Rhino-orbital-cerebral mucormycosis associated with COVID-19 and mortality-related factors: a systematic review
Abstract Introduction and Objective: Rhino-orbito-cerebral mucormycosis (ROCM) emerged as a severe complication during the COVID-19 pandemic, particularly in patients with poorly controlled diabetes or those treated with corticosteroids. This rapidly progressing infection presents high mortality rates and significant challenges in diagnosis and management. The objective of this systematic review was to analyze the clinical factors associated with mortality in patients with COVID-19-related ROCM. Methods: A systematic review was conducted following PRISMA guidelines, using databases such as Scopus, PUBMED, and ScienceDirect. Original studies published in English between December 2019 and December 2024 were included. Study quality was assessed using the Newcastle-Ottawa Scale. A descriptive analysis was performed based on odds ratios (OR), relative risks (RR), and 95 % confidence intervals (95 % CI) reported in the included studies. Associations were considered statistically significant when the confidence interval did not include the null value. A meta-analysis was not performed due to methodological heterogeneity among the studies. Results: Sixteen studies were identified, reporting mortality rates ranging from 4.8 % to 66.7 %. Major risk factors associated with mortality included diabetes mellitus (67.64 %–95.33 %), corticosteroid use (72.3 %–74 %), advanced age, and intracranial or orbital extension of the infection. Early diagnosis and combined treatment (surgical and medical) significantly improved survival rates. Discussion: COVID-19-associated ROCM is strongly linked to diabetes and corticosteroid use, both of which impair immune response and facilitate fungal infection. Infection extension to the central nervous system or orbits markedly increased mortality. The studies emphasized the importance of a multidisciplinary approach and aggressive management to improve patient outcomes. Conclusions: COVID-19-related ROCM is a life-threatening complication with high mortality, primarily associated with diabetes, corticosteroid use, and infection spread. Early diagnosis and combined therapeutic strategies are essential to improve survival. Future research should focus on prospective, multicenter studies to optimize prevention and management strategies.
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Astuti I, Ysrafil. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): an overview of viral structure and host response. Diabetes Metab Syndr. 2020;14(4):407–12. https://doi.org/10.1016/j.dsx.2020.04.020
Lass-Flörl C, Steixner S. The changing epidemiology of fungal infections. Mol Aspects Med. 2023;94:101215. https://doi.org/10.1016/j.mam.2023.101215
Raut A, Huy NT. Rising incidence of mucormycosis in patients with COVID-19: another challenge for India amidst the second wave? Lancet Respir Med. 2021;9(8):e77. https://doi.org/10.1016/S2213-2600(21)00265-4
Eker C, Tarkan O, Surmelioglu O, Dagkiran M, Tanrisever I, Yucel Karakaya SP, et al. Alternating pattern of rhino-orbital–cerebral mucormycosis with COVID-19 in diabetic patients. Eur Arch Otorhinolaryngol. 2023;280(2):849–58. https://doi.org/10.1007/s00405-022-07526-0
Jadhav H, Vishwakarma P, Thamke S, Pundkar S, Takle T, Khairnar M. Correlation of mucormycosis with various clinical parameters among COVID-19 patients: a cross-sectional study. J Maxillofac Oral Surg. 2023. https://doi.org/10.1007/s12663-023-01919-2
Issa RS, Mushtaq G, Unnisa A, Mahli A. A case of concomitant leukemoid reaction and mucormycosis in a patient with severe COVID-19 infection. Turk J Biochem. 2023;48(1):93–6. https://doi.org/10.1515/tjb-2023-0016
Ghasemi S, Dashti M, Fahimipour A, Daryakenari G, Mirzaei F, Akbari F, et al. Onset of mucormycosis in patients with COVID-19: a systematic review on patients’ characteristics. Eur J Dent. 2023;17(1):8–16. https://doi.org/10.1055/s-0042-1751003
Slavin M, van Hal S, Sorrell TC, Lee A, Marriott DJ, Daveson K, et al. Invasive infections due to filamentous fungi other than Aspergillus: epidemiology and determinants of mortality. Clin Microbiol Infect. 2015;21(6):490.e1–e10. https://doi.org/10.1016/j.cmi.2014.12.021
Lin E, Moua T, Limper AH. Pulmonary mucormycosis: clinical features and outcomes. Infection. 2017;45(4):443–8. https://doi.org/10.1007/s15010-017-0991-6
Prakash H, Ghosh AK, Rudramurthy SM, Singh P, Xess I, Savio J, et al. A prospective multicenter study on mucormycosis in India: epidemiology, diagnosis, and treatment. Med Mycol. 2019;57(4):395–402. https://doi.org/10.1093/mmy/myy060
Prakash H, Chakrabarti A. Global epidemiology of mucormycosis. Journal of Fungi 2019;5. https://doi.org/10.3390/jof5010026.
Ribes JA, Vanover-Sams CL, Baker DJ. Zygomycetes in human disease. Clin Microbiol Rev 2000;13. https://doi.org/10.1128/CMR.13.2.236-301.2000.
McMahon D, Frangos J. 15109 Cutaneous zygomycosis presenting as resistant intertrigo in an immunocompromised adult. J Am Acad Dermatol 2020;83. https://doi.org/10.1016/j.jaad.2020.06.202.
