重型新型冠状病毒肺炎抗炎治疗的研究进展_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

李宗儒 , 高占成 ,  公丕花

北京大学人民医院呼吸与危重症科（北京 100044）;

Corresponding author：

公丕花, Email: gardenia1978@163.com

Keywords：

DOI：

10.7507/1671-6205.202008079

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Citation： 李宗儒, 高占成, 公丕花. 重型新型冠状病毒肺炎抗炎治疗的研究进展. Chinese Journal of Respiratory and Critical Care Medicine, 2021, 20(1): 64-69. doi: 10.7507/1671-6205.202008079 Copy

1.	国家卫生健康委办公厅, 国家中医药管理局办公室. 新型冠状病毒肺炎诊疗方案(试行第八版)[EB/OL]. (2020-08-18). http://www.gov.cn/zhengce/zhengceku/2020-08/19/5535757/files/da89edf7cc9244fbb34ecf6c61df40bf.pdf.
2.	Li X, Xu S, Yu M, et al. Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan. J Allergy Clin Immunol, 2020, 146: 110-118.
3.	Sun Y, Dong YL, Wang LF, et al. Characteristics and prognostic factors of disease severity in patients with COVID-19: The Beijing experience. J Autoimmun, 2020, 112: 102473.
4.	Wu CM, Chen XY, Cai YP, 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, 180(7): 934-943.
5.	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.
6.	Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: A clinical-therapeutic staging proposal. J Heart Lung Transplant, 2020, 39: 405-407.
7.	Lu S, Zhou Q, Huang L, et al. Effectiveness and safety of glucocorticoids to treat COVID-19: a rapid review and meta-analysis. Ann Transl Med, 2020, 8: 627.
8.	Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med, 2020, 8: 420-422.
9.	Copin MC, Parmentier E, Duburcq T, et al. Time to consider histologic pattern of lung injury to treat critically ill patients with COVID-19 infection. Intensive Care Med, 2020, 46: 1124-1126.
10.	Wang Y, Jiang W, He Q, et al. A retrospective cohort study of methylprednisolone therapy in severe patients with COVID-19 pneumonia. Signal Transduct Target Ther, 2020, 5: 57.
11.	Fernández-Cruz A, Ruiz-Antorán B, Muñoz-Gómez A, et al. A retrospective controlled cohort study of the impact of glucocorticoid treatment in SARS-CoV-2 Infection Mortality. Antimicrob Agents Chemother, 2020, 64(9): e01168.
12.	Gong Y, Guan L, Jin Z, et al. Effects of methylprednisolone use on viral genomic nucleic acid negative conversion and CT imaging lesion absorption in COVID-19 patients under 50 years old[J/OL]. J Med Virol. [2020-05-22]. https://doi.org/10.1002/jmv.26052.
13.	Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 2020, 395: 497-506.
14.	The RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19 - preliminary report[J/OL]. N Engl J Med. [2020-07-17]. https://www.nejm.org/doi/pdf/10.1056/NEJMoa2021436?articleTools=true.
15.	Tomazini BM, Maia IS, Cavalcanti AB, et al. Effect of dexamethasone on days alive and ventilator-free in patients with moderate or severe acute respiratory distress syndrome and COVID-19: The CoDEX Randomized Clinical Trial. JAMA, 2020, 324(13): 1307-1316.
16.	Jeronimo CMP, Farias MEL, Val FFA, et al. Methylprednisolone as adjunctive therapy for patients hospitalized with Coronavirus Disease 2019 (COVID-19; Metcovid): a randomized, double-blind, Phase IIb, placebo-controlled trial[J/OL]. Clin Infect Dis. [2020-08-12]. https://doi.org/10.1093/cid/ciaa1177.
17.	The Writing Committee for the REMAP-CAP Investigators. Effect of hydrocortisone on mortality and organ support in patients with severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial. JAMA, 2020, 324(13): 1317-1329.
18.	Dequin PF, Heming N, Meziani F, et al. Effect of hydrocortisone on 21-day mortality or respiratory support among critically ill patients with COVID-19: a randomized clinical trial. JAMA, 2020, 324(13): 1298-1306.
19.	Ni YN, Chen G, Sun J, et al. Correction to: The effect of corticosteroids on the mortality of patients with influenza pneumonia: a systematic review and meta-analysis. Crit Care, 2020, 24: 376.
