Black Fungus Mutilating COVID-19 Pandemic in India: Facts and Immunological Perspectives

Year 2022, , 96 - 106, 30.06.2022

Anushka Mondal Mylari Gireeshwar Lekha Govindaraj

https://doi.org/10.26650/EurJBiol.2022.1083922

Abstract

While the world is still struggling with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, an aggressive and rare fungal infection which is commonly ascribed as the black fungus has emerged as a new medical challenge in India. India had already experienced the devastating consequences of the COVID-19 and, being a rare “opportunistic” fungal infection, black fungus infection has severely complicated the post-COVID-19 recoveries. Together with the uncertain treatment modalities at the beginning of the pandemic, indiscriminate use of a plethora of medications has driven the surging cases of black fungus-associated complications. Moreover, low oxygen, high iron levels, and prolonged hospitalization with mechanical ventilators created a superlative condition for contracting black fungus infection. The disease mainly spreads through the respiratory tract and erodes facial structures. Since mucormycosis specifically attacks immunosuppressed patients, the disease started spreading rapidly, with an average mortality rate of 54 %. Common symptoms include blackening over the nose, blurred or double vision, breathing difficulties, chest pain and hemoptysis. Although not contagious, the outcome of the disease is often very frightful. If the infection disseminates systematically, the risk of affecting the vital organs such as the spleen and heart is substantially high. We have tried to provide an epidemiological overview of black fungus infection in India. We focused on drawing a comprehensive fact check of the current situation through an immunological perspective to better understand the infection as a major co-infection in patients affected by COVID-19 and its impact on India's fight against the COVID-19 pandemic.

