Treatment perspectives and challenges in antifungal therapy for mucormycosis in patients with COVID-19
DOI:
https://doi.org/10.33448/rsd-v14i3.48442Keywords:
Fungal infections, Comorbidity, Antifungal agents, Disease management.Abstract
The COVID-19 pandemic has led to an increase in opportunistic infections, such as mucormycosis, better known as “black fungus”, which has become prevalent in various parts of the world, especially in India. This fungal infection is highly debilitating and has high rates of morbidity and mortality, with antifungal therapy focused on conventional antifungal drugs with or without successful treatment. Therefore, the objective of this study was to identify the main perspectives and challenges caused by antifungal treatment in patients who acquired COVID-19 and, consequently, mycosis caused by fungi of the order Mucorales. To this end, an integrative literature review was carried out based on a five-step planning: elaboration of the research question (identification of the problem), search for studies in the literature, evaluation of the studies, data analysis, and presentation of the review, which used the PICO strategy. During the search in the databases, 292 studies were initially found (Science Direct=112, PubMed=35, Scielo=1 and MEDLINE=144), of which 38 studies were included. Among the studies, it was noted that there is a greater need for early diagnosis, as well as the production of intensive clinical management, especially for patients with comorbidities; and there is also a lack of production of specific protocols for cases of mucormycosis related to COVID-19 in order to improve clinical outcomes.
Downloads
References
Abraham, A. M.; Mathew, G.; Thomas, S.; Nair, R.; & Kurian, B. (2024). Observational study on the clinical profile and treatment outcome on long-term follow-up of COVID-19 associated mucormycosis. Journal of Medical Mycology, p. 101491.
Alshahawey, M.; El-Housseiny, G. S.; Elsayed, N. S.; Alshahrani, M. Y.; EL-Wakeel, L. M.; & Aboshanab, K. M. (2022). New insights on mucormycosis and its association with the COVID-19 pandemic. Future Science OA, 8(2), FSO772.
Bayram, N.; Celikbaş, A. K.; Kaşka, B.; Gül, D.; Bozkurt, Y.; Düzenli, N.; & Erdöl, H. (2021). Susceptibility of severe COVID-19 patients to rhino-orbital mucormycosis fungal infection in different clinical manifestations. Japanese Journal of Ophthalmology, 65(4), 515-525.
Chakravarty, J.; Kumar, A.; Singh, A.; Singh, R.; Yadav, R.; & Srivastava, V. (2022). COVID-19-associated mucormycosis: a clinico-epidemiological study. Journal of Diabetes and its Complications, 36(9), 108284.
Chakravarty, J.; Singh, S.; Raut, A.; Sharma, A.; Prasad, S.; Verma, N.; & Pandey, A. (2022). COVID-19-associated Mucormycosis: A clinico-epidemiological study. Journal of Diabetes and its Complications, 36(9), 108284.
Chandra, S.; Sharma, S.; Vats, R.; & Pandey, S. (2021). Isolated cerebral mucormycosis masquerading as a tumor in an immunocompetent patient. Autopsy and Case Reports, 11, e2020233.
Chao, C. ; Lai, C.; & Yu, W. (2022). COVID-19 associated mucormycosis–An emerging threat. Journal of Microbiology, Immunology and Infection, 55(2), 183-190.
Chatterjee, S.; Mondal, S.; Pal, R.; Sinha, P.; Ghosh, S.; & Roy, D. (2022). Pharmacovigilance study of amphotericin B for mucormycosis in post-COVID and non-COVID patients at a tertiary care hospital in Eastern India. Indian Journal of Pharmacology, 54(6), 417-422.
Dandu, H.; Sharma, V.; Singh, R.; Gupta, A.; Khandelwal, P.; Mehrotra, R.; & Kumar, A. (2024). Utility of Itraconazole in Combination with Liposomal Amphotericin B in Rhizopus oryzae Associated Mucormycosis–An Exploratory Study. Mycopathologia, 189(4), 54.
Dave, T. V.; Nair, A. G.; Homi, R.; Desai, S.; Gandhi, R. A.; Shukla, D.; Kalra, M. K.; & Mukherjee, B. (2021). Clinical presentations, management and outcomes of rhino-orbital-cerebral mucormycosis (ROCM) following COVID-19: a multi-centric study. Ophthalmic Plastic & Reconstructive Surgery, 37(5), 488–495.
Dravid, A.; Saoji, R.; Bhalerao, M.; Gaikwad, P.; Doshi, R.; & Jog, S. (2022). Epidemiology, clinical presentation and management of COVID‐19 associated mucormycosis: A single centre experience from Pune, Western India. Mycoses, 65(5), 526-540.
