Document Type : Short Communication

Authors

1 Alzahra Research Institute, Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Neurosurgery, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

3 School of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran

4 Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran

5 Department of Cell and Molecular Biology and Microbiology, School of Biological Science and Technology, University of Isfahan, Isfahan, Iran

Abstract

Background: Scarce data are available on the neurological presentations of coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM) and COVID-19-unrelated rhino-orbito-cerebral mucormycosis (ROCM). This study aimed to compare the neurological presentations and their associated outcomes in patients with CAM and COVID-19-unrelated ROCM.
Methods: In December 2021, a case-control analysis was conducted on the CAM (case group) and COVID-19-unrelated ROCM (control group) referrals of one center in Isfahan, Iran. Confirmed CAM patients from January 2020 to December 2021 constituted the case group, and patients with COVID-19-unrelated ROCM from 2016-2019 constituted the control group. Their data were then analyzed using proper (non) parametric tests and generalized linear models (GLM), therein P-value below 0.05 was considered as the criterion of statistical significance, and the SPSS software was used.
Results: After retrieving data on 177 patients with mucormycosis, 78 patients with CAM were included as the case group and 72 patients with COVID-19-unrelated ROCM were included as the control group. Neurological presentations suggestive of second, third, and eighth cranial nerve involvement were more prevalent in the CAM group (all with P < 0.05). 
The mortality rate in the CAM group was 1.9 times that of the controls (P = 0.01), being explained by higher extent of corticosteroid administration among them. Higher age and presentation with gait ataxia, ptosis, and mydriasis were considered to be predictive of poor prognosis in patients with CAM (all with P < 0.05).
Conclusion: The neurological manifestations of CAM differ from COVID-19-unrelated ROCM based on the presented results, some of which are associated with poor prognosis. Further replication is warranted to confirm our retrospective analyses.

Keywords

  1. Katragkou A, Walsh TJ, Roilides E. Why is mucormycosis more difficult to cure than more common mycoses? Clin Microbiol Infect 2014; 20(Suppl 6): 74-81.
  2. Rees JR, Pinner RW, Hajjeh RA, Brandt ME, Reingold AL. The epidemiological features of invasive mycotic infections in the San Francisco Bay area, 1992-1993: Results of population-based laboratory active surveillance. Clin Infect Dis 1998; 27(5): 1138-47.
  3. Torres-Narbona M, Guinea J, Martinez-Alarcon J, Munoz P, Gadea I, Bouza E. Impact of zygomycosis on microbiology workload: A survey study in Spain. J Clin Microbiol 2007; 45(6): 2051-3.
  4. Bayram N, Ozsaygili C, Sav H, Tekin Y, Gundogan M, Pangal E, et al. Susceptibility of severe COVID-19 patients to rhino-orbital mucormycosis fungal infection in different clinical manifestations. Jpn J Ophthalmol 2021; 65(4): 515-25.
  5. 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.
  6. Fouad YA, Abdelaziz TT, Askoura A, Saleh MI, Mahmoud MS, Ashour DM, et al. Spike in rhino-orbital-cerebral mucormycosis cases presenting to a tertiary care center during the COVID-19 pandemic. Front Med (Lausanne) 2021; 8: 645270.
  7. Singh AK, 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.
  8. 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(2-3): 271-89.
  9. Kumar A, Pulle MV, Asaf BB, Puri HV. Covid-associated pulmonary mucormycosis. Lung India 2022; 39(2): 100-1.
  10. Sarkar S, Gokhale T, Choudhury SS, Deb AK. COVID-19 and orbital mucormycosis. Indian J Ophthalmol 2021; 69(4): 1002-4.
  11. Bhat VK, Bongale KR, Basti SP, Gadag RP, Kizhakkilottu N, Sebastian E, et al. Risk factors for palatal and orbital involvement in mucormycosis epidemic-Report of a center in India. Am J Otolaryngol 2022; 43(2): 103371.
  12. Donnelly JP, Chen SC, Kauffman CA, Steinbach WJ, Baddley JW, Verweij PE, et al. Revision and update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. Clin Infect Dis 2020; 71(6): 1367-76.
  13. World Health Organization. WHO COVID-19 Case Definition [Online]. [cited 2022 Feb 6]; Available from: URL: https://www.who.int/publications-detail-redirect/WHO-2019-nCoV-Surveillance_Casea_Definition-2020.
  14. 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.
  15. 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(5): 567-76.
  16. Gamaletsou MN, Sipsas NV, Roilides E, Walsh TJ. Rhino-orbital-cerebral mucormycosis. Curr Infect Dis Rep 2012; 14(4): 423-34.
  17. Kulkarni R, Pujari SS, Gupta D, Ojha P, Dhamne M, Bolegave V, et al. Cerebrovascular involvement in mucormycosis in COVID-19 pandemic. J Stroke Cerebrovasc Dis 2022; 31(2): 106231.
  18. 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.
  19. 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. Clin Microbiol Infect 2020; 26(7): 944.e9-944.e15.