IMMUNOGENOMIC APPROACH TO THE CLINICAL MANAGEMENT OF COVID-19 SYNDROME

Ümit Yavuz Malkan; Olgu Erkin Çınar; Can Türk; Seyhan Türk; İbrahim Celaleddin Haznedaroğlu

Review

COVID-19 SENDROMUNUN KLİNİK YÖNETİMİNDE İMMUNOGENOMİK YAKLAŞIM

Year 2023, Volume: 4 Issue: Ek Sayı, 266 - 279, 16.10.2023

Ümit Yavuz Malkan , Olgu Erkin Çınar , Can Türk , Seyhan Türk , İbrahim Celaleddin Haznedaroğlu

Abstract

SARS-CoV-2 enfeksiyonu sonucu gelişen ve "COVID-19 sendromu" olarak tanımlanabilecek tablonun üç özel immünogenomik gelişim aşaması vardır; başlatıcı, ilerleyici ve komplikasyon fazları. Her COVID-19 fazı, farklı terapötik klinik müdahaleler gerektiren kritik patobiyolojik korelasyonlara sahiptir. Renin-anjiyotensin sistemi (RAS) genleri, koronavirüs ailesi üyelerinin neden olduğu enfeksiyonların başlaması için gereklidir ve SARS-CoV-2 enfeksiyonunu takiben kritik immün gen ürünleriyle, özellikle de IFN ailesinin üyeleri ile güçlü bir etkileşime sahiptir. Bu makale, COVID-19 immün sendromu olarak tanımlanabilecek multisistemiı tablonun klinikopatolojik seyrine ilişkin daha önce yayınladığımız üç aşamalı modelin kavramları çerçevesinde COVID-19 için tedavi protokollerini güncel bir yaklaşımla gözden geçirmeyi amaçlamaktadır. Mevcut tedavi seçeneklerinin RAS'ı etkileyen gelecekteki olası terapötik adayları da sendromun immünogenomik perspektifiyle ele alınmaktadır.

Keywords

COVID-19, remdesivir, paxlovid, coronavirus, covid-19 tedavisi, covid-19 sendromu

