IL-1受体拮抗剂
在欧洲,anakinra(一种白细胞介素-1 抑制剂)已获批用于需要低或高流量辅助氧疗且具有出现重度呼吸衰竭风险(定义为血可溶性尿激酶纤维蛋白溶酶原激活剂受体 [soluble urokinase plasminogen activator receptor, suPAR] 水平达到至少 6 ng/mL )的 COVID-19 成人患者。当前指南不建议将 anakinra 用于治疗 COVID-19,因为尚无充分证据来支持或反对其应用。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
多项系统评价和荟萃分析发现,与单纯的标准治疗相比,anakinra 可能降低住院患者的死亡率和有创机械通气需求,尤其对于 C 反应蛋白水平 >100 mg/L 的患者。[974]Kyriazopoulou E, Huet T, Cavalli G, et al. Effect of anakinra on mortality in patients with COVID-19: a systematic review and patient-level meta-analysis. Lancet Rheumatol. 2021 Aug 9 [Epub ahead of print].
https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(21)00216-2/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/34396156?tool=bestpractice.com
[975]Barkas F, Ntekouan SF, Kosmidou M, et al. Anakinra in hospitalized non-intubated patients with coronavirus disease 2019: a systematic review and meta-analysis. Rheumatology (Oxford). 2021 May 17 [Epub ahead of print].
https://academic.oup.com/rheumatology/advance-article/doi/10.1093/rheumatology/keab447/6276997
http://www.ncbi.nlm.nih.gov/pubmed/33999135?tool=bestpractice.com
[976]Somagutta MKR, Lourdes Pormento MK, Hamid P, et al. The safety and efficacy of anakinra, an interleukin-1 antagonist in severe cases of COVID-19: a systematic review and meta-analysis. Infect Chemother. 2021 Jun;53(2):221-37.
https://www.icjournal.org/DOIx.php?id=10.3947/ic.2021.0016
http://www.ncbi.nlm.nih.gov/pubmed/34216117?tool=bestpractice.com
然而,一项 Cochrane 评价未发现白细胞介素-1 抑制剂具有重要有益临床效果的证据,而且关于几项结局的证据也不确定。anakinra 可能对治疗后 28 日内症状改善的影响极小或没有影响(中等确定性证据)。尚不确定 anakinra 是否会对治疗后 28 日的死亡人数有影响(低确定性证据)。[977]Davidson M, Menon S, Chaimani A, et al. Interleukin-1 blocking agents for treating COVID-19. Cochrane Database Syst Rev. 2022 Jan 26;(1):CD015308.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD015308/full
http://www.ncbi.nlm.nih.gov/pubmed/35080773?tool=bestpractice.com
秋水仙碱
秋水仙碱是一种下调多促炎通路的抗炎药物。指南反对将秋水仙碱用于治疗 COVID-19,除非是在临床试验的背景下。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
[466]Bhimraj A, Morgan RL, Hirsch Shumaker A, et al. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19 infection. 2022 [internet publication].
https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management
[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication].
https://www.nice.org.uk/guidance/ng191
[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3
一项 Cochrane 评价发现,与单独使用安慰剂或标准治疗相比,使用秋水仙碱对中重度疾病住院患者的死亡率或临床进展可能几乎没有影响(中等确定性证据)。对无症状或轻度疾病患者全因死亡率影响的证据尚不明确;然而,用药可能导致住院率或 28 天死亡率呈现略微下降。[978]Mikolajewska A, Fischer AL, Piechotta V, et al. Colchicine for the treatment of COVID-19. Cochrane Database Syst Rev. 2021 Oct 18;(10):CD015045.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD015045/full
http://www.ncbi.nlm.nih.gov/pubmed/34658014?tool=bestpractice.com
粒细胞-巨噬细胞集落刺激因子抑制剂
在研粒细胞-巨噬细胞集落刺激因子(granulocyte-macrophage colony-stimulating factor, GM-CSF)抑制剂(例如,lenzilumab、mavrilimumab、otilimab)可通过最大程度地减少下游的大量促炎介质生成,从而缓解重症或危重症患者的肺部炎症。当前指南不建议将 GM-CSF 抑制剂用于治疗 COVID-19,因为尚无充分的证据来支持或反对其应用。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
随机对照试验显示使用 lenzilumab 获得积极结果,而使用 mavrilimumab 未获得同样结果。[979]Temesgen Z, Burger CD, Baker J, et al. Lenzilumab in hospitalised patients with COVID-19 pneumonia (LIVE-AIR): a phase 3, randomised, placebo-controlled trial. Lancet Respir Med. 2021 Dec 1 [Epub ahead of print].
