Quantitative Approaches to Understand Differential Immune Responses in COVID-19

2019年底出现的新型冠状病毒SARS-CoV-2是全球大流行和持续公共卫生危机的根源。越来越多的证据表明，失调和过度反应的炎症反应，包括过度炎症和细胞因子风暴，是严重COVID-19的特殊表现。此外，自大流行开始以来，引起COVID-19的SARS-CoV-2病毒已从其来自人类传播动物病毒株的原始RNA序列进化而来。总的来说，感染后的免疫反应机制（由原始或突变株）仍有待描述。在这里，我们将开发定量工具，我们可以询问SARS-CoV-2感染和COVID-19临床表现，以区分临床上可操作的诊断标志物。这将通过学术，工业和医疗保健合作伙伴之间的广泛国际合作来实现，他们将共同开发数学和计算平台，其结果将立即转化为临床前和临床环境，帮助完善实验问题并改善患者护理。最终，通过提高我们对SARS-CoV-2感染和新型冠状病毒免疫反应的理解，我们的研究结果将使候选疗法的搜索和临床前决策过程合理化，并有助于减少临床试验失败和改善患者结局。

The novel coronavirus SARS-CoV-2 that emerged in late 2019 is the source of a global pandemic and ongoing public health crisis. Mounting evidence points to dysregulated and hyper-reactive inflammatory responses, including hyperinflammation and cytokine storms, as particular presentations in severe COVID-19. Further, since the start of the pandemic, the SARS-CoV-2 virus causing COVID-19 has evolved from its original RNA sequence that came from human transmission of an animal viral strain. Overall, the mechanisms of the immune response after infection (by the original or a mutated strain) remain to be delineated. Here we will develop quantitative tools with which we can interrogate SARS-CoV-2 infection and COVID-19 clinical manifestation to distinguish clinically-actionable diagnostic markers. This will be accomplished through a broad, international collaboration between academic, industrial, and health care partners who will work together to develop mathematical and computational platforms whose results will be immediately translated into pre-clinical and clinical settings, aiding to refine experimental questions and improve patient care. Ultimately, by improving our understanding of SARS-CoV-2 infection and immune responses to novel coronavirus, our results will rationalize the search for candidate therapies and the pre-clinical decision making process, and contribute to reducing clinical trial failures and bettering patient outcomes.