References

1. Goker H, Aladag Karakulak E, Demiroglu H, et al. The effects of blood group types on the risk of COVID-19 infection and its clinical outcome. Turk J Med Sci. 2020; 50: 679-83.
2. Yang L, Liu S, Liu J, et al. COVID-19: immunopathogenesis and Immunotherapeutics. Signal Transduct Target Ther. 2020; 5:128.
3. Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020; 579: 270-3.
4. Ciftciler R, Ciftciler AE, Haznedaroglu IC. Local Bone Marrow Renin-Angiotensin System and COVID-19. UHOD. 2020; 30: 001-8.
5. Gupta A, Madhavan MV, Sehgal K, et al. Extrapulmonary manifestations of COVID-19. Nat Med. 2020; 26: 1017-32.
6. Turk C, Turk S, Temirci ES, Malkan UY, Haznedaroglu IC. In vitro analysis of the renin-angiotensin system and inflammatory gene transcripts in human bronchial epithelial cells after infection with severe acute respiratory syndrome coronavirus. JRAAS. 2020; 21: 1470320320928872.
7. Turk C, Turk S, Malkan UY, Haznedaroglu IC. Three critical clinicobiological phases of the human sars-associated coronavirus infections. Eur Rev Med Pharmacol Sci. 2020; 24: 8606-20.
8. Malkan UY, Haznedaroglu IC. Hematological aspects of the COVID-19 syndrome. Eur Rev Med Pharmacol Sci. 2022; 26: 4463-76.
9. Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review. JAMA. 2020; 324: 782-93.
10. Worldometers. COVID-19 Coronavirus Pandemic 2020 Available at: https: //www. worldometers. info/coronavirus/. Accessed November 10, 2022.
11. Türkiye Sağlık Bakanlığı - COVID-19 Erişkin Hasta Tedavi Rehberi. Available at: https: // covid19bilgi. saglik. gov.tr/depo/rehberler/covid-19-rehberi/COVID-19_REHBERI_ERISKIN_HASTA_TEDAVISI.pdf. Accessed November 20, 2022.
12. Shannon P, Markiel A, Ozier O, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003; 13: 2498-504.
13. Kuba K, Imai Y, Rao S, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med. 2005;11:875-9.
14. Ciaglia E, Vecchione C, Puca AA. COVID-19 Infection and Circulating ACE2 Levels: Protective Role in Women and Children. Front Pediatr. 2020; 8: 206.
15. Lange C, Wolf J, Auw-Haedrich C, et al. Expression of the COVID-19 receptor ACE2 in the human conjunctiva. J Med Virol. 2020; 92: 2081-6.
16. Yeager CL, Ashmun RA, Williams RK, et al. Human aminopeptidase N is a receptor for human coronavirus 229E. Nature. 1992; 357: 420-2.
17. Qi F, Qian S, Zhang S, Zhang Z. Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses. Biochem Biophys Res Commun. 2020; 526: 135-40.
18. Thachil J, Tang N, Gando S, et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost. 2020;18: 1023-6.
19. Yao X, Ye F, Zhang M, et al. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020; 71: 732-9.
20. Million M, Gautret P, Colson P, et al. Clinical Efficacy of Chloroquine derivatives in COVID-19 Infection: Comparative meta-analysis between the Big data and the real world. New Microbes New Infect. 2020; 38: 100709.
21. Pathak DSK, Salunke DAA, Thivari DP, et al. No benefit of hydroxychloroquine in COVID-19: Results of Systematic Review and Meta-Analysis of Randomized Controlled Trials". Diabetes Metab Syndr. 2020; 14: 1673-80.
22. World Health Organisation. “Solidarity” clinical trial for COVID-19 treatments: Update on hydroxychloroquine Available at: https: //www. who. int/ emergencies/ diseases/ novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov/solidarity-clinical-trial-for-covid-19-treatments. Accessed December 12, 2022.
23. Geleris J, Sun Y, Platt J, et al. Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19. N Engl J Med. 2020; 382: 2411-8.
24. Food and Drug Administration. Coronavirus (COVID-19) Update: FDA Revokes Emergency Use Authorization for Chloroquine and Hydroxychloroquine. June 15, 2020 Available at: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-revokes-emergency-use-authorization-chloroquine-and. Accessed November 21, 2022.
25. Hernandez AV, Roman YM, Pasupuleti V, Barboza JJ, White CM. Hydroxychloroquine or Chloroquine for Treatment or Prophylaxis of COVID-19: A Living Systematic Review. Ann Intern Med. 2020; 173: 287-96.
26. Chowdhury MS, Rathod J, Gernsheimer J. A Rapid Systematic Review of Clinical Trials Utilizing Chloroquine and Hydroxychloroquine as a Treatment for COVID-19. Acad Emerg Med. 2020; 27: 493-504.
27. Meyerowitz EA, Vannier AGL, Friesen MGN, et al. Rethinking the role of hydroxychloroquine in the treatment of COVID-19. FASEB J. 2020; 34: 6027-37.
28. Pastick KA, Okafor EC, Wang F, et al. Review: Hydroxychloroquine and Chloroquine for Treatment of SARS-CoV-2 (COVID-19). Open Forum Infect Dis. 2020; 7: 130.
29. Schrezenmeier E, Dorner T. Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat Rev Rheumatol. 2020;16:155-66.
30. Liu J, Cao R, Xu M, et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov. 2020; 6: 16.
31. Rother N, Yanginlar C, Lindeboom RGH, et al. Hydroxychloroquine Inhibits the Trained Innate Immune Response to Interferons. Cell Rep Med. 2020; 1: 100146.
32. Xu R, Ji Z, Xu C, Zhu J. The clinical value of using chloroquine or hydroxychloroquine as autophagy inhibitors in the treatment of cancers: A systematic review and meta-analysis. Medicine (Baltimore). 2018; 97: e12912.
33. Gies V, Bekaddour N, Dieudonne Y, et al. Beyond Anti-viral Effects of Chloroquine/Hydroxychloroquine. Front Immunol. 2020;11:1409.
34. Le Page C, Genin P, Baines MG, Hiscott J. Interferon activation and innate immunity. Rev Immunogenet. 2000; 2: 374-86.
35. Bodewes ILA, Gottenberg JE, van Helden-Meeuwsen CG, Mariette X, Versnel MA. Hydroxychloroquine treatment downregulates systemic interferon activation in primary Sjogren's syndrome in the JOQUER randomized trial. Rheumatology. 2020; 59: 107-11.
36. Qin X, Chen G, Feng Y, et al. Early treatment with chloroquine inhibits the immune response against Plasmodium yoelii infection in mice. Tohoku J Exp Med. 2014; 234: 271-80.
37. Paton NI, Goodall RL, Dunn DT, et al. Effects of hydroxychloroquine on immune activation and disease progression among HIV-infected patients not receiving antiretroviral therapy: a randomized controlled trial. JAMA. 2012; 308: 353-61.
38. Morgan MJ, Gamez G, Menke C, et al. Regulation of autophagy and chloroquine sensitivity by oncogenic RAS in vitro is context-dependent. Autophagy. 2014;10:1814-26.
39. Schmukler E, Kloog Y, Pinkas-Kramarski R. Ras and autophagy in cancer development and therapy. Oncotarget. 2014; 5: 577-86.
40. Wang P, Du Y, Wang J. Indentification of breast cancer subtypes sensitive to HCQ-induced autophagy inhibition. Pathol Res Pract. 2019; 215: 152609.
41. Cai Q, Yang M, Liu D, et al. Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study. Engineering. 2020; 6: 1192-8.
42. Furuta Y, Komeno T, Nakamura T. Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase. Proc Jpn Acad Ser B Phys Biol Sci. 2017; 93: 449-63.
43. Furuta Y, Gowen BB, Takahashi K, Shiraki K, Smee DF, Barnard DL. Favipiravir (T-705), a novel viral RNA polymerase inhibitor. Antiviral Res. 2013; 100: 446-54.
44. Shiraki K, Daikoku T. Favipiravir, an anti-influenza drug against life-threatening RNA virus infections. Pharmacol Ther. 2020; 209: 107512.
45. Madelain V, Mentre F, Baize S, et al. Modeling Favipiravir Antiviral Efficacy Against Emerging Viruses: From Animal Studies to Clinical Trials. CPT Pharmacometrics Syst Pharmacol. 2020; 9: 258-71.
46. de la Torre JC. Extending the Antiviral Value of Favipiravir. J Infect Dis. 2018; 218: 509-11.
47. Rosenberg ES, Dufort EM, Udo T, et al. Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State. JAMA. 2020; 323: 2493-502.
48. Risch HA. Early Outpatient Treatment of Symptomatic, High-Risk COVID-19 Patients That Should Be Ramped Up Immediately as Key to the Pandemic Crisis. Am J Epidemiol. 2020; 189: 1218-26.
49. Menzel M, Akbarshahi H, Bjermer L, Uller L. Azithromycin induces anti-viral effects in cultured bronchial epithelial cells from COPD patients. Sci Rep. 2016; 6:28698.
50. Parnham MJ, Erakovic Haber V, Giamarellos-Bourboulis EJ, Perletti G, Verleden GM, Vos R. Azithromycin: mechanisms of action and their relevance for clinical applications. Pharmacol Ther. 2014; 143: 225-45.
51. Meyer M, Huaux F, Gavilanes X, et al. Azithromycin reduces exaggerated cytokine production by M1 alveolar macrophages in cystic fibrosis. Am J Respir Cell Mol Biol. 2009; 41: 590-602.
52. Srivastava P, Jha HC, Salhan S, Mittal A. Azithromycin treatment modulates cytokine production in Chlamydia trachomatis infected women. Basic Clin Pharmacol Toxicol. 2009; 104: 478-82.
53. Bleyzac N, Goutelle S, Bourguignon L, Tod M. Azithromycin for COVID-19: More Than Just an Antimicrobial? Clin Drug Investig. 2020; 40: 683-6.
54. Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020; 30: 269-71.
55. Osborne V, Davies M, Lane S, et al. Lopinavir-Ritonavir in the Treatment of COVID-19: A Dynamic Systematic Benefit-Risk Assessment. Drug Saf. 2020; 43: 809-21.
56. Chandwani A, Shuter J. Lopinavir/ritonavir in the treatment of HIV-1 infection: a review. Ther Clin Risk Manag. 2008; 4: 1023-33.
57. Alves EAR, de Miranda MG, Borges TK, Magalhaes KG, Muniz-Junqueira MI. Anti-HIV drugs, lopinavir/ritonavir and atazanavir, modulate innate immune response triggered by Leishmania in macrophages: the role of NF-kappaB and PPAR-gamma. Int Immunopharmacol. 2015; 24: 314-24.
58. Danaher RJ, Kaetzel CS, Greenberg RN, Wang C, Bruno ME, Miller CS. HIV protease inhibitors alter innate immune response signaling to double-stranded RNA in oral epithelial cells: implications for immune reconstitution inflammatory syndrome? AIDS. 2010; 24: 2587-90.
59. Boccara F, Auclair M, Cohen A, et al. HIV protease inhibitors activate the adipocyte renin angiotensin system. Antivir Ther. 2010; 15: 363-75.
60. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the Treatment of Covid-19 - Final Report. N Engl J Med. 2020; 383: 1813-26.
61. Eastman RT, Roth JS, Brimacombe KR, et al. Remdesivir: A Review of Its Discovery and Development Leading to Emergency Use Authorization for Treatment of COVID-19. ACS Cent Sci. 2020; 6: 672-83.
62. Saha A, Sharma AR, Bhattacharya M, Sharma G, Lee SS, Chakraborty C. Probable Molecular Mechanism of Remdesivir for the Treatment of COVID-19: Need to Know More. Arch Med Res. 2020; 51: 585-6.
63. Jayk Bernal A, Gomes da Silva MM, Musungaie DB, et al. Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients. N Engl J Med. 2022; 386: 509-20.
64. Food and Drug Administration. Coronavirus (COVID-19) Update: FDA Authorizes Additional Oral Antiviral for Treatment of COVID-19 in Certain Adults 2021 Available at: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-additional-oral-antiviral-treatment-covid-19-certain. Accessed October 8, 2022.
65. Wen W, Chen C, Tang J, et al. Efficacy and safety of three new oral antiviral treatment (molnupiravir, fluvoxamine and Paxlovid) for COVID-19：a meta-analysis. Ann Med. 2022;54:516-23.
66. Waters MD, Warren S, Hughes C, Lewis P, Zhang F. Human genetic risk of treatment with antiviral nucleoside analog drugs that induce lethal mutagenesis: The special case of molnupiravir. Environ Mol Mutagen. 2022; 63:37-63.
67. Hammond J, Leister-Tebbe H, Gardner A, et al. Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19. N Engl J Med. 2022; 386: 1397-408.
68. Najjar-Debbiny R, Gronich N, Weber G, et al. Effectiveness of Paxlovid in Reducing Severe Coronavirus Disease 2019 and Mortality in High-Risk Patients. Clin Infect Dis. 2023; 76: 342-9.
69. Wang L, Berger NA, Davis PB, Kaelber DC, Volkow ND, Xu R. COVID-19 rebound after Paxlovid and Molnupiravir during January-June 2022. medRxiv. 2022 Oct 28, doi:10.1101/2022.06.21.22276724.
70. Horby P, Lim WS, Emberson J, et al. Effect of Dexamethasone in Hospitalized Patients with COVID-19. N Engl J Med 2021; 384: 693-704.
71. Giles AJ, Hutchinson MND, Sonnemann HM, et al. Dexamethasone-induced immunosuppression: mechanisms and implications for immunotherapy. J Immunother Cancer. 2018; 6: 51.
72. Xia M, Gasser J, Feige U. Dexamethasone enhances CTLA-4 expression during T cell activation. Cell Mol Life Sci. 1999; 55: 1649-56.
73. Liu C, Ge N, Zhai JL, Zhang JX. Dexamethasone-induced diuresis is associated with inhibition of the renin-angiotensin-aldosterone system in rats. Kaohsiung J Med Sci. 2016; 32: 614-9.
74. Barreto-Chaves ML, Heimann A, Krieger JE. Stimulatory effect of dexamethasone on angiotensin-converting enzyme in neonatal rat cardiac myocytes. Braz J Med Biol Res. 2000; 33: 661-4.
75. Bernstein KE, Khan Z, Giani JF, Cao DY, Bernstein EA, Shen XZ. Angiotensin-converting enzyme in innate and adaptive immunity. Nat Rev Nephrol. 2018; 14: 325-36.
76. Sciascia S, Apra F, Baffa A, et al. Pilot prospective open, single-arm multicentre study on off-label use of tocilizumab in patients with severe COVID-19. Clin Exp Rheumatol. 2020; 38: 529-32.
77. Sebba A. Tocilizumab: the first interleukin-6-receptor inhibitor. Am J Health Syst Pharm. 2008; 65: 1413-8.
78. Zhang C, Wu Z, Li JW, Zhao H, Wang GQ. Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. Int J Antimicrob Agents. 2020; 55: 105954.
79. Tanaka T, Narazaki M, Kishimoto T. Anti-interleukin-6 receptor antibody, tocilizumab, for the treatment of autoimmune diseases. FEBS Lett. 2011; 585: 3699-709.
80. Hung IF, Lung KC, Tso EY, et al. Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet. 2020; 395: 1695-704.
81. Wang N, Zhan Y, Zhu L, et al. Retrospective Multicenter Cohort Study Shows Early Interferon Therapy Is Associated with Favorable Clinical Responses in COVID-19 Patients. Cell Host Microbe. 2020; 28: 455-64.
82. Hojati Z, Kay M, Dehghanian F. Mechanism of Action of Interferon Beta in Treatment of Multiple Sclerosis. In: Minagar, A editor. Multiple Sclerosis, Academic Press; 2016. p. 365-92.
83. Markowitz CE. Interferon-beta: mechanism of action and dosing issues. Neurology. 2007; 68: 8-11.
84. Khsheibun R, Paperna T, Volkowich A, Lejbkowicz I, Avidan N, Miller A. Gene expression profiling of the response to interferon beta in Epstein-Barr-transformed and primary B cells of patients with multiple sclerosis. PLoS One. 2014; 9: e102331.
85. van Holten J, Reedquist K, Sattonet-Roche P, et al. Treatment with recombinant interferon-beta reduces inflammation and slows cartilage destruction in the collagen-induced arthritis model of rheumatoid arthritis. Arthritis Res Ther. 2004; 6: 239-49.
86. Doerner M, Beckmann K, Knappertz V, et al. Effects of inhibitors of the renin-angiotensin system on the efficacy of interferon beta-1b: a post hoc analysis of the BEYOND study. Eur Neurol. 2014; 71: 173-9.
87. Shete A. Urgent need for evaluating agonists of angiotensin-(1-7)/Mas receptor axis for treating patients with COVID-19. Int J Infect Dis. 2020; 96: 348-51.
88. Magrone T, Magrone M, Jirillo E. Focus on Receptors for Coronaviruses with Special Reference to Angiotensin-converting Enzyme 2 as a Potential Drug Target-A Perspective. Endocr Metab Immune Disord Drug Targets. 2020; 20: 807-11.
89. Ciftciler R, Haznedaroglu IC. COVID-19, Renin-Angiotensin System, and Hematopoiesis. Turk J Haematol. 2020; 37: 207-8.
90. Dimova I, Kremensky I. LAMA2 Congenital Muscle Dystrophy: A Novel Pathogenic Mutation in Bulgarian Patient. Case Rep Genet. 2018; 2018: 3028145.
91. Monteil V, Kwon H, Prado P, et al. Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2. Cell. 2020; 181: 905-13.
92. Magalhães GS, Campagnole-Santos MJ, da Glória Rodrigues-Machado M. Renin-Angiotensin System Components in the Lungs. In: Santos, R editor. Angiotensin-(1-7), Springer, Cham; 2019. p.131-52.
93. Zhou Q, Chen V, Shannon CP, et al. Interferon-α2b Treatment for COVID-19. Front Immunol. 2020;11:1061.
94. Acharya D, Liu G, Gack MU. Dysregulation of type I interferon responses in COVID-19. Nat Rev Immunol. 2020; 20: 397-8.
95. Sallard E, Lescure F-X, Yazdanpanah Y, et al. Type 1 interferons as a potential treatment against COVID-19. Antiviral Res. 2020: 104791.
96. Andersson U, Ottestad W, Tracey KJ. Extracellular HMGB1: a therapeutic target in severe pulmonary inflammation including COVID-19? Mol Med. 2020; 26:42.
97. Haznedaroglu IC, Çelebier M. Anti-infective and wound-healing pleiotropic actions of Ankaferd hemostat 2. Turk J Med Sci. 2020; 50: 1434-35.
98. Ciftciler R, Ciftciler AE, Malkan UY, Haznedaroglu IC. Pharmacobiological management of hemostasis within clinical backgrounds via Ankaferd hemostat (Ankaferd blood stopper). SAGE Open Med. 2020; 8: 2050312120907811.
99. Ciftciler R, Haznedaroglu IC. Ankaferd hemostat: from molecules to medicine. Turk J Med Sci. 2020; 50: 1739-50.
100. Ghasemi M, Okay M, Malkan UY, et al. Ankaferd Hemostat Affects Etoposide Resistance of the Malignant Melanoma Cells. UHOD. 2020; 30: 43-53.
101. Celebier M, Haznedaroglu IC. Could Targeting HMGB1 be useful for the Clinical Management of COVID-19 Infection? Comb Chem High Throughput Screen. 2021; 24: 587-90.
102. Escobar LE, Molina-Cruz A, Barillas-Mury C. BCG vaccine protection from severe coronavirus disease 2019. Proc Natl Acad Sci USA. 2020; 117:17720-6.
103. Arvin AM, Fink K, Schmid MA, et al. A perspective on potential antibody-dependent enhancement of SARS-CoV-2. Nature. 2020; 584: 353-63.
104. Mitchell HD, Eisfeld AJ, Stratton KG, et al. The Role of EGFR in Influenza Pathogenicity: Multiple Network-Based Approaches to Identify a Key Regulator of Non-lethal Infections. Front Cell Dev Biol. 2019; 7: 200.
105. Koff JL, Shao MX, Ueki IF, Nadel JA. Multiple TLRs activate EGFR via a signaling cascade to produce innate immune responses in airway epithelium. Am J Physiol Lung Cell Mol Physiol. 2008; 294: 1068-75.
106. Rubin DH, Ruley HE. Cellular genetics of host susceptibility and resistance to virus infection. Crit Rev Eukaryot Gene Expr. 2006; 16: 155-70.
107. St John AL, Rathore APS. Early Insights into Immune Responses during COVID-19. J Immunol. 2020; 205: 555-64.
108. Mangalmurti N, Hunter CA. Cytokine Storms: Understanding COVID-19. Immunity. 2020; 53: 19-25.
109. Wang N, Zhan Y, Zhu L, et al. Retrospective Multicenter Cohort Study Shows Early Interferon Therapy Is Associated with Favorable Clinical Responses in COVID-19 Patients. Cell Host Microbe. 2020; 28: 455-64.
110. Totura AL, Baric RS. SARS coronavirus pathogenesis: host innate immune responses and viral antagonism of interferon. Curr Opin Virol. 2012; 2:264-75.
111. Diamond MS, Farzan M. The broad-spectrum antiviral functions of IFIT and IFITM proteins. Nat Rev Immunol. 2013; 13: 46-57.
112. Gralinski LE, Baric RS. Molecular pathology of emerging coronavirus infections. J Pathol. 2015; 235: 185-95.
113. Erkurt MA, Sarici A, Berber I, Kuku I, Kaya E, Ozgul M. Life-saving effect of convalescent plasma treatment in covid-19 disease: Clinical trial from eastern Anatolia. Transfus Apher Sci. 2020; 59: 102867.
114. Li L, Zhang W, Hu Y, et al. Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial. JAMA. 2020; 324: 460-70.
115. Sayinalp B, Cinar OE, Haznedaroglu IC. Perspectives for immune plasma treatment of COVID-19. Turk J Med Sci. 2021; 51: 1-9.
116. Lang FM, Lee KM, Teijaro JR, Becher B, Hamilton JA. GM-CSF-based treatments in COVID-19: reconciling opposing therapeutic approaches. Nat Rev Immunol. 2020; 20: 507-14.
117. Hadjadj J, Yatim N, Barnabei L, et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science. 2020; 369: 718-724.

