CURRENT THERAPEUTIC OPTIONS FOR CORONAVIRUS DISEASE-2019 – A PHARMACOLOGICAL REVIEW

Authors

  • SASMI MB Department of Pharmacology, Jubilee Mission Medical College and Research Institute, Thrissur, Kerala, India.
  • MARIA JOSE Department of Pharmacology, Jubilee Mission Medical College and Research Institute, Thrissur, Kerala, India.
  • PRAVEENLAL KUTTICHIRA Department of Psychiatry, Jubilee Mission Medical College and Research Institute, Thrissur, Kerala, India.

DOI:

https://doi.org/10.22159/ajpcr.2020.v13i8.38342

Keywords:

Coronavirus disease-2019, Severe acute respiratory syndrome-coronavirus-2, Coronavirus, Drug treatment

Abstract

Objectives: Coronavirus pandemic is currently a global public health emergency. With expanding knowledge of the virus and the disease, new therapeutic targets are emerging widely. There is limited evidence about the use of different treatment options in coronavirus disease-2019 (COVID-19). This review aims to summarize the available evidence regarding therapeutic options in treating coronavirus infection.

Methods: We searched PubMed, Google Scholar, and Cochrane library using pre-specified Medical Subject Headings terms about the role of therapeutic options in COVID-19 patients.

Results: The majority of the published evidence is either case reports or small observational studies. Antimalarial like hydroxychloroquine reported equivocal results with five studies got positive results and five without any added benefit compared with standard of care. Lopinavir/ ritonavir monotherapy does not show any significant role except in combination with other antiviral drugs but encouraging results are emerging with remdesivir. Studies with favipiravir are inconclusive with some exhibit benefit and others not. Limited case series have shown that tocilizumab and convalescent plasma to be useful as adjuvant therapy in critically ill patients.

Conclusion: There is currently no strong evidence for the efficacy of different therapeutic agents in the treatment of COVID-19. More data from ongoing and future trials will add more insight into the role of various drugs.

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References

Coronavirus Disease (COVID-19) Situation Reports. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/ situation-reports. [Last accessed on 2020 May 13].

Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet 2020;395:507-13.

Kumari VB, Patil SM, Shirahatti PS, Sujay S, Tejaswini M, Ranganatha LV, et al. The current status and perspectives for the emerging pandemic: COVID-19. Int J Pharm Pharm Sci 2020;12:38206.

Chen Y, Liu Q, Guo D. Emerging coronaviruses: Genome structure, replication, and pathogenesis. J Med Virol 2020;92:418-23.

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;30:269-71.

Zhou D, Dai SM, Tong Q. COVID-19: A recommendation to examine the effect of hydroxychloroquine in preventing infection and progression. J Antimicrob Chemother 2020;75:1667-70.

Devaux CA, Rolain JM, Colson P, Raoult D. New insights on the antiviral effects of chloroquine against coronavirus: What to expect for COVID-19? Int J Antimicrob Agents 2020;55:105938.

Kalil AC. Treating COVID-19-off-label drug use, compassionate use, and randomized clinical trials during pandemics. JAMA 2020;323:1897-8.

Nutho B, Mahalapbutr P, Hengphasatporn K, Pattaranggoon NC, Simanon N, Shigeta Y, et al. Why are lopinavir and ritonavir effective against the newly emerged coronavirus 2019? Atomistic insights into the inhibitory mechanisms. Biochemistry 2020;59:1769-79.

Zhang L, Lin D, Sun X, Curth U, Drosten C, Sauerhering L, et al. Crystal structure of SARS-CoV-2 main protease provides a basis for the design of improved alpha-ketoamide inhibitors. Science 2020;368:409-12.

Dong L, Hu S, Gao J. Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug Discov Ther 2020;14:58-60.

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.

Sebba A. Tocilizumab: The first interleukin-6-receptor inhibitor. Am J Health Syst Pharm 2008;65:1413-8.

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.

