瑞德西韦同情用药治疗重症COVID-19患者

摘要

背景

瑞德西韦是一种核苷类似物前体药物，能够抑制病毒RNA聚合酶，体外试验显示出抗SARS-CoV-2的活性。

方法

我们以同情用药的方式向住院接受治疗的COVID-19患者（由SARS-CoV-2感染引起）提供了瑞德西韦。患者为SARS-CoV-2感染的确诊患者，他们在呼吸环境空气时的氧饱和度为≤94%或接受氧气支持。患者接受瑞德西韦治疗10日，方案为第1日静脉给药200 mg，在随后9日中每日给药100 mg。本文是基于以下患者队列的数据：2020年1月25日至2020年3月7日期间接受瑞德西韦治疗并且至少有随后1日的临床数据。

结果

61例患者接受了至少一次瑞德西韦治疗，其中8例患者的数据无法分析（7例患者缺乏治疗后的数据，1例患者给药错误）。53例患者的数据可供分析，其中美国22例患者，欧洲或加拿大22例，日本9例。基线时，30例患者（57%）正在接受机械通气治疗，4例（8%）正在接受体外膜氧合。中位随访时间为18日，在此期间有36例患者（68%）的氧气支持分级有所改善；其中，机械通气支持的30例患者中，17例（57%）拔除气管插管。共计25例患者（47%）出院，7例患者（13%）死亡；在接受有创通气的患者中，死亡率为18%（34例患者中死亡6例），而未接受有创通气的患者死亡率为5%（19例患者中死亡1例）。

结论

在因重症COVID-19住院治疗并接受瑞德西韦同情用药的53例患者队列中，36例（68%）观察到临床获益。疗效判断有待于目前正在实施的瑞德西韦的随机、安慰剂对照试验的结果（由吉利德科学公司资助）。