https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00494-X/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/34863332?tool=bestpractice.com
[980]Cremer PC, Abbate A, Hudock K, et al. Mavrilimumab in patients with severe COVID-19 pneumonia and systemic hyperinflammation (MASH-COVID): an investigator initiated, multicentre, double-blind, randomised, placebo-controlled trial. Lancet Rheumatol. 2021 Jun;3(6):e410-8.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969143
http://www.ncbi.nlm.nih.gov/pubmed/33754144?tool=bestpractice.com
恢复期血浆
高滴度恢复期血浆是含严重急性呼吸综合征冠状病毒 2(severe acute respiratory syndrome coronavirus 2, SARS-CoV-2)感染患者康复后高滴度 SARS-CoV-2 抗体的一种血制品。指南反对将恢复期血浆用于治疗 COVID-19 住院患者,除非是在临床试验的背景下。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
[466]Bhimraj A, Morgan RL, Hirsch Shumaker A, et al. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19 infection. 2022 [internet publication].
https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management
[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3
尚无充分证据支持或反对将恢复期血浆用于免疫功能低下患者的治疗。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
关于非重症患者的指南建议存在冲突。部分指南建议将其用于特定患者(例如,有进展为重症高风险的门诊患者)。[466]Bhimraj A, Morgan RL, Hirsch Shumaker A, et al. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19 infection. 2022 [internet publication].
https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management
[981]Estcourt LJ, Cohn CS, Pagano MB, et al. Clinical practice guidelines from the association for the advancement of blood and biotherapies (AABB): COVID-19 convalescent plasma. Ann Intern Med. 2022 Sep;175(9):1310-21.
https://www.acpjournals.org/doi/10.7326/M22-1079
http://www.ncbi.nlm.nih.gov/pubmed/35969859?tool=bestpractice.com
而其他指南反对将其用于这类患者。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3
不建议使用在奥密克戎变异株出现前采集的恢复期血浆。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
一项 Cochrane 评价发现,恢复期血浆未降低死亡率,并且对治疗中至重度疾病的临床改善措施影响极小或并无影响。[982]Piechotta V, Iannizzi C, Chai KL, et al. Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review. Cochrane Database Syst Rev. 2021 May 20;5(5):CD013600.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013600.pub4/full
http://www.ncbi.nlm.nih.gov/pubmed/34013969?tool=bestpractice.com
一项实时系统评价和网络荟萃分析发现,恢复期血浆可能不会为任何疾病严重程度的患者带来任何有意义的获益,但高滴度恢复期血浆是否能够带来任何获益仍不确定。[983]Siemieniuk RA, Bartoszko JJ, Díaz Martinez JP, et al. Antibody and cellular therapies for treatment of covid-19: a living systematic review and network meta-analysis. BMJ. 2021 Sep 23;374:n2231.
https://www.bmj.com/content/374/bmj.n2231
http://www.ncbi.nlm.nih.gov/pubmed/34556486?tool=bestpractice.com
荟萃得出的证据存在冲突。虽然部分荟萃分析发现,与安慰剂或标准治疗相比,恢复期血浆治疗与全因死亡降低(或任何其他结局获益)不具显著相关性,但其他分析发现死亡率降低,特别是在分析中排除使用低滴度恢复期血浆的试验时。[984]Janiaud P, Axfors C, Schmitt AM, et al. Association of convalescent plasma treatment with clinical outcomes in patients with COVID-19: a systematic review and meta-analysis. JAMA. 2021 Mar 23;325(12):1185-95.
https://jamanetwork.com/journals/jama/fullarticle/2777060
http://www.ncbi.nlm.nih.gov/pubmed/33635310?tool=bestpractice.com
[985]Gupta T, Kannan S, Kalra B, et al. Systematic review and meta-analysis of randomised controlled trials testing the safety and efficacy of convalescent plasma in the treatment of coronavirus disease 2019 (COVID-19): evidence-base for practise and implications for research. Transfus Med. 2021 Jun 29 [Epub ahead of print].
https://onlinelibrary.wiley.com/doi/10.1111/tme.12803
http://www.ncbi.nlm.nih.gov/pubmed/34189780?tool=bestpractice.com
[986]Klassen SA, Senefeld JW, Johnson PW, et al. The effect of convalescent plasma therapy on mortality among patients with COVID-19: systematic review and meta-analysis. Mayo Clin Proc. 2021 May;96(5):1262-75.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888247
http://www.ncbi.nlm.nih.gov/pubmed/33958057?tool=bestpractice.com
[987]Wardhani SO, Fajar JK, Wulandari L, et al. Association between convalescent plasma and the risk of mortality among patients with COVID-19: a meta-analysis. F1000Res. 2021 Feb 3;10:64.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182694
http://www.ncbi.nlm.nih.gov/pubmed/34136130?tool=bestpractice.com
[988]Kloypan C, Saesong M, Sangsuemoon J, et al. Convalescent plasma for COVID-19: a meta-analysis of clinical trials and real-world evidence. Eur J Clin Invest. 2021 Aug 10:e13663.