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. Clinical Microbiology and Infection 2019;25. https://doi.org/10.1016/j.cmi.2018.07.011.
Petrikkos G, Skiada A, Lortholary O, Roilides E, Walsh TJ, Kontoyiannis DP. Epidemiology and clinical manifestations of mucormycosis. Clinical Infectious Diseases 2012;54. https://doi.org/10.1093/cid/cir866.
Sodhi SPS, Brar GK, Sodhi DPS, Brar GS, Gupta S, Malhotra M. Post COVID Fungal Osteomyelitis—Another Killer. J Pharm Bioallied Sci 2023;15. https://doi.org/10.4103/jpbs.jpbs_37_23.
Mukherjee B, Raichura ND, Alam MS. Fungal infections of the orbit. Indian J Ophthalmol 2016;64. https://doi.org/10.4103/0301-4738.185588.
Nicolás S, Enmanuel P, Betsabe S, Patricia L. Cavernous Sinus Thrombosis as a Complication of Cerebro-Rhino Orbital Mucormycosis Associated With Covid-19: A Case Report. International Journal of Oral and Dental Health 2022;8. https://doi.org/10.23937/2469-5734/1510147.
Castañeda Solís KB, Granados Jaramillo C, Barbosa Salazar E, Lozano Hernández DI, Tello Zavala C, Gómez Gutiérrez B. Black fungus in India, is it really pathophysiological related to COVID-19? Ther Adv Infect Dis 2021;8.
Karkhur S, Soni D, Chauhan K, Sarkar D, Gautam M, Verma S, et al. Rhino-orbito-cerebral mucormycosis and its resurgence during COVID-19 pandemic: A review. Indian J Ophthalmol 2023;71. https://doi.org/10.4103/ijo.IJO_1219_22.
Thornton CR. The potential for rapid antigen testing for mucormycosis in the context of COVID-19. Expert Rev Mol Diagn 2024;24. https://doi.org/10.1080/14737159.2023.2233906.
DiBartolo MA, Kelley PS. Rhino-Orbital-Cerebral Mucormycosis (ROCM):A comprehensive case review. Aviat Space Environ Med 2011;82. https://doi.org/10.3357/ASEM.3036.2011.
Rincón CCA, Silva-Ramos CR, Arancibia JA, Prada-Avella MC, Suárez A. Rhino-orbito-cerebral mucormycosis in an acute lymphoblastic leukemia pediatric patient. Case report and review of literature. Infezioni in Medicina 2022;30. https://doi.org/10.53854/liim-3002-17.
Manchanda S, Semalti K, Bhalla AS, Thakar A, Sikka K, Verma H. Revisiting rhino-orbito-cerebral acute invasive fungal sinusitis in the era of COVID-19: pictorial review. Emerg Radiol 2021;28. https://doi.org/10.1007/s10140-021-01980-9.
Ostovan VR, Tabrizi R, Bazrafshan H, Bahrami Z, Khazraei H, Khazraei S, et al. Mortality-Related Risk Factors for Coronavirus Disease (COVID-19)-Associated Mucormycosis: a systematic review and meta-analysis. Curr Fungal Infect Rep 2022;16. https://doi.org/10.1007/s12281-022-00440-2.
Chopra S, Setiya S, Waknis PP, Kale L, Tidke S. Various Treatment Modalities in COVID-19 Associated Facial Mucormycosis and the Need for its Surgical Management: A Systematic Review. J Maxillofac Oral Surg 2023. https://doi.org/10.1007/s12663-023-01878-8.
Wei LW, Zhu PQ, Chen XQ, Yu J. Mucormycosis in Mainland China: A Systematic Review of Case Reports. Mycopathologia 2022;187. https://doi.org/10.1007/s11046-021-00607-4.
Nagarkar NM, Sahu V, Arora R, Pathak M, Shambharkar MS, Naveen P. Mortality and its determinants after an outbreak of post COVID-19 associated rhino-orbito-cerebral mucormycosis in Central India. Int Ophthalmol 2023;43. https://doi.org/10.1007/s10792-023-02634-0.
Patel A, Kaur H, Xess I, Michael JS, Savio J, Rudramurthy S, et al. A multicentre observational study on the epidemiology, risk factors, management and outcomes of mucormycosis in India. Clinical Microbiology and Infection 2020;26. https://doi.org/10.1016/j.cmi.2019.11.021.
Skiada A, Pagano L, Groll A, Zimmerli S, Dupont B, Lagrou K, 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. Clinical Microbiology and Infection 2011;17. https://doi.org/10.1111/j.1469-0691.2010.03456.x.
Davitt E, Davitt C, Mazer MB, Areti SS, Hotchkiss RS, Remy KE. COVID-19 disease and immune dysregulation. Best Pract Res Clin Haematol 2022;35. https://doi.org/10.1016/j.beha.2022.101401.
Proal AD, VanElzakker MB. Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms. Front Microbiol 2021;12. https://doi.org/10.3389/fmicb.2021.698169.
Tariq S, Van Eeden C, Tervaert JWC, Osman MS. COVID-19, rheumatic diseases and immune dysregulation—a perspective. Clin Rheumatol 2021;40. https://doi.org/10.1007/s10067-020-05529-y.