Keywords

Black fungus, COVID-19, Mucormycosis, Epidemiology, India

References

• 1. Bar-Or I, Yaniv K, Shagan M, Ozer E, Weil M, Indenbaum V, et al. Regressing SARS-CoV-2 sewage measurements onto COVID-19 burden in the population: A Proof-of-Concept for quantitative en-vironmental surveillance. Front Public Health 2022; 9: 561710. google scholar
• 2. Sahu RK, Salem-Bekhit MM, Bhattacharjee B, Almoshari Y, Ikbal AMA, Alshamrani M, et al. Mucormycosis in indian covid-19 pa-tients: Insight into its pathogenesis, clinical manifestation, and management strategies. Antibiotics (Basel) 2021;10(9): 1079. google scholar
• 3. Valente Aguiar PD, Carvalho B, Monteiro P, Linhares P, Camacho O, Vaz R. Hyperbaric oxygen treatment: Results in seven patients with severe bacterial postoperative central nervous system infections and refractory mucormycosis. Diving Hyperb Med 2021; 51(1): 86-93. google scholar
• 4. Afzal ProfS, Nasir M. Aspergillosis and Mucormycosis in COVID-19 Patients; a Systematic Review and Meta-analysis. medRxiv. Pub-lished online 2021. google scholar
• 5. Domingo FR, Waddell LA, Cheung AM, Cooper CL, Belcourt VJ, Zuckermann AME, et al. Prevalence of long-term effects in individ-uals diagnosed with COVID-19: a living systematic review. medRx-iv. Published online 2021. google scholar
• 6. Chavda VP, Apostolopoulos V. Mucormycosis - An opportunistic infection in the aged immunocompromised individual: A reason for concern in COVID-19. Maturitas 2021; 154: 58-61. google scholar
• 7. Russell CD, Fairfield CJ, Drake TM, Turtle L, Seaton RA, Wootton Dan G, et al. Co-infections, secondary infections, and antimicrobial use in patients hospitalised with COVID-19 during the first pandemic wave from the ISARIC WHO CCP-UK study: a multicentre, prospec-tive cohort study. Lancet Microbe 2021; 2(8): e354-e365 google scholar
• 8. Musuuza JS, Watson L, Parmasad V, Putman-Buehler N, Chris-tensen L, Safdar N. Prevalence and outcomes of co-infection and superinfection with SARS-CoV-2 and other pathogens: A system-atic review and meta-analysis. PLoS One 2021; 16(5): e0251170. google scholar
• 9. Kalfaoglu B, Almeida-Santos J, Tye CA, Satou Y, Ono M. T-cell dys-regulation in COVID-19. Biochem Biophys Res Commun 2021; 538: 204-210. google scholar
• 10. Graichen H. What is the difference between the first and the sec-ond/third wave of Covid-19? - German perspective. J Orthop 2021; 24: A1-A3. google scholar
• 11. Kanungo R. Mucormycosis: New actor in the saga of COVID-19. J Curr Res Sci Med 2021; 7(1). google scholar
• 12. Chowdhary S, Alexander A, Ganesan S, Raj JV, Chakkalakkoombil SV, Lakshmanan J, et al. Cavernous sinus thrombosis in COVID-19 associated rhino-orbital Mucormycosis: A Retrospective Audit in the First Wave of the Pandemic, 2021, PREPRINT (Version 1) avail-able at Research Square. Doi: 10.21203/rs.3.rs-693804/v1 google scholar
• 13. Ademe M. Immunomodulation for the treatment of fungal infec-tions: Opportunities and challenges. Front Cell Infect Microbiol 2020; 10: 469. google scholar
• 14. Jenks JD, Gangneux JP, Schwartz IS, Alastruey-Izquierdo A, Lagrou K, Thompson GR, et al. Diagnosis of breakthrough fungal infec-tions in the clinical mycology laboratory: An ecmm consensus statement. J Fungi (Basel) 2020; 6(4): 216. google scholar
• 15. Skiada A, Pavleas I, Drogari-Apiranthitou M. Epidemiology and diag-nosis of mucormycosis: An update. J Fungi (Basel) 2020; 6(4): 265. google scholar
• 16. Mekki SO, Hassan AA, Falemban A, Alkotani N, Alsharif SM, Haron A, et al. Pulmonary Mucormycosis: A Case Report of a Rare Infection with Potential Diagnostic Problems. Case Rep Pathol 2020: 5845394. google scholar
• 17. Ragab D, Salah Eldin H, Taeimah M, Khattab R, Salem R. The COVID-19 Cytokine Storm; What We Know So Far. Front Immunol 2020; 11: 1446. google scholar
• 18. Lansbury L, Lim B, Baskaran V, Lim WS. Co-infections in people with COVID-19: a systematic review and meta-analysis. J Infect 2020;81(2):266-275. google scholar