https://onlinelibrary.wiley.com/doi/10.1111/eci.13663
http://www.ncbi.nlm.nih.gov/pubmed/34375445?tool=bestpractice.com
[989]Axfors C, Janiaud P, Schmitt AM, et al. Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials. BMC Infect Dis. 2021 Nov 20;21(1):1170.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8605464
http://www.ncbi.nlm.nih.gov/pubmed/34800996?tool=bestpractice.com
静脉注射免疫球蛋白
静脉用免疫球蛋白(intravenous immunoglobulin, IVIG)是自健康供体采集血清制备的血制品。它具有免疫调节作用,可抑制过度活跃的免疫反应。当前指南不建议将 SARS-CoV-2 特异性 IVIG 用于治疗 COVID-19,因为尚无充分证据来支持或反对其应用。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
指南反对将非 SARS-CoV-2 特异性 IVIG 用于治疗 COVID-19,用于临床试验除外,除非另有说明。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
一项实时系统评价和网络荟萃分析发现,IVIG 可能不会为任何疾病严重程度的患者带来任何有意义的获益。[983]Siemieniuk RA, Bartoszko JJ, Díaz Martinez JP, et al. Antibody and cellular therapies for treatment of covid-19: a living systematic review and network meta-analysis. BMJ. 2021 Sep 23;374:n2231.
https://www.bmj.com/content/374/bmj.n2231
http://www.ncbi.nlm.nih.gov/pubmed/34556486?tool=bestpractice.com
然而,另一项荟萃分析发现,IVIG 降低了危重症患者的死亡率,但重症和非重症亚组的差异无显著统计学意义。[990]Xiang HR, Cheng X, Li Y, et al. Efficacy of IVIG (intravenous immunoglobulin) for corona virus disease 2019 (COVID-19): A meta-analysis. Int Immunopharmacol. 2021 Jul;96:107732.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084608
http://www.ncbi.nlm.nih.gov/pubmed/34162133?tool=bestpractice.com
干细胞治疗
间充质干细胞为一种在研产品,已在对其免疫调节特性展开研究。指南反对将间充质干细胞用于治疗 COVID-19,除非是在临床试验的背景下。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
多项系统评价和荟萃分析发现,间充质干细胞可能降低重症或危重症患者的不良事件发生率和死亡率。但是证据有限。[991]Li Y, Wei Z, Ma X, et al. Efficacy and safety of mesenchymal stromal cells therapy for COVID-19 infection: a systematic review and meta-analysis. Curr Stem Cell Res Ther. 2021 Dec 6 [Epub ahead of print].
http://www.ncbi.nlm.nih.gov/pubmed/34872483?tool=bestpractice.com
[992]Kirkham AM, Bailey AJM, Monaghan M, et al. Updated living systematic review and meta-analysis of controlled trials of mesenchymal stromal cells to treat COVID-19: a framework for accelerated synthesis of trial evidence for rapid approval - FASTER approval. Stem Cells Transl Med. 2022 Jun 27 [Epub ahead of print].
https://academic.oup.com/stcltm/advance-article/doi/10.1093/stcltm/szac038/6618504
http://www.ncbi.nlm.nih.gov/pubmed/35758400?tool=bestpractice.com
[993]Yao W, Dong H, Qi J, et al. Safety and efficacy of mesenchymal stem cells in severe/critical patients with COVID-19: a systematic review and meta-analysis. EClinicalMedicine. 2022 Sep;51:101545.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9270852
http://www.ncbi.nlm.nih.gov/pubmed/35844767?tool=bestpractice.com
干扰素
干扰素为具有抗病毒特性的细胞因子家族。指南反对将干扰素(α、β 或 λ)用于治疗 COVID-19,除非是在临床试验的背景下。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
WHO “团结”试验发现,从总体死亡率、起始通气和住院时间情况来看,干扰素-β 对住院患者似乎影响极小或并无影响。[994]WHO Solidarity Trial Consortium; Pan H, Peto R, Henao-Restrepo AM, et al. Repurposed antiviral drugs for Covid-19: interim WHO Solidarity trial results. N Engl J Med. 2021 Feb 11;384(6):497-511.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727327
http://www.ncbi.nlm.nih.gov/pubmed/33264556?tool=bestpractice.com
一项 2 期试验发现,与安慰剂相比,聚乙二醇干扰素-λ 在用药第 7 日降低了门诊轻至中度疾病患者的病毒载量,并增加了鼻咽拭子呈阴性的受试者数量。[995]Feld JJ, Kandel C, Biondi MJ, et al. Peginterferon lambda for the treatment of outpatients with COVID-19: a phase 2, placebo-controlled randomised trial. Lancet Respir Med. 2021 May;9(5):498-510.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906707
http://www.ncbi.nlm.nih.gov/pubmed/33556319?tool=bestpractice.com
伊维菌素
伊维菌素是一种广谱抗寄生虫药,其在体外试验中被证实对 SARS-CoV-2 有效。[996]Caly L, Druce JD, Catton MG, et al. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res. 2020 Jun;178:104787.
