Insight into ongoing and emerging therapeutic options for COVID-19: a review
Keywords:SARS-CoV-2, Antivirals, Cytokine storm, Immunomodulators, COVID-19 vaccine
The outbreak of novel coronavirus (COVID-19) has evolved into a global pandemic and has posed significant threats to health and the economy worldwide. It can manifest from mild disease to severe respiratory failure requiring intensive care management. Currently, there is no sufficient evidence that any existing drugs can effectively treat SARS-CoV-2 pneumonia though supportive care remains the mainstay of treatment. However, there are many ongoing clinical trials of potential anti-COVID-19 therapies including the vaccines. In the current review, we Summarized the information available about COVID-19 medications, and treatment options.
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. Lanc. 2020;395(10223):507-13.
Adhikari S, Meng S, Wu Y, Mao Y, Ye R, Wang Q et al. Epidemiology, causes, clinical manifestation and diagnosis, prevention and control of coronavirus disease (COVID-19) during the early outbreak period: a scoping review. Infect Disea Pover. 2020;9(1).
World Health Organization (2020) Coronavirus disease 2019 (COVID-19) situation report-183. World Health Organization https://www.who.int/docs /default-source/wha-70-and-phe/20200721-covid-19-sitrep-183.pdf?sfvrsn=b3869b3_2. Accessed on 22 July 2020.
Ashour H, Elkhatib W, Rahman M, Elshabrawy H. Insights into the Recent 2019 Novel Coronavirus (SARS-CoV-2) in Light of Past Human Coronavirus Outbreaks. Pathog. 2020;9(3):186.
Chan JF, Yuan S, Kok KH,Wang KK,Chu H, Yang J et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lanc. 2020;395(10223):514-23.
Ghinai I, McPherson TD, Hunter JC,Kirking HL,Christansen D,Joshi K et al. First known person-to-person transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the USA. Lanc. 2020;395.
Chinazzi M, Davis J, Ajelli M, Gioannini C, Litvinova M, Merler S et al. The effect of travel restrictions on the spread of the 2019 novel coronavirus (COVID-19) outbreak. Sci. 2020;9757.
Zhang J, Dong X, Cao Y, Yuan Y, Yang Y, Yan Y et al. Clinical characteristics of 140 patients infected with SARS‐CoV‐2 in Wuhan, China. Allerg. 2020;75(7):1730-41.
Xiong Y, Sun D, Liu Y, Fan Y, Zhao L, Li X et al. Clinical and high-resolution CT features of the COVID-19 infection: comparison of the initial and follow-up changes. Investig Radiol. 2020;55(6):332-9.
Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Seminars in Immunopathol. 2017;39(5):529-39.
Gordon C, Tchesnokov E, Feng J, Porter D, Götte M. The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus. J Biologic Chemis. 2020;295(15):4773-9.
Hoenen T, Groseth A, Feldmann H. Therapeutic strategies to target the Ebola virus life cycle. Nat Rev Microbiol. 2019;17(10):593-606.
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).
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.
Pizzorno A, Padey B, Julien T, Trouillet-Assant S, Traversier A, Errazuriz-Cerda E et al. Characterization and Treatment of SARS-CoV-2 in Nasal and Bronchial Human Airway Epithelia. Cell Reports Medicine. 2020;1(4):100059.
Sheahan TP, Sims AC, Leist SR, Schafer A, Won J, Brown AJ et al. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun 2020;11:222.
Barlow A, Landolf K, Barlow B, Yeung S, Heavner J, Claassen C et al. Review of Emerging Pharmacotherapy for the Treatment of Coronavirus Disease 2019. Pharmacotherapy. J Hum Pharmacol Dr Ther. 2020;40(5):416-37.
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 Eng J Med. 2020;382(24):2327-36.
Williamson B, Feldmann F, Schwarz B, Meade-White K, Porter D, Schulz J et al. Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. Natu. 2020;585(7824):273-6.
Beigel J, Tomashek K, Dodd L, Mehta A, Zingman B, Kalil A et al. Remdesivir for the Treatment of Covid-19- Preliminary Report. N Eng J Med. 2020;1-11.
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. Lanc. 2020;395(10236):1569-78.
Aschenbrenner D. Remdesivir Receives Emergency Use Authorization for Severely Ill Patients with COVID-19. Americ J Nurs. 2020;120(7):26
Furuta Y, Gowen BB, Takahashi K, Shiraki K, Smee DF, Brnard DL. Favipiravir (T-705), a novel viral RNA polymerase inhibitor. Antiviral Res. 2013;100(2):446-54.
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 research. 2020;30(3):269-71.
Kumagai Y, Murakawa Y, Hasunuma T, Aso M, Yuji W, Sakurai T et al. Lack of effect of favipiravir, a novel antiviral agent, on QT interval in healthy Japanese adults. Int J Clin Pharmacol Ther. 2015;53(10):866-84.
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. Engineer. 2020
Sheahan T, Sims A, Leist S, Schäfer A, Won J, Brown A et al. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Natu Communicat. 2020;11(1)
Chan JF, Yao Y, Yeung ML, Deng W, Bao L, Jia L, et al. Treatment with lopinavir/ritonavir or interferon-β1b improves outcome of MERS-CoV infection in a nonhuman primate model of common marmoset. The J Infect Disea. 2015;212(12):1904-13.
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. New Engl J Med. 2020.
Knowles SR, Phillips EJ, Dresser L, Matukas L. Common adverse events associated with the use of ribavirin for severe acute respiratory syndrome in Canada. Clinical infectious diseases. 2003;37(8):1139-42.
