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Current Medicinal Chemistry

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ISSN (Online): 1875-533X

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Review Article

Antibody Responses and CNS Pathophysiology of Mucormycosis in Chronic SARS Cov-2 Infection: Current Therapies Against Mucormycosis

Author(s): Narasimha M. Beeraka, Junqi Liu, Olga Sukocheva, Mikhail Y. Sinelnikov and Ruitai Fan*

Volume 29, Issue 32, 2022

Published on: 13 July, 2022

Page: [5348 - 5357] Pages: 10

DOI: 10.2174/0929867329666220430125326

Price: $65

Abstract

The incidence rate of opportunistic secondary infections through invasive fungi has been observed to be 14.5% to 27% in the SARS CoV pandemic during the year 2003. However, the incidence of SARS CoV-2 is accompanied by a substantial rise in secondary opportunistic infections like mucormycosis (black fungus), mainly in the immunocompromised individuals and diabetic patients taking steroids. Substantial rates of COVID-19 cases with mucormycosis were reported in India and other parts of the world. Previous research reports delineated the ability of Mucorales to invade the various tissues like lungs, brain, and sinus through the GRP78, and subsequently, this infection could invoke crusting, edema, and necrosis of the brain parenchyma, ptosis, proptosis, and vision loss due to intraorbital and intracranial complications. Similarities of these pathophysiological complications with already existing diseases are causing clinicians to face several challenges in order to diagnose and treat this disease effectively at the early stage. This minireview depicts the mucormycosis-induced immune and pathophysiological alterations in COVID-19 patients comorbid with diabetes and immunosuppression and also reported the various clinical manifestations, the therapeutic modalities, and the failures of anti-fungal vaccines. Therefore, the emerging mucormycosis in COVID-19 patients needs rapid investigation and selective optimization of the effective therapeutic modalities, including antifungal vaccines, to minimize the mortality rate.

Keywords: Mucormycosis, corticosteroids, antifungal therapy failure, clinical reports, CNS pathophysiology, chronic SARS Cov-2, antibody responses.