• 19. Guo H, Hu BJ, Yang XL, Zeng LP, Li B, Ouyang S, et al. Evolutionary Arms Race between Virus and Host Drives Genetic Diversity in Bat Severe Acute Respiratory Syndrome-Related Coronavirus Spike Genes. J Virol 2020; 94(20): e00902-20. google scholar
• 20. Cuervo NZ, Grandvaux N. Ace2: Evidence of role as entry recep-tor for sars-cov-2 and implications in comorbidities. Elife 2020; 9: e61390. google scholar
• 21. Huang Y, Yang C, Xu X feng, Xu W, Liu S wen. Structural and function-al properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol Sin 2020; 41(9): 1141-9. google scholar
• 22. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020; 395(10224): 565-574. google scholar
• 23. Reid G, Lynch III JP, Fishbein MC, Clark NM. Mucormycosis. Semin Respir Crit Care Med 2020; 41(1): 99-114. google scholar
• 24. Bhandari J, Thada PK and Nagalli S. Rhinocerebral mucormycosis. StatPearls.; 2020. google scholar
• 25. Yao H, Liu Y, Ma ZF, Zhang H, Fu T, Li Z, et al. Analysis of nutrition-al quality of black fungus cultivated with corn stalks. J Food Qual 2019; 2019. google scholar
• 26. Cornely OA, Alastruey-Izquierdo A, Arenz D, Chen SCA, Dannaoui E, Hochhegger B, et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Con-federation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. Lancet Infect Dis 2019; 19(12): e405-e421. google scholar
• 27. Azhar EI, Hui DSC, Memish ZA, Drosten C, Zumla A. The Mid-dle East Respiratory Syndrome (MERS). Infect Dis Clin North Am 2019;33(4):891-905. google scholar
• 28. Hui DSC, Zumla A. Severe Acute Respiratory Syndrome: Histori-cal, Epidemiologic, and Clinical Features. Infect Dis Clin North Am 2019; 33(4): 869-89. google scholar
• 29. Bennett M, Kaide CG, Matheson E, Bari V. Hyperbaric Oxygen Ther-apy and Utilization in Infectious Disease. Curr Emerg Hosp Med Rep 2018; 6(3). google scholar
• 30. Warnatsch A, Tsourouktsoglou TD, Branzk N, Wang Q, Reincke S, Herbst S, et al. Reactive Oxygen Species Localization Programs Inflammation to Clear Microbes of Different Size. Immunity 2017; 46(3): 421-32. google scholar
• 31. Castrejon-Perez AD, Miranda I, Welsh O, Welsh EC, Ocampo-Can-diani J. Cutaneous mucormycosis. An Bras Dermatol 2017; 92(3): 304-11. google scholar
• 32. Lionakis MS, Iliev ID, Hohl TM. Immunity against fungi. JCI Insight 2017; 2(11): e93156. google scholar
• 33. Yamin HS, Alastal AY, Bakri I. Pulmonary mucormycosis over 130 years: A case report and literature review. Turk Thorac J 2017; 18(1): 1-5. google scholar
• 34. Schroeder MR, Stephens DS. Macrolide resistance in Streptococcus pneumoniae. Front Cell Infect Microbiol 2016; 6: 98. google scholar
• 35. Gebremariam T, Lin L, Liu M, Kontoyiannis DP, French S, Edwards JE, et al. Bicarbonate correction of ketoacidosis alters host-patho-gen interactions and alleviates mucormycosis. J Clin Invest 2016; 126(6): 2280-94. google scholar
• 36. Roth S, Bergmann H, Jaeger M, Yeroslaviz A, Neumann K, Koenig PA, et al. Vav Proteins Are Key Regulators of Card9 Signaling for Innate Antifungal Immunity. Cell Rep 2016; 17(10): 2572-83. google scholar
• 37. Erwig LP, Gow NAR. Interactions of fungal pathogens with phago-cytes. Nat Rev Microbiol 2016; 14(3): 163-76. google scholar
• 38. Wang XM, Guo LC, Xue SL, Chen Y bin. Pulmonary mucormycosis: A case report and review of the literature. Oncol Lett 2016; 11(5): 3049-53. google scholar
• 39. Yang HN, Wang CL. Looks like tuberculous meningitis, but not: A case of rhinocerebral mucormycosis with garcin syndrome. Front Neurol 2016; 7: 181. google scholar
• 40. Mattingly JK, Ramakrishnan VR. Rhinocerebral Mucormycosis of the Optic Nerve. Otolaryngol Head Neck Surg 2016;155(5):888-9. google scholar
• 41. Paczosa MK, Mecsas J. Klebsiella pneumoniae: Going on the Of-fense with a Strong Defense. Microbiol Mol Biol Rev 2016; 80(3): 629-61. google scholar
