qPCR 检测的横断面 Ct 分布可为社区中 COVID-19 的传播提供早期预警信号。

Cross-sectional Ct distributions from qPCR tests can provide an early warning signal for the spread of COVID-19 in communities.

机构信息

Thermo Fisher Scientific, South San Francisco, CA, United States.

Department of Chemistry and Chemical Biology, Northeastern University, Burlington, MA, United States.

出版信息

Front Public Health. 2023 Sep 29;11:1185720. doi: 10.3389/fpubh.2023.1185720. eCollection 2023.

Abstract

BACKGROUND

SARS-CoV-2 PCR testing data has been widely used for COVID-19 surveillance. Existing COVID-19 forecasting models mainly rely on case counts obtained from qPCR results, even though the binary PCR results provide a limited picture of the pandemic trajectory. Most forecasting models have failed to accurately predict the COVID-19 waves before they occur. Recently a model utilizing cross-sectional population cycle threshold (Ct-the number of cycles required for the fluorescent signal to cross the background threshold) values obtained from PCR tests (Ct-based model) was developed to overcome the limitations of using only binary PCR results. In this study, we aimed to improve on COVID-19 forecasting models using features derived from the Ct-based model, to detect epidemic waves earlier than case-based trajectories.

METHODS

PCR data was collected weekly at Northeastern University (NU) between August 2020 and January 2022. Campus and county epidemic trajectories were generated from case counts. A novel forecasting approach was developed by enhancing a recent deep learning model with Ct-based features and applied in Suffolk County and NU campus. For this, cross-sectional Ct values from PCR data were used to generate Ct-based epidemic trajectories, including effective reproductive rate (Rt) and incidence. The improvement in forecasting performance was compared using absolute errors and residual squared errors with respect to actual observed cases at the 7-day and 14-day forecasting horizons. The model was also tested prospectively over the period January 2022 to April 2022.

RESULTS

Rt curves estimated from the Ct-based model indicated epidemic waves 12 to 14 days earlier than Rt curves from NU campus and Suffolk County cases, with a correlation of 0.57. Enhancing the forecasting models with Ct-based information significantly decreased absolute error (decrease of 49.4 and 221.5 for the 7 and 14-day forecasting horizons) and residual squared error (40.6 and 217.1 for the 7 and 14-day forecasting horizons) compared to the original model without Ct features.

CONCLUSION

Ct-based epidemic trajectories can herald an earlier signal for impending epidemic waves in the community and forecast transmission peaks. Moreover, COVID-19 forecasting models can be enhanced using these Ct features to improve their forecasting accuracy. In this study, we make the case that public health agencies should publish Ct values along with the binary positive/negative PCR results. Early and accurate forecasting of epidemic waves can inform public health policies and countermeasures which can mitigate spread.

摘要

背景

SARS-CoV-2 PCR 检测数据已被广泛用于 COVID-19 监测。现有的 COVID-19 预测模型主要依赖于从 qPCR 结果获得的病例数,尽管二进制 PCR 结果提供了疫情轨迹的有限图景。大多数预测模型都未能在疫情发生之前准确预测 COVID-19 浪潮。最近,开发了一种利用从 PCR 测试中获得的横截面人群循环阈值 (Ct-荧光信号越过背景阈值所需的循环数) 值的模型 (基于 Ct 的模型),以克服仅使用二进制 PCR 结果的局限性。在这项研究中,我们旨在使用基于 Ct 的模型的衍生特征改进 COVID-19 预测模型,以便比基于病例的轨迹更早地检测到疫情浪潮。

方法

2020 年 8 月至 2022 年 1 月,在东北大学 (NU) 每周收集 PCR 数据。从病例数生成校园和县疫情轨迹。通过增强最近的深度学习模型与基于 Ct 的特征,并应用于萨福克县和 NU 校园,开发了一种新的预测方法。为此,使用来自 PCR 数据的横截面 Ct 值生成基于 Ct 的疫情轨迹,包括有效繁殖率 (Rt) 和发病率。使用 7 天和 14 天预测期的实际观察病例的绝对误差和残差平方误差来比较预测性能的提高。该模型还在 2022 年 1 月至 2022 年 4 月期间进行了前瞻性测试。

结果

基于 Ct 的模型估计的 Rt 曲线比 NU 校园和萨福克县病例的 Rt 曲线早 12 到 14 天指示疫情浪潮,相关性为 0.57。与没有 Ct 特征的原始模型相比,使用 Ct 信息增强预测模型显著降低了绝对误差 (7 天和 14 天预测期的降幅分别为 49.4 和 221.5) 和残差平方误差 (7 天和 14 天预测期的降幅分别为 40.6 和 217.1)。

结论

基于 Ct 的疫情轨迹可以为社区即将到来的疫情浪潮发出更早的信号,并预测传播高峰。此外,可以使用这些 Ct 特征增强 COVID-19 预测模型,以提高其预测准确性。在这项研究中,我们认为公共卫生机构应该公布 Ct 值以及二进制阳性/阴性 PCR 结果。对疫情浪潮的早期和准确预测可以为公共卫生政策和对策提供信息,从而减轻传播。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c29e/10570742/2d0f8c49daab/fpubh-11-1185720-g0001.jpg

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