Hughes S, Troise O, Donaldson H, Mughal N, Moore LSP. Bacterial and fungal coinfection among hospitalized patients with COVID-19: a retrospective cohort study in a UK secondary-care setting. Clinical Microbiology and Infection 2020;26. https://doi.org/10.1016/j.cmi.2020.06.025.
Pandiar D, Kumar NS, Anand R, Kamboj M, Narwal A, Shameena PM. Does COVID 19 generate a milieu for propagation of mucormycosis? Med Hypotheses 2021;152. https://doi.org/10.1016/j.mehy.2021.110613.
Saleeb MF, Sabry SM, Mahmoud MS, Nassif MM. Risk factors affecting outcome of rhino-orbital-cerebral mucormycosis in COVID-19 patients. Egyptian Journal of Otolaryngology 2023;39. https://doi.org/10.1186/s43163-023-00406-2.
Choksi T, Agrawal A, Date P, Rathod D, Gharat A, Ingole A, et al. Cumulative Mortality and Factors Associated with Outcomes of Mucormycosis after COVID-19 at a Multispecialty Tertiary Care Center in India. JAMA Ophthalmol 2022;140. https://doi.org/10.1001/jamaophthalmol.2021.5201.
Singh A, Goel G, Khan M, Kanodia A, Sikka K, Thakar A. Factors affecting clinical outcome in COVID-associated rhino-orbito-cerebral mucormycosis (CAROM) patients—An ambispective, single-arm, observational study. Am J Otolaryngol 2023;44. https://doi.org/10.1016/j.amjoto.2023.103975.
Martínez MAS, Lugo-Machado JA, Canché-Martín E, Sainz-Fuentes N, Reina-Loaiza R, Rodríguez-Quintana S, et al. Factors associated with survival in diabetic patients with rhino-orbito-cerebral mucormycosis. Rom J Rhinol 2021;11. https://doi.org/10.2478/rjr-2021-0011.
Alejandra Quintero Bauman, Lugo Machado JA, Sainz Fuentes N, Arellano Rodríguez IC, Canche Martín EM, Reina Loaiza JR, et al. Factores de riesgo asociados con mortalidad en pacientes con mucormicosis rino-órbito-cerebral y COVID-19. Med Int Méx 2023;39:734–42. https://doi.org/10.24245/mim.v39i5.8443.
Cag Y, Erdem H, Gunduz M, Komur S, Ankarali H, Ural S, et al. Survival in rhino-orbito-cerebral mucormycosis: An international, multicenter ID-IRI study. Eur J Intern Med 2022;100. https://doi.org/10.1016/j.ejim.2022.03.008.
Hutton B, Catalá-López F, Moher D. The PRISMA statement extension for systematic reviews incorporating network meta-analysis: PRISMA-NMA. Med Clin (Barc) (Eng Ed) 2016;147:262–6. https://doi.org/10.1016/j.medcle.2016.10.003.
Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group T. Ítems de referencia para publicar Revisiones Sistemáticas y Metaanálisis: La Declaración PRISMA. Rev Esp Nutr Hum Diet 2014;18. https://doi.org/10.14306/renhyd.18.3.114.
Wells G, Shea B, O’Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality if nonrandomized studies in meta-analyses. (Available from: URL: Http://WwwOhri.ca/Programs/Clinical_epidemiology/OxfordAsp) 2012. https://doi.org/10.2307/632432.
Wells G, Shea B, O’Connell D, Peterson J. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa, ON: Ottawa Hospital Research Institute 2000.
Yu F, Liu C, Sharmin S. Performance, usability, and user experience of Rayyan for systematic reviews. Proc Assoc Inf Sci Technol 2022;59. https://doi.org/10.1002/pra2.745.
Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan-a web and mobile app for systematic reviews. Syst Rev 2016;5. https://doi.org/10.1186/s13643-016-0384-4.
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 Maxillofac Oral Surg 2021;20. https://doi.org/10.1007/s12663-021-01532-1.
Dravid A, Kashiva R, Khan Z, Bande B, Memon D, Kodre A, et al. Epidemiology, clinical presentation and management of COVID-19 associated mucormycosis: A single centre experience from Pune, Western India. Mycoses 2022;65:526–40. https://doi.org/10.1111/myc.13435.
Keshri A, Mathialagan A, Aishwarya A, Ravisankar, Bhuskute G, Kanaujia V, et al. Is mucormycosis the end? A comprehensive management of orbit in COVID associated rhino-orbital–cerebral mucormycosis: preserving the salvageable. Eur Arch Otorhinolaryngol 2023;280:819–27. https://doi.org/10.1007/s00405-022-07620-3.
Fakhim H, Irani S, Yassin Z, Badali H, Nasri E, Nasoori Y, et al. Features and evaluation of mucormycosis in COVID-19 patients from two referral hospitals in Iran. J Med Mycol 2024;34. https://doi.org/10.1016/j.mycmed.2024.101480.
Nair KS, Alagesan M, Jose D, Yoganathan C, Saravanan R, Karthikeyan K, et al. Clinical profile and factors associated with adverse outcomes in coronavirus disease 2019-associated mucormycosis: a single-centre study. US Endocrinol 2023;19:73–9. https://doi.org/10.17925/EE.2023.19.2.2.