https://www.sciencedirect.com/science/article/pii/S0166354220302011
http://www.ncbi.nlm.nih.gov/pubmed/32251768?tool=bestpractice.com
指南不建议将伊维菌素用于治疗 COVID-19,除非是在临床试验的背景下。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
[466]Bhimraj A, Morgan RL, Hirsch Shumaker A, et al. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19 infection. 2022 [internet publication].
https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management
[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication].
https://www.nice.org.uk/guidance/ng191
[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3
尚无充分的证据来明确伊维菌素的有益或有害程度。对于多数主要结局,包括死亡、机械通气、收治入院、住院时间和病毒清除,证据确定性等级为极低。[736]Rochwerg B, Siemieniuk RA, Agoritsas T, et al. A living WHO guideline on drugs for covid-19. BMJ. 2020 Sep 4;370:m3379.
https://www.bmj.com/content/370/bmj.m3379.long
http://www.ncbi.nlm.nih.gov/pubmed/32887691?tool=bestpractice.com
[737]Rochwerg B, Siemieniuk RA, Lamontagne R, et al. Update to living WHO guideline on drugs for covid-19. BMJ. 2021 Jul 6;374:n1703.
http://www.ncbi.nlm.nih.gov/pubmed/34230027?tool=bestpractice.com
荟萃分析数据存在冲突。一项有关 24 项随机对照试验的荟萃分析发现,伊维菌素带来了显著的生存获益(中等确定性证据)和病情改善和恶化方面的可能临床获益(低确定性证据)。总体而言,证据表明早期使用可能降低并发症发生率和死亡率。[997]Bryant A, Lawrie TA, Dowswell T, et al. Ivermectin for prevention and treatment of COVID-19 infection: a systematic review, meta-analysis, and trial sequential analysis to inform clinical guidelines. Am J Ther. 2021 Jun 21;28(4):e434-60.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248252
http://www.ncbi.nlm.nih.gov/pubmed/34145166?tool=bestpractice.com
其他荟萃分析也支持临床结果获得改善,但相关证据质量为极低至低。[998]Kory P, Meduri GU, Varon J, et al. Review of the emerging evidence demonstrating the efficacy of ivermectin in the prophylaxis and treatment of COVID-19. Am J Ther. 2021 Apr 22;28(3):e299-318.
https://journals.lww.com/americantherapeutics/Fulltext/2021/06000/Review_of_the_Emerging_Evidence_Demonstrating_the.4.aspx
http://www.ncbi.nlm.nih.gov/pubmed/34375047?tool=bestpractice.com
[999]Zein AFMZ, Sulistiyana CS, Raffaelo WM, et al. Ivermectin and mortality in patients with COVID-19: a systematic review, meta-analysis, and meta-regression of randomized controlled trials. Diabetes Metab Syndr. 2021 Jun 27;15(4):102186.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236126
http://www.ncbi.nlm.nih.gov/pubmed/34237554?tool=bestpractice.com
[1000]Kow CS, Merchant HA, Mustafa ZU, et al. The association between the use of ivermectin and mortality in patients with COVID-19: a meta-analysis. Pharmacol Rep. 2021 Mar 29 [Epub ahead of print].
