Clinical evidence of an interferon-glucocorticoid therapeutic synergy in COVID-19.
Clinical evidence of an interferon-glucocorticoid therapeutic synergy in COVID-19.
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DOI：
10.1038/s41392-021-00496-5
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发表时间：
2021-03-03
影响因子：
39.3
通讯作者：
Hong P
中科院分区：
文献类型：
--
作者：
Lu Y;Liu F;Tong G;Qiu F;Song P;Wang X;Zou X;Wan D;Cui M;Xu Y;Zheng Z;Hong P
合成糖皮质激素地塞米松是第一个试验证明通过抑制免疫系统降低COVID-19死亡率的药物。相反，干扰素是宿主抗病毒免疫的重要组成部分，可被糖皮质激素直接抑制。为了研究治疗性干扰素是否可以补偿糖皮质激素诱导的抗病毒免疫丧失，我们回顾性分析了387例PCR确认的COVID-19患者的队列，这些患者半随机暴露于干扰素和条件性暴露于糖皮质激素。在接受糖皮质激素治疗的患者中，早期干扰素治疗与较早出院（校正HR 1.68，95% CI 1.19-2.37）和症状缓解（校正HR 1.48，95% CI 1.06-2.08）相关，而这些相关性在糖皮质激素非使用者中不显著。仅在糖皮质激素使用者中，早期干扰素治疗也与较低的长期病毒脱落患病率相关（校正OR 0.24，95%CI 0.10-0.57）。此外，这些关联是糖皮质激素累积剂量和时间依赖性的。这些发现揭示了干扰素和糖皮质激素在COVID-19中的潜在治疗协同作用，值得进一步研究。
Synthetic glucocorticoid dexamethasone is the first trial-proven drug that reduces COVID-19 mortality by suppressing immune system. In contrast, interferons are a crucial component of host antiviral immunity and can be directly suppressed by glucocorticoids. To investigate whether therapeutic interferons can compensate glucocorticoids-induced loss of antiviral immunity, we retrospectively analyzed a cohort of 387 PCR-confirmed COVID-19 patients with quasi-random exposure to interferons and conditional exposure to glucocorticoids. Among patients receiving glucocorticoids, early interferon therapy was associated with earlier hospital discharge (adjusted HR 1.68, 95% CI 1.19–2.37) and symptom relief (adjusted HR 1.48, 95% CI 1.06–2.08), while these associations were insignificant among glucocorticoids nonusers. Early interferon therapy was also associated with lower prevalence of prolonged viral shedding (adjusted OR 0.24, 95% CI 0.10–0.57) only among glucocorticoids users. Additionally, these associations were glucocorticoid cumulative dose- and timing-dependent. These findings reveal potential therapeutic synergy between interferons and glucocorticoids in COVID-19 that warrants further investigation.
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DOI：
10.1056/nejmoa2022926
发表时间：
2020-11-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
RECOVERY Collaborative Group;Horby P;Mafham M;Linsell L;Bell JL;Staplin N;Emberson JR;Wiselka M;Ustianowski A;Elmahi E;Prudon B;Whitehouse T;Felton T;Williams J;Faccenda J;Underwood J;Baillie JK;Chappell LC;Faust SN;Jaki T;Jeffery K;Lim WS;Montgomery A;Rowan K;Tarning J;Watson JA;White NJ;Juszczak E;Haynes R;Landray MJ
通讯作者：
Landray MJ
影响因子：
56.9
作者：
Broggi, Achille;Ghosh, Sreya;Zanoni, Ivan
通讯作者：
Zanoni, Ivan
影响因子：
11.8
作者：
Fadel, Raef;Morrison, Austin R.;Ramesh, Mayur S.
通讯作者：
Ramesh, Mayur S.
用糖固醇治疗严重的急性呼吸道综合征：广州体验。
影响因子：
9.6
作者：
Chen RC;Tang XP;Tan SY;Liang BL;Wan ZY;Fang JQ;Zhong N
通讯作者：
Zhong N
影响因子：
27.4
作者：
Ramiro, Sofia;Mostard, Remy L. M.;Landewe, Robert B. M.
通讯作者：
Landewe, Robert B. M.