20.	Steinberg KP, Hudson LD, Goodman RB, et al. Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med, 2006, 354: 1671-1684.
21.	Villar J, Ferrando C, Martinez D, et al. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. Lancet Respir Med, 2020, 8: 267-276.
22.	Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet, 2020, 395: 507-513.
23.	Canton R, Gijon D, Ruiz-Garbajosa P. Antimicrobial resistance in ICUs: an update in the light of the COVID-19 pandemic. Curr Opin Crit Care, 2020, 26: 433-441.
24.	Xu X, Han M, Li T, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A, 2020, 117: 10970-10975.
25.	Toniati P, Piva S, Cattalini M, et al. Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: A single center study of 100 patients in Brescia, Italy. Autoimmun Rev, 2020, 19: 102568.
26.	Rojas-Marte G, Khalid M, Mukhtar O, et al. Outcomes in patients with severe COVID-19 disease treated with tocilizumab: a case-controlled study. QJM, 2020, 113(8): 546-550.
27.	Somers EC, Eschenauer GA, Troost JP, et al. Tocilizumab for treatment of mechanically ventilated patients with COVID-19[J/OL]. medRxiv. [2020-06-03]. https://www.medrxiv.org/content/10.1101/2020.05.29.20117358v1.
28.	Quartuccio L, Sonaglia A, Pecori D, et al. Higher levels of IL-6 early after tocilizumab distinguish survivors from non-survivors in COVID-19 pneumonia: a possible indication for deeper targeting IL-6[J/OL]. J Med Virol. [2020-05-22]. https://doi.org/10.1002/jmv.26149.
29.	Benucci M, Giannasi G, Cecchini P, et al. COVID-19 pneumonia treated with Sarilumab: a clinical series of eight patients[J/OL]. J Med Virol. [2020-05-22]. https://doi.org/10.1002/jmv.26062.
30.	Della-Torre E, Campochiaro C, Cavalli G, et al. Interleukin-6 blockade with sarilumab in severe COVID-19 pneumonia with systemic hyperinflammation: an open-label cohort study. Ann Rheum Dis, 2020, 79(10): 1277-1285.
31.	Jamilloux Y, Henry T, Belot A, et al. Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions. Autoimmun Rev, 2020, 19: 102567.
32.	Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet, 2020, 395: 1033-1034.
33.	Dimopoulos G, de Mast Q, Markou N, et al. Favorable anakinra responses in severe Covid-19 patients with secondary hemophagocytic lymphohistiocytosis. Cell Host Microbe, 2020, 28: 117-123.
34.	Cavalli G, De Luca G, Campochiaro C, et al. Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study. Lancet Rheumatol, 2020, 2: e325-e331.
35.	Pesu M, Laurence A, Kishore N, et al. Therapeutic targeting of Janus kinases. Immunol Rev, 2008, 223: 132-142.
36.	Yeleswaram S, Smith P, Burn T, et al. Inhibition of cytokine signaling by ruxolitinib and implications for COVID-19 treatment. Clin Immunol, 2020, 218: 108517.
37.	Cao Y, Wei J, Zou L, et al. Ruxolitinib in treatment of severe coronavirus disease 2019(COVID-19): a multicenter, single-blind, randomized controlled trial. J Allergy Clin Immunol, 2020, 146: 137-146.
38.	Innes AJ, Cook LB, Marks S, et al. Ruxolitinib for tocilizumab-refractory severe COVID-19 infection. Br J Haematol, 2020, 190(4): 8198-e200.
39.	CJ Jorgensen S, LY Tse C, Burry L, et al. Baricitinib: a review of pharmacology, safety and emerging clinical experience in COVID-19. Pharmacotherapy, 2020, 40(8): 843-856.
40.	Richardson P, Griffin I, Tucker C, et al. Baricitinib as potential treatment for 2019-nCoV acute respiratory disease. Lancet, 2020, 395: e30-e31.
41.	Cantini F, Niccoli L, Nannini C, et al. Beneficial impact of Baricitinib in COVID-19 moderate pneumonia; multicentre study. J Infect, 2020, 71(4): 647-679.
42.	Titanji BK, Farley MM, Mehta A, et al. Use of baricitinib in patients with moderate and severe Coronavirus Diseasse 2019[J/OL]. Clin Infect Dis. [2020-06-29]. https://doi.org/10.1093/cid/ciaa879.

