An emergence of mucormycosis during the COVID‑19 pandemic (Review)

Gayathri,Devaraja; Soundarya,Rajanna

doi:10.3892/wasj.2024.228

An emergence of mucormycosis during the COVID‑19 pandemic (Review)

Authors:
- Devaraja Gayathri
- Rajanna Soundarya
View Affiliations

Affiliations: Department of Studies in Microbiology, Davangere University, Davangere, Karnataka 577007, India
Published online on: January 29, 2024 https://doi.org/10.3892/wasj.2024.228
Article Number: 13
Copyright : © Gayathri et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Mucormycosis was highly prevalent during the coronavirus disease 2019 pandemic, particularly during the second wave, causing increased health risks to immunosuppressed or compromised individuals. This infection is long‑standing, lasting for years, specifically in immunocompromised individuals. There are no apparent risk factors and the fungus affects skin/subcutaneous tissues, resulting in the loss of facial aesthetics. In addition, individuals with a hyperglycaemic condition or diabetes mellitus, the fungus can lead to more severe complications, which are often fatal. While in patients with diabetic ketoacidosis, a high risk of infection with Rhizopus oryzae is observed, with the production of ketoreductase; this enzyme in turn hydrolyses host ketone bodies. Relatively effective medications are becoming available; however, the prognosis of patients affected by this fungus may improve with an increase in awareness and early diagnosis with the intervention of expert surgeons, radiologists and microbiologists to effectively combat the condition. The present review discusses the types, symptoms and available treatment strategies for mucormycosis.

View Figures

View References

1	Pushparaj K, Bhotla HK, Arumugam VA, Pappusamy M, Easwaran M and Balasubramanian B: Mucormycosis (black fungus) ensuing COVID-19 and comorbidity meets-Magnifying global pandemic grieve and catastrophe begins. Sci Total Environ. 805(150355)2022.PubMed/NCBI View Article : Google Scholar
2	Hernandez-Ramirez G, Barber D, Tome-Amat J, Garrido-Arandia M and Diaz-Perales A: Alternaria as an inducer of allergic sensitization. J Fungi (Basel). 7(838)2021.PubMed/NCBI View Article : Google Scholar
3	Ibrahim AS, Spellberg B, Walsh TJ and Kontoyiannis DP: Pathogenesis of mucormycosis. Clin Infect Dis. 54 (Suppl 1):S16–S22. 2012.PubMed/NCBI View Article : Google Scholar
4	Skiada A, Pavleas I and Drogari-Apiranthitou M: Epidemiology and diagnosis of mucormycosis: An update. J Fungi (Basel). 6(265)2020.PubMed/NCBI View Article : Google Scholar
5	Singh AK, Singh R, Joshi SR and Misra A: Mucormycosis in COVID-19: A systematic review of cases reported worldwide and in India. Diabetes Metab Syndr. 15(102146)2021.PubMed/NCBI View Article : Google Scholar
6	Skiada A, Lass-Floerl C, Klimko N, Ibrahim A, Roilides E and Petrikkos G: Challenges in the diagnosis and treatment of mucormycosis. Med Mycol. 56 (Suppl 1):S93–S101. 2018.PubMed/NCBI View Article : Google Scholar
7	Borkar SG: Mucormycosis: A surge in mucorales fungal infection in post-covid patients in Indian States and insight into known and unknown factors. Int J Global Health. 1:26–60. 2021.
8	Lu XL, Najafzadeh MJ, Dolatabadi S, Ran YP, Gerrits van den Ende AH, Shen YN, Li CY, Xi LY, Hao F, Zhang QQ, et al: Taxonomy and epidemiology of Mucor irregularis, agent of chronic cutaneous mucormycosis. Persoonia. 30:48–56. 2013.PubMed/NCBI View Article : Google Scholar
9	Aranjani JM, Manuel A, Abdul Razack HI and Mathew ST: COVID-19-associated mucormycosis: Evidence-based critical review of an emerging infection burden during the pandemic's second wave in India. PLoS Negl Trop Dis. 15(e0009921)2021.PubMed/NCBI View Article : Google Scholar
10	Alom S, Ali F and Md ZK: A comprehensive review on mucormycosis (Black fungus) and its association with covid-19. Curr Trends Pharm Res. 8:11–40. 2021.
