.019]
3. Saberi Hasanabadi P, Ataee R. A review on current side effects of used drugs during treatment of patients with COVID-19. Pharm Biomed Res. 2021; 7 (4): 251-60. [DOI:10.18502/pbr.v7i4.9371]
4. Roden MM, Zaoutis TE, Buchanan WL. Epidemiology and outcome of mucormycosis: a review of 929 reported cases. Clin Infect Dis. 2005; 41: 634-53. [DOI:10.1086/432579]
5. Kontoyiannis DP. Decrease in the number of reported cases of zygomycosis among patients with diabetes mellitus: a hypothesis. Clin Infect Dis. 2007; 44 (8): 1089-90. [DOI:10.1086/512817]
6. Bouza, E, Munoz P, Guinea J. Mucormycosis: an emerging disease? Clin Microbiol Infect. 2006; 12 (7): 7-23. [DOI:10.1111/j.1469-0691.2006.01604.x]
7. Gomes MZ, Lewis RE, Kontoyiannis DP. Mucormycosis caused by unusual mucormycetes, non-Rhizopus,-Mucor, and-Lichtheimia species. Clin Microbiol Rev. 2011; 24 (2); 411-45. [DOI:10.1128/CMR.00056-10]
8. Sanghvi D, Kale H. Imaging of COVID-19-associated craniofacial mucormycosis: a black and white review of the "black fungus". Clin Radiol. 2021; 76 (11): 812-9. [DOI:10.1016/j.crad.2021.07.004]
9. Malhotra HS, Gupta P, Mehrotra D, Dandu H, Kohli N, Verma V, et al. COVID-19 associated mucormycosis: Staging and management recommendations (Report of a multi-disciplinary expert committee). J Oral Biol. Craniofac. 2021; 11(4): 569-80. [DOI:10.1016/j.jobcr.2021.08.001]
10. Sachdev SS, Chettiankandy TJ, Gaikwad R, Suryawanshi S, Yaduwanshi K. COVID-19 associated Mucormycosis: The call for dental practitioners. Clin Dent. 2021; 15 (6): 19-23. [DOI:10.33882/ClinicalDent.15.28778]
11. Selarka L, Sharma S, Saini D, Sharma S, Batra A, Waghmare VT, et al. Mucormycosis and COVID‐19: An epidemic within a pandemic in India. Mycoses. 2021; 64 (10): 1253-60. [DOI:10.1111/myc.13353]
12. Dubey S, Mukherjee D, Sarkar P, Mukhopadhyay P, Barman D, Bandopadhyay M, et al. COVID-19 associated rhino-orbital-cerebral mucormycosis: An observational study from Eastern India, with special emphasis on neurological spectrum. Diabetes Metab Syndr. 2021; 15 (5): 102267. [DOI:10.1016/j.dsx.2021.102267]
13. Al-Ajam MR, Bizri AR, Mokhbat J, Weedon J, Lutwick L. Mucormycosis in the Eastern Mediterranean: a seasonal disease. Epidemiol Infect. 2006; 134 (2): 341-6. [DOI:10.1017/S0950268805004930]
14. Talmi YP, Goldschmied-Reouven A, Bakon M, Barshack I, Wolf M, Horowitz Z, et al. Rhino-orbital and rhino-orbito-cerebral mucormycosis. Otolaryngol Head Neck Surg. 2002; 127 (1): 22-31. [DOI:10.1067/mhn.2002.126587]
15. Sivagnanam S, Sengupta DJ, Hoogestraat D, Jain R, Stednick Z, Fredricks DN, et al. Seasonal clustering of sinopulmonary mucormycosis in patients with hematologic malignancies at a large comprehensive cancer center. Antimicrob Resist Infect Control. 2017; 6: 123. [DOI:10.1186/s13756-017-0282-0]
16. Chakrabarti A, Singh R. Mucormycosis in India: unique features. Mycoses. 2014; 57: 85-90. [DOI:10.1111/myc.12243]
17. Jeong W, Keighley C, Wolfe R, Lee WL, Slavin MA, Kong DCM, et al. The epidemiology and clinical manifestations of mucormycosis: a systematic review and meta-analysis of case reports. Clin Microbiol Infect. 2019; 25 (1): 26-34. [DOI:10.1016/j.cmi.2018.07.011]