Mair-Jenkins J, Saavedra-Campos M, Baillie JK, Cleary P, Khaw FM, Lim WS, et al, Convalescent Plasma Study Group. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: A systematic review and exploratory meta-analysis. J Infect Dis 2015;211:80-90.

Liu J, Cao R, Xu M, Wang X, Zhang H, Hu H, et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov 2020;6:16.

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;71:732-9.

Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, 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;56:105949.

Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Sevestre J, et al. Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study. Travel Med Infect Dis 2020;34:101663.

Chen J, Liu D, Liu L, Liu P, Xu Q, Xia L, et al. A pilot study of hydroxychloroquine in treatment of patients with moderate COVID-19. J Zhejiang Univ 2020;49:215-9.

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; [Preprint].

Tang W, Cao Z, Han M, Wang Z, Chen J, Sun W, et al. Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: Open label, randomised controlled trial. BMJ 2020;369:m1849.

Molina JM, Delaugerre C, Le Goff J, Mela-Lima B, Ponscarme D, Goldwirt L, et al. No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection. Med Mal Infect 2020;50:384.

Million M, Lagier JC, Gautret P, Colson P, Fournier PE, Amrane S, et al. Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: A retrospective analysis of 1061 cases in Marseille, France. Travel Med Infect Dis 2020;35:101738.

Mahevas M, Tran VT, Roumier M, Chabrol A, Paule R, Guillaud C, et al. No evidence of clinical efficacy of hydroxychloroquine in patients hospitalized for COVID-19 infection with oxygen requirement: Results of a study using routinely collected data to emulate a target trial. MedRxiv 2020; [Preprint].

Magagnoli J, Narendran S, Pereira F, Cummings TH, Hardin JW, Sutton SS, et al. Outcomes of Hydroxychloroquine Usage in United States Veterans Hospitalized with COVID-19; 2020. Available from: http://www.sciencedirect.com/science/article/pii/S2666634020300064.

Geleris J, Sun Y, Platt J, Zucker J, Baldwin M, Hripcsak G, et al. Observational study of hydroxychloroquine in hospitalized patients with covid-19. N Engl J Med 2020;382:2411-8.

Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends 2020;14:72-3.

Huang M, Tang T, Pang P, Li M, Ma R, Lu J, et al. Treating COVID-19 with chloroquine. J Mol Cell Biol 2020;12:322-5.

Borba MG, Val FF, Sampaio VS, Alexandre MA, Melo GC, Brito M, et al. Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: A randomized clinical trial. JAMA Netw Open 2020;3:e208857.

Singh B, Ryan H, Kredo T, Chaplin M, Fletcher T. Chloroquine or hydroxychloroquine for prevention and treatment of COVID‐19. Cochrane Database Syst Rev 2020;4:CD013587.

Yao TT, Qian JD, Zhu WY, Wang Y, Wang GQ. A systematic review of lopinavir therapy for SARS coronavirus and MERS coronavirus-a possible reference for coronavirus disease-19 treatment option. J Med Virol 2020;92:556-63.

Choy KT, Wong AY, Kaewpreedee P, Sia SF, Chen D, Hui KP, et al. Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro. Antiviral Res 2020;178:104786.

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;382:1787-99.

Li Y, Xie Z, Lin W, Cai W, Wen C, Guan Y, et al. An exploratory randomized, controlled study on the efficacy and safety of lopinavir/ ritonavir or arbidol treating adult patients hospitalized with mild/ moderate COVID-19 (ELACOI). MedRxiv 2020; [In press].

Yan D, Liu XY, Zhu YN, Huang L, Dan BT, Zhang GJ, et al. Factors associated with prolonged viral shedding and impact of lopinavir/ ritonavir treatment in hospitalised non-critically ill patients with SARS-CoV-2 infection. Eur Respir J 2020;56:2000799.

Ye XT, Luo YL, Xia SC, Sun QF, Ding JG, Zhou Y, et al. Clinical efficacy of lopinavir/ritonavir in the treatment of coronavirus disease 2019. Eur Rev Med Pharmacol Sci 2020;24:3390-6.