Muraleedharan M, Panda NK, Angrish P, Arora K, Patro SK, Bansal S, et al. As the virus sowed, the fungus reaped! A comparative analysis of the clinico-epidemiological characteristics of rhino-orbital mucormycosis before and during COVID-19 pandemic. Mycoses 2022;65:567–76. https://doi.org/10.1111/myc.13437.
Avatef Fazeli M, Rezaei L, Javadirad E, Iranfar K, Khosravi A, Amini Saman J, et al. Increased incidence of rhino-orbital mucormycosis in an educational therapeutic hospital during the COVID-19 pandemic in western Iran: an observational study. Mycoses 2021;64:1366–77. https://doi.org/10.1111/myc.13351.
Rajabi MT, Aghajani A, Rafizadeh SM, Jamshidian Tehrani M, Poursayed Lazarjani SZ, Keshmirshekan MM, et al. COVID-19 associated rhino-orbito-cerebral mucormycosis, risk factors and outcome predictors; a multicentric study. Int Ophthalmol 2023;43:1375–86. https://doi.org/10.1007/s10792-022-02536-7.
Kordjazi M, Bazgir N, Eftekharian K, Farajpour M, Dilmaghani NA. Manifestations of mucormycosis and its complications in COVID-19 patients: a case series study. Ear Nose Throat J 2024;103:145S–52S. https://doi.org/10.1177/01455613221143859.
Fatima N, Ahmed S, Shameem M, Ahmed A, Hasan W, Khan PA. Rhino-orbito-cerebral mucormycosis during Covid-19 pandemic—a prospective observational study. Indian J Med Microbiol 2023;46. https://doi.org/10.1016/j.ijmmb.2023.100467.
Nagarkar NM, Sahu V, Arora R, Pathak M, Shambharkar MS, Naveen P. Mortality and its determinants after an outbreak of post COVID-19 associated rhino-orbito-cerebral mucormycosis in Central India. Int Ophthalmol 2023;43:2363–70. https://doi.org/10.1007/s10792-023-02634-0.
Rudramurthy SM, Singh S, Kanaujia R, Chaudhary H, Muthu V, Panda N, et al. Clinical and mycologic characteristics of emerging mucormycosis agent Rhizopus homothallicus. Emerg Infect Dis 2023;29:1313–22. https://doi.org/10.3201/eid2907.221491.
Kumari S, Pandey S, Verma M, Rana AK, Kumari S. Clinicopathological challenges in tumors of the nasal cavity and paranasal sinuses: our experience. Cureus 2022;14(9):e29128. https://doi.org/10.7759/cureus.29128.
Yadav V, Bhagat S, Goel K, Sibia RS, Sharma DK, Sidhu T, et al. Outcomes of COVID-19-associated mucormycosis epidemic in India: A prospective 2-year follow-up study. World J Otorhinolaryngol Head Neck Surg 2024. https://doi.org/10.1002/wjo2.162.
Shaikh Z, Mishra A, Chadaram S, Preetam C, Biswas R, Adhikari A, et al. To evaluate the efficacy of topical anti-fungal therapy in postoperative cases of COVID Associated Mucormycosis (CAM): A single-blinded randomized control trial. Am J Otolaryngol 2023;44. https://doi.org/10.1016/j.amjoto.2022.103702.
Yadav H, Sen S, Nath T, Mazumdar S, Jain A, Verma P, et al. Analysis of COVID-19-associated rhino-orbital-cerebral mucormycosis patients in a tertiary care center in Northern India. Indian J Ophthalmol 2022;70:2163–8. https://doi.org/10.4103/ijo.IJO_340_22.
Watanabe A, So M, Mitaka H, Ishisaka Y, Takagi H, Inokuchi R, et al. Clinical features and mortality of COVID-19-associated mucormycosis: a systematic review and meta-analysis. Mycopathologia 2022;187:271–89. https://doi.org/10.1007/s11046-022-00627-8.
Khanam A, Hithamani G, Naveen J, Pradeep SR, Barman S, Srinivasan K. Management of invasive infections in diabetes mellitus: a comprehensive review. Biologics 2023;3. https://doi.org/10.3390/biologics3010004.
Bhattacharyya A, Sarma P, Sharma D, Das K, Kaur H, Prajapat M, et al. Rhino-orbital-cerebral-mucormycosis in COVID-19: a systematic review. Indian J Pharmacol 2021;53:317–27. https://doi.org/10.4103/ijp.ijp_419_21.
Dessie ZG, Zewotir T. Mortality-related risk factors of COVID-19: a systematic review and meta-analysis of 42 studies and 423,117 patients. BMC Infect Dis 2021;21. https://doi.org/10.1186/s12879-021-06536-3.
Alejandra Quintero Bauman, Lugo Machado JA, Sainz Fuentes N, Arellano Rodríguez IC, Canche Martín EM, Reina Loaiza JR, et al. Factores de riesgo asociados con mortalidad en pacientes con mucormicosis rino-órbito-cerebral y COVID-19. Med Int Méx 2023;39:734–42. https://doi.org/10.24245/mim.v39i5.8443.
Kulkarni R, Pujari S, Gupta D, Advani S, Soni A, Duberkar D, et al. Rhino-orbito-cerebral mycosis and COVID-19: From bad to worse? Ann Indian Acad Neurol 2022;25. https://doi.org/10.4103/aian.aian_463_21.
