Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD 21218, United States of America.
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States of America.
Epidemics. 2023 Sep;44:100710. doi: 10.1016/j.epidem.2023.100710. Epub 2023 Jul 22.
The spread of SARS-CoV-2, like that of many other pathogens, is governed by heterogeneity. "Superspreading," or "over-dispersion," is an important factor in transmission, yet it is hard to quantify. Estimates from contact tracing data are prone to potential biases due to the increased likelihood of detecting large clusters of cases, and may reflect variation in contact behavior more than biological heterogeneity. In contrast, the average number of secondary infections per contact is routinely estimated from household surveys, and these studies can minimize biases by testing all members of a household. However, the models used to analyze household transmission data typically assume that infectiousness and susceptibility are the same for all individuals or vary only with predetermined traits such as age. Here we develop and apply a combined forward simulation and inference method to quantify the degree of inter-individual variation in both infectiousness and susceptibility from observations of the distribution of infections in household surveys. First, analyzing simulated data, we show our method can reliably ascertain the presence, type, and amount of these heterogeneities given data from a sufficiently large sample of households. We then analyze a collection of household studies of COVID-19 from diverse settings around the world, and find strong evidence for large heterogeneity in both the infectiousness and susceptibility of individuals. Our results also provide a framework to improve the design of studies to evaluate household interventions in the presence of realistic heterogeneity between individuals.
SARS-CoV-2 的传播与许多其他病原体一样,受到异质性的控制。“超级传播”或“过度离散”是传播的一个重要因素,但很难量化。由于检测到大病例群的可能性增加,接触追踪数据的估计容易受到潜在偏差的影响,并且可能更多地反映接触行为的变化,而不是生物学异质性。相比之下,从家庭调查中通常可以估算每个接触者的平均二次感染数,这些研究通过测试家庭中的所有成员,可以最大限度地减少偏差。然而,用于分析家庭传播数据的模型通常假设所有个体的传染性和易感性相同,或者仅随预定特征(如年龄)而变化。在这里,我们开发并应用了一种组合的正向模拟和推断方法,从家庭调查中感染分布的观察结果来量化传染性和易感性的个体间变异程度。首先,通过分析模拟数据,我们表明,我们的方法可以在来自足够大的家庭样本的数据的基础上,可靠地确定这些异质性的存在、类型和数量。然后,我们分析了来自世界各地不同环境的 COVID-19 家庭研究的集合,发现个体的传染性和易感性都存在很大的异质性。我们的结果还为在个体之间存在现实异质性的情况下,改进评估家庭干预措施的研究设计提供了框架。