A severe inflammatory immune response with hypercytokinemia occurs in patients hospitalized with severe influenza, such as avian influenza A(H5N1), A(H7N9), and seasonal A(H1N1)pdm09 virus infections. The role of immunomodulatory therapy is unclear as there have been limited published data based on randomized controlled trials (RCTs). Passive immunotherapy such as convalescent plasma and hyperimmune globulin have some studies demonstrating benefit when administered as an adjunctive therapy for severe influenza. Triple combination of oseltamivir, clarithromycin, and naproxen for severe influenza has one study supporting its use, and confirmatory studies would be of great interest. Likewise, confirmatory studies of sirolimus without concomitant corticosteroid therapy should be explored as a research priority. Other agents with potential immunomodulating effects, including non-immune intravenous immunoglobulin, N-acetylcysteine, acute use of statins, macrolides, pamidronate, nitazoxanide, chloroquine, antiC5a antibody, interferons, human mesenchymal stromal cells, mycophenolic acid, peroxisome proliferator-activated receptors agonists, non-steroidal anti-inflammatory agents, mesalazine, herbal medicine, and the role of plasmapheresis and hemoperfusion as rescue therapy have supportive preclinical or observational clinical data, and deserve more investigation preferably by RCTs. Systemic corticosteroids administered in high dose may increase the risk of mortality and morbidity in patients with severe influenza and should not be used, while the clinical utility of low dose systemic corticosteroids requires further investigation.

患有严重流感（例如甲型 H5N1、甲型 H7N9 禽流感和季节性甲型 H1N1）pdm09 病毒感染的住院患者会出现严重的炎症免疫反应并伴有高细胞因子血症。免疫调节疗法的作用尚不清楚，因为基于随机对照试验（RCT）的已发表数据有限。一些研究表明，被动免疫疗法（例如恢复期血浆和超免疫球蛋白）作为严重流感的辅助疗法具有益处。奥司他韦、克拉霉素和萘普生三联疗法治疗严重流感已有一项研究支持其使用，并且验证性研究将引起人们极大的兴趣。同样，应将探索不伴随皮质类固醇治疗的西罗莫司验证性研究作为研究重点。其他具有潜在免疫调节作用的药物，包括非免疫静脉注射免疫球蛋白、N-乙酰半胱氨酸、急性使用他汀类药物、大环内酯类、帕米膦酸、硝唑尼特、氯喹、抗C5a抗体、干扰素、人间充质基质细胞、霉酚酸、过氧化物酶体增殖物激活受体激动剂、非甾体类抗炎药、美沙拉嗪、草药以及血浆置换和血液灌流作为挽救治疗的作用都有支持性的临床前或观察性临床数据，值得通过随机对照试验进行更多研究。高剂量全身性皮质类固醇可能会增加重症流感患者的死亡和发病风险，不宜使用，而低剂量全身性皮质类固醇的临床效用需要进一步研究。