IMMUNOGENOMIC APPROACH TO THE CLINICAL MANAGEMENT OF COVID-19 SYNDROME

Year 2023, Volume: 4 Issue: Ek Sayı, 266 - 279, 16.10.2023

Ümit Yavuz Malkan , Olgu Erkin Çınar , Can Türk , Seyhan Türk , İbrahim Celaleddin Haznedaroğlu

Abstract

The COVID-19 syndrome following the SARS-CoV-2 infection has three unique immunogenomic disease development phases; initiating, propagating, and complicating. Each COVID-19 phase has critical pathobiological correlations requiring distinct therapeutic clinical interventions. Renin-angiotensin system (RAS) genes are essential for initiating infections caused by coronavirus family members and may have a strong association with the exchange of critical immune genes, particularly IFN-family, in due course following the SARS-CoV-2 infection. This paper aims to review therapeutic protocols for COVID-19 within the concepts of our previously published three-phase model regarding the clinicopathological course of COVID-19 immune syndrome. The current treatment options have been reviewed in this synopsis within our three-phase disease schedule. Possible future drug candidates affecting the RAS are also considered from the immunogenomical perspective of the syndrome.

Keywords

covid-19, remdesivir, paxlovid, covid-19 treatment, covid-19 syndrome, coronavirus