登录后，可阅读全文

作者信息

Jonathan Grein, M.D., Norio Ohmagari, M.D., Ph.D., Daniel Shin, M.D., George Diaz, M.D., Erika Asperges, M.D., Antonella Castagna, M.D., Torsten Feldt, M.D., Gary Green, M.D., Margaret L. Green, M.D., M.P.H., François-Xavier Lescure, M.D., Ph.D., Emanuele Nicastri, M.D., Rentaro Oda, M.D., Kikuo Yo, M.D., D.M.Sc., Eugenia Quiros-Roldan, M.D., Alex Studemeister, M.D., John Redinski, D.O., Seema Ahmed, M.D., Jorge Bernett, M.D., Daniel Chelliah, M.D., Danny Chen, M.D., Shingo Chihara, M.D., Stuart H. Cohen, M.D., Jennifer Cunningham, M.D., Antonella D’Arminio Monforte, M.D., Saad Ismail, M.D., Hideaki Kato, M.D., Giuseppe Lapadula, M.D., Erwan L’Her, M.D., Ph.D., Toshitaka Maeno, M.D., Sumit Majumder, M.D., Marco Massari, M.D., Marta Mora-Rillo, M.D., Yoshikazu Mutoh, M.D., Duc Nguyen, M.D., Pharm.D., Ewa Verweij, M.D., Alexander Zoufaly, M.D., Anu O. Osinusi, M.D., Adam DeZure, M.D., Yang Zhao, Ph.D., Lijie Zhong, Ph.D., Anand Chokkalingam, Ph.D., Emon Elboudwarej, Ph.D., Laura Telep, M.P.H., Leighann Timbs, B.A., Ilana Henne, M.S., Scott Sellers, Ph.D., Huyen Cao, M.D., Susanna K. Tan, M.D., Lucinda Winterbourne, B.A., Polly Desai, M.P.H., Robertino Mera, M.D., Ph.D., Anuj Gaggar, M.D., Ph.D., Robert P. Myers, M.D., Diana M. Brainard, M.D., Richard Childs, M.D., and Timothy Flanigan, M.D.
From Cedars–Sinai Medical Center, Los Angeles (J.G.), El Camino Hospital, Mountain View (D.S., D. Chelliah), Sutter Santa Rosa Regional Hospital, Santa Rosa (G.G.), Regional Medical Center (A.S., J.R.) and Good Samaritan Hospital (S.M.), San Jose, John Muir Health, Walnut Creek (J.B.), UC Davis Health, Sacramento (S.H.C.), NorthBay Medical Center, Fairfield (S.I.), and Gilead Sciences, Foster City (A.O.O., A.D., Y.Z., L.Z., A. Chokkalingam, E.E., L. Telep, L. Timbs, I.H., S.S., H.C., S.K.T., L.W., P.D., R.M., A.G., R.P.M., D.M.B.) — all in California; the National Center for Global Health and Medicine, Tokyo (N.O.), Tokyo Bay Urayasu Ichikawa Medical Center, Urayasu City (R.O.), Hiratsuka City Hospital, Hiratsuka (K.Y.), Yokohama City University Hospital, Yokohama (H.K.), Gunma University Hospital, Gunma (T.M.), and Tosei General Hospital, Seto (Y.M.) — all in Japan; Providence Regional Medical Center Everett, Everett (G.D.), and University of Washington Medical Center–Northwest (M.L.G.) and Virginia Mason Medical Center (S. Chihara), Seattle — all in Washington; Fondazione IRCCS Policlinico San Matteo, Pavia (E.A.), IRCCS, San Raffaele Scientific Institute (A. Castagna) and Azienda Socio Sanitaria Territoriale Spedali (ASST) Santi Paolo e Carlo, Department of Health Services, University of Milan (A.D.M.), Milan, National Institute for Infectious Diseases, IRCCS, L. Spallanzani, Rome (E.N.), Università degli Study of Brescia, ASST Civili di Brescia, Brescia (E.Q.-R.), San Gerardo Hospital, ASST Monza, University of Milan–Bicocca, Monza (G.L.), and Azienda Unite Sanitarie Locali–IRCCS, Reggio Emilia (M.M.) — all in Italy; Universitätsklinikum Düsseldorf, Düsseldorf, Germany (T. Feldt); Université de Paris, Infection, Antimicrobiens, Modélisation, Evolution (IAME), INSERM, and Assistance Publique–Hôpitaux de Paris, Department of Infectious Diseases, Bichat Hospital, Paris (F.-X.L.), Centre Hospitalier Régional et Universitaire de Brest–La Cavale Blanche, Brest (E.L.), and Division of Infectious Diseases and Tropical Medicine, University Hospital of Bordeaux, Bordeaux (D.N.) — all in France; St. Alexius Medical Center, Hoffman Estates, IL (S.A.); Mackenzie Health, Richmond Hill, ON, Canada (D. Chen); Columbia University Irving Medical Center, New York (J.C.); Hospital Universitario La Paz–Carlos III, Instituto de Investigación Hospital Universitario La Paz, Madrid (M.M.-R.); Bernhoven Hospital, Uden, the Netherlands (E.V.); Kaiser Franz Josef Hospital, Vienna (A.Z.); the U.S. Public Health Service Commissioned Corps, Washington, DC (R.C.); and Miriam Hospital, Providence, RI (T. Flanigan). Address reprint requests to Dr. Brainard at Gilead Sciences, 333 Lakeside Dr., Foster City, CA 94404, or at diana.brainard@gilead.com.

参考文献

1. Cucinotta D, Vanelli M. WHO declares COVID-19 a pandemic. Acta Biomed 2020;91:157-160.

2. Spinelli A, Pellino G. COVID-19 pandemic: perspectives on an unfolding crisis. Br J Surg 2020 March 19 (Epub ahead of print).

