Insight in the Current Progress in the Largest Clinical Trials for Covid-19 Drug Management (As of January 2021)

1. Liu Y, Gayle AA, Wilder-Smith A, Rocklöv J. The reproductive number of COVID-19 is higher compared to SARS coronavirus. J Travel Med. 2020 Mar 13; 27(2): taaa021.10.1093/jtm/taaa021Search in Google Scholar

2. Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. 2020; 5(4): 536–544.10.1038/s41564-020-0695-zSearch in Google Scholar

3. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W; China Novel Coronavirus Investigating and Research Team. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020 Feb 20; 382(8): 727–733.10.1056/NEJMoa2001017Search in Google Scholar

4. Cucinotta D, Vanelli M. WHO Declares COVID-19 a Pandemic. Acta Biomed. 2020 Mar 19;91(1):157-160.Search in Google Scholar

5. Gilbert GL. Commentary: SARS, MERS and COVID-19-new threats; old lessons. Int J Epidemiol. 2020 Jun 1; 49(3): 726–728.10.1093/ije/dyaa061Search in Google Scholar

6. Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. Structural basis for the recognition of SARSCoV-2 by full-length human ACE2. Science. 2020 March 27; 367(6485): 1444–1448.10.1126/science.abb2762Search in Google Scholar

7. Gupta, A., Madhavan, M.V., Sehgal, K. et al. Extrapulmonary manifestations of COVID-19. Nat Med 26, 1017–1032 (2020).10.1038/s41591-020-0968-3Search in Google Scholar

8. Chen Y, Liu Q, Guo D. Emerging coronaviruses: genome structure, replication, and pathogenesis. J Med Virol. 2020; 92(4): 418–23.10.1002/jmv.25681Search in Google Scholar

9. European Medicine Agency [EMA]. COVID-19 latest updates. 12 January 2021. https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19/treatments-vaccines-covid-19 (Date accessed: 13 January 2021).Search in Google Scholar

10. RECOVERY Collaborative Group, Horby P, Mafham M, et al.; Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19. N Engl J Med. 2020 Nov 19; 383(21): 2030–2040.10.1056/NEJMoa2022926Search in Google Scholar

11. RECOVERY Collaborative Group. Lopinavir-ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2020 Oct 5; 396(10259): 1345–52.10.1016/S0140-6736(20)32013-4Search in Google Scholar

12. RECOVERY Collaborative Group, Horby P, Lim WS et al; Dexamethasone in Hospitalized Patients with Covid-19 – Preliminary Report. N Engl J Med. 2020 Jul 17: NEJMoa2021436.Search in Google Scholar

13. Peter W Horby, Mark Campbell et al; Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): preliminary results of a randomised, controlled, open-label, platform trial, medRxiv 2021.02.11.21249258Search in Google Scholar

14. WHO Solidarity Trial Consortium, Pan H, et al. Repurposed Antiviral Drugs for Covid-19 – Interim WHO Solidarity Trial Results. N Engl J Med. 2020 Dec 2: NEJMoa2023184.Search in Google Scholar

15. Ader F; Discovery French Trial Management Team. Protocol for the DisCoVeRy trial: multicentre, adaptive, randomised trial of the safety and efficacy of treatments for COVID-19 in hospitalised adults. BMJ Open. 2020; 10(9): e041437. Published 2020 Sep 21.10.1136/bmjopen-2020-041437750725032958495Search in Google Scholar

16. Halimi, V., Daci, A., Ridova, N. et al. The use of remdesivir outside of clinical trials during the COVID-19 pandemic. J of Pharm Policy and Pract13, 61 (2020).10.1186/s40545-020-00258-8750305432968487Search in Google Scholar

17. Halimi V, Daci A, Stojanovska S, Panovska-Stavridis I, Stevanovic M, Filipce V, Grozdanova A. Current regulatory approaches for accessing potential COVID-19 therapies. J Pharm Policy Pract. 2020 May 16;13:16.10.1186/s40545-020-00222-6Search in Google Scholar

18. Kaur, H., Shekhar, N., Sharma, S. et al. Ivermectin as a potential drug for treatment of COVID-19: an in-sync review with clinical and computational attributes. Pharmacol. Rep (2021).10.1007/s43440-020-00195-ySearch in Google Scholar

19. Warren TK, Jordan R, Lo MK, et al. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature. 2016: Mar 17;531(7594): 381–5.10.1038/nature17180Search in Google Scholar

20. Mulangu S, Dodd LE, Davey RT, Jr, et al. A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics. The New England journal of medicine. 2019; Dec 12; 381(24): 2293–2303.10.1056/NEJMoa1910993Search in Google Scholar

21. Sheahan TP, Sims AC, Graham RL, et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med. 2017. Jun 28; 9 (396): eaal3653.10.1126/scitranslmed.aal3653Search in Google Scholar