John TM, Jacob CN, Kontoyiannis DP. When uncontrolled diabetes mellitus and severe COVID-19 converge: the perfect storm for mucormycosis. J Fungi 2021;7. https://doi.org/10.3390/jof7040298.
Das D, Bajaj M, Modaboyina S, Agrawal S. Rhino-orbito-cerebral mucormycosis in COVID 19 patients: understanding the pathophysiology. Kerala J Ophthalmol 2021;33. https://doi.org/10.4103/kjo.kjo_152_21.
Kumar S, Kumar H, Mali M, Meena BL. A study of rhino-orbito-cerebral mucormycosis with COVID-19: a new challenge in North West of Rajasthan. Ann Afr Med 2022;21(4):383-389. https://doi.org/10.4103/aam.aam_129_21.
Lass-Flörl C, Steixner S. The changing epidemiology of fungal infections. Mol Aspects Med. 2023;94:101215. https://doi.org/10.1016/j.mam.2023.101215
Raut A, Huy NT. Rising incidence of mucormycosis in patients with COVID-19: another challenge for India amidst the second wave? Lancet Respir Med. 2021;9(8):e77. https://doi.org/10.1016/S2213-2600(21)00265-4
Eker C, Tarkan O, Surmelioglu O, Dagkiran M, Tanrisever I, Yucel Karakaya SP, et al. Alternating pattern of rhino-orbital–cerebral mucormycosis with COVID-19 in diabetic patients. Eur Arch Otorhinolaryngol. 2023;280(2):849–58. https://doi.org/10.1007/s00405-022-07526-0
Jadhav H, Vishwakarma P, Thamke S, Pundkar S, Takle T, Khairnar M. Correlation of mucormycosis with various clinical parameters among COVID-19 patients: a cross-sectional study. J Maxillofac Oral Surg. 2023. https://doi.org/10.1007/s12663-023-01919-2
Issa RS, Mushtaq G, Unnisa A, Mahli A. A case of concomitant leukemoid reaction and mucormycosis in a patient with severe COVID-19 infection. Turk J Biochem. 2023;48(1):93–6. https://doi.org/10.1515/tjb-2023-0016
Ghasemi S, Dashti M, Fahimipour A, Daryakenari G, Mirzaei F, Akbari F, et al. Onset of mucormycosis in patients with COVID-19: a systematic review on patients’ characteristics. Eur J Dent. 2023;17(1):8–16. https://doi.org/10.1055/s-0042-1751003
Slavin M, van Hal S, Sorrell TC, Lee A, Marriott DJ, Daveson K, et al. Invasive infections due to filamentous fungi other than Aspergillus: epidemiology and determinants of mortality. Clin Microbiol Infect. 2015;21(6):490.e1–e10. https://doi.org/10.1016/j.cmi.2014.12.021
Lin E, Moua T, Limper AH. Pulmonary mucormycosis: clinical features and outcomes. Infection. 2017;45(4):443–8. https://doi.org/10.1007/s15010-017-0991-6
Prakash H, Ghosh AK, Rudramurthy SM, Singh P, Xess I, Savio J, et al. A prospective multicenter study on mucormycosis in India: epidemiology, diagnosis, and treatment. Med Mycol. 2019;57(4):395–402. https://doi.org/10.1093/mmy/myy060
Prakash H, Chakrabarti A. Global epidemiology of mucormycosis. Journal of Fungi 2019;5. https://doi.org/10.3390/jof5010026.
Ribes JA, Vanover-Sams CL, Baker DJ. Zygomycetes in human disease. Clin Microbiol Rev 2000;13. https://doi.org/10.1128/CMR.13.2.236-301.2000.
McMahon D, Frangos J. 15109 Cutaneous zygomycosis presenting as resistant intertrigo in an immunocompromised adult. J Am Acad Dermatol 2020;83. https://doi.org/10.1016/j.jaad.2020.06.202.
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. Clinical Microbiology and Infection 2019;25. https://doi.org/10.1016/j.cmi.2018.07.011.
Petrikkos G, Skiada A, Lortholary O, Roilides E, Walsh TJ, Kontoyiannis DP. Epidemiology and clinical manifestations of mucormycosis. Clinical Infectious Diseases 2012;54. https://doi.org/10.1093/cid/cir866.
Sodhi SPS, Brar GK, Sodhi DPS, Brar GS, Gupta S, Malhotra M. Post COVID Fungal Osteomyelitis—Another Killer. J Pharm Bioallied Sci 2023;15. https://doi.org/10.4103/jpbs.jpbs_37_23.
Mukherjee B, Raichura ND, Alam MS. Fungal infections of the orbit. Indian J Ophthalmol 2016;64. https://doi.org/10.4103/0301-4738.185588.
Nicolás S, Enmanuel P, Betsabe S, Patricia L. Cavernous Sinus Thrombosis as a Complication of Cerebro-Rhino Orbital Mucormycosis Associated With Covid-19: A Case Report. International Journal of Oral and Dental Health 2022;8. https://doi.org/10.23937/2469-5734/1510147.
