Fighting COVID-19: What Are the Available Options?
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus, and its infection, coronavirus disease 2019 (COVID-19), have quickly become a worldwide threat. It is essential for clinicians to learn about this pandemic to manage patients. Among different aspects of the condition, is the treatment of this disease. Unfortunately, currently there is no effective treatment option that can be supported by evidence-based medicine. This review analyzes information from literature on treatments.
2. Fintelman-Rodrigues N, Sacramento CQ, Lima CR, da Silva FS, Ferreira A, Mattos M, et al. Atazanavir inhibits SARS-CoV-2 replication and pro-inflammatory cytokine production. bioRxiv. 2020.
3. Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. A trial of lopinavir–ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. 2020;382(19):1787-99.
4. Agostini ML, Andres EL, Sims AC, Graham RL, Sheahan TP, Lu X, et al. Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. MBio. 2018;9(2):e00221-18.
5. Mulangu S, Dodd LE, Davey Jr RT, Tshiani Mbaya O, Proschan M, Mukadi D, et al. A randomized, controlled trial of Ebola virus disease therapeutics. N Engl J Med. 2019;381(24):2293-303.
6. Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269-71.
7. Grein J, Ohmagari N, Shin D, Diaz G, Asperges E, Castagna A, et al. Compassionate use of remdesivir for patients with severe Covid-19. N Engl J Med. 2020; [Epub ahead of print].
8. NIH Clinical Trial Shows Remdesivir Accelerates Recovery from Advanced COVID-19. April 29, 2020. [Available from: https://wwwniaidnihgov/news-events/nih-clinical-trial-shows-remdesivir-accelerates-recovery-advanced-covid-19].
9. 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(7):449-63.
10. Dong L, Hu S, Gao J. Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug Discov Ther. 2020;14(1):58-60.
11. Chen C, Huang J, Cheng Z, Wu J, Chen S, Zhang Y, et al. Favipiravir versus arbidol for COVID-19: a randomized clinical trial. MedRxiv. 2020.
12. Huang L, Zhang L, Liu Y, Luo R, Zeng L, Telegina I, et al. Arbidol for preventing and treating influenza in adults and children. Cochrane Database Syst Rev. 2017;2:CD011489.
13. Lawitz E, Mangia A, Wyles D, Rodriguez-Torres M, Hassanein T, Gordon SC, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013;368(20):1878-87.
14. Elfiky AA. Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study. Life Sci. 2020:117592.
15. A prospective randomized controlled trial comparing Sovodak (Sofosbuvir plus Daclatasvir) in participants with moderate to severe Coronavirus disease (COVID-19) compared to standard of care treatment. 2020. [Available from: https://en.irct.ir/trial/46463].
16. Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic treatments for coronavirus disease 2019 (COVID-19): a review. JAMA. 2020; [Epub ahead of print].
17. Sinha N, Balayla G. Hydroxychloroquine and covid-19. Postgrad Med J. 2020; [Epub ahead of print].
18. Sperber K, Quraishi H, Kalb T, Panja A, Stecher V, Mayer L. Selective regulation of cytokine secretion by hydroxychloroquine: inhibition of interleukin 1 alpha (IL-1-alpha) and IL-6 in human monocytes and T cells. J Rheumatol. 1993;20(5):803-8.
19. Kwiek JJ, Haystead TA, Rudolph J. Kinetic mechanism of quinone oxidoreductase 2 and its inhibition by the antimalarial quinolines. Biochemistry. 2004;43(15):4538-47.
20. Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, 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; [Epub ahead of print].
21. Gautret P, Lagier JC, Parola P, Meddeb L, Mailhe M, Doudier B, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020; [Epub ahead of print].
22. Kalil AC. Treating COVID-19—off-label drug use, compassionate use, and randomized clinical trials during pandemics. JAMA. 2020; [Epub ahead of print].
23. Chen Z, Hu J, Zhang Z, Jiang S, Han S, Yan D, et al. Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial. MedRxiv. 2020.
24. Liu B, Li M, Zhou Z, Guan X, Xiang Y. Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)? J Autoimmun. 2020;111:102452.
25. Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, et al. Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clin Infect Dis. 2020; [Epub ahead of print].
26. Hellewell S, Semple BD, Morganti-Kossmann MC. Therapies negating neuroinflammation after brain trauma. Brain Res. 2016;1640:36-56.
27. Chen C, Zhang X, Ju Z, He W. Advances in the research of cytokine storm mechanism induced by Corona Virus Disease 2019 and the corresponding immunotherapies. Zhonghua Shao Shang Za Zhi. 2020; [Epub ahead of print].