11	Serris A, Danion F and Lanternier F: Disease entities in mucormycosis. J Fungi (Basel). 5(23)2019.PubMed/NCBI View Article : Google Scholar
12	Ghosh D, Dey S, Chakraborty H, Mukherjee S, Halder A, Sarkar A and Sarkar J: Mucormycosis: A new threat to Coronavirus disease 2019 with special emphasis on India. Clin Epidemiol Glob Health. 15(101013)2022.PubMed/NCBI View Article : Google Scholar
13	Dulski TM, DeLong M, Garner K, Patil N, Cima MJ, Rothfeldt L and Kothari A: Notes from the field: COVID-19-Associated Mucormycosis-Arkansas, July-September 2021. MMWR Morb Mortal Wkly Rep. 70:1750–1751. 2021.PubMed/NCBI View Article : Google Scholar
14	Bourcier J, Heudes PM, Morio F, Gastinne T, Chevallier P, Rialland-Battisti F and Peterlin P: Prevalence of the reversed halo sign in neutropenic patients compared with non-neutropenic patients: Data from a single-centre study involving 27 patients with pulmonary mucormycosis (2003-2016). Mycoses. 60:526–533. 2017.PubMed/NCBI View Article : Google Scholar
15	Pérez ADC and Welsh EC: Cutaneous mucormycosis. An Bras Dermatol. 92:304–311. 2017.PubMed/NCBI View Article : Google Scholar
16	Huang SF, Ying-Jung Wu A, Shin-Jung Lee S, Huang YS, Lee CY, Yang TL, Wang HW, Chen HJ, Chen YC, Ho TS, et al: Review of COVID-19 associated pulmonary aspergillosis and mucormycosis. J Microbiol Immunol Infect. 56:442–454. 2023.PubMed/NCBI View Article : Google Scholar
17	Spellberg B: Gastrointestinal mucormycosis: An evolving disease. Gastroenterol Hepatol (N Y). 8:140–142. 2012.PubMed/NCBI
18	Suresh S and Radha KV: Effect of a mixed substrate on phytase production by Rhizopus oligosporus MTCC 556 using solid state fermentation and determination of dephytinization activities in food grains. Food Sci Biotechnology. 24:551–559. 2015.
19	Lin CY, Wang IT, Chang CC, Lee WC, Liu WL, Huang YC, Chang KW, Huang HY, Hsiao HL, Kao KC, et al: Comparison of clinical manifestation, diagnosis, and outcomes of invasive pulmonary aspergillosis and pulmonary mucormycosis. Microorganisms. 7(531)2019.PubMed/NCBI View Article : Google Scholar
20	Shirane S, Watanabe D, Sekiya N, Horiguchi SI and Najima Y: Paraplegia via hematogenous dissemination of Cunninghamella elegans (mucormycosis) after hematopoietic stem cell transplantation. Int J Infect Dis. 113:210–212. 2021.PubMed/NCBI View Article : Google Scholar
21	Rammaert B, Lanternier F, Zahar JR, Dannaoui E, Bougnoux ME, Lecuit M and Lortholary O: Healthcare-associated mucormycosis. Clin Infect Dis. 54 (Suppl 1):S44–S54. 2012.PubMed/NCBI View Article : Google Scholar
22	India Today: Black fungus detected in Covid-19 survivors, 8 lose eyesight in Surat. India Today TV, New Delhi, 2021. https://www.indiatoday.in/coronavirus-outbreak/story/black-fungus-mucormycosis-detected-covid19-survivors-8-lose-eyesight-surat-fungal-infection-symptoms-1799971-2021-05-07?utm_source=washare&utm_medium=socialicons&utm_campaign=shareurltracking. Updated: May 20, 2021.