Eshraghi, B.; Rahimi, M.; Amini, A.; Shirazi, M. T.; Nasiri, M.; Karimi, Z.; & Sadeghi, A. (2024). Risk Factors of COVID-19 associated mucormycosis in Iranian patients: a multicenter study. BMC Infectious Diseases, 24(1), 852.
Gandhi, A.; Kumar, A.; Gupta, N.; Sharma, P.; Yadav, H.; & Sharma, R. (2023). Battling the emerging epidemic of rhino-orbital-cerebral mucormycosis (ROCM) in COVID-19 pandemic: an interventional study. International Ophthalmology, 43(5), 1571–1580.
Ghelfenstein-Ferreira, T.; Serris, A.; Salmona, M.; Lanternier, F.; & Alanio, A. (2024). Revealing the hidden interplay: The unexplored relationship between fungi and viruses beyond HIV, SARS-CoV-2, and influenza. Medical Mycology, 62(4), myae021.
He, Q.; Liu, X.; Zhao, S.; Zhang, J.; Chen, S.; Li, M.; & Zhou, Yu. (2023). Efficacy and safety of glucocorticoids use in patients with COVID-19: a systematic review and network meta-analysis. BMC Infectious Diseases, 23(1), 896.
Hussain, M. K.; Khan, M. S.; Ahmad, I.; Shariq, A.; Singh, M.; Naeem, A.; & Khan, R. A. (2023). Mucormycosis: A hidden mystery of fungal infection, possible diagnosis, treatment and development of new therapeutic agents. European Journal of Medicinal Chemistry, 246, 115010.
Jain, V.; Sharma, A.; Kapoor, S.; Gupta, P.; Kumar, A.; & Agrawal, R. (2023). Hit or Miss: The dilemma of specimen selection for microbiological diagnosis of rhino-orbital-cerebral-COVID-associated mucormycosis (ROCM-CAM). Infectious Disorders-Drug Targets (Formerly Current Drug Targets-Infectious Disorders), 23(1), 62-69.
Keshri, A.; Kumar, A.; Kumar, S.; Pandey, R.; & Singh, P. (2023). Is mucormycosis the end? A comprehensive management of orbit in COVID-associated rhino-orbital–cerebral mucormycosis: preserving the salvageable. European Archives of Oto-Rhino-Laryngology, 280(2), 819-827.
Khare, P.; Chaurasia, Y.; & Bhatnagar, S. (2022). Exploring the globe salvaging treatment options in patients of COVID-19-associated mucormycosis with orbital involvement. Indian Journal of Ophthalmology, 70(10), 3638-3642.
Kulkarni, R.; Misra, U. K.; Meshram, C.; Kochar, D.; Modi, M.; Vishnu, Venugopalan, Y.; Garg, R. K.; & Surya, N. (2022). Epidemic of mucormycosis in COVID-19 pandemic: a position paper. Annals of Indian Academy of Neurology, 25(1), 7–10.
Lockhart, Shawn R.; & Guarner, J. Emerging and reemerging fungal infections. (2019). In: Seminars in diagnostic pathology. WB Saunders. p. 177-181.
Madikonda, P. K.; Perugu, S. B.; & Ramadevi, C. H. (2022) Effect of Ayurvedic Intervention as an adjunct therapy in Post COVID-19 Mucormycosis (PCM): a non-randomized parallel group study. Journal of Ayurveda and Integrative Medicine, 13(4), 100672.
Madikonda, P. K.; Perugu, S. B.; & Ramadevi, C. H. (2022). Effect of Ayurvedic Intervention as an adjunct therapy in Post COVID-19 Mucormycosis (PCM): a non-randomized parallel group study. Journal of Ayurveda and Integrative Medicine, 13(4), 100672.
Manesh, A.; John, A. O.; Mathew, S. K.; Jayaseelan, V. P.; Thomas, P. P.; Karthik, R.; & Abraham, O. C. (2023). Short intravenous amphotericin B followed by oral posaconazole using a simple, stratified treatment approach for diabetes or COVID-19-associated rhino-orbito-cerebral mucormycosis: a prospective cohort study. Clinical Microbiology and Infection, 29(10), 1298-1305.
Meher, R.; Kaushalya, B.; Khatri, I.; Khurana, N.; Panda, S.; Tripathy, A.; & Sahoo, N. (2022). COVID associated mucormycosis: a preliminary study from a dedicated COVID Hospital in Delhi. American Journal of Otolaryngology, 43(1), 103220.
Merchán-Hamann, E.; & Tauil, P. L. (2021). Proposta de classificação dos diferentes tipos de estudos epidemiológicos descritivos. Epidemiologia e Serviços de Saúde, 30, e2018126.