Castañeda Solís KB, Granados Jaramillo C, Barbosa Salazar E, Lozano Hernández DI, Tello Zavala C, Gómez Gutiérrez B. Black fungus in India, is it really pathophysiological related to COVID-19? Ther Adv Infect Dis 2021;8.
Karkhur S, Soni D, Chauhan K, Sarkar D, Gautam M, Verma S, et al. Rhino-orbito-cerebral mucormycosis and its resurgence during COVID-19 pandemic: A review. Indian J Ophthalmol 2023;71. https://doi.org/10.4103/ijo.IJO_1219_22.
Thornton CR. The potential for rapid antigen testing for mucormycosis in the context of COVID-19. Expert Rev Mol Diagn 2024;24. https://doi.org/10.1080/14737159.2023.2233906.
DiBartolo MA, Kelley PS. Rhino-Orbital-Cerebral Mucormycosis (ROCM):A comprehensive case review. Aviat Space Environ Med 2011;82. https://doi.org/10.3357/ASEM.3036.2011.
Rincón CCA, Silva-Ramos CR, Arancibia JA, Prada-Avella MC, Suárez A. Rhino-orbito-cerebral mucormycosis in an acute lymphoblastic leukemia pediatric patient. Case report and review of literature. Infezioni in Medicina 2022;30. https://doi.org/10.53854/liim-3002-17.
Manchanda S, Semalti K, Bhalla AS, Thakar A, Sikka K, Verma H. Revisiting rhino-orbito-cerebral acute invasive fungal sinusitis in the era of COVID-19: pictorial review. Emerg Radiol 2021;28. https://doi.org/10.1007/s10140-021-01980-9.
Ostovan VR, Tabrizi R, Bazrafshan H, Bahrami Z, Khazraei H, Khazraei S, et al. Mortality-Related Risk Factors for Coronavirus Disease (COVID-19)-Associated Mucormycosis: a systematic review and meta-analysis. Curr Fungal Infect Rep 2022;16. https://doi.org/10.1007/s12281-022-00440-2.
Chopra S, Setiya S, Waknis PP, Kale L, Tidke S. Various Treatment Modalities in COVID-19 Associated Facial Mucormycosis and the Need for its Surgical Management: A Systematic Review. J Maxillofac Oral Surg 2023. https://doi.org/10.1007/s12663-023-01878-8.
Wei LW, Zhu PQ, Chen XQ, Yu J. Mucormycosis in Mainland China: A Systematic Review of Case Reports. Mycopathologia 2022;187. https://doi.org/10.1007/s11046-021-00607-4.
Nagarkar NM, Sahu V, Arora R, Pathak M, Shambharkar MS, Naveen P. Mortality and its determinants after an outbreak of post COVID-19 associated rhino-orbito-cerebral mucormycosis in Central India. Int Ophthalmol 2023;43. https://doi.org/10.1007/s10792-023-02634-0.
Patel A, Kaur H, Xess I, Michael JS, Savio J, Rudramurthy S, et al. A multicentre observational study on the epidemiology, risk factors, management and outcomes of mucormycosis in India. Clinical Microbiology and Infection 2020;26. https://doi.org/10.1016/j.cmi.2019.11.021.
Skiada A, Pagano L, Groll A, Zimmerli S, Dupont B, Lagrou K, 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. Clinical Microbiology and Infection 2011;17. https://doi.org/10.1111/j.1469-0691.2010.03456.x.
Davitt E, Davitt C, Mazer MB, Areti SS, Hotchkiss RS, Remy KE. COVID-19 disease and immune dysregulation. Best Pract Res Clin Haematol 2022;35. https://doi.org/10.1016/j.beha.2022.101401.
Proal AD, VanElzakker MB. Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms. Front Microbiol 2021;12. https://doi.org/10.3389/fmicb.2021.698169.
Tariq S, Van Eeden C, Tervaert JWC, Osman MS. COVID-19, rheumatic diseases and immune dysregulation—a perspective. Clin Rheumatol 2021;40. https://doi.org/10.1007/s10067-020-05529-y.
Hughes S, Troise O, Donaldson H, Mughal N, Moore LSP. Bacterial and fungal coinfection among hospitalized patients with COVID-19: a retrospective cohort study in a UK secondary-care setting. Clinical Microbiology and Infection 2020;26. https://doi.org/10.1016/j.cmi.2020.06.025.
Pandiar D, Kumar NS, Anand R, Kamboj M, Narwal A, Shameena PM. Does COVID 19 generate a milieu for propagation of mucormycosis? Med Hypotheses 2021;152. https://doi.org/10.1016/j.mehy.2021.110613.
Saleeb MF, Sabry SM, Mahmoud MS, Nassif MM. Risk factors affecting outcome of rhino-orbital-cerebral mucormycosis in COVID-19 patients. Egyptian Journal of Otolaryngology 2023;39. https://doi.org/10.1186/s43163-023-00406-2.
Choksi T, Agrawal A, Date P, Rathod D, Gharat A, Ingole A, et al. Cumulative Mortality and Factors Associated with Outcomes of Mucormycosis after COVID-19 at a Multispecialty Tertiary Care Center in India. JAMA Ophthalmol 2022;140. https://doi.org/10.1001/jamaophthalmol.2021.5201.