References

1. Goker H, Aladag Karakulak E, Demiroglu H, et al. The effects of blood group types on the risk of COVID-19 infection and its clinical outcome. Turk J Med Sci. 2020; 50: 679-83.
2. Yang L, Liu S, Liu J, et al. COVID-19: immunopathogenesis and Immunotherapeutics. Signal Transduct Target Ther. 2020; 5:128.
3. Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020; 579: 270-3.
4. Ciftciler R, Ciftciler AE, Haznedaroglu IC. Local Bone Marrow Renin-Angiotensin System and COVID-19. UHOD. 2020; 30: 001-8.
5. Gupta A, Madhavan MV, Sehgal K, et al. Extrapulmonary manifestations of COVID-19. Nat Med. 2020; 26: 1017-32.
6. Turk C, Turk S, Temirci ES, Malkan UY, Haznedaroglu IC. In vitro analysis of the renin-angiotensin system and inflammatory gene transcripts in human bronchial epithelial cells after infection with severe acute respiratory syndrome coronavirus. JRAAS. 2020; 21: 1470320320928872.
7. Turk C, Turk S, Malkan UY, Haznedaroglu IC. Three critical clinicobiological phases of the human sars-associated coronavirus infections. Eur Rev Med Pharmacol Sci. 2020; 24: 8606-20.
8. Malkan UY, Haznedaroglu IC. Hematological aspects of the COVID-19 syndrome. Eur Rev Med Pharmacol Sci. 2022; 26: 4463-76.
9. Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review. JAMA. 2020; 324: 782-93.
10. Worldometers. COVID-19 Coronavirus Pandemic 2020 Available at: https: //www. worldometers. info/coronavirus/. Accessed November 10, 2022.
11. Türkiye Sağlık Bakanlığı - COVID-19 Erişkin Hasta Tedavi Rehberi. Available at: https: // covid19bilgi. saglik. gov.tr/depo/rehberler/covid-19-rehberi/COVID-19_REHBERI_ERISKIN_HASTA_TEDAVISI.pdf. Accessed November 20, 2022.
12. Shannon P, Markiel A, Ozier O, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003; 13: 2498-504.
13. Kuba K, Imai Y, Rao S, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med. 2005;11:875-9.
14. Ciaglia E, Vecchione C, Puca AA. COVID-19 Infection and Circulating ACE2 Levels: Protective Role in Women and Children. Front Pediatr. 2020; 8: 206.
15. Lange C, Wolf J, Auw-Haedrich C, et al. Expression of the COVID-19 receptor ACE2 in the human conjunctiva. J Med Virol. 2020; 92: 2081-6.
16. Yeager CL, Ashmun RA, Williams RK, et al. Human aminopeptidase N is a receptor for human coronavirus 229E. Nature. 1992; 357: 420-2.
17. Qi F, Qian S, Zhang S, Zhang Z. Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses. Biochem Biophys Res Commun. 2020; 526: 135-40.
18. Thachil J, Tang N, Gando S, et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost. 2020;18: 1023-6.
19. Yao X, Ye F, Zhang M, et al. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020; 71: 732-9.
20. Million M, Gautret P, Colson P, et al. Clinical Efficacy of Chloroquine derivatives in COVID-19 Infection: Comparative meta-analysis between the Big data and the real world. New Microbes New Infect. 2020; 38: 100709.
21. Pathak DSK, Salunke DAA, Thivari DP, et al. No benefit of hydroxychloroquine in COVID-19: Results of Systematic Review and Meta-Analysis of Randomized Controlled Trials". Diabetes Metab Syndr. 2020; 14: 1673-80.
22. World Health Organisation. “Solidarity” clinical trial for COVID-19 treatments: Update on hydroxychloroquine Available at: https: //www. who. int/ emergencies/ diseases/ novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov/solidarity-clinical-trial-for-covid-19-treatments. Accessed December 12, 2022.
23. Geleris J, Sun Y, Platt J, et al. Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19. N Engl J Med. 2020; 382: 2411-8.
24. Food and Drug Administration. Coronavirus (COVID-19) Update: FDA Revokes Emergency Use Authorization for Chloroquine and Hydroxychloroquine. June 15, 2020 Available at: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-revokes-emergency-use-authorization-chloroquine-and. Accessed November 21, 2022.
25. Hernandez AV, Roman YM, Pasupuleti V, Barboza JJ, White CM. Hydroxychloroquine or Chloroquine for Treatment or Prophylaxis of COVID-19: A Living Systematic Review. Ann Intern Med. 2020; 173: 287-96.
26. Chowdhury MS, Rathod J, Gernsheimer J. A Rapid Systematic Review of Clinical Trials Utilizing Chloroquine and Hydroxychloroquine as a Treatment for COVID-19. Acad Emerg Med. 2020; 27: 493-504.
27. Meyerowitz EA, Vannier AGL, Friesen MGN, et al. Rethinking the role of hydroxychloroquine in the treatment of COVID-19. FASEB J. 2020; 34: 6027-37.
28. Pastick KA, Okafor EC, Wang F, et al. Review: Hydroxychloroquine and Chloroquine for Treatment of SARS-CoV-2 (COVID-19). Open Forum Infect Dis. 2020; 7: 130.
29. Schrezenmeier E, Dorner T. Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat Rev Rheumatol. 2020;16:155-66.
30. Liu J, Cao R, Xu M, et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov. 2020; 6: 16.
31. Rother N, Yanginlar C, Lindeboom RGH, et al. Hydroxychloroquine Inhibits the Trained Innate Immune Response to Interferons. Cell Rep Med. 2020; 1: 100146.
32. Xu R, Ji Z, Xu C, Zhu J. The clinical value of using chloroquine or hydroxychloroquine as autophagy inhibitors in the treatment of cancers: A systematic review and meta-analysis. Medicine (Baltimore). 2018; 97: e12912.
33. Gies V, Bekaddour N, Dieudonne Y, et al. Beyond Anti-viral Effects of Chloroquine/Hydroxychloroquine. Front Immunol. 2020;11:1409.
34. Le Page C, Genin P, Baines MG, Hiscott J. Interferon activation and innate immunity. Rev Immunogenet. 2000; 2: 374-86.
35. Bodewes ILA, Gottenberg JE, van Helden-Meeuwsen CG, Mariette X, Versnel MA. Hydroxychloroquine treatment downregulates systemic interferon activation in primary Sjogren's syndrome in the JOQUER randomized trial. Rheumatology. 2020; 59: 107-11.
36. Qin X, Chen G, Feng Y, et al. Early treatment with chloroquine inhibits the immune response against Plasmodium yoelii infection in mice. Tohoku J Exp Med. 2014; 234: 271-80.
37. Paton NI, Goodall RL, Dunn DT, et al. Effects of hydroxychloroquine on immune activation and disease progression among HIV-infected patients not receiving antiretroviral therapy: a randomized controlled trial. JAMA. 2012; 308: 353-61.
38. Morgan MJ, Gamez G, Menke C, et al. Regulation of autophagy and chloroquine sensitivity by oncogenic RAS in vitro is context-dependent. Autophagy. 2014;10:1814-26.
39. Schmukler E, Kloog Y, Pinkas-Kramarski R. Ras and autophagy in cancer development and therapy. Oncotarget. 2014; 5: 577-86.
