Quantitative Approaches to Understand Differential Immune Responses in COVID-19

2019年末出现的新型冠状病毒SARS-CoV-2是全球大流行和持续的公共卫生危机的源头。越来越多的证据表明，调控失调和高反应性的炎症反应，包括高度炎症和细胞因子风暴，是严重新冠肺炎的特殊表现。此外，自疫情开始以来，导致新冠肺炎的SARS-CoV-2病毒是从最初的来自人类传播动物病毒株的rna序列进化而来的。总体而言，感染(由原始毒株或突变毒株)后的免疫反应机制仍有待描述。在这里，我们将开发定量工具，用于询问SARS-CoV-2感染和新冠肺炎的临床表现，以区分临床上可操作的诊断标志物。这将通过学术界、产业界和医疗保健合作伙伴之间的广泛国际合作来实现，这些合作伙伴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，帮助完善实验问题和改善患者护理。最终，通过提高我们对SARS-CoV-2感染和对新型冠状病毒的免疫反应的了解，我们的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果。

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.