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005369
http://www.ncbi.nlm.nih.gov/pubmed/33779964?tool=bestpractice.com
[1001]Padhy BM, Mohanty RR, Das S, et al. Therapeutic potential of ivermectin as add on treatment in COVID 19: a systematic review and meta-analysis. J Pharm Pharm Sci. 2020;23:462-9.
https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/31457/21594
http://www.ncbi.nlm.nih.gov/pubmed/33227231?tool=bestpractice.com
[1002]Bartoszko JJ, Siemieniuk RAC, Kum E, et al. Prophylaxis against covid-19: living systematic review and network meta-analysis. BMJ. 2021 Apr 26;373:n949.
https://www.bmj.com/content/373/bmj.n949
http://www.ncbi.nlm.nih.gov/pubmed/33903131?tool=bestpractice.com
[1003]Azeez TA, Lakoh S, Adeleke AA, et al. Chemoprophylaxis against COVID-19 among health-care workers using ivermectin in low- and middle-income countries: a systematic review and meta-analysis. Indian J Pharmacol. 2021 Nov-Dec;53(6):493-8.
https://www.ijp-online.com/article.asp?issn=0253-7613;year=2021;volume=53;issue=6;spage=493;epage=498;aulast=Azeez
http://www.ncbi.nlm.nih.gov/pubmed/34975139?tool=bestpractice.com
然而,其他荟萃分析发现,伊维菌素并未降低全因死亡率或改善其他临床结局。[1002]Bartoszko JJ, Siemieniuk RAC, Kum E, et al. Prophylaxis against covid-19: living systematic review and network meta-analysis. BMJ. 2021 Apr 26;373:n949.
https://www.bmj.com/content/373/bmj.n949
http://www.ncbi.nlm.nih.gov/pubmed/33903131?tool=bestpractice.com
[1004]Roman YM, Burela PA, Pasupuleti V, et al. Ivermectin for the treatment of COVID-19: a systematic review and meta-analysis of randomized controlled trials. Clin Infect Dis. 2021 Jun 28 [Epub ahead of print].
https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab591/6310839
http://www.ncbi.nlm.nih.gov/pubmed/34181716?tool=bestpractice.com
[1005]Deng J, Zhou F, Ali S, et al. Efficacy and safety of ivermectin for the treatment of COVID-19: a systematic review and meta-analysis. QJM. 2021 Sep 27 [Epub ahead of print].
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500108
http://www.ncbi.nlm.nih.gov/pubmed/34570241?tool=bestpractice.com
[1006]Bitterman A, Martins CP, Cices A, et al. Comparison of trials using ivermectin for COVID-19 between regions with high and low prevalence of strongyloidiasis: a meta-analysis. JAMA Netw Open. 2022 Mar 1;5(3):e223079.
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2790173
http://www.ncbi.nlm.nih.gov/pubmed/35311963?tool=bestpractice.com
[1007]Marcolino MS, Meira KC, Guimarães NS, et al. Systematic review and meta-analysis of ivermectin for treatment of COVID-19: evidence beyond the hype. BMC Infect Dis. 2022 Jul 23;22(1):639.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9308124
http://www.ncbi.nlm.nih.gov/pubmed/35870876?tool=bestpractice.com
Cochrane 评价发现,无证据支持使用伊维菌素进行治疗或感染预防,但证据基础有限(截至 2021 年 5 月 26 日)。基于极低至低质量证据,伊维菌素安全性和有效性尚未确定。总体而言,现有的可靠证据不支持在设计良好的随机试验研究之外,使用伊维菌素进行治疗或预防。[1008]Popp M, Stegemann M, Metzendorf MI, et al. Ivermectin for preventing and treating COVID-19. Cochrane Database Syst Rev. 2021 Jul 28;(7):CD015017.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD015017.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/34318930?tool=bestpractice.com
nitazoxanide
nitazoxanide 是一种广谱抗寄生虫药物,其在体外试验中被证实对 SARS-CoV-2 有效。指南反对将 nitazoxanide 用于治疗 COVID-19,除非是在临床试验的背景下。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
一项系统评价和荟萃分析发现,与安慰剂相比,nitazoxanide 未降低轻度至中度疾病患者的病毒载量、聚合酶链反应检测的阳性发生率、疾病进展或死亡风险。[1009]Martins-Filho PR, do Nascimento-Júnior EM, Barreto-Alves JA, et al. Efficacy and safety of nitazoxanide in treating SARS-CoV-2 infection: a systematic review and meta-analysis of blinded, placebo-controlled, randomized clinical trials. Eur J Clin Pharmacol. 2022 Sep 6 [Epub ahead of print].