18. Muthu V, Rudramurthy SM, Chakrabarti A, Agarwal R. Epidemiology and pathophysiology of COVID-19-associated mucormycosis: India versus the rest of the world. Mycopathologia. 2021; 186 (6): 739-54. [DOI:10.1007/s11046-021-00584-8]
19. Skiada A, Pavleas I, Drogari-Apiranthitou M. Epidemiology and diagnosis of mucormycosis: an update. J Fungi. 2020; 6 (4): 265. [DOI:10.3390/jof6040265]
20. Saberi-Hasanabadi P, Mohammadi H. COVID‐19 Pandemic: Management and Challenges. Pharm Biomed Res. 2021; 7 (2): 67-78. [DOI:10.18502/pbr.v7i2.7359]
21. Dolatabadi S, Ahmadi B, Rezaei-Matehkolaei A, Zarrinfar H, Skiada A, Mirhendi H, et al. Mucormycosis in Iran: A six-year retrospective experience. J Mycol Med. 2018; 28 (2): 269-73. [DOI:10.1016/j.mycmed.2018.02.014]
22. Sharma A, Goel A. Mucormycosis: risk factors, diagnosis, treatments, and challenges during COVID-19 pandemic. Folia Microbiol. 2022; 67 (3): 363-87. [DOI:10.1007/s12223-021-00934-5]
23. Llata E, Blossom DB, Khoury HJ, Rao CY, Wannemuehler KA, Noble-Wang J, et al. A cluster of mucormycosis infections in hematology patients: challenges in investigation and control of invasive mold infections in high-risk pat ient populations. Diagn Microbiol Infect Dis. 2011; 71 (1): 72-80. [DOI:10.1016/j.diagmicrobio.2010.12.022]
24. Mahalaxmi I, Jayaramayya K, Venkatesan D, Subramaniam MD, Renu K, Vijayakumar P, et al. Mucormycosis: An opportunistic pathogen during COVID-19. Environ Res. 2021; 201: 111643. [DOI:10.1016/j.envres.2021.111643]
25. Kumar M, Sarma DK, Shubham S, Kumawat M, Verma V, Singh B, et al. Mucormycosis in COVID-19 pandemic: Risk factors and linkages. Curr Res Microb Sci. 2021; 2: 100057. [DOI:10.1016/j.crmicr.2021.100057]
26. Chauhan K, Soni D, Sarkar D, Karuna T, Sharma B, Singh S, et al. Mucormycosis after COVID-19 in a patient with diabetes. Lancet. 2021; 398 (10301): 10. [DOI:10.1016/S0140-6736(21)01641-X]
27. Naseef PP, Elayadeth-Meethal M, Salim KM, Anjana A, Muhas C, Vajid KA, et al. Therapeutic potential of induced iron depletion using iron chelators in Covid-19. Saudi J Biol Sci. 2022; 29 (4): 1947-56. [DOI:10.1016/j.sjbs.2021.11.061]
28. Khatri A, Chang KM, Berlinrut I, Wallach F. Mucormycosis after Coronavirus disease 2019 infection in a heart transplant recipient-case report and review of literature. J Mycol Med. 2021; 101125. [DOI:10.1016/j.mycmed.2021.101125]
29. Mishra N, Mutya VSS, Thomas A, Rai G, Reddy B, Mohanan AA, et al. A case series of invasive mucormycosis in patients with COVID-19 infection. Int J Otorhinolaryngol Head Neck Surg. 2021; 7 (5): 867-70. [DOI:10.18203/issn.2454-5929.ijohns20211583]
30. Garg D, Muthu V, Sehgal IS, Ramachandran R, Kaur H, Bhalla A, et al. Coronavirus disease (COVID-19) associated mucormycosis (CAM): case report and systematic review of literature. Mycopathologia. 2021; 186 (2): 289-98. [DOI:10.1007/s11046-021-00528-2]
31. Choudhary NK, Jain AK, Soni R, Gehlot N. Mucormycosis: A deadly black fungus infection among COVID-19 patients in India. Clin Epidemiol Glob Health. 2021; 100900. [DOI:10.1016/j.cegh.2021.100900]
32. Ramphul K, Verma R, Kumar N, Ramphul Y, Mejias S, Lohana P. Rising concerns of Mucormycosis (Zygomycosis) among COVID-19 patients; an analysis and review based on case reports in literature. Acta Biomed. 2021; 92 (4): e2021271.