• 42. Alaa Abdul-Hussein Al-Daamy, Haider Abd-Al Ameer, Hasan Zuher, Hussein Monather, Bashaer Ahmmed, Niesreen Kadhim. Antifun-gal activity of propolis against Dermatophytes and Candida albi-cans isolated from human mouth. J contemp med sci 2015; 1(3). google scholar
• 43. Deng Z, Ma S, Zhou H, Zang A, Fang Y, Li T, et al. Tyrosine phos-phatase SHP-2 mediates C-type lectin receptor-induced activation of the kinase Syk and anti-fungal T H 17 responses. Nat Immunol 2015; 16(6): 642-52. google scholar
• 44. Underhill DM, Pearlman E. Immune Interactions with Patho-genic and Commensal Fungi: A Two-Way Street. Immunity 2015;43(5):845-58. google scholar
• 45. Shin S, Jung S, Menzel F, Heller K, Lee H, Lee S. Molecular phylog-eny of black fungus gnats (Diptera: Sciaroidea: Sciaridae) and the evolution of larval habitats. Mol Phylogenet Evol 2013; 66(3): 83346. google scholar
• 46. Guymer C, Khurana S, Suppiah R, Hennessey I, Cooper C. Success-ful treatment of disseminated mucormycosis in a neutropenic patient with T-cell acute lymphoblastic leukaemia. BMJ Case Rep 2013; 2013: bcr2013009577. google scholar
• 47. Lewis RE, Kontoyiannis DP. Epidemiology and treatment of mucor-mycosis. Future Microbiol 2013; 8(9): 1163-75. google scholar
• 48. Ibrahim AS, Spellberg B, Walsh TJ, Kontoyiannis DP. Pathogenesis of mucormycosis. Clin Infect Dis 2012; 54(Suppl 1): S16-22. google scholar
• 49. Neblett Fanfair R, Benedict K, Bos J, Bennett SD, Lo YC, Adebanjo T, et al. Necrotizing Cutaneous Mucormycosis after a Tornado in Joplin, Missouri, in 2011. N Engl J Med 2012; 367(23): 2214-25. google scholar
• 50. Petrikkos G, Skiada A, Lortholary O, Roilides E, Walsh TJ, Kontoyian-nis DP. Epidemiology and clinical manifestations of mucormycosis. Clin Infect Dis 2012; 54(Suppl 1): S23-34. google scholar
• 51. Rammaert B, Lanternier F, Zahar JR, Dannaoui E, Bougnoux ME, Le-cuit M, et al. Healthcare-associated mucormycosis. Clin Infect Dis 2012; 54(Suppl 1): S44-54. google scholar
• 52. Lalayanni C, Baliakas P, Xochelli A, Apostolou C, Arabatzis M, Velegraki A, et al. Outbreak of cutaneous zygomycosis associated with the use of adhesive tape in haematology patients. J Hosp In-fect 2012; 81(3): 213-5. google scholar
• 53. Skiada A, Rigopoulos D, Larios G, Petrikkos G, Katsambas A. Global epidemiology of cutaneous zygomycosis. Clin Dermatol 2012; 30(6): 628-32. google scholar
• 54. Morton J, Nguyen V, Ali T. Mucormycosis of the intestine: A rare complication in Crohn’s disease. Gastroenterol Hepatol (N Y) 2012; 8(2): 137-40. google scholar
• 55. Spellberg B. Gastrointestinal mucormycosis: An evolving disease. Gastroenterol Hepatol (N Y) 2012; 8(2): 140-2. google scholar
• 56. Walsh TJ, Gamaletsou MN, McGinnis MR, Hayden RT, Kontoyiannis DP. Early clinical and laboratory diagnosis of invasive pulmonary, extrapulmonary, and disseminated mucormycosis (zygomycosis). Clin Infect Dis 2012; 54(Suppl 1): S55-60. google scholar
• 57. Goodridge HS, Reyes CN, Becker CA, Katsumoto TR, Ma J, Wolf AJ, et al. Activation of the innate immune receptor Dectin-1 upon forma-tion of a Phagocytic synapse-TM. Nature 2011; 472(7344): 471-5. google scholar
• 58. Liu M, Spellberg B, Phan QT, Fu Yue Fu Yong Lee AS, Edwards JE, Filler SG, et al. The endothelial cell receptor GRP78 is required for mucormycosis pathogenesis in diabetic mice. J Clin Invest 2010; 120(6): 1914-24. google scholar
• 59. Pappas PG, Alexander BD, Andes DR, Hadley S, Kauffman CA, Freif-eld A, et al. Invasive fungal infections among organ transplant re-cipients: results of the transplant-associated infection surveillance network (Transnet). Clin Infect Dis 2010;50(8):1101-11. google scholar
• 60. Cano P, Horseman MA, Surani S. Rhinocerebral mucormycosis com-plicated by bacterial brain abscess. Am J Med Sci 2010;340(6):507-10. google scholar
• 61. Mezhir JJ, Mullane KM, Zarling J, Satoskar R, Pai RK, Roggin KK. Successful nonoperative management of gastrointestinal mucor-mycosis: Novel therapy for invasive disease. Surg Infect (Larchmt) 2009; 10(5): 447-51. google scholar