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9446612
http://www.ncbi.nlm.nih.gov/pubmed/36066651?tool=bestpractice.com
氟伏沙明
氟伏沙明是一种选择性 5-羟色胺再摄取抑制剂,具有抗炎作用和潜在抗病毒作用。指南反对将氟伏沙明用于治疗 COVID-19,因为尚无充分的证据来支持或反对其应用。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
[466]Bhimraj A, Morgan RL, Hirsch Shumaker A, et al. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19 infection. 2022 [internet publication].
https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management
[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3
一项有关随机对照试验的荟萃分析(纳入了 TOGETHER 试验)发现,与使用安慰剂相比,接受氟伏沙明治疗的患者出现临床恶化或住院的可能性更小,但对单独的住院数据的分析不具有统计学意义。[1010]Guo CM, Harari O, Chernecki C, et al. Fluvoxamine for the early treatment of COVID-19: a meta-analysis of randomized clinical trials. Am J Trop Med Hyg. 2022 Mar 9 [Epub ahead of print].
https://www.ajtmh.org/view/journals/tpmd/aop/article-10.4269-ajtmh.21-1310/article-10.4269-ajtmh.21-1310.xml
http://www.ncbi.nlm.nih.gov/pubmed/35263710?tool=bestpractice.com
sabizabulin
sabizabulin 是一种与细胞中微管结合的在研药物(类似于秋水仙碱),从而可干扰 SARS-CoV-2 病毒的生命周期,并且具有抗病毒和抗炎作用。欧洲药品管理局已开始审查有关 sabizabulin 用于治疗 COVID-19 的现有数据。[1011]European Medicines Agency. EMA reviewing data on sabizabulin for COVID-19. 2022 [internet publication].
https://www.ema.europa.eu/en/news/ema-reviewing-data-sabizabulin-covid-19
来自一项小型 3 期试验(纳入 204 例患者)的中期结果发现,与安慰剂相比,sabizabulin 降低了死亡率(20% v 45%)。[1012]Barnette KG, Gordon MS, Rodriguez D, et al. Oral sabizabulin for high-risk, hospitalized adults with Covid-19: interim analysis. NEJM Evid. 2022 Jul 6 [Epub ahead of print].
https://evidence.nejm.org/doi/10.1056/EVIDoa2200145
vilobelimab
vilobelimab 是一种用于治疗 COVID-19 的在研首创抗 C5a 单克隆抗体。C5a 在重度肺损伤中发挥一定作用。一项 3 期双盲、随机、安慰剂对照试验发现,与使用安慰剂相比,在标准治疗基础上加用 vilobelimab 降低了接受有创机械通气治疗的危重患者的 20 日和 60 日死亡率(绝对风险降低 11%)。[1013]Vlaar APJ, Witzenrath M, van Paassen P, et al. Anti-C5a antibody (vilobelimab) therapy for critically ill, invasively mechanically ventilated patients with COVID-19 (PANAMO): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Respir Med. 2022 Sep 7 [Epub ahead of print].
https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(22)00297-1/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/36087611?tool=bestpractice.com
制造商已向美国食品药品监督管理局申请用于治疗危重患者的紧急使用授权。
吸入性皮质类固醇
吸入性皮质类固醇被认为可调节感染后上呼吸道和循环中的炎症通路。当前指南不建议将吸入性皮质类固醇用于治疗 COVID-19,除非是在临床试验的背景下,因为尚无充分证据来支持或反对其应用。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
[466]Bhimraj A, Morgan RL, Hirsch Shumaker A, et al. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19 infection. 2022 [internet publication].
https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management
[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication].
https://www.nice.org.uk/guidance/ng191
一项 Cochrane 评价发现,吸入性皮质类固醇(布地奈德和环索奈德)可能减少了收住院或死亡的复合终点,并增加了轻症患者的首发症状 14 日缓解率(中等确定性证据)。然而,吸入性皮质类固醇对 30 日全因死亡率的影响极小或没有影响,但可能缩短症状缓解时间(低确定性性证据)。[1014]Griesel M, Wagner C, Mikolajewska A, et al. Inhaled corticosteroids for the treatment of COVID-19. Cochrane Database Syst Rev. 2022 Mar 9;(3):CD015125.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD015125/full
http://www.ncbi.nlm.nih.gov/pubmed/35262185?tool=bestpractice.com
抗生素
已在对阿奇霉素和四环素用于治疗 COVID-19 进行研究。指南反对在无其他抗生素使用适应证时将其用于治疗 COVID-19。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication].