40. Wang P, Du Y, Wang J. Indentification of breast cancer subtypes sensitive to HCQ-induced autophagy inhibition. Pathol Res Pract. 2019; 215: 152609.
41. Cai Q, Yang M, Liu D, et al. Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study. Engineering. 2020; 6: 1192-8.
42. Furuta Y, Komeno T, Nakamura T. Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase. Proc Jpn Acad Ser B Phys Biol Sci. 2017; 93: 449-63.
43. Furuta Y, Gowen BB, Takahashi K, Shiraki K, Smee DF, Barnard DL. Favipiravir (T-705), a novel viral RNA polymerase inhibitor. Antiviral Res. 2013; 100: 446-54.
44. Shiraki K, Daikoku T. Favipiravir, an anti-influenza drug against life-threatening RNA virus infections. Pharmacol Ther. 2020; 209: 107512.
45. Madelain V, Mentre F, Baize S, et al. Modeling Favipiravir Antiviral Efficacy Against Emerging Viruses: From Animal Studies to Clinical Trials. CPT Pharmacometrics Syst Pharmacol. 2020; 9: 258-71.
46. de la Torre JC. Extending the Antiviral Value of Favipiravir. J Infect Dis. 2018; 218: 509-11.
47. Rosenberg ES, Dufort EM, Udo T, et al. Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State. JAMA. 2020; 323: 2493-502.
48. Risch HA. Early Outpatient Treatment of Symptomatic, High-Risk COVID-19 Patients That Should Be Ramped Up Immediately as Key to the Pandemic Crisis. Am J Epidemiol. 2020; 189: 1218-26.
49. Menzel M, Akbarshahi H, Bjermer L, Uller L. Azithromycin induces anti-viral effects in cultured bronchial epithelial cells from COPD patients. Sci Rep. 2016; 6:28698.
50. Parnham MJ, Erakovic Haber V, Giamarellos-Bourboulis EJ, Perletti G, Verleden GM, Vos R. Azithromycin: mechanisms of action and their relevance for clinical applications. Pharmacol Ther. 2014; 143: 225-45.
51. Meyer M, Huaux F, Gavilanes X, et al. Azithromycin reduces exaggerated cytokine production by M1 alveolar macrophages in cystic fibrosis. Am J Respir Cell Mol Biol. 2009; 41: 590-602.
52. Srivastava P, Jha HC, Salhan S, Mittal A. Azithromycin treatment modulates cytokine production in Chlamydia trachomatis infected women. Basic Clin Pharmacol Toxicol. 2009; 104: 478-82.
53. Bleyzac N, Goutelle S, Bourguignon L, Tod M. Azithromycin for COVID-19: More Than Just an Antimicrobial? Clin Drug Investig. 2020; 40: 683-6.
54. Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020; 30: 269-71.
55. Osborne V, Davies M, Lane S, et al. Lopinavir-Ritonavir in the Treatment of COVID-19: A Dynamic Systematic Benefit-Risk Assessment. Drug Saf. 2020; 43: 809-21.
56. Chandwani A, Shuter J. Lopinavir/ritonavir in the treatment of HIV-1 infection: a review. Ther Clin Risk Manag. 2008; 4: 1023-33.
57. Alves EAR, de Miranda MG, Borges TK, Magalhaes KG, Muniz-Junqueira MI. Anti-HIV drugs, lopinavir/ritonavir and atazanavir, modulate innate immune response triggered by Leishmania in macrophages: the role of NF-kappaB and PPAR-gamma. Int Immunopharmacol. 2015; 24: 314-24.
58. Danaher RJ, Kaetzel CS, Greenberg RN, Wang C, Bruno ME, Miller CS. HIV protease inhibitors alter innate immune response signaling to double-stranded RNA in oral epithelial cells: implications for immune reconstitution inflammatory syndrome? AIDS. 2010; 24: 2587-90.
59. Boccara F, Auclair M, Cohen A, et al. HIV protease inhibitors activate the adipocyte renin angiotensin system. Antivir Ther. 2010; 15: 363-75.
60. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the Treatment of Covid-19 - Final Report. N Engl J Med. 2020; 383: 1813-26.
61. Eastman RT, Roth JS, Brimacombe KR, et al. Remdesivir: A Review of Its Discovery and Development Leading to Emergency Use Authorization for Treatment of COVID-19. ACS Cent Sci. 2020; 6: 672-83.
62. Saha A, Sharma AR, Bhattacharya M, Sharma G, Lee SS, Chakraborty C. Probable Molecular Mechanism of Remdesivir for the Treatment of COVID-19: Need to Know More. Arch Med Res. 2020; 51: 585-6.
63. Jayk Bernal A, Gomes da Silva MM, Musungaie DB, et al. Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients. N Engl J Med. 2022; 386: 509-20.
64. Food and Drug Administration. Coronavirus (COVID-19) Update: FDA Authorizes Additional Oral Antiviral for Treatment of COVID-19 in Certain Adults 2021 Available at: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-additional-oral-antiviral-treatment-covid-19-certain. Accessed October 8, 2022.
65. Wen W, Chen C, Tang J, et al. Efficacy and safety of three new oral antiviral treatment (molnupiravir, fluvoxamine and Paxlovid) for COVID-19：a meta-analysis. Ann Med. 2022;54:516-23.
66. Waters MD, Warren S, Hughes C, Lewis P, Zhang F. Human genetic risk of treatment with antiviral nucleoside analog drugs that induce lethal mutagenesis: The special case of molnupiravir. Environ Mol Mutagen. 2022; 63:37-63.
67. Hammond J, Leister-Tebbe H, Gardner A, et al. Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19. N Engl J Med. 2022; 386: 1397-408.
68. Najjar-Debbiny R, Gronich N, Weber G, et al. Effectiveness of Paxlovid in Reducing Severe Coronavirus Disease 2019 and Mortality in High-Risk Patients. Clin Infect Dis. 2023; 76: 342-9.
69. Wang L, Berger NA, Davis PB, Kaelber DC, Volkow ND, Xu R. COVID-19 rebound after Paxlovid and Molnupiravir during January-June 2022. medRxiv. 2022 Oct 28, doi:10.1101/2022.06.21.22276724.
70. Horby P, Lim WS, Emberson J, et al. Effect of Dexamethasone in Hospitalized Patients with COVID-19. N Engl J Med 2021; 384: 693-704.
71. Giles AJ, Hutchinson MND, Sonnemann HM, et al. Dexamethasone-induced immunosuppression: mechanisms and implications for immunotherapy. J Immunother Cancer. 2018; 6: 51.
72. Xia M, Gasser J, Feige U. Dexamethasone enhances CTLA-4 expression during T cell activation. Cell Mol Life Sci. 1999; 55: 1649-56.
73. Liu C, Ge N, Zhai JL, Zhang JX. Dexamethasone-induced diuresis is associated with inhibition of the renin-angiotensin-aldosterone system in rats. Kaohsiung J Med Sci. 2016; 32: 614-9.
74. Barreto-Chaves ML, Heimann A, Krieger JE. Stimulatory effect of dexamethasone on angiotensin-converting enzyme in neonatal rat cardiac myocytes. Braz J Med Biol Res. 2000; 33: 661-4.
75. Bernstein KE, Khan Z, Giani JF, Cao DY, Bernstein EA, Shen XZ. Angiotensin-converting enzyme in innate and adaptive immunity. Nat Rev Nephrol. 2018; 14: 325-36.
76. Sciascia S, Apra F, Baffa A, et al. Pilot prospective open, single-arm multicentre study on off-label use of tocilizumab in patients with severe COVID-19. Clin Exp Rheumatol. 2020; 38: 529-32.
77. Sebba A. Tocilizumab: the first interleukin-6-receptor inhibitor. Am J Health Syst Pharm. 2008; 65: 1413-8.