23	Reed C, Bryant R, Ibrahim AS, Edwards J Jr, Filler SG, Goldberg R and Spellberg B: Combination polyene-caspofungin treatment of rhino-orbital-cerebral mucormycosis. Clin Infect Dis. 47:364–371. 2008.PubMed/NCBI View Article : Google Scholar
24	Vaughan C, Bartolo A, Vallabh N and Leong SC: A meta-analysis of survival factors in rhino-orbital-cerebral mucormycosis-has anything changed in the past 20 years. Clin Otolaryngol. 43:1454–1464. 2018.PubMed/NCBI View Article : Google Scholar
25	Yohai RA, Bullock JD, Aziz AA and Markert RJ: Survival factors in rhino-orbital-cerebral mucormycosis. Surv Ophthalmol. 39:3–22. 1994.PubMed/NCBI View Article : Google Scholar
26	Jeong W, Keighley C, Wolfe R, Lee WL, Slavin MA, Kong DCM and Chen SA: The epidemiology and clinical manifestations of mucormycosis: A systematic review and meta-analysis of case reports. Clin Microbiol Infect. 25:26–34. 2019.PubMed/NCBI View Article : Google Scholar
27	Roden MM, Zaoutis TE, Buchanan WL, Knudsen TA, Sarkisova TA, Schaufele RL, Sein M, Sein T, Chiou CC, Chu JH, et al: Epidemiology and outcome of zygomycosis: A review of 929 reported cases. Clin Infect Dis. 41:634–653. 2005.PubMed/NCBI View Article : Google Scholar
28	Prakash H and Chakrabarti A: Global epidemiology of mucormycosis. J Fungi (Basel). 5(26)2019.PubMed/NCBI View Article : Google Scholar
29	Tedder M, Spratt JA, Anstadt MP, Hegde SS, Tedder SD and Lowe JE: Pulmonary mucormycosis: Results of medical and surgical therapy. Ann Thor Surg. 57:1044–1050. 1994.PubMed/NCBI View Article : Google Scholar
30	Lee FY, Mossad SB and Adal KA: Pulmonary mucormycosis: The last 30 years. Arch Internal Med. 159:1301–1309. 1999.PubMed/NCBI View Article : Google Scholar
31	Feng J and Sun X: Characteristics of pulmonary mucormycosis and predictive risk factors for the outcome. Infection. 46:503–512. 2018.PubMed/NCBI View Article : Google Scholar
32	Skiada A, Rigopoulos D, Larios G, Petrikkos G and Katsambas A: Global epidemiology of cutaneous zygomycosis. Clin Dermatol. 30:628–632. 2012.PubMed/NCBI View Article : Google Scholar
33	Chakrabarti A, Das A, Mandal J, Shivaprakash MR, George VK, Tarai B, Rao P, Panda N, Verma SC and Sakhuja V: The rising trend of invasive zygomycosis in patients with uncontrolled diabetes mellitus. Med Mycol. 44:335–342. 2006.PubMed/NCBI View Article : Google Scholar
34	Simbli M, Hakim F, Koudieh M and Tleyjeh IM: Nosocomial post-traumatic cutaneous mucormycosis: A systematic review. Scand J Infectious Dis. 40:577–582. 2008.PubMed/NCBI View Article : Google Scholar
35	Kaur H, Ghosh A, Rudramurthy SM and Chakrabarti A: Gastrointestinal mucormycosis in apparently immunocompetent hosts-A review. Mycoses. 61:898–908. 2018.PubMed/NCBI View Article : Google Scholar
36	Dioverti MV, Cawcutt KA, Abidi M, Sohail MR, Walker RC and Osmon DR: Gastrointestinal mucormycosis in immunocompromised hosts. Mycoses. 58:714–718. 2015.PubMed/NCBI View Article : Google Scholar
37	Guinea J, Escribano P, Vena A, Muñoz P, Martínez-Jiménez MDC, Padilla B and Bouza E: Increasing incidence of mucormycosis in a large Spanish hospital from 2007 to 2015: Epidemiology and microbiological characterization of the isolates. PLoS One. 12(e0179136)2017.PubMed/NCBI View Article : Google Scholar
38	Chakrabarti A, Chatterjee SS, Das A, Panda N, Shivaprakash MR, Kaur A, Varma SC, Singhi S, Bhansali A and Sakhuja V: Invasive zygomycosis in India: Experience in a tertiary care hospital. Postgraduate Med J. 85:573–581. 2009.PubMed/NCBI View Article : Google Scholar
39	Jianhong L, Xianliang H and Xuewu J: Isolated renal mucormycosis in children. J Urol. 171:387–388. 2004.PubMed/NCBI View Article : Google Scholar
40	Bhadauria D, Etta P, Chelappan A, Gurjar M, Kaul A, Sharma RK, Gupta A, Prasad N, Marak RS, Jain M, et al: Isolated bilateral renal mucormycosis in apparently immunocompetent patients-a case series from India and review of the literature. Clin Kidney J. 11:769–776. 2018.PubMed/NCBI View Article : Google Scholar
41	Skiada A, Pagano L, Groll A, Zimmerli S, Dupont B, Lagrou K, Lagrou K, Lass-Florl C, Bouza E, Klimko N, et al: Zygomycosis in Europe: Analysis of 230 cases accrued by the registry of the European Confederation of Medical Mycology (ECMM) Working Group on Zygomycosis between 2005 and 2007. Clin Microbiol Infect. 17:1859–1867. 2011.PubMed/NCBI View Article : Google Scholar