1. 国家卫生健康委办公厅, 国家中医药管理局办公室. 新型冠状病毒肺炎诊疗方案(试行第八版)[EB/OL]. (2020-08-18). http://www.gov.cn/zhengce/zhengceku/2020-08/19/5535757/files/da89edf7cc9244fbb34ecf6c61df40bf.pdf.
2. Li X, Xu S, Yu M, et al. Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan. J Allergy Clin Immunol, 2020, 146: 110-118.
3. Sun Y, Dong YL, Wang LF, et al. Characteristics and prognostic factors of disease severity in patients with COVID-19: The Beijing experience. J Autoimmun, 2020, 112: 102473.
4. Wu CM, Chen XY, Cai YP, 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, 180(7): 934-943.
5. 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.
6. Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: A clinical-therapeutic staging proposal. J Heart Lung Transplant, 2020, 39: 405-407.
7. Lu S, Zhou Q, Huang L, et al. Effectiveness and safety of glucocorticoids to treat COVID-19: a rapid review and meta-analysis. Ann Transl Med, 2020, 8: 627.
8. Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med, 2020, 8: 420-422.
9. Copin MC, Parmentier E, Duburcq T, et al. Time to consider histologic pattern of lung injury to treat critically ill patients with COVID-19 infection. Intensive Care Med, 2020, 46: 1124-1126.
10. Wang Y, Jiang W, He Q, et al. A retrospective cohort study of methylprednisolone therapy in severe patients with COVID-19 pneumonia. Signal Transduct Target Ther, 2020, 5: 57.
11. Fernández-Cruz A, Ruiz-Antorán B, Muñoz-Gómez A, et al. A retrospective controlled cohort study of the impact of glucocorticoid treatment in SARS-CoV-2 Infection Mortality. Antimicrob Agents Chemother, 2020, 64(9): e01168.
12. Gong Y, Guan L, Jin Z, et al. Effects of methylprednisolone use on viral genomic nucleic acid negative conversion and CT imaging lesion absorption in COVID-19 patients under 50 years old[J/OL]. J Med Virol. [2020-05-22]. https://doi.org/10.1002/jmv.26052.
13. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 2020, 395: 497-506.
14. The RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19 - preliminary report[J/OL]. N Engl J Med. [2020-07-17]. https://www.nejm.org/doi/pdf/10.1056/NEJMoa2021436?articleTools=true.
15. Tomazini BM, Maia IS, Cavalcanti AB, et al. Effect of dexamethasone on days alive and ventilator-free in patients with moderate or severe acute respiratory distress syndrome and COVID-19: The CoDEX Randomized Clinical Trial. JAMA, 2020, 324(13): 1307-1316.
16. Jeronimo CMP, Farias MEL, Val FFA, et al. Methylprednisolone as adjunctive therapy for patients hospitalized with Coronavirus Disease 2019 (COVID-19; Metcovid): a randomized, double-blind, Phase IIb, placebo-controlled trial[J/OL]. Clin Infect Dis. [2020-08-12]. https://doi.org/10.1093/cid/ciaa1177.
17. The Writing Committee for the REMAP-CAP Investigators. Effect of hydrocortisone on mortality and organ support in patients with severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial. JAMA, 2020, 324(13): 1317-1329.
18. Dequin PF, Heming N, Meziani F, et al. Effect of hydrocortisone on 21-day mortality or respiratory support among critically ill patients with COVID-19: a randomized clinical trial. JAMA, 2020, 324(13): 1298-1306.
19. Ni YN, Chen G, Sun J, et al. Correction to: The effect of corticosteroids on the mortality of patients with influenza pneumonia: a systematic review and meta-analysis. Crit Care, 2020, 24: 376.
20. Steinberg KP, Hudson LD, Goodman RB, et al. Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med, 2006, 354: 1671-1684.
21. Villar J, Ferrando C, Martinez D, et al. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. Lancet Respir Med, 2020, 8: 267-276.
22. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet, 2020, 395: 507-513.
23. Canton R, Gijon D, Ruiz-Garbajosa P. Antimicrobial resistance in ICUs: an update in the light of the COVID-19 pandemic. Curr Opin Crit Care, 2020, 26: 433-441.
24. Xu X, Han M, Li T, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A, 2020, 117: 10970-10975.
25. Toniati P, Piva S, Cattalini M, et al. Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: A single center study of 100 patients in Brescia, Italy. Autoimmun Rev, 2020, 19: 102568.
26. Rojas-Marte G, Khalid M, Mukhtar O, et al. Outcomes in patients with severe COVID-19 disease treated with tocilizumab: a case-controlled study. QJM, 2020, 113(8): 546-550.
27. Somers EC, Eschenauer GA, Troost JP, et al. Tocilizumab for treatment of mechanically ventilated patients with COVID-19[J/OL]. medRxiv. [2020-06-03]. https://www.medrxiv.org/content/10.1101/2020.05.29.20117358v1.
28. Quartuccio L, Sonaglia A, Pecori D, et al. Higher levels of IL-6 early after tocilizumab distinguish survivors from non-survivors in COVID-19 pneumonia: a possible indication for deeper targeting IL-6[J/OL]. J Med Virol. [2020-05-22]. https://doi.org/10.1002/jmv.26149.
29. Benucci M, Giannasi G, Cecchini P, et al. COVID-19 pneumonia treated with Sarilumab: a clinical series of eight patients[J/OL]. J Med Virol. [2020-05-22]. https://doi.org/10.1002/jmv.26062.
30. Della-Torre E, Campochiaro C, Cavalli G, et al. Interleukin-6 blockade with sarilumab in severe COVID-19 pneumonia with systemic hyperinflammation: an open-label cohort study. Ann Rheum Dis, 2020, 79(10): 1277-1285.
31. Jamilloux Y, Henry T, Belot A, et al. Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions. Autoimmun Rev, 2020, 19: 102567.
32. Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet, 2020, 395: 1033-1034.
33. Dimopoulos G, de Mast Q, Markou N, et al. Favorable anakinra responses in severe Covid-19 patients with secondary hemophagocytic lymphohistiocytosis. Cell Host Microbe, 2020, 28: 117-123.
34. Cavalli G, De Luca G, Campochiaro C, et al. Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study. Lancet Rheumatol, 2020, 2: e325-e331.
35. Pesu M, Laurence A, Kishore N, et al. Therapeutic targeting of Janus kinases. Immunol Rev, 2008, 223: 132-142.
36. Yeleswaram S, Smith P, Burn T, et al. Inhibition of cytokine signaling by ruxolitinib and implications for COVID-19 treatment. Clin Immunol, 2020, 218: 108517.
37. Cao Y, Wei J, Zou L, et al. Ruxolitinib in treatment of severe coronavirus disease 2019(COVID-19): a multicenter, single-blind, randomized controlled trial. J Allergy Clin Immunol, 2020, 146: 137-146.
38. Innes AJ, Cook LB, Marks S, et al. Ruxolitinib for tocilizumab-refractory severe COVID-19 infection. Br J Haematol, 2020, 190(4): 8198-e200.
39. CJ Jorgensen S, LY Tse C, Burry L, et al. Baricitinib: a review of pharmacology, safety and emerging clinical experience in COVID-19. Pharmacotherapy, 2020, 40(8): 843-856.
40. Richardson P, Griffin I, Tucker C, et al. Baricitinib as potential treatment for 2019-nCoV acute respiratory disease. Lancet, 2020, 395: e30-e31.
41. Cantini F, Niccoli L, Nannini C, et al. Beneficial impact of Baricitinib in COVID-19 moderate pneumonia; multicentre study. J Infect, 2020, 71(4): 647-679.
42. Titanji BK, Farley MM, Mehta A, et al. Use of baricitinib in patients with moderate and severe Coronavirus Diseasse 2019[J/OL]. Clin Infect Dis. [2020-06-29]. https://doi.org/10.1093/cid/ciaa879.

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