22. Sheahan TP, Sims AC, Leist SR, et al. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nature communications. 2020 Jan 10; 11(1): 222.10.1038/s41467-019-13940-6Search in Google Scholar

23. Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell research. 2020 Mar; 30(3): 269–271.10.1038/s41422-020-0282-0Search in Google Scholar

24. S.A. Kujawski, K.K. Wong, J.P. Collins, et al. First 12 patients with coronavirus disease 2019 (COVID-19) in the United States. medRxiv (2020).Search in Google Scholar

25. J. Grein, N. Ohmagari, D. Shin, et al. Compassionate use of remdesivir for patients with severe COVID-19. N Engl J Med. 2020 Jun 11; 382: 2327–36.10.1056/NEJMc2015312Search in Google Scholar

26. Wang Y, Zhang D, Du G, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2020; 395 (10236): 1569–78.10.1016/S0140-6736(20)31022-9Search in Google Scholar

27. Beigel JH, Tomashek KM,et.al; ACTT-1 Study Group Members. Remdesivir for the Treatment of Covid-19 - Final Report. N Engl J Med. 2020 Nov 5; 383(19): 1813–1826.Search in Google Scholar

28. Spinner CD, Gottlieb RL, et.al; Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19: A Randomized Clinical Trial. JAMA. 2020 Sep 15; 324(11): 1048–1057.Search in Google Scholar

29. Goldman JD, Lye DCB, et.al; Remdesivir for 5 or 10 Days in Patients with Severe Covid-19. N Engl J Med. 2020 Nov 5; 383(19): 1827–1837.10.1056/NEJMoa2015301737706232459919Search in Google Scholar

30. Food and Drug Administration [FDA]. Corona-virus (COVID-19) Update: FDA Approves First Treatment For COVID-19. 22 October 2020. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-covid-19 (Date accessed 30 November 2020).10.1002/cpu.30542Search in Google Scholar

31. World Health Organization [WHO] WHO recommends against the use of remdesivir in COVID-19 patients. https://www.who.int/news-room/feature-stories/detail/who-recommends-against-the-use-of-remdesivir-in-covid-19-patients (Date accessed 30 November 2020).Search in Google Scholar

32. National Institutes for Health [NIH]. NIH clinical trial testing antiviral remdesivir plus anti-inflammatory drug baricitinib for COVID-19 begins. 08 May 2020. https://www.nih.gov/news-events/news-releases/nih-clinical-trial-testing-antiviral-remdesivir-plus-anti-inflammatory-drug-baricitinib-covid-19-begins (Date acessed: 28 November 2020).Search in Google Scholar

33. Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Bioscience trends. 2020 Mar 16; 14(1): 72–73.10.5582/bst.2020.0104732074550Search in Google Scholar

34. Biot C, Daher W, Chavain N, et al. Design and synthesis of hydroxyferroquine derivatives with antimalarial and antiviral activities. Journal of medicinal chemistry. 2006; 49(9): 2845–2849.10.1021/jm060185616640347Search in Google Scholar

35. 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). Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2020 Jul 28; 71(15): 732–739.10.1093/cid/ciaa237710813032150618Search in Google Scholar

36. P. Gautret, J.C. Lagier, P. Parola, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial [published online ahead of print] Int J Antimicrob Agents. 2020 Jul; 56(1); 105949.10.1016/j.ijantimicag.2020.106063735751532674928Search in Google Scholar

37. Rosenke K, Jarvis MA, Feldmann F, et al. Hydroxychloroquine proves ineffective in hamsters and macaques infected with SARS-CoV 2. June 11, 2020 (https://www.biorxiv.org/content/10.1101/2020.06.10.145144v1). Preprint.10.1101/2020.06.10.145144730190232577633Search in Google Scholar

38. Skipper CP, Pastick KA, et.al; Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19 : A Randomized Trial. Ann Intern Med. 2020 Oct 20; 173(8): 623–631.Search in Google Scholar

39. Mitjà O, Corbacho-Monné M, et al.; BCN PEPCoV-2 RESEARCH GROUP. Hydroxychloroquine for Early Treatment of Adults with Mild Covid-19: A Randomized-Controlled Trial. Clin Infect Dis. 2020 Jul 16:ciaa1009.Search in Google Scholar

40. Ratia K, Pegan S, Takayama J, et al. A noncova-lent class of papain-like protease/deubiquitinase inhibitors blocks SARS virus replication. Proceedings of the National Academy of Sciences of the United States of America. 2008; 105(42): 16119–24.10.1073/pnas.0805240105257100118852458Search in Google Scholar

41. Chan KS, Lai ST, Chu CM, et al. Treatment of severe acute respiratory syndrome with lopinavir/ritonavir: a multicentre retrospective matched cohort study. Hong Kong Med J. 2003; 9(6): 399–406.Search in Google Scholar