• 62. Simbli M, Hakim F, Koudieh M, Tleyjeh IM. Nosocomial post-trau-matic cutaneous mucormycosis: A systematic review. Scand J In-fect Dis 2008; 40(6-7): 577-82. google scholar
• 63. Page A v., Evans AJ, Snell L, Liles WC. Primary cutaneous mucormy-cosis in a lung transplant recipient: Case report and concise review of the literature. Transpl Infect Dis 2008; 10(6): 419-25. google scholar
• 64. Garg R, Marak Rungmei SK, Verma S, Singh J, Sanjay, Prasad R. Pul-monary mucormycosis mimicking as pulmonary tuberculosis : A case report. Lung India 2008; 25(3): 129-31. google scholar
• 65. LeibundGut-Landmann S, GroB O, Robinson MJ, Osorio F, Slack EC, Tsoni SV, et al. Syk- and CARD9-dependent coupling of innate im-munity to the induction of T helper cells that produce interleukin 17. Nat Immunol 2007; 8(6): 630-8. google scholar
• 66. Rappleye CA, Eissenberg LG, Goldman WE. Histoplasma capsu-latum a-(1,3)-glucan blocks innate immune recognition by the 0-glucan receptor. Proc Natl Acad SciUSA 2007; 104(4): 1366-70. google scholar
• 67. Zaoutis TE, Roilides E, Chiou CC, et al. Zygomycosis in children: A systematic review and analysis of reported cases. Pediatr Infect Dis J 2007; 26(8): 723-7. google scholar
• 68. Ward AB. Hemiplegic shoulder pain. J Neurol Neurosurg Psychiatry 2007; 78(8): 789. google scholar
• 69. Thapar VK, Deshpande A, Jain VK, Bhowate P, Madiwale C. Isolated breast mucormycosis. J Postgrad Med 2006; 52(2): 134-5. google scholar
• 70. Pellacchia V, Terenzi V, Moricca LM, Buonaccorsi S, Indrizzi E, Fini G. Brain abscess by mycotic and bacterial infection in a diabetic patient: Clinical report and review of literature. J Craniofac Surg 2006; 17(3): 578-84. google scholar
• 71. Rogers NC, Slack EC, Edwards AD, Nolte MA, Schulz O, Schweighof-fer E, et al. Syk-dependent cytokine induction by dectin-1 reveals a novel pattern recognition pathway for C type lectins. Immunity 2005; 22(4): 507-17. google scholar
• 72. Roden MM, Zaoutis TE, Buchanan WL, Knudsen TA, Sarkisova TA, Schaufele RL, et al. Epidemiology and outcome of zygomycosis: A review of 929 reported cases. Clin Infect Dis 2005; 41(5): 634-53. google scholar
• 73. Spellberg B, Edwards J, Ibrahim A. Novel perspectives on mucor-mycosis: Pathophysiology, presentation, and management. Clin Microbiol Rev 2005; 18(3): 556-69. google scholar
• 74. MaravPPoma E, Rodnguez-Tudela JL,deJalönJG, Manrique-Larral-de A, Torroba L, Urtasun J, et al. Outbreak of gastric mucormycosis associated with the use of wooden tongue depressors in critically ill patients. Intensive Care Med 2004; 30(4): 724-8. google scholar
• 75. Pagano L, Offidani M, Fianchi L, Nosari A, Candoni A, Picardi M. & GIMEMA (Gruppo Italiano Malattie EMatologiche dell’Adulto) In-fection Program. Mucormycosis in hematologic patients. Haema-tologica 2004; 89(2): 207-14. google scholar
• 76. Boxer L, Dale DC. Neutropenia: Causes and consequences. Semin Hematol 2002; 39(2): 75-81. google scholar
• 77. Chander J. Textbook of Medical Mycology.; 2002. google scholar
• 78. Hosseini M. Gastrointestinal mucormycosis mimicking ischemic colitis in a patient with systemic lupus erythematosus. Am J Gas-troenterol 1998; 93(8): 1360-2. google scholar
• 79. Raleigh AB. Hepatic mucormycosis in a bone marrow transplant re-cipient who ingested naturopathic medicine. Clin Infect Dis 1996; 22(3): 521-4. google scholar
• 80. Brullet E, Andreu X, Elias J, Roig J, Cervantes M. Gastric mucormy-cosis in a patient with acquired immunodeficiency syndrome. Gas-trointest Endosc 1993; 39(1): 106-7. google scholar
• 81. Helenglass G, Elliott JA, Lucie NP. An unusual presentation of op-portunistic mucormycosis. Br Med J (Clin Res Ed) 1981; 282(6258): 108-9. google scholar
• 82. Ho KL. Acute subdural hematoma and intracerebral hemorrhage: Rare complications of Rhinocerebral Mucormycosis. Arch Otolar-yngol 1979; 105(5): 279-81. google scholar
• 83. Baker RD. Mucormycosis—a new disease? J Am Med Assoc 1957; 163(10): 805-8. google scholar