Singh A, Goel G, Khan M, Kanodia A, Sikka K, Thakar A. Factors affecting clinical outcome in COVID-associated rhino-orbito-cerebral mucormycosis (CAROM) patients—An ambispective, single-arm, observational study. Am J Otolaryngol 2023;44. https://doi.org/10.1016/j.amjoto.2023.103975.
Martínez MAS, Lugo-Machado JA, Canché-Martín E, Sainz-Fuentes N, Reina-Loaiza R, Rodríguez-Quintana S, et al. Factors associated with survival in diabetic patients with rhino-orbito-cerebral mucormycosis. Rom J Rhinol 2021;11. https://doi.org/10.2478/rjr-2021-0011.
Alejandra Quintero Bauman, Lugo Machado JA, Sainz Fuentes N, Arellano Rodríguez IC, Canche Martín EM, Reina Loaiza JR, et al. Factores de riesgo asociados con mortalidad en pacientes con mucormicosis rino-órbito-cerebral y COVID-19. Med Int Méx 2023;39:734–42. https://doi.org/10.24245/mim.v39i5.8443.
Cag Y, Erdem H, Gunduz M, Komur S, Ankarali H, Ural S, et al. Survival in rhino-orbito-cerebral mucormycosis: An international, multicenter ID-IRI study. Eur J Intern Med 2022;100. https://doi.org/10.1016/j.ejim.2022.03.008.
Hutton B, Catalá-López F, Moher D. The PRISMA statement extension for systematic reviews incorporating network meta-analysis: PRISMA-NMA. Med Clin (Barc) (Eng Ed) 2016;147:262–6. https://doi.org/10.1016/j.medcle.2016.10.003.
Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group T. Ítems de referencia para publicar Revisiones Sistemáticas y Metaanálisis: La Declaración PRISMA. Rev Esp Nutr Hum Diet 2014;18. https://doi.org/10.14306/renhyd.18.3.114.
Wells G, Shea B, O’Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality if nonrandomized studies in meta-analyses. (Available from: URL: Http://WwwOhri.ca/Programs/Clinical_epidemiology/OxfordAsp) 2012. https://doi.org/10.2307/632432.
Wells G, Shea B, O’Connell D, Peterson J. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa, ON: Ottawa Hospital Research Institute 2000.
Yu F, Liu C, Sharmin S. Performance, usability, and user experience of Rayyan for systematic reviews. Proc Assoc Inf Sci Technol 2022;59. https://doi.org/10.1002/pra2.745.
Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan-a web and mobile app for systematic reviews. Syst Rev 2016;5. https://doi.org/10.1186/s13643-016-0384-4.
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 Maxillofac Oral Surg 2021;20. https://doi.org/10.1007/s12663-021-01532-1.
Dravid A, Kashiva R, Khan Z, Bande B, Memon D, Kodre A, et al. Epidemiology, clinical presentation and management of COVID-19 associated mucormycosis: A single centre experience from Pune, Western India. Mycoses 2022;65:526–40. https://doi.org/10.1111/myc.13435.
Keshri A, Mathialagan A, Aishwarya A, Ravisankar, Bhuskute G, Kanaujia V, et al. Is mucormycosis the end? A comprehensive management of orbit in COVID associated rhino-orbital–cerebral mucormycosis: preserving the salvageable. Eur Arch Otorhinolaryngol 2023;280:819–27. https://doi.org/10.1007/s00405-022-07620-3.
Fakhim H, Irani S, Yassin Z, Badali H, Nasri E, Nasoori Y, et al. Features and evaluation of mucormycosis in COVID-19 patients from two referral hospitals in Iran. J Med Mycol 2024;34. https://doi.org/10.1016/j.mycmed.2024.101480.
Nair KS, Alagesan M, Jose D, Yoganathan C, Saravanan R, Karthikeyan K, et al. Clinical profile and factors associated with adverse outcomes in coronavirus disease 2019-associated mucormycosis: a single-centre study. US Endocrinol 2023;19:73–9. https://doi.org/10.17925/EE.2023.19.2.2.
Muraleedharan M, Panda NK, Angrish P, Arora K, Patro SK, Bansal S, et al. As the virus sowed, the fungus reaped! A comparative analysis of the clinico-epidemiological characteristics of rhino-orbital mucormycosis before and during COVID-19 pandemic. Mycoses 2022;65:567–76. https://doi.org/10.1111/myc.13437.
Avatef Fazeli M, Rezaei L, Javadirad E, Iranfar K, Khosravi A, Amini Saman J, et al. Increased incidence of rhino-orbital mucormycosis in an educational therapeutic hospital during the COVID-19 pandemic in western Iran: an observational study. Mycoses 2021;64:1366–77. https://doi.org/10.1111/myc.13351.
Rajabi MT, Aghajani A, Rafizadeh SM, Jamshidian Tehrani M, Poursayed Lazarjani SZ, Keshmirshekan MM, et al. COVID-19 associated rhino-orbito-cerebral mucormycosis, risk factors and outcome predictors; a multicentric study. Int Ophthalmol 2023;43:1375–86. https://doi.org/10.1007/s10792-022-02536-7.
Kordjazi M, Bazgir N, Eftekharian K, Farajpour M, Dilmaghani NA. Manifestations of mucormycosis and its complications in COVID-19 patients: a case series study. Ear Nose Throat J 2024;103:145S–52S. https://doi.org/10.1177/01455613221143859.
