RAPID: Mathematical Models for Understanding Key Epidemiological Parameters and Transmission of SARS-CoV-2

由SARS-CoV-2病毒引起的新冠肺炎大流行代表了一场真正的全球紧急情况和危机，需要立即应对。目前，我们还不能很好地了解关键流行病学参数的定量估计，如从感染到感染的时间、感染的持续时间，以及这些持续时间如何受到症状严重程度的影响。我们不知道有多少传播是由无症状个人和有轻微、中度或严重症状的个人推动的。最后，我们不知道病毒载量如何与个人的传染性有关。通过构建多尺度模型，并将来自不同生物尺度的多个数据流整合到一个连贯的模型框架中，该项目将通过数学建模解决这些未知问题，从而增进我们对新冠肺炎传播的理解。然后，这种理解将被用来对干预措施的影响做出准确的预测和评估，即应对当前新冠肺炎全球大流行亟需的智力进步。该项目的结果将通过团队成员参与和维护的定期会议和联系，提交给公共卫生专业人员和政府官员，以帮助决策。例如，联合皮克定期参加CDC建模小组每周一次的会议，并每月与白宫委托的一个名为PPFST的工作组举行会议。联合PIs Hengartner和Romero-Severnson与新墨西哥州卫生部有密切联系。这项研究项目的目的是促进对SARS-CoV-2的关键流行病学参数和决定因素的基本了解，这些参数和决定因素对于更好地量化和预测SARS-CoV-2的传播动态至关重要。研究人员将在多个尺度上使用SARS-CoV-2动态的数学模型。首先，PI将开发SARS-CoV-2感染的宿主内模型，并将该模型与文献中的数据进行匹配，以估计参数，如从细胞感染到病毒释放到体液中的时间、受感染细胞产生病毒的速度、受感染细胞的寿命以及其他与传播和疾病严重程度有关的因素。另一个目的是使用该模型来预测药物治疗的有效性作为个人病毒载量的函数。其次，PI将宿主内的动态与临床因素联系起来，例如从感染到病毒脱落之间的时间，到症状的时间，在某些情况下还与死亡时间，这些对于了解传播动力学和干预效果是重要的。最终，该项目将提供一个量化框架来评估药物和非药物干预措施的有效性，例如隔离、学校关闭和其他社会距离手段。这笔赠款是使用分配给MP的冠状病毒援助、救济和经济安全(CARE)法案补充条款提供的资金发放的。这一奖励反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

The COVID-19 pandemic, caused by SARS-CoV-2, represents a true global emergency and crisis that needs to be addressed immediately. Currently we do not have a good understanding of quantitative estimates of key epidemiological parameters, such as the time from infection to becoming infectious, the duration of infectiousness, and how these durations are affected by symptom severity. We do not know how much transmission is driven by asymptomatic individuals and individuals with mild, moderate, or severe symptoms. Lastly, we do not know how the viral load relates to the infectiousness of an individual. By constructing multiscale models and integrating multiple streams of data from different biological scales into a coherent model framework, the project will address these unknowns through mathematical modeling and thus advance our understanding of COVID-19 transmission. This understanding will be then used to make precise predictions and evaluations of the impacts of interventions, i.e. much needed intellectual advancement to address the current COVID-19 global pandemic. The results of the project will be presented to public health professionals and government officials to aid decision making through regular meetings and connections that the team members participate and maintain. For example, co-PI Ke regularly participates in weekly CDC modeling group meetings and in monthly meetings with a working group commissioned by the White House called PPFST. Co-PIs Hengartner and Romero-Severnson have close connections with the New Mexico Department of Health. The PIs will ensure that the project is designed and formulated to address critical public health questions and that the results can be used by public health officials.The objective of this research project is to advance the fundamental understanding of key epidemiological parameters and determinants for SARS-CoV-2 that are essential to better quantify and predict SARS-CoV-2 transmission dynamics. The investigators will use mathematical modeling of SARS-CoV-2 dynamics across multiple scales. First, the PI will develop within-host models of SARS-CoV-2 infection and will fit the model to data from literature to estimate parameters such as the time from cell infection to release of virus into bodily fluids, the rate of viral production from infected cells, the infected cell lifespan, and other factors that link to transmission and disease severity. Another aim is to use the model to predict the effectiveness of drug therapy as a function of person's viral load. Second, the PI will tie the within-host dynamics to clinical factors, such as the time between infection and viral shedding, time to symptoms, and in some cases to time of death, which are important in understanding transmission dynamics and intervention effectiveness. Ultimately, this project will provide a quantitative framework to evaluate the effectiveness of pharmaceutical and non-pharmaceutical interventions, e.g., quarantine, school closures, and other means of social distancing.This grant is being awarded using funds made available by the Coronavirus Aid, Relief, and Economic Security (CARES) Act supplement allocated to MPS.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.