78. Zhang C, Wu Z, Li JW, Zhao H, Wang GQ. Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. Int J Antimicrob Agents. 2020; 55: 105954.
79. Tanaka T, Narazaki M, Kishimoto T. Anti-interleukin-6 receptor antibody, tocilizumab, for the treatment of autoimmune diseases. FEBS Lett. 2011; 585: 3699-709.
80. Hung IF, Lung KC, Tso EY, et al. Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet. 2020; 395: 1695-704.
81. Wang N, Zhan Y, Zhu L, et al. Retrospective Multicenter Cohort Study Shows Early Interferon Therapy Is Associated with Favorable Clinical Responses in COVID-19 Patients. Cell Host Microbe. 2020; 28: 455-64.
82. Hojati Z, Kay M, Dehghanian F. Mechanism of Action of Interferon Beta in Treatment of Multiple Sclerosis. In: Minagar, A editor. Multiple Sclerosis, Academic Press; 2016. p. 365-92.
83. Markowitz CE. Interferon-beta: mechanism of action and dosing issues. Neurology. 2007; 68: 8-11.
84. Khsheibun R, Paperna T, Volkowich A, Lejbkowicz I, Avidan N, Miller A. Gene expression profiling of the response to interferon beta in Epstein-Barr-transformed and primary B cells of patients with multiple sclerosis. PLoS One. 2014; 9: e102331.
85. van Holten J, Reedquist K, Sattonet-Roche P, et al. Treatment with recombinant interferon-beta reduces inflammation and slows cartilage destruction in the collagen-induced arthritis model of rheumatoid arthritis. Arthritis Res Ther. 2004; 6: 239-49.
86. Doerner M, Beckmann K, Knappertz V, et al. Effects of inhibitors of the renin-angiotensin system on the efficacy of interferon beta-1b: a post hoc analysis of the BEYOND study. Eur Neurol. 2014; 71: 173-9.
87. Shete A. Urgent need for evaluating agonists of angiotensin-(1-7)/Mas receptor axis for treating patients with COVID-19. Int J Infect Dis. 2020; 96: 348-51.
88. Magrone T, Magrone M, Jirillo E. Focus on Receptors for Coronaviruses with Special Reference to Angiotensin-converting Enzyme 2 as a Potential Drug Target-A Perspective. Endocr Metab Immune Disord Drug Targets. 2020; 20: 807-11.
89. Ciftciler R, Haznedaroglu IC. COVID-19, Renin-Angiotensin System, and Hematopoiesis. Turk J Haematol. 2020; 37: 207-8.
90. Dimova I, Kremensky I. LAMA2 Congenital Muscle Dystrophy: A Novel Pathogenic Mutation in Bulgarian Patient. Case Rep Genet. 2018; 2018: 3028145.
91. Monteil V, Kwon H, Prado P, et al. Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2. Cell. 2020; 181: 905-13.
92. Magalhães GS, Campagnole-Santos MJ, da Glória Rodrigues-Machado M. Renin-Angiotensin System Components in the Lungs. In: Santos, R editor. Angiotensin-(1-7), Springer, Cham; 2019. p.131-52.
93. Zhou Q, Chen V, Shannon CP, et al. Interferon-α2b Treatment for COVID-19. Front Immunol. 2020;11:1061.
94. Acharya D, Liu G, Gack MU. Dysregulation of type I interferon responses in COVID-19. Nat Rev Immunol. 2020; 20: 397-8.
95. Sallard E, Lescure F-X, Yazdanpanah Y, et al. Type 1 interferons as a potential treatment against COVID-19. Antiviral Res. 2020: 104791.
96. Andersson U, Ottestad W, Tracey KJ. Extracellular HMGB1: a therapeutic target in severe pulmonary inflammation including COVID-19? Mol Med. 2020; 26:42.
97. Haznedaroglu IC, Çelebier M. Anti-infective and wound-healing pleiotropic actions of Ankaferd hemostat 2. Turk J Med Sci. 2020; 50: 1434-35.
98. Ciftciler R, Ciftciler AE, Malkan UY, Haznedaroglu IC. Pharmacobiological management of hemostasis within clinical backgrounds via Ankaferd hemostat (Ankaferd blood stopper). SAGE Open Med. 2020; 8: 2050312120907811.
99. Ciftciler R, Haznedaroglu IC. Ankaferd hemostat: from molecules to medicine. Turk J Med Sci. 2020; 50: 1739-50.
100. Ghasemi M, Okay M, Malkan UY, et al. Ankaferd Hemostat Affects Etoposide Resistance of the Malignant Melanoma Cells. UHOD. 2020; 30: 43-53.
101. Celebier M, Haznedaroglu IC. Could Targeting HMGB1 be useful for the Clinical Management of COVID-19 Infection? Comb Chem High Throughput Screen. 2021; 24: 587-90.
102. Escobar LE, Molina-Cruz A, Barillas-Mury C. BCG vaccine protection from severe coronavirus disease 2019. Proc Natl Acad Sci USA. 2020; 117:17720-6.
103. Arvin AM, Fink K, Schmid MA, et al. A perspective on potential antibody-dependent enhancement of SARS-CoV-2. Nature. 2020; 584: 353-63.
104. Mitchell HD, Eisfeld AJ, Stratton KG, et al. The Role of EGFR in Influenza Pathogenicity: Multiple Network-Based Approaches to Identify a Key Regulator of Non-lethal Infections. Front Cell Dev Biol. 2019; 7: 200.
105. Koff JL, Shao MX, Ueki IF, Nadel JA. Multiple TLRs activate EGFR via a signaling cascade to produce innate immune responses in airway epithelium. Am J Physiol Lung Cell Mol Physiol. 2008; 294: 1068-75.
106. Rubin DH, Ruley HE. Cellular genetics of host susceptibility and resistance to virus infection. Crit Rev Eukaryot Gene Expr. 2006; 16: 155-70.
107. St John AL, Rathore APS. Early Insights into Immune Responses during COVID-19. J Immunol. 2020; 205: 555-64.
108. Mangalmurti N, Hunter CA. Cytokine Storms: Understanding COVID-19. Immunity. 2020; 53: 19-25.
109. Wang N, Zhan Y, Zhu L, et al. Retrospective Multicenter Cohort Study Shows Early Interferon Therapy Is Associated with Favorable Clinical Responses in COVID-19 Patients. Cell Host Microbe. 2020; 28: 455-64.
110. Totura AL, Baric RS. SARS coronavirus pathogenesis: host innate immune responses and viral antagonism of interferon. Curr Opin Virol. 2012; 2:264-75.
111. Diamond MS, Farzan M. The broad-spectrum antiviral functions of IFIT and IFITM proteins. Nat Rev Immunol. 2013; 13: 46-57.
112. Gralinski LE, Baric RS. Molecular pathology of emerging coronavirus infections. J Pathol. 2015; 235: 185-95.
113. Erkurt MA, Sarici A, Berber I, Kuku I, Kaya E, Ozgul M. Life-saving effect of convalescent plasma treatment in covid-19 disease: Clinical trial from eastern Anatolia. Transfus Apher Sci. 2020; 59: 102867.
114. Li L, Zhang W, Hu Y, et al. Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial. JAMA. 2020; 324: 460-70.
115. Sayinalp B, Cinar OE, Haznedaroglu IC. Perspectives for immune plasma treatment of COVID-19. Turk J Med Sci. 2021; 51: 1-9.
116. Lang FM, Lee KM, Teijaro JR, Becher B, Hamilton JA. GM-CSF-based treatments in COVID-19: reconciling opposing therapeutic approaches. Nat Rev Immunol. 2020; 20: 507-14.
117. Hadjadj J, Yatim N, Barnabei L, et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science. 2020; 369: 718-724.