28. Monteleone G, Sarzi-Puttini PC, Ardizzone S. Preventing COVID-19-induced pneumonia with anticytokine therapy. Lancet Rheumatol. 2020 May;2(5):e255-6.
29. Vincent J-L. Annual update in intensive care and emergency medicine 2012: Springer Science & Business Media; 2012.
30. Peters vTA, Kox M, Pickkers P, Abdo WF. Reduced glial activity after surgery: A sign of immunoparalysis of the brain? Ann Neurol. 2017;82(1):152.
31. Leentjens J, Kox M, van der Hoeven JG, Netea MG, Pickkers P. Immunotherapy for the adjunctive treatment of sepsis: from immunosuppression to immunostimulation. Time for a paradigm change? Am J Respir Crit Care Med. 2013;187(12):1287-93.
32. Peyrin-Biroulet L, Van Assche G, Gómez-Ulloa D, García-Álvarez L, Lara N, Black CM, et al. Systematic review of tumor necrosis factor antagonists in extraintestinal manifestations in inflammatory bowel disease. Clin Gastroenterol Hepatol. 2017;15(1):25-36.e27.
33. Osterman MT, Lichtenstein GR. Infliximab vs Adalimumab for UC: Is There A Difference? Clin Gastroenterol Hepatol. 2017;15(8):1197-9.
34. Cholapranee A, Hazlewood GS, Kaplan GG, Peyrin‐Biroulet L, Ananthakrishnan AN. Systematic review with meta‐analysis: comparative efficacy of biologics for induction and maintenance of mucosal healing in Crohn's disease and ulcerative colitis controlled trials. Aliment Pharmacol Ther. 2017;45(10):1291-302.
35. Targan SR, Hanauer SB, Van Deventer SJ, Mayer L, Present DH, Braakman T, DeWoody KL, Schaible TF, Rutgeerts PJ. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor α for Crohn's disease. N Engl J Med. 1997;337(15):1029-36.
36. Schett G, Sticherling M, Neurath MF. COVID-19: risk for cytokine targeting in chronic inflammatory diseases? Nat Rev Immunol. 2020;20(5):271-2.
37. Wisniewski A, Kirchgesner J, Seksik P, Landman C, Bourrier A, Nion-Larmurier I, et al. Increased incidence of systemic serious viral infections in patients with inflammatory bowel disease associates with active disease and use of thiopurines. United European Gastroenterol J. 2020;8(3):303-13.
38. Kirchgesner J, Lemaitre M, Carrat F, Zureik M, Carbonnel F, Dray-Spira R. Risk of serious and opportunistic infections associated with treatment of inflammatory bowel diseases. Gastroenterology. 2018;155(2):337-46.e10.
39. Queiroz NSF, Barros LL, Azevedo MFCd, Oba J, Sobrado CW, Carlos AdS, et al. Management of inflammatory bowel disease patients in the COVID-19 pandemic era: a Brazilian tertiary referral center guidance. Clinics. 2020;75:e1909.
40. D'Antiga L. Coronaviruses and immunosuppressed patients. The facts during the third epidemic. Liver Transpl. 2020;26(6):832-4.
41. Dipasquale V, Romano C. Pharmacological treatments and infectious diseases in pediatric inflammatory bowel disease. Expert Rev Gastroenterol Hepatol. 2018;12(3):237-47.
42. Alvisi P, Dipasquale V, Barabino A, Martellossi S, Miele E, Lionetti P, et al. Infections and malignancies risks related to TNF-α-blocking agents in pediatric inflammatory bowel diseases. Expert Rev Gastroenterol Hepatol. 2019;13(10):957-61.
43. Tanaka T, Narazaki M, Kishimoto T. Immunotherapeutic implications of IL-6 blockade for cytokine storm. Immunotherapy. 2016;8(8):959-70.
44. Gao Y, Li T, Han M, Li X, Wu D, Xu Y, et al. Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID‐19. J Med Virol. 2020; [Epub ahead of print].
45. Charles P, Elliott MJ, Davis D, Potter A, Kalden JR, Antoni C, et al. Regulation of cytokines, cytokine inhibitors, and acute-phase proteins following anti-TNF-α therapy in rheumatoid arthritis. J Immunol. 1999;163(3):1521-8.
46. Dvorak HF, Brown LF, Detmar M, Dvorak AM. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol. 1995;146(5):1029-39.
47. Feldmann M, Maini RN. Anti-TNFα therapy of rheumatoid arthritis: what have we learned? Ann Rev Immunol. 2001;19(1):163-96.