42. 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 May 7; 382(19): 1787–1799.10.1056/NEJMc200804332369281Search in Google Scholar

43. Joshi S, Parkar J et al. Role of favipiravir in the treatment of COVID-19, International Journal of Infectious Diseases, 2021 Jan; 102: 501–508.10.1016/j.ijid.2020.10.069783186333130203Search in Google Scholar

44. Ruan Q, Yang K, Wang W,et al. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med 2020 May; 46(5): 846–848.10.1007/s00134-020-05991-x708011632125452Search in Google Scholar

45. Chen RC, Tang XP, Tan SY, et al. Treatment of severe acute respiratory syndrome with glucosteroids: the Guangzhou experience. Chest. 2006; 129(6): 1441–1452.10.1378/chest.129.6.1441Search in Google Scholar

46. Lee N, Allen Chan KC, Hui DS, et al. Effects of early corticosteroid treatment on plasma SARS-associated Coronavirus RNA concentrations in adult patients. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 2004; 31(4): 304–309.10.1016/j.jcv.2004.07.006Search in Google Scholar

47. Arabi YM, Mandourah Y, Al-Hameed F, et al. Corticosteroid Therapy for Critically Ill Patients with Middle East Respiratory Syndrome. American journal of respiratory and critical care medicine. 2018; 197(6): 757–767.10.1164/rccm.201706-1172OCSearch in Google Scholar

48. Shang L, Zhao J, Hu Y, et al. On the use of corticosteroids for 2019-nCoV pneumonia. Lancet. 2020; 395(10225): 683–4.10.1016/S0140-6736(20)30361-5Search in Google Scholar

49. Edalatifard M, Akhtari M et al; Intravenous methylprednisolone pulse as a treatment for hospitalised severe COVID-19 patients: results from a randomised controlled clinical trial. Eur Respir J. 2020 Sep 17:2002808.10.1183/13993003.02808-2020Search in Google Scholar

50. Somers EC, Eschenauer GA, Troost JP, et al. Tocilizumab for treatment of mechanically ventilated patients with COVID-19. Clinical Infectious Diseases. 2020 Jul 11; ciaa95410.1101/2020.05.29.20117358Search in Google Scholar

51. Rossotti R, Travi G, Ughi et al, et al. Safety and efficacy of anti-IL6-receptor tocilizumab use in severe and critical patients affected by coronavirus disease 2019: a comparative analysis. J Infect 2020 Oct; 81(4): e11-e1710.1016/j.jinf.2020.07.008Search in Google Scholar

52. Guaraldi G, Meschiari M, Cozzi-Lepri A, et al. Tocilizumab in patients with severe COVID-19: a retrospective cohort study. Lancet Rheumatol. 2020 Aug; 2(8): e474-e48410.1016/S2665-9913(20)30173-9Search in Google Scholar

53. Ivan Rosas, Norbert Bräu et al; Tocilizumab in Hospitalized Patients With COVID-19 Pneumonia, medRxiv 2020.08.27.20183442.Search in Google Scholar

54. Stone JH, Frigault MJ, et al; Tocilizumab Trial Investigators. Efficacy of Tocilizumab in Patients Hospitalized with Covid-19. N Engl J Med. 2020 Dec 10; 383(24): 2333–2344.Search in Google Scholar

55. Chen L, Xiong J, Bao L, et al. Convalescent plasma as a potential therapy for COVID-19. Lancet Infect Dis. 2020 Apr; 20(4): 398–400.10.1016/S1473-3099(20)30141-9Search in Google Scholar

56. 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: 460–470.10.1001/jama.2020.10044727088332492084Search in Google Scholar

57. Gharbharan A, Jordans CCE, Geurts van KesselC, et al. Convalescent plasma for COVID-19: a randomized clinical trial. July 3, 2020 (medrxiv 2020.07.01.20139857v1)Search in Google Scholar

58. Agarwal A, Mukherjee A, Kumar G, et al. Convalescent plasma in the management of moderate covid-19 in adults in India: open-label phase II multicentre randomised controlled trial (PLACID Trial). BMJ 2020; 371: m3939-m3939.10.1136/bmj.m3939757866233093056Search in Google Scholar

59. Simonovich VA, Burgos Pratx LD, et al; PlasmAr Study Group. A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia. N Engl J Med. 2020 Nov 24.Search in Google Scholar

60. Weinreich DM et al; REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19. N Engl J Med. 2021 Jan 21; 384(3): 238–251.10.1056/NEJMoa2035002778110233332778Search in Google Scholar

61. Chen P, Nirula A, Heller B, Gottlieb RL, Boscia J, Morris J, et al. (January 2021). “SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19”. The New England Journal of Medicine. 384 (3): 229–237.10.1056/NEJMoa2029849764662533113295Search in Google Scholar