Falzarano D, de Wit E, Rasmussen A, Feldmann F, Okumura A, Scott D et al. Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV–infected rhesus macaques. Natu Medic. 2013;19(10):1313-17.
Elfiky AA. Anti-HCV, nucleotide inhibitors, repurposing against COVID-19. Lif Sci. 2020;248:117477
Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R. Effects of chloroquine on viral infections: an old drug against today's diseases? Lanc Infect Dis. 2003;3(11):722-7.
Vincent MJ, Bergeron E, Benjannet S, Erickson BR, Rollin PE, Ksiazek TG, et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J. 2005;2:69.
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). Clinic Infect Diseas. 2020.
Gautret P, Lagier J, Parola P, Hoang V, 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 Agen. 2020:105949.
Clinicaltrials.gov. Bethesda, MD: National Library of Medicine (US). 2020 Feb 19-Identifier NCT04276688, Lopinavir/Ritonavir, Ribavirin and IFN-beta Combination for CoV Treatment; 2020 Feb 28. Available at: https://clinicaltrials.gov/ct2/show /NCT04276688. Accessed on 02 May 2020.
Italian ANSA news agency. March 13, 2020. 3 patients get better on arthritis drug. Available at: http://www.ansa.it/english/news/general_news /2020/03/13/3-patients-get-better-on-arthritis-drug_90d4764d-d93f-463e-ab07-168b34b084d0. html. Accessed on 05 May 2020.
Xu X, Han M, Li T, Sun W, Wang D, Fu B et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proceed Nation Acad Sci. 2020;117(20):10970-75.
Srivastava A. Itolizumab in Psoriasis. Indian J Dermatol. 2017;62(4):418-21.
Times of India (internet). Biocon’s Itolizumab approved for COVID-19 treatment: All you need to know. Available at: https://timesofindia .indiatimes.com/india/biocons-itolizumab-approved-for-covid-19-treatment-all-you-need-to-know/articleshow/76957822.cms. Accessed on 18 July 2020.
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. Foru Infect Disea. 2020;7(3).
Li T, Lu H, Zhang W. Clinical observation and management of COVID-19 patients. Emerg Microbes Infect. 2020;9(1):687-90.
Stockman LJ, Bellamy R, Garner P. SARS: Systematic review of treatment effects. PLoS Med 2006;3(9):e343.
Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lanc. 2020;395(10223):473-5
Mahase E. Covid-19: Demand for dexamethasone surges as RECOVERY trial publishes preprint. Brit Med J. 2020;m2512.
Tanne JH. Covid-19: FDA approves use of convalescent plasma to treat critically ill patients. Brit Med J. 2020;368
Bloch EM, Shoham S, Casadevall A, Sachais BS, Shaz B, Winters JL, et al. Deployment of convalescent plasma for the prevention and treatment of COVID-19. J Clin Invest 2020.
Stebbing J, Phelan A, Griffin I, Tucker C, Oechsle O, Smith D et al. COVID-19: combining antiviral and anti-inflammatory treatments. Lanc Infect Disea. 2020;20(4):400-2.
ClinicalTrials.gov (2020). Bevacizumab in Severe or Critical Patients With COVID-19 Pneumonia (BEST-CP). Available at: https://clinicaltrials.gov/ct2/show/ NCT04275414. Accessed on 20 May 2020.
ClinicalTrials.gov (2020). Eculizumab (Soliris) in Covid-19 Infected Patients (SOLID-C19). Available at: https://clinicaltrials.gov/ct2/show/NCT04288713. Accessed on 10 May 2020.
Wagstaff KM, Sivakumaran H, Heaton SM, Harrich D, Jans DA. Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. Biochem J. 2012;443(3):851-6.
Clinicaltrials.gov. 2020. Hydroxychloroquine and Ivermectin for the Treatment of COVID-19 Infection. Available at https://clinicaltrials.gov/ct2/show/ NCT04391127. Accessed on 02 April 2020.
Xia J. The Efficacy and Safety of Thalidomide in the Adjuvant Treatment of Moderate New Coronavirus (COVID-19) Pneumonia-Tabular View. Clinic Tria. (2020). Available at: https://clinicaltrials.gov/ ct2/show/NCT04273529. Accessed on 05 May 2020.
Carr A. A new clinical trial to test high-dose vitamin C in patients with COVID-19. Critic Car. 2020;24(1).
Draft landscape of COVID-19 candidate vaccines [Internet]. Who.int. 2020. Available at: https://www.who.int/publications /m/item/draft-landscape-of-covid-19-candidate-vaccines. Accessed on 02 April 2020.
Folegatti PM, Ewer KJ, Aley PK, Angus B, Becker S, Belij-Rammerstorfer S, et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lanc. 2020;396(10249):467-78.
Smith D. Coronavirus vaccine: Are we close to finding one? Here's what's happening. CNET. 2020 Available at: https://www.cnet.com/how-to/coronavirus-vaccine-are-we-close-to-finding-one-heres-whats-happening/. Accessed on 20 July 2020.
Belouzard S, Millet JK, Licitra BN, Whittaker GR. Mechanisms of coronavirus cell entry mediated by the viral spike protein. Virus. 2012;4:1011-33.
Jackson LA, Anderson EJ, Rouphael NG, Roberts PC, Makhene M, Coler RN, McCullough MP, Chappell JD, Denison MR, Stevens LJ, Pruijssers AJ. An mRNA vaccine against SARS-CoV-2-preliminary report. N Engla J Medic. 2020.
Coronavirus Vaccine Tracker. Nytimes.com. 2020. Available at: https://www.nytimes.com/interactive /2020/science/coronavirus-vaccine-tracker.html. Accessed on 20 July 2020.