Combining Antivirals and Immunomodulators to Fight COVID-19.
Combining Antivirals and Immunomodulators to Fight COVID-19.
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DOI：
10.1016/j.it.2020.11.003
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发表时间：
2021-01
影响因子：
16.8
通讯作者：
Trautmann A
中科院分区：
文献类型：
--
作者：
Feuillet V;Canard B;Trautmann A
大多数严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染者仍然没有症状，而少数感染者则面临死亡危险。在这里，我们推测大多数个体强大的抗病能力是由于 I 型干扰素 (IFNα/β) 的快速产生，这可能足以降低病毒血症。少数预先存在慢性炎症状态的感染者无法做出这种早期有效反应，导致有害炎症反应延迟。为了改善流行病学情况，我们建议结合以下措施：(i) 开发有效的抗病毒药物，尽早施用以协助内源性 IFNα/β 的产生； (ii) 增强早期干扰素反应； (iii) 需要时给予抗炎治疗，但不要太早，以免干扰内源性抗病毒反应。尽管 2019 年冠状病毒病 (COVID-19) 大流行是例外，但我们可以从之前的疫情（冠状病毒、登革热、流感病毒）中吸取教训，特别是在考虑药物设计和细胞因子风暴时。我们建议对 COVID-19 患者的有效治疗应结合抗病毒药物和免疫调节剂。这种组合，尤其是免疫调节剂的使用，可以根据疾病阶段进行调整。目前正在针对 COVID-19 进行测试的重新用途抗病毒药物中，没有一种药物显示出高效力。我们认为，针对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染的先天 1 型干扰素 (IFNα/β) 依赖性抗病毒免疫反应应该得到增强。为此，我们提出了两种假定的方法：抑制转化生长因子 (TGFβ) 信号传导，或许还有施用 1,8-桉树脑。我们建议，在有意将抗病毒药物与免疫调节剂（例如增强 IFNα/β 的药物）结合使用时，在 COVID-19 期间进行早期诊断至关重要，最好是在病程早期进行诊断，以降低细胞因子风暴表现的风险。当疾病变得严重时，新的组合应优先针对细胞因子风暴。
The majority of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals remain paucisymptomatic, contrasting with a minority of infected individuals in danger of death. Here, we speculate that the robust disease resistance of most individuals is due to a swift production of type I interferon (IFNα/β), presumably sufficient to lower the viremia. A minority of infected individuals with a preexisting chronic inflammatory state fail to mount this early efficient response, leading to a delayed harmful inflammatory response. To improve the epidemiological scenario, we propose combining: (i) the development of efficient antivirals administered early enough to assist in the production of endogenous IFNα/β; (ii) potentiating early IFN responses; (iii) administering anti-inflammatory treatments when needed, but not too early to interfere with endogenous antiviral responses. Although the coronavirus disease 2019 (COVID-19) pandemic is exceptional, lessons may be learned from previous outbreaks (coronavirus, dengue, influenza viruses), especially when considering drug design and cytokine storms. We propose that efficient treatments for COVID-19 patients should combine antivirals and immunomodulators. This combination and, especially the use of immunomodulators, might be adapted according to the disease stage. Among the repurposed antiviral drugs currently being tested against COVID-19, none shows high potency. We posit that the innate type 1 interferon (IFNα/β)-dependent antiviral immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection should be amplified. To this end, we propose two putative approaches: the inhibition of transforming growth factor (TGFβ) signaling, and perhaps, the administration of 1,8-cineole. We suggest that an early diagnosis during COVID-19 is essential when aiming to purposely combine antivirals with the use of an immunomodulator (e.g., a drug to potentiate IFNα/β), ideally early in the disease course to lower the risk of cytokine storm manifestation. When the disease becomes severe, the new combination should prioritize targeting of the cytokine storm.
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DOI：
10.2183/pjab.93.027
发表时间：
2017
期刊：
Proceedings of the Japan Academy. Series B, Physical and biological sciences
影响因子：
--
作者：
Furuta Y;Komeno T;Nakamura T
通讯作者：
Nakamura T
影响因子：
15.9
作者：
Brook CE;Dobson AP
通讯作者：
Dobson AP
危及生命的Covid-19患者中针对I型IFN的自身抗体。
DOI：
10.1126/science.abd4585
发表时间：
2020-10-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bastard P;Rosen LB;Zhang Q;Michailidis E;Hoffmann HH;Zhang Y;Dorgham K;Philippot Q;Rosain J;Béziat V;Manry J;Shaw E;Haljasmägi L;Peterson P;Lorenzo L;Bizien L;Trouillet-Assant S;Dobbs K;de Jesus AA;Belot A;Kallaste A;Catherinot E;Tandjaoui-Lambiotte Y;Le Pen J;Kerner G;Bigio B;Seeleuthner Y;Yang R;Bolze A;Spaan AN;Delmonte OM;Abers MS;Aiuti A;Casari G;Lampasona V;Piemonti L;Ciceri F;Bilguvar K;Lifton RP;Vasse M;Smadja DM;Migaud M;Hadjadj J;Terrier B;Duffy D;Quintana-Murci L;van de Beek D;Roussel L;Vinh DC;Tangye SG;Haerynck F;Dalmau D;Martinez-Picado J;Brodin P;Nussenzweig MC;Boisson-Dupuis S;Rodríguez-Gallego C;Vogt G;Mogensen TH;Oler AJ;Gu J;Burbelo PD;Cohen JI;Biondi A;Bettini LR;D'Angio M;Bonfanti P;Rossignol P;Mayaux J;Rieux-Laucat F;Husebye ES;Fusco F;Ursini MV;Imberti L;Sottini A;Paghera S;Quiros-Roldan E;Rossi C;Castagnoli R;Montagna D;Licari A;Marseglia GL;Duval X;Ghosn J;HGID Lab;NIAID-USUHS Immune Response to COVID Group;COVID Clinicians;COVID-STORM Clinicians;Imagine COVID Group;French COVID Cohort Study Group;Milieu Intérieur Consortium;CoV-Contact Cohort;Amsterdam UMC Covid-19 Biobank;COVID Human Genetic Effort;Tsang JS;Goldbach-Mansky R;Kisand K;Lionakis MS;Puel A;Zhang SY;Holland SM;Gorochov G;Jouanguy E;Rice CM;Cobat A;Notarangelo LD;Abel L;Su HC;Casanova JL
通讯作者：
Casanova JL
病毒逃避干扰素的十种策略。
影响因子：
30.3
作者：
García-Sastre A
通讯作者：
García-Sastre A
影响因子：
5.6
作者：
BOSSARTWHITAKER, P;CARSON, M;AIR, GM
通讯作者：
AIR, GM