Deng L, Li C, Zeng Q, Liu X, Li X, Zhang H, et al. Arbidol combined with LPV/r versus LPV/r alone against corona virus disease 2019: A retrospective cohort study. J Infect 2020;81:e1-5.

Wang Z, Chen X, Lu Y, Chen F, Zhang W. Clinical characteristics and therapeutic procedure for four cases with 2019 novel coronavirus pneumonia receiving combined Chinese and Western medicine treatment. Biosci Trends 2020;14:64-8.

Liu F, Xu A, Zhang Y, Xuan W, Yan T, Pan K, et al. Patients of COVID-19 may benefit from sustained lopinavir-combined regimen and the increase of eosinophil may predict the outcome of COVID-19 progression. Int J Infect Dis 2020;95:183-91.

Young BE, Ong SW, Kalimuddin S, Low JG, Tan SY, Loh J, et al, Singapore 2019 Novel Coronavirus Outbreak Research Team. Epidemiologic features and clinical course of patients infected with SARS-CoV-2 in Singapore. JAMA 2020;323:1488-94.

Lim J, Jeon S, Shin HY, Kim MJ, Seong YM, Lee WJ, et al. Case of the index patient who caused tertiary transmission of COVID-19 infection in Korea: The application of lopinavir/ritonavir for the treatment of COVID-19 infected pneumonia monitored by quantitative RT-PCR. J Korean Med Sci 2020;35:e79.

Han WZ, Quan B, Guo Y, Zhang J, Lu Y, Feng G, et al. The course of clinical diagnosis and treatment of a case infected with coronavirus disease 2019. J Med Virol 2020;92:461-3.

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:e00221-18.

Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H, et al, Washington State 2019-nCoV Case Investigation Team. First case of 2019 novel coronavirus in the United States. N Engl J Med 2020;382:929-36.

Kujawski S, Wong K, Collins J, Epstein L, Killerby M, Midgley C, et al. First 12 patients with coronavirus disease 2019 (COVID-19) in the United States. MedRxiv 2020; [Preprint].

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;382:2327-36.

Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y, et al. Remdesivir in adults with severe COVID-19: A randomised, double-blind, placebo-controlled, multicentre trial. Lancet 2020;395:1569-78.

Available from: https://www.clinicaltrials.gov. [Last accessed on 2020 Apr 25].

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; [Preprint].

Cai Q, Yang M, Liu D, Chen J, Shu D, Xia J, et al. Experimental treatment with favipiravir for COVID-19: An open-label control study. Engineering (Beijing) 2020;[In press].

Stockman LJ, Bellamy R, Garner P. SARS: Systematic review of treatment effects. PLoS Med 2006;3:e343.

Lu H. Drug treatment options for the 2019-new coronavirus (2019- nCoV). Biosci Trends 2020;14:69-71.

Haviernik J, Stefanik M, Fojtikova M, Kali S, Tordo N, Rudolf I, et al. arbidol (umifenovir): A broad-spectrum antiviral drug that inhibits medically important arthropod-borne flaviviruses. Viruses 2018;10:184.

Mantlo E, Bukreyeva N, Maruyama J, Paessler S, Huang C. Antiviral activities of Type I interferons to SARS-CoV-2 infection. Antiviral Res 2020;179:104811.

Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, et al. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. JAMA 2020;323:1582-9.

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. Open Forum Infect Dis 2020;7:ofaa102.

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;117:9490-6.

Ye M, Fu D, Ren Y, Wang F, Wang D, Zhang F, et al. Treatment with convalescent plasma for COVID-19 patients in Wuhan, China. J Med Virol 2020;4:1-12.

Zhang B, Liu S, Tan T, Huang W, Dong Y, Chen L, et al. Treatment with convalescent plasma for critically ill patients with severe acute respiratory syndrome Coronavirus 2 infection. Chest 2020;158:e9-13.

Xu X, Han M, Li T, Sun W, Wang D, Fu B, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A 2020;117:10970-5.