https://www.nice.org.uk/guidance/ng191
一项 Cochrane 评价发现,与单纯的标准治疗相比,阿奇霉素并未降低住院患者 28 日全因死亡率(高确定性证据)。中至重度疾病的住院患者在临床恶化或临床改善等方面并未因阿奇霉素获益(中等确定性证据)。在门诊情况下使用阿奇霉素并无获益(低确定性证据)。[1015]Popp M, Stegemann M, Riemer M, et al. Antibiotics for the treatment of COVID-19. Cochrane Database Syst Rev. 2021 Oct 22;(10):CD015025.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD015025/full
http://www.ncbi.nlm.nih.gov/pubmed/34679203?tool=bestpractice.com
英国 PRINCIPLE 试验发现,对于社区中具有不良结局高风险的疑似疾病患者,使用多西环素并不会使康复时间、收治入院或死亡人数发生有临床意义的减少。[1016]Butler CC, Yu LM, Dorward J, et al. Doxycycline for community treatment of suspected COVID-19 in people at high risk of adverse outcomes in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial. Lancet Respir Med. 2021 Sep;9(9):1010-20.
https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00310-6/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/34329624?tool=bestpractice.com
维生素和矿物质
维生素 C、维生素 D 和锌在治疗病毒性呼吸道感染方面已显示出前景。[1017]Jolliffe DA, Camargo CA Jr, Sluyter JD, et al. Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials. Lancet Diabetes Endocrinol. 2021 May;9(5):276-92.
https://www.thelancet.com/journals/landia/article/PIIS2213-8587(21)00051-6/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/33798465?tool=bestpractice.com
[1018]Boretti A, Banik BK. Intravenous vitamin C for reduction of cytokines storm in acute respiratory distress syndrome. PharmaNutrition. 2020 Apr 21:100190.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7172861
http://www.ncbi.nlm.nih.gov/pubmed/32322486?tool=bestpractice.com
[1019]Abioye AI, Bromage S, Fawzi W. Effect of micronutrient supplements on influenza and other respiratory tract infections among adults: a systematic review and meta-analysis. BMJ Glob Health. 2021 Jan;6(1):e003176.
https://gh.bmj.com/content/6/1/e003176.long
http://www.ncbi.nlm.nih.gov/pubmed/33472840?tool=bestpractice.com
当前指南不建议将维生素 C、维生素 D 和锌用于治疗 COVID-19,除非是作为临床试验的一部分,因为尚无充分证据来支持或反对其应用。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication].
https://www.nice.org.uk/guidance/ng191
一项荟萃分析发现,大剂量维生素 C 降低了重症和死亡风险。[1020]Bhowmik KK, Barek MA, Aziz MA, et al. Impact of high-dose vitamin C on the mortality, severity, and duration of hospital stay in COVID-19 patients: a meta-analysis. Health Sci Rep. 2022 Sep;5(5):e762.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9358542
http://www.ncbi.nlm.nih.gov/pubmed/35949675?tool=bestpractice.com
然而,这些发现与其他荟萃分析结果不一致,而需要通过进一步的大规模研究加以证实。[1021]Rawat D, Roy A, Maitra S, et al. Vitamin C and COVID-19 treatment: a systematic review and meta-analysis of randomized controlled trials. Diabetes Metab Syndr. 2021 Oct 28;15(6):102324.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8552785
http://www.ncbi.nlm.nih.gov/pubmed/34739908?tool=bestpractice.com
[1022]Kwak SG, Choo YJ, Chang MC. The effectiveness of high-dose intravenous vitamin C for patients with coronavirus disease 2019: a systematic review and meta-analysis. Complement Ther Med. 2021 Dec 22;64:102797.
https://www.sciencedirect.com/science/article/pii/S0965229921001382?via%3Dihub
http://www.ncbi.nlm.nih.gov/pubmed/34953366?tool=bestpractice.com
一项 Cochrane 评价发现,当前尚无充分证据确定补充维生素 D 的获益和危害,而且证据非常不确定。所纳入的研究存在显著的临床和方法学异质性,主要是由于不同的补充方法、制剂、参与者的维生素 D 营养状态和所报告的结局。[1023]Stroehlein JK, Wallqvist J, Iannizzi C, et al. Vitamin D supplementation for the treatment of COVID-19: a living systematic review. Cochrane Database Syst Rev. 2021 May 24;(5):CD015043.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD015043/full
http://www.ncbi.nlm.nih.gov/pubmed/34029377?tool=bestpractice.com
荟萃分析已发现,维生素 D 可能与临床结局改善(包括重症监护病房收治和死亡风险降低)相关,其对降低疾病严重程度可能具有潜在作用,但指出还需其他证据。[1024]Pal R, Banerjee M, Bhadada SK, et al. Vitamin D supplementation and clinical outcomes in COVID-19: a systematic review and meta-analysis. J Endocrinol Invest. 2021 Jun 24 [Epub ahead of print].