42	Anjum NA: Mucormycosis: Botanical insights into the major causative agents, 8 June, 2021.
43	Prakash H, Singh S, Rudramurthy SM, Singh P, Mehta N, Shaw D and Ghosh AK: An aero mycological analysis of Mucormycetes in indoor and outdoor environments of northern India. Med Mycol. 58:118–123. 2020.PubMed/NCBI View Article : Google Scholar
44	Prakash H and Chakrabarti A: Epidemiology of mucormycosis in India. Microorganisms. 9(523)2021.PubMed/NCBI View Article : Google Scholar
45	Ravindra K and Ahlawat A: Five probable factors responsible for the COVID-associated mucormycosis outbreak in India. Int J Infectious Dis. 112:278–280. 2021.PubMed/NCBI View Article : Google Scholar
46	Alim A, Pati BK, Sarfraz A and Bharti B: Rhinocerebral mucormycosis in a diabetic patient: A case report with brief review. Int J Med Res Prof. 5:150–154. 2019.
47	Mohindra S, Mohindra S, Gupta R, Bakshi J and Gupta SK: Rhinocerebral mucormycosis: The disease spectrum in 27 patients. Mycoses. 50:290–296. 2007.PubMed/NCBI View Article : Google Scholar
48	Almas T, Nazar W, Khedro T, Kanawati MA, Adnan A, Almuhaileej M, Alshamlan A, Abdulhadi A, Manamperi KT and Sarfraz S: COVID-19 and mucormycosis superinfection: Exploring the missing pathophysiological links. Ann Med Surg (Lond). 68(102655)2021.PubMed/NCBI View Article : Google Scholar
49	Aggarwal S, Gollapudi S, Yel L, Gupta AS and Gupta S: TNF-α-induced apoptosis in neonatal lymphocytes: TNFRp55 expression and downstream pathways of apoptosis. Genes Immunity. 1:271–279. 2000.PubMed/NCBI View Article : Google Scholar
50	Fischer K, Hoffmann P, Voelkl S, Meidenbauer N, Ammer J, Edinger M, Gottfried E, Schwarz S, Rothe G, Hoves S, et al: Inhibitory effect of tumor cell-derived lactic acid on human T cells. Blood. 109:3812–3819. 2007.PubMed/NCBI View Article : Google Scholar
51	Johnson AK, Ghazarian Z, Cendrowski KD and Persichino JG: Pulmonary aspergillosis and mucormycosis in a patient with COVID-19. Med Mycol Case Rep. 32:64–67. 2021.PubMed/NCBI View Article : Google Scholar
52	Patel A, Kaur H, Xess I, Michael JS, Savio J, Rudramurthy S, Singh R, Shastri P, Umabala P, Sardana R, et al: A multicentre observational study on the epidemiology, risk factors, management and outcomes of mucormycosis in India. Clin Microbiol Infect. 26:944.e9–944.e15. 2020.PubMed/NCBI View Article : Google Scholar
53	Khanna M, Challa S, Kabeil AS, Inyang B, Gondal FJ, Abah GA, Minnal Dhandapani M, Manne M and Mohammed L: Risk of mucormycosis in diabetes mellitus: A systematic review. Cureus. 13(e18827)2021.PubMed/NCBI View Article : Google Scholar
54	Indu DP, Yadhav MLK and Chetana GS: Is serum ferritin an early marker for COVID-19-associated mucormycosis? Cureus. 15(e36734)2023.PubMed/NCBI View Article : Google Scholar
55	Pilmis B, Alanio A, Lortholary O and Lanternier F: Recent advances in the understanding and management of mucormycosis. F1000Research. 7(F1000 Faculty Rev-1429)2018.PubMed/NCBI View Article : Google Scholar
56	Millon L, Larosa F, Lepiller Q, Legrand F, Rocchi S, Daguindau E, Scherer E, Bellanger AP, Leroy J and Grenouillet F: Quantitative polymerase chain reaction detection of circulating DNA in serum for early diagnosis of mucormycosis in immunocompromised patients. Clin Infect Dis. 56:e95–e101. 2013.PubMed/NCBI View Article : Google Scholar
57	Guegan H, Iriart X, Bougnoux ME, Berry A, Robert-Gangneux F and Gangneux JP: Evaluation of MucorGenius^® mucorales PCR assay for the diagnosis of pulmonary mucormycosis. J Infect. 81:311–317. 2020.PubMed/NCBI View Article : Google Scholar
58	Muley P, Chitguppi R and Jambure R: Proposal for a novel grading system for rhino-maxillary mucormycosis based on the analysis of 30 cases. (May 27, 2021). Available at SSRN: https://ssrn.com/abstract=3854282 or http://dx.doi.org/10.2139/ssrn.3854282.