33. Patel A, Agarwal R, Rudramurthy SM, Shevkani M, Xess I, Sharma R, et al. Multicenter epidemiologic study of coronavirus disease-associated mucormycosis. India Emerg Infect Dis. 2021; 27 (9): 2349-59. [DOI:10.3201/eid2709.210934]
34. 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. [DOI:10.4103/ijo.IJO_1565_21]
35. Seidel D, Simon M, Sprute R, Lubnow M, Evert K, Speer C, et al. Results from a national survey on COVID‐19‐associated mucormycosis in Germany: 13 patients from six tertiary hospitals. Mycoses. 2022; 65 (1): 103-9. [DOI:10.1111/myc.13379]
36. Bari MS, Hossain MJ, Akhter S, Emran TB. Delta variant and black fungal invasion: A bidirectional assault might worsen the massive second/third stream of COVID-19 outbreak in South-Asia. Ethics Med Public Health. 2021; 19: 100722. [DOI:10.1016/j.jemep.2021.100722]
37. Banerjee I, Robinson J, Asim M, Sathian B, Banerjee I. Mucormycosis and COVID-19 an epidemic in a pandemic? Nepal J Epidemiol. 2021; 11 (2): 1034-9. [DOI:10.3126/nje.v11i2.37342]
38. Drissi C. Black fungus, the dark side of COVID-19. J Neuroradiol. 2021; 48 (5): 317-18. [DOI:10.1016/j.neurad.2021.07.003]
39. Ravindra K, Ahlawat A. Five probable factors responsible for the COVID-associated mucormycosis outbreak in India. Int J Infect Dis. 2021; 112: 278-80. [DOI:10.1016/j.ijid.2021.09.057]
40. Bhogireddy R, Krishnamurthy V, Pullaiah CP, Manohar S. Is Mucormycosis an inevitable complication of Covid-19 in India? Braz J Infect Dis. 2021; 25 (3): 101597. [DOI:10.1016/j.bjid.2021.101597]
41. Dilek A, Ozaras R, Ozkaya S, Sunbul M, Sen EI, Leblebicioglu H. COVID-19-associated mucormycosis: Case report and systematic review. Travel Med Infect Dis. 2021; 102148. [DOI:10.1016/j.tmaid.2021.102148]
42. Thakar A, Lal D. "Black fungus": a perspective on the coronavirus disease 2019 (COVID‐19)‐associated rhino‐orbital mucormycosis epidemic in India. Int Forum Allergy Rhinol. 2021; 11 (8): 1278-9. [DOI:10.1002/alr.22855]
43. Yasmin F, Najeeb H, Naeem A, Dapke K, Phadke R, Asghar MS, et al. COVID-19 associated mucormycosis: a systematic review from diagnostic challenges to management. Diseases, 2021; 9 (4): 65. [DOI:10.3390/diseases9040065]
44. Thajeb P, Thajeb T, Dai D. Fatal strokes in patients with rhino-orbito-cerebral mucormycosis and associated vasculopathy. Scand J Infect Dis. 2004; 36 (9): 643-8. [DOI:10.1080/00365540410020794]
45. Moorthy A, Gaikwad R, Krishna S, Hegde R, Tripathi KK, Kale PG, et al. SARS-CoV-2, Uncontrolled Diabetes and Corticosteroids-An Unholy Trinity in Invasive Fungal Infections of the Maxillofacial Region? A Retrospective, Multi-centric Analysis. J Oral Maxillofac Surg. 2021; 20 (3): 418-25. [DOI:10.1007/s12663-021-01532-1]
46. Rashid HU, Rashid M, Khan N, Ansari SS, Bibi N. Taking a step down on the reconstruction ladder for head and neck reconstruction during the COVID-19 pandemic. BMC Surg. 2021; 21: 120. [DOI:10.1186/s12893-021-01134-1]
47. Kanwar A, Jordan A, Olewiler S, Wehberg K, Cortes M, Jackson BR. A fatal case of Rhizopus azygosporus pneumonia following COVID-19. J Fungi. 2021; 7 (3): 174. [DOI:10.3390/jof7030174]
48. Mehta S, Pandey A. Rhino-orbital mucormycosis associated with COVID-19. Cureus. 2020; 12 (9): e10726. [DOI:10.7759/cureus.10726]
49. Werthman-Ehrenreich A. Mucormycosis with orbital compartment syndrome in a patient with COVID-19. Am J Emerg Med. 2021; 42: 264-5. [DOI:10.1016/j.ajem.2020.09.032]
50. Mekonnen ZK, Ashraf DC, Jankowski T, Grob SR, Vagefi MR, Kersten RC, et al. Acute invasive rhino-orbital mucormycosis in a patient with COVID-19-associated acute respiratory distress syndrome. Ophthalmic Plast Reconstr Surg. 2021; 37 (2): e40-e80. [DOI:10.1097/IOP.0000000000001889]
51. Hanley B, Naresh KN, Roufosse C, Nicholson AG, Weir J, Cooke GS, et al. Histopathological findings and viral tropism in UK patients with severe fatal COVID-19: a post-mortem study. Lancet Microbe. 2020; 1 (6): 245-53. [DOI:10.1016/S2666-5247(20)30115-4]