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[1]
Karnik, M.; Beeraka, N.M.; Uthaiah, C.A.; Nataraj, S.M.; Bettadapura, A.D.S.; Aliev, G.; Madhunapantula, S.V. A review on SARS-CoV-2-induced neuroinflammation, neurodevelopmental complications, and recent updates on the vaccine development. Mol. Neurobiol., 2021, 58(9), 4535-4563.
[http://dx.doi.org/10.1007/s12035-021-02399-6] [PMID: 34089508]
[2]
Beeraka, N.M.; Tulimilli, S.V.; Karnik, M.; Sadhu, S.P.; Pragada, R.R.; Aliev, G.; Madhunapantula, S.V. The current status and challenges in the development of vaccines and drugs against severe acute respiratory syndrome-corona virus-2 (SARS-CoV-2). BioMed. Res. Int., 2021, 2021, 8160860.
[3]
Herrera, A.S.; Beeraka, N.M.; Sinelnikov, M.Y.; Nikolenko, V.N.; Giller, D.B.; Solis, L.F.T.; Mikhaleva, L.M.; Somasundaram, S.G.; Kirkland, C.E.; Aliev, G. The beneficial effects of QIAPI 1® against pentavalent arsenic-induced lung toxicity a hypothetical model for SARS CoV2-induced lung toxicity. Curr. Pharm. Biotechnol., 2021.
[4]
Beeraka, N.M.; Sadhu, S.P.; Madhunapantula, S.V.; Rao Pragada, R.; Svistunov, A.A.; Nikolenko, V.N.; Mikhaleva, L.M.; Aliev, G. Strategies for targeting SARS CoV-2: Small molecule inhibitors—The current status. Front. Immunol., 2020, 11, 552925.
[http://dx.doi.org/10.3389/fimmu.2020.552925] [PMID: 33072093]
[5]
Eyre, D.W.; Taylor, D.; Purver, M.; Chapman, D.; Fowler, T.; Pouwels, K.B.; Walker, A.S.; Peto, T.E.A. Effect of covid-19 vaccination on transmission of alpha and delta variants. N. Engl. J. Med., 2022, 386(8), 744-756.
[http://dx.doi.org/10.1056/NEJMoa2116597] [PMID: 34986294]
[6]
Collie, S.; Champion, J.; Moultrie, H.; Bekker, L-G.; Gray, G. Effectiveness of BNT162b2 vaccine against omicron variant in South Africa. N. Engl. J. Med., 2021.
[PMID: 34965358]
[7]
Durai, P.; Beeraka, N.M.; Vikram, H.; Krishnan, P.; Gudur, P.; Raghavendra, N.M.; Kumar, P. Advances in PPARs molecular dynamics and glitazones as a repurposing therapeutic strategy through mitochondrial redox dynamics against neurodegeneration. Curr. Neuropharmacol., 2022, 20(5), 893-915.
[http://dx.doi.org/10.2174/1570159X19666211109141330] [PMID: 34751120]
[8]
Sukocheva, O.A.; Maksoud, R.; Beeraka, N.M.; Madhunapantula, S.V.; Sinelnikov, M.; Nikolenko, V.N.; Neganova, M.E.; Klochkov, S.G.; Kamal, M.A.; Staines, D.R. Analysis of post COVID-19 condition and its overlap with myalgic encephalomyelitis/chronic fatigue syndrome. J. Adv. Res., 2021.
[http://dx.doi.org/10.1016/j.jare.2021.11.013]
[9]
Beeraka, N.M.; Vikram, P.R.H.; Greeshma, M.V.; Uthaiah, C.A.; Huria, T.; Liu, J.; Kumar, P.; Nikolenko, V.N.; Bulygin, K.V.; Sinelnikov, M.Y.; Sukocheva, O.; Fan, R. Recent investigations on neurotransmitters’ role in acute white matter injury of perinatal glia and pharmacotherapies-glia dynamics in stem cell therapy. Mol. Neurobiol., 2022, 59(4), 2009-2026.
[http://dx.doi.org/10.1007/s12035-021-02700-7] [PMID: 35041139]
[10]
Jalessi, M.; Bagheri, S.H.; Azad, Z.; Firouzabadi, F.D.; Amini, E.; Alizadeh, R.; Chaibakhsh, S.; Ghalehbaghi, B.; Hopkins, C.; Farhadi, M. The outcome of olfactory impairment in patients with otherwise paucisymptomatic coronavirus disease 2019 during the pandemic. J. Laryngol. Otol., 2021, 135(5), 426-435.
[http://dx.doi.org/10.1017/S0022215121001110] [PMID: 33883051]
[11]
Raut, A.; Huy, N.T. Rising incidence of mucormycosis in patients with COVID-19: Another challenge for India amidst the second wave? Lancet Respir. Med., 2021, 9(8), e77.
[http://dx.doi.org/10.1016/S2213-2600(21)00265-4] [PMID: 34090607]
[12]
Mehta, S.; Pandey, A. Rhino-orbital mucormycosis associated with COVID-19. Cureus, 2020, 12(9), e10726.
[13]