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223190
http://www.ncbi.nlm.nih.gov/pubmed/34165766?tool=bestpractice.com
[1025]Szarpak L, Filipiak KJ, Gasecka A, et al. Vitamin D supplementation to treat SARS-CoV-2 positive patients: evidence from meta-analysis. Cardiol J. 2021 Oct 13 [Epub ahead of print].
https://journals.viamedica.pl/cardiology_journal/article/view/85559
http://www.ncbi.nlm.nih.gov/pubmed/34642923?tool=bestpractice.com
[1026]Tentolouris N, Samakidou G, Eleftheriadou I, et al. The effect of vitamin D supplementation on mortality and intensive care unit admission of COVID-19 patients: a systematic review, meta-analysis and meta-regression. Diabetes Metab Res Rev. 2021 Dec 29 [Epub ahead of print].
https://onlinelibrary.wiley.com/doi/10.1002/dmrr.3517
http://www.ncbi.nlm.nih.gov/pubmed/34965318?tool=bestpractice.com
[1027]Shah K, Varna VP, Sharma U, et al. Does vitamin D supplementation reduce COVID-19 severity? A systematic review. QJM. 2022 Feb 15 [Epub ahead of print].
http://www.ncbi.nlm.nih.gov/pubmed/35166850?tool=bestpractice.com
[1028]Hosseini B, El Abd A, Ducharme FM. Effects of vitamin D supplementation on COVID-19 related outcomes: a systematic review and meta-analysis. Nutrients. 2022 May 20;14(10):2134.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9147949
http://www.ncbi.nlm.nih.gov/pubmed/35631275?tool=bestpractice.com
[1029]D'Ecclesiis O, Gavioli C, Martinoli C, et al. Vitamin D and SARS-CoV2 infection, severity and mortality: a systematic review and meta-analysis. PLoS One. 2022 Jul 6;17(7):e0268396.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9258852
http://www.ncbi.nlm.nih.gov/pubmed/35793346?tool=bestpractice.com
英国英国国家卫生与临床优化研究所建议,在 10 月至 3 月初之间(或根据年龄和维生素 D 缺乏风险在一年中其他时间)给予成人(包括孕妇和母乳喂养的女性)、青年和 4 岁以上儿童维生素 D 补充剂,维持骨骼和肌肉健康,但不建议仅为预防或治疗 COVID-19 使用补充剂,除非作为临床试验的一部分。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication].
https://www.nice.org.uk/guidance/ng191
[1030]National Institute for Health and Care Excellence. COVID-19 rapid guideline: vitamin D. 2020 [internet publication].
https://www.nice.org.uk/guidance/ng187
一项荟萃分析发现,锌补充剂可能与死亡风险降低有关。[1031]Tabatabaeizadeh SA. Zinc supplementation and COVID-19 mortality: a meta-analysis. Eur J Med Res. 2022 May 23;27(1):70.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9125011
http://www.ncbi.nlm.nih.gov/pubmed/35599332?tool=bestpractice.com
肺移植
对于罹患 COVID-19 相关性急性呼吸窘迫综合征(acute respiratory distress syndrome, ARDS),尽管给予了最大程度通气支持、体外膜肺氧合和最佳治疗,但仍无法康复的患者,肺移植被用作挽救疗法。2020 年 8 月至 2021 年 9 月期间,美国为此进行了 214 例肺移植(占全国肺移植的 7%)。此类患者的 3 个月生存率接近因 COVID-19 以外原因接受肺移植的患者。[1032]Roach A, Chikwe J, Catarino P, et al. Lung transplantation for Covid-19-related respiratory failure in the United States. N Engl J Med. 2022 Jan 26 [Epub ahead of print].
https://www.nejm.org/doi/full/10.1056/NEJMc2117024
http://www.ncbi.nlm.nih.gov/pubmed/35081299?tool=bestpractice.com
在一项包含 30 名接受肺移植的 COVID-19 相关性 ARDS 患者回顾性病例系列事件报告研究中,生存率为 100%(中位随访时间 351 天)。[1033]Kurihara C, Manerikar A, Querrey M, et al. Clinical characteristics and outcomes of patients with COVID-19-associated acute respiratory distress syndrome who underwent lung transplant. JAMA. 2022 Jan 27 [Epub ahead of print].
https://jamanetwork.com/journals/jama/fullarticle/2788640
http://www.ncbi.nlm.nih.gov/pubmed/35085383?tool=bestpractice.com
临床试验
各种其他治疗方法正在全世界进行临床试验。 目前正在开展国际试验,以确定可能获益的治疗方法,例如世界卫生组织团结试验和英国 COVID-19 治疗随机评估(randomised evaluation of COVID-19 therapy, RECOVERY)试验。