Fatima N, Ahmed S, Shameem M, Ahmed A, Hasan W, Khan PA. Rhino-orbito-cerebral mucormycosis during Covid-19 pandemic—a prospective observational study. Indian J Med Microbiol 2023;46. https://doi.org/10.1016/j.ijmmb.2023.100467.
Nagarkar NM, Sahu V, Arora R, Pathak M, Shambharkar MS, Naveen P. Mortality and its determinants after an outbreak of post COVID-19 associated rhino-orbito-cerebral mucormycosis in Central India. Int Ophthalmol 2023;43:2363–70. https://doi.org/10.1007/s10792-023-02634-0.
Rudramurthy SM, Singh S, Kanaujia R, Chaudhary H, Muthu V, Panda N, et al. Clinical and mycologic characteristics of emerging mucormycosis agent Rhizopus homothallicus. Emerg Infect Dis 2023;29:1313–22. https://doi.org/10.3201/eid2907.221491.
Kumari S, Pandey S, Verma M, Rana AK, Kumari S. Clinicopathological challenges in tumors of the nasal cavity and paranasal sinuses: our experience. Cureus 2022;14(9):e29128. https://doi.org/10.7759/cureus.29128.
Yadav V, Bhagat S, Goel K, Sibia RS, Sharma DK, Sidhu T, et al. Outcomes of COVID-19-associated mucormycosis epidemic in India: A prospective 2-year follow-up study. World J Otorhinolaryngol Head Neck Surg 2024. https://doi.org/10.1002/wjo2.162.
Shaikh Z, Mishra A, Chadaram S, Preetam C, Biswas R, Adhikari A, et al. To evaluate the efficacy of topical anti-fungal therapy in postoperative cases of COVID Associated Mucormycosis (CAM): A single-blinded randomized control trial. Am J Otolaryngol 2023;44. https://doi.org/10.1016/j.amjoto.2022.103702.
Yadav H, Sen S, Nath T, Mazumdar S, Jain A, Verma P, et al. Analysis of COVID-19-associated rhino-orbital-cerebral mucormycosis patients in a tertiary care center in Northern India. Indian J Ophthalmol 2022;70:2163–8. https://doi.org/10.4103/ijo.IJO_340_22.
Watanabe A, So M, Mitaka H, Ishisaka Y, Takagi H, Inokuchi R, et al. Clinical features and mortality of COVID-19-associated mucormycosis: a systematic review and meta-analysis. Mycopathologia 2022;187:271–89. https://doi.org/10.1007/s11046-022-00627-8.
Khanam A, Hithamani G, Naveen J, Pradeep SR, Barman S, Srinivasan K. Management of invasive infections in diabetes mellitus: a comprehensive review. Biologics 2023;3. https://doi.org/10.3390/biologics3010004.
Bhattacharyya A, Sarma P, Sharma D, Das K, Kaur H, Prajapat M, et al. Rhino-orbital-cerebral-mucormycosis in COVID-19: a systematic review. Indian J Pharmacol 2021;53:317–27. https://doi.org/10.4103/ijp.ijp_419_21.
Dessie ZG, Zewotir T. Mortality-related risk factors of COVID-19: a systematic review and meta-analysis of 42 studies and 423,117 patients. BMC Infect Dis 2021;21. https://doi.org/10.1186/s12879-021-06536-3.
Alejandra Quintero Bauman, Lugo Machado JA, Sainz Fuentes N, Arellano Rodríguez IC, Canche Martín EM, Reina Loaiza JR, et al. Factores de riesgo asociados con mortalidad en pacientes con mucormicosis rino-órbito-cerebral y COVID-19. Med Int Méx 2023;39:734–42. https://doi.org/10.24245/mim.v39i5.8443.
Kulkarni R, Pujari S, Gupta D, Advani S, Soni A, Duberkar D, et al. Rhino-orbito-cerebral mycosis and COVID-19: From bad to worse? Ann Indian Acad Neurol 2022;25. https://doi.org/10.4103/aian.aian_463_21.
John TM, Jacob CN, Kontoyiannis DP. When uncontrolled diabetes mellitus and severe COVID-19 converge: the perfect storm for mucormycosis. J Fungi 2021;7. https://doi.org/10.3390/jof7040298.
Das D, Bajaj M, Modaboyina S, Agrawal S. Rhino-orbito-cerebral mucormycosis in COVID 19 patients: understanding the pathophysiology. Kerala J Ophthalmol 2021;33. https://doi.org/10.4103/kjo.kjo_152_21.
Kumar S, Kumar H, Mali M, Meena BL. A study of rhino-orbito-cerebral mucormycosis with COVID-19: a new challenge in North West of Rajasthan. Ann Afr Med 2022;21(4):383-389. https://doi.org/10.4103/aam.aam_129_21.
Lugo Machado, J. A., Espinoza Morales, D. I., Serrano Armenta, J., Gutiérrez Pérez, M. L., & Zazueta Cárdenas, A. (2025). Rhino-orbital-cerebral mucormycosis associated with COVID-19 and mortality-related factors: a systematic review. Revista ORL, e33029. https://doi.org/10.14201/orl.33029
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