Yang, W.; Cao, Q.; Qin, L.; Wang, X.; Cheng, Z.; Pan, A.; Dai, J.; Sun, Q.; Zhao, F.; Qu, J.; Yan, F. Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19):A multi-center study in Wenzhou city, Zhejiang, China. J. Infect., 2020, 80(4), 388-393.
[http://dx.doi.org/10.1016/j.jinf.2020.02.016] [PMID: 32112884]
[14]
Revannavar, S.M.; P S, S.; Samaga, L.; v K, V. COVID-19 triggering mucormycosis in a susceptible patient: A new phenomenon in the developing world? BMJ Case Rep., 2021, 14(4), e241663.
[http://dx.doi.org/10.1136/bcr-2021-241663] [PMID: 33906877]
[15]
Erener, S. Diabetes, infection risk and COVID-19. Mol. Metab., 2020, 39, 101044.
[http://dx.doi.org/10.1016/j.molmet.2020.101044] [PMID: 32585364]
[16]
Bhandari, J.; Thada, P.K.; Nagalli, S. Rhinocerebral Mucormycosis; StatPearls: Treasure Island, 2021.
[17]
Arndt, S.; Aschendorff, A.; Echternach, M.; Daemmrich, T.D.; Maier, W. Rhino-orbital-cerebral mucormycosis and aspergillosis: Differential diagnosis and treatment. Eur. Arch. Otorhinolaryngol., 2009, 266(1), 71-76.
[http://dx.doi.org/10.1007/s00405-008-0692-y] [PMID: 18470529]
[18]
Levitz, S.M.; Selsted, M.E.; Ganz, T.; Lehrer, R.I.; Diamond, R.D. In vitro killing of spores and hyphae of Aspergillus fumigatus and Rhizopus oryzae by rabbit neutrophil cationic peptides and bronchoalveolar macrophages. J. Infect. Dis., 1986, 154(3), 483-489.
[http://dx.doi.org/10.1093/infdis/154.3.483] [PMID: 3525696]
[19]
Waldorf, A.R.; Ruderman, N.; Diamond, R.D. Specific susceptibility to mucormycosis in murine diabetes and bronchoalveolar macrophage defense against Rhizopus. J. Clin. Invest., 1984, 74(1), 150-160.
[http://dx.doi.org/10.1172/JCI111395] [PMID: 6736246]
[20]
McCarthy, M.; Rosengart, A.; Schuetz, A.N.; Kontoyiannis, D.P.; Walsh, T.J. Mold infections of the central nervous system. N. Engl. J. Med., 2014, 371(2), 150-160.
[http://dx.doi.org/10.1056/NEJMra1216008] [PMID: 25006721]
[21]
Ochiai, H.; Iseda, T.; Miyahara, S.; Goya, T.; Wakisaka, S.; Ochiai, H. Rhinocerebral mucormycosis—case report. Neurol. Med. Chir. (Tokyo), 1993, 33(6), 373-376.
[http://dx.doi.org/10.2176/nmc.33.373]
[22]
Mantadakis, E.; Samonis, G. Clinical presentation of zygomycosis. Clin. Microbiol. Infect., 2009, 15(Suppl. 5), 15-20.
[http://dx.doi.org/10.1111/j.1469-0691.2009.02974.x] [PMID: 19754751]
[23]
Terry, A.R.; Kahle, K.T.; Larvie, M.; Vyas, J.M.; Stemmer-Rachamimov, A. Case records of the massachusetts general hospital. Case 5-2016. A 43-year-old man with altered mental status and a history of alcohol use. N. Engl. J. Med., 2016, 374(7), 671-680.
[http://dx.doi.org/10.1056/NEJMcpc1509361] [PMID: 26886525]
[24]
Dusart, A.; Duprez, T.; Van Snick, S.; Godfraind, C.; Sindic, C. Fatal rhinocerebral mucormycosis with intracavernous carotid aneurysm and thrombosis: A late complication of transsphenoidal surgery? Acta Neurol. Belg., 2013, 113(2), 179-184.
[http://dx.doi.org/10.1007/s13760-012-0151-9] [PMID: 23135781]
[25]
Bannykh, S.I.; Hunt, B.; Moser, F. Intra-arterial spread of Mucormycetes mediates early ischemic necrosis of brain and suggests new venues for prophylactic therapy. Neuropathology, 2018, 38(5), 539-541.
[http://dx.doi.org/10.1111/neup.12501] [PMID: 29974522]
[26]
Economides, M.P.; Ballester, L.Y.; Kumar, V.A.; Jiang, Y.; Tarrand, J.; Prieto, V.; Torres, H.A.; Kontoyiannis, D.P. Invasive mold infections of the central nervous system in patients with hematologic cancer or stem cell transplantation (2000-2016): Uncommon, with improved survival but still deadly often. J. Infect., 2017, 75(6), 572-580.
[http://dx.doi.org/10.1016/j.jinf.2017.09.011] [PMID: 28919347]
[27]