There are 117 citations in total.

Details

Primary Language	English
Subjects	Clinical Sciences
Journal Section	Review
Authors	Ümit Yavuz Malkan 0000-0001-5444-4895 Olgu Erkin Çınar 0000-0003-1226-5797 Can Türk 0000-0003-1514-7294 Seyhan Türk 0000-0003-3843-4173 İbrahim Celaleddin Haznedaroğlu 0000-0001-8028-9462
Early Pub Date	October 16, 2023
Publication Date	October 16, 2023
Published in Issue	Year 2023 Volume: 4 Issue: Ek Sayı

Cite

APA	Malkan, Ü. Y., Çınar, O. E., Türk, C., Türk, S., et al. (2023). IMMUNOGENOMIC APPROACH TO THE CLINICAL MANAGEMENT OF COVID-19 SYNDROME. Eskisehir Medical Journal, 4(Ek Sayı), 266-279.
AMA	Malkan ÜY, Çınar OE, Türk C, Türk S, Haznedaroğlu İC. IMMUNOGENOMIC APPROACH TO THE CLINICAL MANAGEMENT OF COVID-19 SYNDROME. Eskisehir Med J. October 2023;4(Ek Sayı):266-279.
Chicago	Malkan, Ümit Yavuz, Olgu Erkin Çınar, Can Türk, Seyhan Türk, and İbrahim Celaleddin Haznedaroğlu. “IMMUNOGENOMIC APPROACH TO THE CLINICAL MANAGEMENT OF COVID-19 SYNDROME”. Eskisehir Medical Journal 4, no. Ek Sayı (October 2023): 266-79.
EndNote	Malkan ÜY, Çınar OE, Türk C, Türk S, Haznedaroğlu İC (October 1, 2023) IMMUNOGENOMIC APPROACH TO THE CLINICAL MANAGEMENT OF COVID-19 SYNDROME. Eskisehir Medical Journal 4 Ek Sayı 266–279.
IEEE	Ü. Y. Malkan, O. E. Çınar, C. Türk, S. Türk, and İ. C. Haznedaroğlu, “IMMUNOGENOMIC APPROACH TO THE CLINICAL MANAGEMENT OF COVID-19 SYNDROME”, Eskisehir Med J, vol. 4, no. Ek Sayı, pp. 266–279, 2023.
ISNAD	Malkan, Ümit Yavuz et al. “IMMUNOGENOMIC APPROACH TO THE CLINICAL MANAGEMENT OF COVID-19 SYNDROME”. Eskisehir Medical Journal 4/Ek Sayı (October 2023), 266-279.
JAMA	Malkan ÜY, Çınar OE, Türk C, Türk S, Haznedaroğlu İC. IMMUNOGENOMIC APPROACH TO THE CLINICAL MANAGEMENT OF COVID-19 SYNDROME. Eskisehir Med J. 2023;4:266–279.
MLA	Malkan, Ümit Yavuz et al. “IMMUNOGENOMIC APPROACH TO THE CLINICAL MANAGEMENT OF COVID-19 SYNDROME”. Eskisehir Medical Journal, vol. 4, no. Ek Sayı, 2023, pp. 266-79.
Vancouver	Malkan ÜY, Çınar OE, Türk C, Türk S, Haznedaroğlu İC. IMMUNOGENOMIC APPROACH TO THE CLINICAL MANAGEMENT OF COVID-19 SYNDROME. Eskisehir Med J. 2023;4(Ek Sayı):266-79.

Download Cover Image

Article Files

Full Text

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.