Mitra, S.; Janweja, M.; & Sengupta, A. (2021). Post-COVID-19 rhino-orbito-cerebral mucormycosis: a new addition to challenges in pandemic control. European Archives of Oto-Rhino-Laryngology, p. 1-6.
Mrig, S.; Ahuja, R.; Prasad, K. T. V.; Shukla, S.; Gupta, M.; Verma, A. K.; & Singh, D. (2022). Adjunctive use of saturated solution of potassium iodide (SSKI) with liposomal amphotericin B (L-AMB) in mucormycosis achieves favorable response, shortened dose and duration of amphotericin: A retrospective study from a COVID-19 tertiary care center. American Journal of Otolaryngology, 43(3), 103465.
Nagarkar, N. M.; Gupta, V.; Sharma, P.; Choubey, V.; Sharma, D.; & Jain, P. (2023). Mortality and its determinants after an outbreak of post COVID-19 associated rhino-orbito-cerebral mucormycosis in Central India. International Ophthalmology, 43(7), 2363-2370.
Nair, A. G.; Gupta, R.; Kumar, A.; Goel, M.; Goel, N.; & Rajan, J. (2021). Rhino-orbital mucormycosis following COVID-19 in previously non-diabetic, immunocompetent patients. Orbit, 40(6), 499-504.
Organização Mundial da Saúde. (s.d.). Mucormicose. https://www.who.int/india/home/emergencies/coronavirus-disease-(covid-19)/mucormycosis.
Pakdel, F.; Maleki, M.; Ahmadi, M.; Mokhtari, E.; Khoshdel, A. R.; Abbasi, H.; Jamali, S. H.; & Hashemi, S. J. (2021). Mucormycosis in patients with COVID‐19: a cross‐sectional descriptive multicentre study from Iran. Mycoses, 64(10), 1238-1252.
Patel, A.; Kothari, A.; Aggarwal, R.; Singh, A. K.; Das, S.; Saha, R.; Mukherjee, P.; & Mehra, S. (2021). Multicenter epidemiologic study of coronavirus disease–associated mucormycosis, India. Emerging Infectious Diseases, 27(9), 2349.
Pereira, A. S., Shitsuka, D. M., Parreira, F. J., & Shitsuka, R. (2018). Metodologia da pesquisa científica. free e-book]. Editora UAB/NTE/UFSM, Brasil.
Prakash, Hariprasath; Chakrabarti, & Arunaloke. (2019). Global epidemiology of mucormycosis. Journal of Fungi, 5(1), 26.
Pulle, M. V.; Reddy, V.; Jain, R.; Kumar, A.; Singh, P.; Sharma, S.; & Gupta, K. (2023). COVID associated pulmonary mucormycosis: Outcomes of surgical therapy. Asian Cardiovascular and Thoracic Annals, 31(2), 133-141.
Raj, A.; Sharma, R.; Gupta, P.; Singh, N.; Chaudhary, V.; & Yadav, R. (2024). Survival benefit of exenteration in COVID-19-associated rhino-orbital mucormycosis. Indian Journal of Ophthalmology, 72(2), 190-194.
Rajendra Santosh, Ab; Muddana, K.; & Bakki, Sr. (2021). Fungal infections of oral cavity: diagnosis, management, and association with COVID-19. SN Comprehensive Clinical Medicine, 3(6), 1373–1384.
Ramaswami, A.; Srivastava, S.; Shankar, S.; Sarin, Y. K.; Gupta, S.; Pandey, P.; & Singh, V. (2021). COVID-19-associated mucormycosis presenting to the Emergency Department—an observational study of 70 patients. QJM: An International Journal of Medicine, 114(7), 464-470.
Ravani, S. A.; Agarwal, D.; Gupta, M.; Gupta, S.; Rakheja, V.; Kadwani, H.; & Goyal, S. (2021). Rise of the phoenix: Mucormycosis in COVID-19 times. Indian Journal of Ophthalmology, 69(6), 1563-1568.
Sahu, M.; Maji, A.; Panda, S.; Das, S.; Roy, S.; Mahakur, B.; & Parida, P. K. (2023). COVID-19 associated multisystemic mucormycosis from India: a multicentric retrospective study on clinical profile, predisposing factors, cumulative mortality and factors affecting outcome. Infection, 51(2), 407-416.
Schwarz, P.; Cornely, O. A. & Dannaoui, E. (2019). Antifungal combinations in Mucorales: a microbiological perspective. Mycoses, 62(9), 746–760.
Selarka, L.; Chauhan, Z.; Shah, M.; Trivedi, M.; Patel, S.; Sheth, R. & Shah, M. (2021). Mucormycosis and COVID‐19: an epidemic within a pandemic in India. Mycoses, 64(10), 1253-1260.