52. do Monte Junior ES, Dos Santos MEL, Ribeiro IB, de Oliveira Luz G, Baba ER, Hirsch BS, et al. Rare and fatal gastrointestinal mucormycosis (Zygomycosis) in a COVID-19 patient: a case report. Clin Endosc. 2020; 53 (6): 746-9. [DOI:10.5946/ce.2020.180]
53. Ahmadikia K, Hashemi SJ, Khodavaisy S, Getso MI, Alijani N, Badali H, et al. The double‐edged sword of systemic corticosteroid therapy in viral pneumonia: A case report and comparative review of influenza‐associated mucormycosis versus COVID‐19 associated mucormycosis. Mycoses. 2020; 64 (8): 798-808. [DOI:10.1111/myc.13256]
54. Pakdel F, Ahmadikia K, Salehi M, Tabari A, Jafari R, Mehrparvar G, et al. Mucormycosis in patients with COVID‐19: A cross‐sectional descriptive multicentre study from Iran. Mycoses. 2021; 64 (10): 1238-52. [DOI:10.1111/myc.13334]
55. Saberi-Hasanabadi P, Farmad ME, Aboulfazli S, Kheirandish A, Ataie A, Boshtam S, et al. Azithromycin for COVID-19: Pharmacological Mechanisms, Challenges, and Prospects. Acta Med Iran. 2023; 61 (7): 378-86. [DOI:10.18502/acta.v61i7.14492]
56. Maini A, Tomar G, Khanna D, Kini Y, Mehta H, Bhagyasree V. Sino-orbital mucormycosis in a COVID-19 patient: A case report. Int J Surg Case Rep. 2021; 82: 105957. [DOI:10.1016/j.ijscr.2021.105957]
57. Martin H, Danila S, Agostinho C. The emergence of COVID-19 associated mucormycosis: Analysis of cases from 18 countries. Lancet Microbe. 2022; 3 (7): e543-e52. [DOI:10.1016/S2666-5247(21)00237-8]
58. Gamaletsou MN, Sipsas NV, Roilides E, Walsh TJ. Rhino-orbital-cerebral mucormycosis. Curr Infect Dis Rep. 2012; 14 (4): 423-34. [DOI:10.1007/s11908-012-0272-6]
59. Desai SM, Gujarathi-Saraf A, Agarwal EA. Imaging findings using a combined MRI/CT protocol to identify the "entire iceberg" in post-COVID-19 mucormycosis presenting clinically as only "the tip". Clin Radiol. 2021; 76 (10): 784.e27-784.e33. [DOI:10.1016/j.crad.2021.07.002]
60. Fazel R, Krumholz HM, Wang Y, Ross JS, Chen J, Ting HH, et al. Exposure to low-dose ionizing radiation from medical imaging procedures. N Engl J Med. 2009; 361 (9): 849-57. [DOI:10.1056/NEJMoa0901249]
61. Joshi AR, Muthe MM, Patankar SH, Athawale A, Achhapalia Y. CT and MRI findings of invasive mucormycosis in the setting of COVID-19: experience from a single center in India. Am J Roentgenol. 2021; 217(6): 1431-2. [DOI:10.2214/AJR.21.26205]
62. Azhar A, Khan WH, Khan PA, Alhosaini K, Owais M, Ahmad A. Mucormycosis and COVID-19 pandemic: Clinical and diagnostic approach. J Infect Public Health. 2022; 15 (4): 466-79. [DOI:10.1016/j.jiph.2022.02.007]
63. Kozel TR, Wickes B. Fungal diagnostics. Cold Spring Harb Perspect Med. 2014; 4 (4): a019299. [DOI:10.1101/cshperspect.a019299]
64. Reed C, Bryant R, Ibrahim AS, Edwards Jr, Filler SG, Goldberg R, et al. Combination polyene-caspofungin treatment of rhino-orbital-cerebral mucormycosis. Clin Infect Dis. 2008; 47 (3): 364-71. [DOI:10.1086/589857]
65. Candrilli S, Mauskopf J. How much does a hospital day cost. In 11th Annual International Meeting of the International Society for Pharmacoeconomics and Outcomes Research. 2006.
66. Spellberg B, Fu Y, Edwards Jr, Ibrahim AS. Combination therapy with amphotericin B lipid complex and caspofungin acetate of disseminated zygomycosis in diabetic ketoacidotic mice. Antimicrob. Agents Chemother. 2005; 49 (2): 830-2. [DOI:10.1128/AAC.49.2.830-832.2005]
67. Ibrahim AS, Bowman JC, Avanessian V, Brown K, Spellberg B, Edwards Jr, et al. Caspofungin inhibits Rhizopus oryzae 1, 3-β-d-glucan synthase, lowers burden in brain measured by quantitative PCR, and improves survival at a low but not a high dose during murine disseminated zygomycosis. Antimicrob. Agents Chemother. 2005; 49 (2): 721-7. [DOI:10.1128/AAC.49.2.721-727.2005]
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