3. Fauci AS, Lane HC, Redfield RR. Covid-19 — navigating the uncharted. N Engl J Med 2020;382:1268-1269.

4. Mahase E, Kmietowicz Z. Covid-19: doctors are told not to perform CPR on patients in cardiac arrest. BMJ 2020;368:m1282-m1282.

5. Rodriguez-Morales AJ, Cardona-Ospina JA, Gutiérrez-Ocampo E, et al. Clinical, laboratory and imaging features of COVID-19: a systematic review and meta-analysis. Travel Med Infect Dis 2020 March 13 (Epub ahead of print).

6. Weiss P, Murdoch DR. Clinical course and mortality risk of severe COVID-19. Lancet 2020;395:1014-1015.

7. Wu C, Chen X, Cai Y, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med 2020 March 13 (Epub ahead of print).

8. Onder G, Rezza G, Brusaferro S. Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy. JAMA 2020 March 23 (Epub ahead of print).

9. Poston JT, Patel BK, Davis AM. Management of critically ill adults with COVID-19. JAMA 2020 March 26 (Epub ahead of print).

10. Cao B, Wang Y, Wen D, et al. A trial of lopinavir–ritonavir in adults hospitalized with severe Covid-19. N Engl J Med 2020;382:1787-1799.

11. Shen C, Wang Z, Zhao F, et al. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. JAMA 2020 March 27 (Epub ahead of print).

12. Touret F, de Lamballerie X. Of chloroquine and COVID-19. Antiviral Res 2020 March 5 (Epub ahead of print).

13. Baden LR, Rubin EJ. Covid-19 — the search for effective therapy. N Engl J Med 2020;382:1851-1852.

14. de Wit E, Feldmann F, Cronin J, et al. Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection. Proc Natl Acad Sci U S A 2020;117:6771-6776.

15. Sheahan TP, Sims AC, Graham RL, et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med 2017;9(396):eaal3653-eaal3653.

16. Sheahan TP, Sims AC, Leist SR, et al. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun 2020;11:222-222.

17. 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;30:269-271.

18. Mulangu S, Dodd LE, Davey RT Jr, et al. A randomized, controlled trial of Ebola virus disease therapeutics. N Engl J Med 2019;381:2293-2303.

19. European Medicines Agency. Summary on compassionate use: Remdesivir Gilead. April 3, 2020 (https://www.ema.europa.eu/en/documents/other/summary-compassionate-use-remdesivir-gilead_en.pdf. opens in new tab).

20. Kujawski SA, Wong KK, Collins JP, et al. First 12 patients with coronavirus disease 2019 (COVID-19) in the United States. medRxiv, March 12, 2020 (https://www.medrxiv.org/content/10.1101/2020.03.09.20032896v1. opens in new tab).

21. Holshue ML, DeBolt C, Lindquist S, et al. First case of 2019 novel coronavirus in the United States. N Engl J Med 2020;382:929-936.

22. Lescure FX, Bouadma L, Nguyen D, et al. Clinical and virological data of the first cases of COVID-19 in Europe: a case series. Lancet Infect Dis 2020 March 27 (Epub ahead of print).

23. Arentz M, Yim E, Klaff L, et al. Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington State. JAMA 2020 March 19 (Epub ahead of print).

24. Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020 February 7 (Epub ahead of print).

25. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA 2020 February 24 (Epub ahead of print).

26. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;395:1054-1062.

27. Bhatraju PK, Ghassemieh BJ, Nichols M, et al. Covid-19 in critically ill patients in the Seattle region — case series. N Engl J Med 2020;382:2012-2022.

28. ICNARC report on COVID-19 in critical care. London: Intensive Care National Audit & Research Centre, March 27, 2020 (https://www.icnarc.org/DataServices/Attachments/Download/b5f59585-5870-ea11-9124-00505601089b. opens in new tab).

29. Zhang C, Shi L, Wang FS. Liver injury in COVID-19: management and challenges. Lancet Gastroenterol Hepatol 2020 March 4 (Epub ahead of print).