Luo P, Liu Y, Qiu L, Liu X, Liu D, Li J. Tocilizumab treatment in COVID-19: A single center experience. J Med Virol 2020;92:814-8.

Sciascia S, Aprà F, Baffa A, Baldovino S, Boaro D, Boero R, 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.

Odièvre MH, de Marcellus C, Le Pointe HD, Allali S, Romain AS, Youn J, et al. Dramatic improvement after tocilizumab of severe COVID-19 in a child with sickle cell disease and acute chest syndrome. Am J Hematol 2020;5:E192-4.

Hammami MB, Garibaldi B, Shah P, Liu G, Jain T, Chen PH, et al. Clinical course of COVID-19 in a liver transplant recipient on hemodialysis and response to tocilizumab therapy: A case report. Am J Transplant 2020;5:1-6.

Ferrey AJ, Choi G, Hanna RM, Chang Y, Tantisattamo E, Ivaturi K, et al. A case of novel coronavirus disease 19 in a chronic hemodialysis patient presenting with gastroenteritis and developing severe pulmonary disease. Am J Nephrol 2020;51:337-42.

Michot JM, Albiges L, Chaput N, Saada V, Pommeret F, Griscelli F, et al. Tocilizumab, an anti-IL-6 receptor antibody, to treat COVID-19- related respiratory failure: A case report. Ann Oncol 2020;31:961-4.

Mihai C, Dobrota R, Schröder M, Garaiman A, Jordan S, Becker MO, et al. COVID-19 in a patient with systemic sclerosis treated with tocilizumab for SSc-ILD. Ann Rheum Dis 2020;79:668-9.

Zhang X, Song K, Tong F, Fei M, Guo H, Lu Z, et al. First case of COVID-19 in a patient withmultiple myeloma successfully treated with tocilizumab. Blood Adv 2020;4:1307-10.

Radbel J, Narayanan N, Bhatt PJ. Use of tocilizumab for COVID-19- induced cytokine release syndrome: A cautionary case report. Chest 2020;158:e15-9.

Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet 2020;395:473-5.

Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antivir Res 2020;178:104787.

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;382:2431-40.

Mehra MR, Desai SS, Kuy S, Henry TD, Patel AN. Cardiovascular disease, drug therapy, and mortality in covid-19. N Engl J Med 2020;382:e102.

Sarma P, Kaur H, Kumar H, Mahendru D, Avti P, Bhattacharyya A, et al. Virological and clinical cure in covid-19 patients treated with hydroxychloroquine: A systematic review and meta-analysis. J Med Virol 2020;92:776-85.

Cao YC, Deng QX, Dai SX. Remdesivir for severe acute respiratory syndrome coronavirus 2 causing COVID-19: An evaluation of the evidence. Travel Med Infect Dis 2020;35:101647.

Alzghari SK, Acuña VS. Supportive treatment with tocilizumab for COVID-19: A systematic review. J ClinVirol 2020;127:104380.

Divya SM, Thomas NV. Potential therapeutic avenues for COVID-19 therapy. Int J Pharm Pharm Sci 2020;2020:12.

Revised Guidelines on Clinical Management of COVID-19. Government of India Ministry of Health and Family Welfare Directorate General of Health Services (EMR Division); 2020. Available from: http://www.mohfw.gov.in. [Last accessed on 2020 May 13].

Bhatnagar T, Murhekar MV, Soneja M, Gupta N, Giri S, Wig N, et al. Lopinavir/ritonavir combination therapy amongst symptomatic coronavirus disease 2019 patients in India: Protocol for restricted public health emergency use. Indian J Med Res 2020;151:184-9.

Published

07-08-2020

How to Cite

MB, S., M. JOSE, and P. KUTTICHIRA. “CURRENT THERAPEUTIC OPTIONS FOR CORONAVIRUS DISEASE-2019 – A PHARMACOLOGICAL REVIEW”. Asian Journal of Pharmaceutical and Clinical Research, vol. 13, no. 8, Aug. 2020, pp. 42-50, doi:10.22159/ajpcr.2020.v13i8.38342.

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Section

Review Article(s)