Potency and timing of antiviral therapy as determinants of duration of SARS-CoV-2 shedding and intensity of inflammatory response.
Potency and timing of antiviral therapy as determinants of duration of SARS-CoV-2 shedding and intensity of inflammatory response.
复制标题
抗病毒疗法的效力和时机是SARS-COV-2脱落持续时间的决定因素和炎症反应的强度。
DOI：
10.1126/sciadv.abc7112
复制
发表时间：
2020-11
期刊：
影响因子：
13.6
通讯作者：
Schiffer JT
中科院分区：
文献类型：
--
作者：
Goyal A;Cardozo-Ojeda EF;Schiffer JT
我们开发了一个数学模型来预测不同可能的COVID-19治疗方法的结果。为了应对COVID-19大流行，必须找到拯救生命的抗病毒疗法。可以进行的临床试验数量有限。我们开发了数学模型来预测多种治疗方法。我们的模型概括了治疗后的病毒动力学，并预测了三个阶段的免疫反应。用瑞德西韦、赛林克斯、中和抗体或细胞免疫疗法的模拟治疗表明，如果体内效力足够高，则快速消除病毒是可能的。在出现症状时病毒载量峰值后不久给予的治疗可能会减少脱落持续时间和免疫应答强度，但对病毒曲线下面积（AUC）影响不大，这是由早期高病毒载量驱动的。在症状前感染期间病毒高峰之前给予有效治疗可降低AUC。在病毒高峰期前给予中等效力的药物可能会出现耐药性。我们的结果支持早期治疗COVID-19，如果脱落持续时间，而不是AUC，是最能预测临床严重程度。
We developed a mathematical model to predict the outcomes of different possible COVID-19 treatments. To affect the COVID-19 pandemic, lifesaving antiviral therapies must be identified. The number of clinical trials that can be performed is limited. We developed mathematical models to project multiple therapeutic approaches. Our models recapitulate off-treatment viral dynamics and predict a three-phase immune response. Simulated treatment with remdesivir, selinexor, neutralizing antibodies, or cellular immunotherapy demonstrates that rapid viral elimination is possible if in vivo potency is sufficiently high. Therapies dosed soon after peak viral load when symptoms develop may decrease shedding duration and immune response intensity but have little effect on viral area under the curve (AUC), which is driven by high early viral loads. Potent therapy dosed before viral peak during presymptomatic infection could lower AUC. Drug resistance may emerge with a moderately potent agent dosed before viral peak. Our results support early treatment for COVID-19 if shedding duration, not AUC, is most predictive of clinical severity.
登录
查看更多内容
影响因子：
3.5
作者：
Goncalves, Antonio;Bertrand, Julie;Guedj, Jeremie
通讯作者：
Guedj, Jeremie
影响因子：
11.8
作者：
Chemaly, Roy F.;Shah, Dimpy P.;Boeckh, Michael J.
通讯作者：
Boeckh, Michael J.
影响因子：
20.3
作者：
Garzon, Ramiro;Savona, Michael;Stone, Richard
通讯作者：
Stone, Richard
COVID-19 患者支气管肺泡免疫细胞的单细胞景观。
影响因子：
82.9
作者：
Liao, Mingfeng;Liu, Yang;Zhang, Zheng
通讯作者：
Zhang, Zheng
影响因子：
12.7
作者：
Huang, KJ;Su, IJ;Lei, HY
通讯作者：
Lei, HY