48. Paleolog EM, Young S, Stark AC, McCloskey RV, Feldmann M, Maini RN. Modulation of angiogenic vascular endothelial growth factor by tumor necrosis factor α and interleukin‐1 in rheumatoid arthritis. Arthritis Rheum. 1998;41(7):1258-65.
49. Arabi YM, Mandourah Y, Al-Hameed F, Sindi AA, Almekhlafi GA, Hussein MA, et al. Corticosteroid therapy for critically ill patients with Middle East respiratory syndrome. Am J Respir Crit Care Med. 2018;197(6):757-67.
50. Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014;124(2):188-95.
51. Burmester GR, Rubbert-Roth A, Cantagrel A, Hall S, Leszczynski P, Feldman D, et al. Efficacy and safety of subcutaneous tocilizumab versus intravenous tocilizumab in combination with traditional DMARDs in patients with RA at week 97 (SUMMACTA). Ann Rheum Dis. 2016;75(1):68-74.
52. Bennardo F, Buffone C, Giudice A. New therapeutic opportunities for COVID-19 patients with Tocilizumab: Possible correlation of interleukin-6 receptor inhibitors with osteonecrosis of the jaws. Oral Oncol. 2020; [Epub ahead of print].
53. Jin YH, Cai L, Cheng ZS, Cheng H, Deng T, Fan YP, et al. A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Mil Med Res. 2020;7(1):4.
54. Conti P, Ronconi G, Caraffa A, Gallenga C, Ross R, Frydas I, et al. Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies. J Biol Regul Homeost Agents. 2020; [Epub ahead of print].
55. Feldmann M, Maini RN, Woody JN, Holgate ST, Winter G, Rowland M, et al. Trials of anti-tumour necrosis factor therapy for COVID-19 are urgently needed. Lancet. 2020;395(10234):1407-9.
56. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033-4.
57. Michot J-M, Albiges L, Chaput N, Saada V, Pommeret F, Griscelli F, et al. Tocilizumab, an anti-IL6 receptor antibody, to treat COVID-19-related respiratory failure: a case report. Ann Oncol. 2020; [Epub ahead of print].
58. Rütter A, Luger TA. High-dose intravenous immunoglobulins: an approach to treat severe immune-mediated and autoimmune diseases of the skin. J Am Acad Dermatol. 2001;44(6):1010-24.
59. Dalakas MC. Mechanisms of action of IVIg and therapeutic considerations in the treatment of acute and chronic demyelinating neuropathies. Neurology. 2002;59(12 suppl 6):S13-21.
60. Cao W, Liu X, Bai T, Fan H, Hong K, Song H, et al. High-dose intravenous immunoglobulin as a therapeutic option for deteriorating patients with coronavirus disease 2019. InOpen Forum Infectious Diseases 2020 Mar (Vol. 7, No. 3, p. ofaa102). US: Oxford University Press.
61. Alhazzani W, Møller MH, Arabi YM, Loeb M, Gong MN, Fan E, et al. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19). Intensive Care Med. 2020;46(5):854-87.
62. Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8(4):420-2.
63. Lee N, Chan KA, Hui DS, Ng EK, Wu A, Chiu RW, et al. Effects of early corticosteroid treatment on plasma SARS-associated Coronavirus RNA concentrations in adult patients. J Clin Virol. 2004;31(4):304-9.
64. Ni YN, Chen G, Sun J, Liang B-M, Liang ZA. The effect of corticosteroids on mortality of patients with influenza pneumonia: a systematic review and meta-analysis. Crit Care. 2019;23(1):99.
65. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506.
66. Xiao J, Ma L, Gao J, Yang Z, Xing X, Zhao H, et al. Glucocorticoid-induced diabetes in severe acute respiratory syndrome: the impact of high dosage and duration of methylprednisolone therapy. Zhonghua Nei Ke Za Zhi. 2004;43(3):179-82.
67. Griffith JF, Antonio GE, Kumta SM, Hui DSC, Wong JKT, Joynt GM, et al. Osteonecrosis of hip and knee in patients with severe acute respiratory syndrome treated with steroids. Radiology. 2005;235(1):168-75.
68. World Health Organization. Clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected: interim guidance. March 13, 2020. [Available from: https://apps.who.int/iris/handle/10665/331446].