Liu, M.; Spellberg, B.; Phan, Q.T.; Fu, Y.; Fu, Y.; Lee, A.S.; Edwards, J.E., Jr.; Filler, S.G.; Ibrahim, A.S. The endothelial cell receptor GRP78 is required for mucormycosis pathogenesis in diabetic mice. J. Clin. Invest., 2010, 120(6), 1914-1924.
[http://dx.doi.org/10.1172/JCI42164] [PMID: 20484814]
[28]
Gebremariam, T.; Liu, M.; Luo, G.; Bruno, V.; Phan, Q.T.; Waring, A.J.; Edwards, J.E., Jr; Filler, S.G.; Yeaman, M.R.; Ibrahim, A.S. CotH3 mediates fungal invasion of host cells during mucormycosis. J. Clin. Invest., 2014, 124(1), 237-250.
[http://dx.doi.org/10.1172/JCI71349] [PMID: 24355926]
[29]
Chikley, A.; Ben-Ami, R.; Kontoyiannis, D.P. Mucormycosis of the central nervous system. J. Fungi (Basel), 2019, 5(3), 59.
[http://dx.doi.org/10.3390/jof5030059] [PMID: 31288475]
[30]
Dyer, O. Covid-19: India sees record deaths as “black fungus” spreads fear. Brit. Med. J., 2021.
[31]
Salem, S.R.; Beeraka, N.M.; Roaeid, R.B.; Huria, T.R. Use of metformin according to renal function in patients with type II diabetes. JAMA, 2014, 312(24), 2668-2675.
[32]
Ferguson, B.J. Mucormycosis of the nose and paranasal sinuses. Otolaryngol. Clin. North Am., 2000, 33(2), 349-365.
[http://dx.doi.org/10.1016/S0030-6665(00)80010-9] [PMID: 10736409]
[33]
Saldanha, M.; Reddy, R.; Vincent, M.J. of the article: Paranasal mucormycosis in COVID-19 patient. Indian J. Otolaryngol. Head Neck Surg., 2021, 1-4.
[http://dx.doi.org/10.1007/s12070-021-02574-0] [PMID: 33903850]
[34]
Janjua, O.S.; Shaikh, M.S.; Fareed, M.A.; Qureshi, S.M.; Khan, M.I.; Hashem, D.; Zafar, M.S. Dental and oral manifestations of COVID-19 related mucormycosis: Diagnoses, management strategies and outcomes. J. Fungi (Basel), 2021, 8(1), 44.
[http://dx.doi.org/10.3390/jof8010044] [PMID: 35049983]
[35]
Vučićević Boras, V.; Jurlina, M.; Brailo, V.; Đurić Vuković, K.; Rončević, P.; Bašić Kinda, S.; Vidović Juras, D.; Gabrić, D. Oral mucormycosis and aspergillosis in the patient with acute leukemia. Acta Stomatol. Croat., 2019, 53(3), 274-277.
[http://dx.doi.org/10.15644/asc53/3/9] [PMID: 31749459]
[36]
Ibrahim, A.S.; Spellberg, B.; Walsh, T.J.; Kontoyiannis, D.P. Pathogenesis of mucormycosis. Clin. Infect. Dis., 2012, 54(Suppl. 1), S16-S22.
[http://dx.doi.org/10.1093/cid/cir865] [PMID: 22247441]
[37]
Hingad, N.; Kumar, G.; Deshmukh, R. Oral mucormycosis causing necrotizing lesion in a diabetic patient: A case report. Int. J. Oral Maxillofacial Pathol., 2012, 3, 08-12.
[38]
Cornely, O.A.; Arikan-Akdagli, S.; Dannaoui, E.; Groll, A.H.; Lagrou, K.; Chakrabarti, A.; Lanternier, F.; Pagano, L.; Skiada, A.; Akova, M.; Arendrup, M.C.; Boekhout, T.; Chowdhary, A.; Cuenca-Estrella, M.; Freiberger, T.; Guinea, J.; Guarro, J.; de Hoog, S.; Hope, W.; Johnson, E.; Kathuria, S.; Lackner, M.; Lass-Flörl, C.; Lortholary, O.; Meis, J.F.; Meletiadis, J.; Muñoz, P.; Richardson, M.; Roilides, E.; Tortorano, A.M.; Ullmann, A.J.; van Diepeningen, A.; Verweij, P.; Petrikkos, G. European society of clinical microbiology and infectious diseases fungal infection study group; European confederation of medical mycology. ESCMID and ECMM joint clinical guidelines for the diagnosis and management of mucormycosis 2013. Clin. Microbiol. Infect., 2014, 20(Suppl. 3), 5-26.
[http://dx.doi.org/10.1111/1469-0691.12371] [PMID: 24479848]
[39]
Santosh, A.B.R.; Muddana, K.; Bakki, S.R. Response to commentary: Fungal infections of oral cavity: Diagnosis, management, and association with COVID-19. SN Compr. Clin. Med., 2021, 3(11), 1-2.
[http://dx.doi.org/10.1007/s42399-021-01033-9] [PMID: 34541457]
[40]
Poignon, C.; Blaize, M.; Vezinet, C.; Lampros, A.; Monsel, A.; Fekkar, A. Invasive pulmonary fusariosis in an immunocompetent critically ill patient with severe COVID-19. Clin. Microbiol. Infect., 2020, 26(11), 1582-1584.