59	Tissot F, Agrawal S, Pagano L, Petrikkos G, Groll AH, Skiada A, Lass-Flörl C, Calandra T, Viscoli C and Herbrecht R: ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica. 102:433–444. 2017.PubMed/NCBI View Article : Google Scholar
60	Meyer RD: Current role of therapy with amphotericin B. Clinical infectious diseases. 14 (Suppl 1):S154–S160. 1992.PubMed/NCBI View Article : Google Scholar
61	Dash AK, Patro S, Patro SK, Gupta AK and Biswal RN: Amphotericin B emulsion in rhino-orbital mucormycosis: Is it most effective? Clinical Rhinol An Inter J. 9:40–42. 2016.
62	Torrado JJ, Espada R, Ballesteros MP and Torrado-Santiago S: Amphotericin B formulations and drug targeting. J Pharm Sci. 97:2405–2425. 2008.PubMed/NCBI View Article : Google Scholar
63	Liu T, Wang L and Liu CT: Cavitary pulmonary mucormycosis caused by Cunninghamella in a patient with diabetes. Am J Med Sci. 364:245–247. 2022.PubMed/NCBI View Article : Google Scholar
64	Fernández-García R, Muñoz-García JC, Wallace M, Fabian L, González-Burgos E, Gómez-Serranillos MP, Raposo R, Bolás-Fernández F, Ballesteros MP, Healy AM, et al: Self-assembling, supramolecular chemistry and pharmacology of amphotericin B: Poly-aggregates, oligomers and monomers. J Control Release. 341:716–732. 2022.PubMed/NCBI View Article : Google Scholar
65	Kim MJ, Park PW, Ahn JY, Kim KH, Seo JY, Jeong JH, Park MJ, Jung JW and Seo YH: Fatal pulmonary mucormycosis caused by Rhizopus microsporus in a patient with diabetes. Ann Lab Med. 34:76–79. 2014.PubMed/NCBI View Article : Google Scholar
66	Odds FC, Brown AJ and Gow NA: Antifungal agents: Mechanisms of action. Trends Microbiol. 11:272–279. 2003.PubMed/NCBI View Article : Google Scholar
67	Pettit NN and Carver PL: Isavuconazole: A new option for the management of invasive fungal infections. Ann Pharmacother. 49:825–842. 2015.PubMed/NCBI View Article : Google Scholar
68	Marty FM, Ostrosky-Zeichner L, Cornely OA, Mullane KM, Perfect JR, Thompson GR III, Alangaden GJ, Brown JM, Fredricks DN, Heinz WJ, et al: Isavuconazole treatment for mucormycosis: A single-arm open-label trial and case-control analysis. Lancet Infect Dis. 16:828–837. 2016.PubMed/NCBI View Article : Google Scholar
69	Mohsina FP, Faheem IP, Tabassum S, Shah I and Ahmad A: An insight of mucormycosis (black fungus) in ayurveda. Open J Pharmacol Pharmacother. 6:13–17. 2021.
70	Adluri USP and Perugu S: Evaluation of efficacy and safety of adjuvant Ayurvedic therapy in patients with severe post-covid mucor-mycosis at a Government tertiary care hospital-A Case-Control study. J Ayurveda Integr Med. 13(100585)2022.PubMed/NCBI View Article : Google Scholar
71	Jangid R and Begum T: Antimycotic activity of some medicinal plants against Mucor circinelloides. Biomed Res Int. 2022(3523920)2022.PubMed/NCBI View Article : Google Scholar
72	Balkrishna A, Rastogi S, Kharayat B, Tomer M, Varshney Y, Singh K, Kumari P, Dev R, Srivastava J, Haldar S and Varshney A: Anu taila, an herbal nasal drop, suppresses mucormycosis by regulating host TNF-α response and fungal ergosterol biosynthesis. J Appl Microbiol. 132:3355–3374. 2022.PubMed/NCBI View Article : Google Scholar
73	Sharma S, Grover M, Bhargava S, Samdani S and Kataria T: Post coronavirus disease mucormycosis: A deadly addition to the pandemic spectrum. J Laryngol Otol. 135:442–447. 2021.PubMed/NCBI View Article : Google Scholar
74	Szebenyi C, Gu Y, Gebremariam T, Kocsubé S, Kiss-Vetráb S, Jáger O, Patai R, Spisák K, Sinka R, Binder U, et al: CotH genes are necessary for normal spore formation and virulence in Mucor lusitanicus. mBio. 14(e0338622)2023.PubMed/NCBI View Article : Google Scholar
75	Chaudhary P and Singh P: Isolation, identification and molecular characterization of microflora obtained from spices and spice mixes. World J Pharmaceutical Res. 3:2020–2030. 2014.