69. Cyclosporine Side Effects. Nov 21, 2019. [Available from: https://www.drugs.com/sfx/cyclosporine-side-effects.html].
70. Tacrolimus (Systemic). Feb 10, 2020. [Available from: https://www.drugs.com/ppa/tacrolimus-systemic.html].
71. Rabie R, Mumtaz K, Renner EL. Efficacy of antiviral therapy for hepatitis C after liver transplantation with cyclosporine and tacrolimus: A systematic review and meta‐analysis. Liver Transpl. 2013;19(1):36-48.
72. Clinical Trial to Evaluate Methylprednisolone Pulses and Tacrolimus in Patients With COVID-19 Lung Injury (TACROVID). [Available from: http://clinicaltrials.gov/ct2/show/NCT04341038?term=cyclosporine &cond=COVID&draw=2&rank=1].
73. Lu H. Drug treatment options for the 2019-new coronavirus (2019-nCoV). Biosci Trends. 2020;14(1):69-71.
74. Chen J, LIU D, LIU L, LIU P, XU Q, XIA L, et al. A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19). J Zhejiang Univ (Med Sci), 2020;49(2):215-9.
75. Cortegiani A, Ingoglia G, Ippolito M, Giarratano A, Einav S. A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J Crit Care. 2020; [Epub ahead of print].
76. Duan K, Liu B, Li C, Zhang H, Yu T, Qu J, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci U S A. 2020;117(17):9490-6.
77. Zhang L, Liu Y. Potential interventions for novel coronavirus in China: a systemic review. J Med Virol. 2020; [Epub ahead of print].
78. Kandeel M, Al-Nazawi M. Virtual screening and repurposing of FDA approved drugs against COVID-19 main protease. Life Sci. 2020;251:117627.
79. Carr AC, Rosengrave PC, Bayer S, Chambers S, Mehrtens J, Shaw GM. Hypovitaminosis C and vitamin C deficiency in critically ill patients despite recommended enteral and parenteral intakes. Crit Care. 2017;21(1):300.
80. Panarese A, Shahini E. Covid‐19, and vitamin D. Aliment Pharmacol Ther. 2020;51(10):993-5.
81. Carr AC. A new clinical trial to test high-dose vitamin C in patients with COVID-19. Crit Care. 2020;24(1):133.
82. Tsujino I, Ushikoshi-Nakayama R, Yamazaki T, Matsumoto N, Saito I. Pulmonary activation of vitamin D3 and preventive effect against interstitial pneumonia. J Clin Biochem Nutr. 2019;65(3):245-51.
83. Razzaque MS. COVID-19 Pandemic: Can Maintaining Optimal Zinc Balance Enhance Host Resistance? Preprints. 2020:2020040006.
84. Scholz M, Derwand R. Does Zinc Supplementation Enhance the Clinical Efficacy of Chloroquine/Hydroxychloroquine to Win Todays Battle Against COVID-19? Med Hypotheses. 2020; [Epub ahead of print].
85. Schönbeck U, Libby P. Inflammation, immunity, and HMG-CoA reductase inhibitors: statins as antiinflammatory agents? Circulation. 2004;109(21 Suppl 1):II18-26.
86. Dashti‐Khavidaki S, Khalili H. Considerations for statin therapy in patients with COVID‐19. Pharmacotherapy. 2020;40(5):484-6.
87. Little P. Non-steroidal anti-inflammatory drugs and covid-19. BMJ. 2020;368:m1185.
88. Mehra MR, Desai SS, Kuy S, Henry TD, Patel AN. Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19. N Engl J Med. 2020; [Epub ahead of print].
89. Mancia G, Rea F, Ludergnani M, Apolone G, Corrao G. Renin–Angiotensin–Aldosterone System Blockers and the Risk of Covid-19. N Engl J Med. 2020; [Epub ahead of print].
90. Reynolds HR, Adhikari S, Pulgarin C, Troxel AB, Iturrate E, Johnson SB, et al. Renin–Angiotensin–Aldosterone System Inhibitors and Risk of Covid-19. N Engl J Med. 2020; [Epub ahead of print].
91. Massachusetts General Hospital. COVID-19 Treatment Guidance. May 19, 2020 [Available from: https://www.massgeneral.org/assets/MGH/pdf/news/coronavirus/mass-general-COVID-19-treatment-guidance.pdf].
92. Sodhi M, Etminan M. Therapeutic Potential for Tetracyclines in the Treatment of COVID‐19. Pharmacotherapy. 2020;40(5):487-8.
93. Wang J, Hajizadeh N, Moore EE, McIntyre RC, Moore PK, Veress LA, et al. Tissue plasminogen activator (tpa) treatment for COVID‐19 associated acute respiratory distress syndrome (ARDS): a case series. J Thromb Haemost. 2020; [Epub ahead of print].
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