[http://dx.doi.org/10.1016/j.cmi.2020.06.026] [PMID: 32619736]
[41]
Ahmadikia, K.; Hashemi, S.J.; Khodavaisy, S.; Getso, M.I.; Alijani, N.; Badali, H.; Mirhendi, H.; Salehi, M.; Tabari, A.; Mohammadi Ardehali, M.; Kord, M.; Roilides, E.; Rezaie, S. 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, 2021, 64(8), 798-808.
[http://dx.doi.org/10.1111/myc.13256] [PMID: 33590551]
[42]
Garlapati, K.; Chavva, S.; Vaddeswarupu, R.M.; Surampudi, J. Fulminant mucormycosis involving paranasal sinuses: A rare case report. Case Reports Dentist., 2014, 2014, 465919.
[http://dx.doi.org/10.1155/2014/465919]
[43]
Quah, W.; Gunavathy, M. Orbital apex syndrome: An unusual complication of invasive mucormycosis. Proc. Singapore Healthcare, 2018, 27(4), 287-289.
[http://dx.doi.org/10.1177/2010105818758089]
[44]
Hanley, B.; Naresh, K.N.; Roufosse, C.; Nicholson, A.G.; Weir, J.; Cooke, G.S.; Thursz, M.; Manousou, P.; Corbett, R.; Goldin, R.; Al-Sarraj, S.; Abdolrasouli, A.; Swann, O.C.; Baillon, L.; Penn, R.; Barclay, W.S.; Viola, P.; Osborn, M. Histopathological findings and viral tropism in UK patients with severe fatal COVID-19: A post-mortem study. Lancet Microbe, 2020, 1(6), e245-e253.
[http://dx.doi.org/10.1016/S2666-5247(20)30115-4] [PMID: 32844161]
[45]
Riley, T.T.; Muzny, C.A.; Swiatlo, E.; Legendre, D.P. Breaking the mold: A review of mucormycosis and current pharmacological treatment options. Ann. Pharmacother., 2016, 50(9), 747-757.
[http://dx.doi.org/10.1177/1060028016655425] [PMID: 27307416]
[46]
Alekseyev, K.; Didenko, L.; Chaudhry, B. Rhinocerebral mucormycosis and COVID-19 pneumonia. J. Med. Cases, 2021, 12(3), 85-89.
[http://dx.doi.org/10.14740/jmc3637] [PMID: 33984095]
[47]
Sahoo, J.P.; Mishra, A.P.; Pradhan, P.; Samal, K.C. Misfortune never comes alone-the new “black fungus” accompanying COVID-19 wave. Biot. Res. Today, 2021, 3, 318-320.
[48]
Short, K.R.; Kasper, J.; van der Aa, S.; Andeweg, A.C.; Zaaraoui-Boutahar, F.; Goeijenbier, M.; Richard, M.; Herold, S.; Becker, C.; Scott, D.P.; Limpens, R.W.; Koster, A.J.; Bárcena, M.; Fouchier, R.A.; Kirkpatrick, C.J.; Kuiken, T. Influenza virus damages the alveolar barrier by disrupting epithelial cell tight junctions. Eur. Respir. J., 2016, 47(3), 954-966.
[http://dx.doi.org/10.1183/13993003.01282-2015] [PMID: 26743480]
[49]
Koehler, P.; Bassetti, M.; Chakrabarti, A.; Chen, S.C.; Colombo, A.L.; Hoenigl, M.; Klimko, N.; Lass-Flörl, C.; Oladele, R.O.; Vinh, D.C. Defining and managing COVID-19-associated pulmonary aspergillosis: The 2020 ECMM/ISHAM consensus criteria for research and clinical guidance. Lancet Infect. Dis., 2021, 21(6), e149-e162.
[PMID: 33333012]
[50]
Kuehn, B.M. Pulmonary fungal infections affect patients with COVID-19. JAMA, 2020, 324(22), 2248-2248.
[http://dx.doi.org/10.1001/jama.2020.22914] [PMID: 33289826]
[51]
Song, G.; Liang, G.; Liu, W. Fungal co-infections associated with global COVID-19 pandemic: A clinical and diagnostic perspective from China. Mycopathologia, 2020, 185(4), 599-606.
[http://dx.doi.org/10.1007/s11046-020-00462-9] [PMID: 32737747]
[52]
Yang, X.; Yu, Y.; Xu, J.; Shu, H.; Xia, J.; Liu, H.; Wu, Y.; Zhang, L.; Yu, Z.; Fang, M.; Yu, T.; Wang, Y.; Pan, S.; Zou, X.; Yuan, S.; Shang, Y. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study. Lancet Respir. Med., 2020, 8(5), 475-481.
[http://dx.doi.org/10.1016/S2213-2600(20)30079-5] [PMID: 32105632]
[53]
Gangneux, J-P.; Bougnoux, M-E.; Dannaoui, E.; Cornet, M.; Zahar, J.R. Invasive fungal diseases during COVID-19: We should be prepared. J. Mycol. Med., 2020, 30(2), 100971.
[http://dx.doi.org/10.1016/j.mycmed.2020.100971] [PMID: 32307254]

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