Shaikh, Z.; Khan, S.; Patil, M.; Desai, R. & Joshi, A. (2023). To evaluate the efficacy of topical anti-fungal therapy in postoperative cases of COVID Associated Mucormycosis (CAM): A single-blinded randomized control trial. American Journal of Otolaryngology, 44(2), 103702.
Shakrawal, J.; Agarwal, A.; Sharma, S.; Khandelwal, A.; Singh, V. & Verma, S. (2023). Outcomes of transcutaneous retrobulbar Amphotericin B (TRAMB) as an adjuvant therapy for rhino-orbital-cerebral mucormycosis (ROCM) following COVID-19. International Ophthalmology, 43(6), 1919-1926.
Sharma, A. & Goel, A. (2022). Mucormycosis: risk factors, diagnosis, treatments, and challenges during COVID-19 pandemic. Folia Microbiologica, 67(3), 363–387.
Sharma, S.; Grover, M.; Bhargava, S.; Samdhani, S. & Kotwal, A. (2021). Post coronavirus disease mucormycosis: a deadly addition to the pandemic spectrum. The Journal of Laryngology & Otology, 135(5), 442-447.
Shen, M.; Li, J.; Zhang, Y.; Wang, X.; Zhou, Y. & Chen, H. (2023). The outcome and the risk factors of mucormycosis among patients with hematological diseases: A systematic and meta-analysis. Frontiers in Medicine, 10, 1268840.
Smith, C. & Lee, S. C. (2022). Current treatments against mucormycosis and future directions. PLoS Pathogens, 18(10), e1010858.
Snyder, Hannah (2019). Literature review as a research methodology: An overview and guidelines. Journal of business research, 104, 333-339.
Soman, R.; Chakraborty, S. & Joe, G. (2022). Posaconazole or isavuconazole as sole or predominant antifungal therapy for COVID-19-associated mucormycosis: A retrospective observational case series. International Journal of Infectious Diseases, 120, 177-178.
Soni, K.; Agarwal, A.; Singh, P.; Verma, A.; Pandey, R. & Shukla, R. (2022). Surgical & medical management of ROCM (Rhino-orbito-cerebral mucormycosis) epidemic in COVID-19 era and its outcomes – A tertiary care center experience. Journal of Medical Mycology, 32(2), 101238.
Tashiro, M.; Hayakawa, J.; Wakatsuki, H.; Kasai, D.; Tanaka, Reiko; Takashima, A.; Kohno, S. & Matsumoto, T. (2023). Prognostic association of liposomal amphotericin B doses above 5 mg/kg/d in mucormycosis: a nationwide epidemiologic and treatment analysis in Japan. In: Open Forum Infectious Diseases. US: Oxford University Press. p. ofad480.
Vare, A. A.; Mundhe, S. A.; Ghanvate, S. A.; Jadhav, S. P. & Shetty, V. P. (2021). Incidence, cumulative mortality and factors affecting the outcome of COVID-19-associated mucormycosis from Western India. Indian Journal of Ophthalmology, 69(12), 3678-3683.
Vijayasekhar, M. V.; Sharma, P.; Reddy, K. S.; Kumar, P. & Kumar, N. (2022). Post-covid cerebral mucormycosis, varied presentations and surgical strategies of a newer epidemic: an institutional experience. Neurology India, 70(3), 1052-1056.
Whittemore, R. & Knafl, K. (2005). The integrative review: updated methodology. Journal of advanced nursing, 52(5), 546-553.
Yadav, D. S.; Jain, A.; Sharma, P.; Agarwal, A.; Singh, R.; Meena, M. & Bhati, P. (2023). Coronavirus Disease-19-associated Mucormycosis: A Single-center Observational Study of 69 Patients. The Journal of the Association of Physicians of India, 72(10), 24-31, 2023.
Yadav, H.; Aggarwal, S.; Kaushik, G.; Sharma, R.; Singh, A.; Garg, D. & Mahajan, M. (2022). Analysis of COVID-19-associated rhino-orbital-cerebral mucormycosis patients in a tertiary care center in Northern India. Indian Journal of Ophthalmology, 70(6), 2163–2168.
Yadav, R.; Singh, A.; Mittal, S.; Khanna, R. C.; Singh, S.; Anupurath, S. & Singh, N. (2022). Corneal manifestations and treatment among patients with COVID-19-associated rhino-orbito-cerebral mucormycosis. Indian Journal of Ophthalmology, 71(1), 101-108.
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Franciele Maiara de Araújo Castro; Francisca Karolina de Luna Souto; Paula Raquel Ribeiro Silva; Igara Oliveira Lima; Wylly Araújo de Oliveira
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
1) Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
2) Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
3) Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.
