Evolution of disease transmission rate during the course of SARS-COV-2: Patterns and determinants Jie Zhu UNSW Sydney https://orcid.org/0000-0002-1863-9262 Blanca Gallego ( [email protected] ) UNSW Sydney Research Article Keywords: Public Health Intervention, Stochastic Model, Epidemic Modelling Posted Date: April 7th, 2021 DOI: https://doi.org/10.21203/rs.3.rs-44647/v2 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Version of Record: A version of this preprint was published on May 26th, 2021. See the published version at https://doi.org/10.1038/s41598-021-90347-8. Evolution of disease transmission during the course of SARS-COV-2: patterns and determinants Jie Zhu, Blanca Gallego∗ Centre for Big Data Research in Health, UNSW Sydney, Sydney, 2052, NSW, Australia Abstract Background This has been the first time in recent history when extreme measures that have deep and wide impact on our economic and social systems, such as lock downs and border closings, have been adopted at a global scale. These measures have been taken in response to the severe acute respiratory syndrome coronavirus SARS-CoV-2 pandemic, declared a Public Health Emergency of International Concern on 30 January 2020. Epidemic models are being used by governments across the world to inform social distancing and other public health strategies to reduce the spread of the virus. These models, which vary widely in their complexity, simulate interventions by manipulating model parameters that control social mixing, healthcare provision and other behavioral and environmental processes of disease transmission and recovery. The validity of these parameters is challenged by the uncertainty of the impact on disease transmission from socio-economic factors and public health interventions. Although sensitivity of the models to small variations in parameters are often carried out, the forecasting accuracy of these models is rarely investigated during an outbreak. Methods We fitted a stochastic transmission model on reported cases, recoveries and deaths associated with the infection of SARS-CoV-2 across 101 countries that had adopted at least one social-distancing policy by 15 May 2020. The dy- namics of disease transmission was represented in terms of the daily effective reproduction number (Rt). Countries were grouped according to their initial temporal Rt patterns using a hierarchical clustering algorithm. We then com- puted the time lagged cross correlation among the daily number of policies implemented (policy volume), the daily effective reproduction number, and the daily incidence counts for each country. Finally, we provided forecasts of incidence counts up to 30-days from the time of prediction for each country repeated over 230 daily rolling windows from 15 May to 31 Dec 2020. The forecasting accuracy of the model when Rt is updated every time a new prediction is made was compared with the accuracy using a static Rt. Findings We identified 5 groups of countries with distinct transmission patterns during the first 6 months of the pandemic. Early adoption of social distancing measures and a shorter gap between any two interventions were associated with a reduction on the duration of outbreaks (with correlation coefficients of -0.26 and 0.24 respectively). Sustained social distancing appeared to play a role in the prevention of the second transmission peak. By 15 May 2020, the average of the median Rt across examined countries had reduced from its peak of 20.5 (17.79, 23.20) to 1.3 (0.94, 1.74). The time lagged cross correlation analysis revealed that increased policy volume was associated with lower future Rt (the negative correlation was minimized when Rt lagged the policy volume by 75 days), while a lower Rt was associated with lower future policy volume (the positive correlation was maximized when Rt led by 102 days). Rt led the daily incidence counts by 78 days, with lower incidence counts being associated with lower future policy volume (the positive correlation was maximized when counts led the volume by 135 days). On the other hand, higher policy volume was not associated with lower incidence counts within a lag of up to 180 days. The outbreak prediction accuracy of the stochastic transmission model using dynamically updated Rt produced an average AUROC of 0.72 (0.708, 0.723) compared to 0.56 (0.555, 0.568) when Rt was kept constant. Prediction 1 accuracy declined with forecasting time. Interpretation Understanding the evolution of the daily effective reproduction number during an epidemic is an important comple- mentary piece of information to reported daily counts, recoveries and deaths. This is because Rt provides an early signal of the efficacy of containment measures. Using updated Rt values produces significantly better predictions of future outbreaks. Our results found a substantial variation in the effect of early public health interventions on the evolution of Rt over time and across countries, which could not be explained solely by the timing and number of the adopted interventions. This suggests that further knowledge about the idiosyncrasy of the implementation and effectiveness thereof is required. Although sustained containment measures have successfully lowered growth rate of disease transmission, more than half of the studied countries failed to maintain an effective reproduction number close to or below 1. This resulted in continued growth in reported cases. 1 Introduction Mathematical and computational models of disease outbreaks are used to generate knowledge about the biological, behavioral and environmental processes of disease transmission, as well as to forecast disease progression. Public health responders rely on insights provided by these models to guide disease control strategies. 1 As an example, in mid March 2020, the British government changed its SARS-CoV-2 response policy following a brief on simulation results from Ferguson et al. 2, which indicated an unacceptable forecasted number of deaths in the absence of more stringent control measures. Different models have been applied to model the spatial and temporal dynamics of SARS-CoV-2 (see the review study 3). They range from simple deterministic population-based models 4–6, that assume uniform mixing, to complex agent-based models 2,7 in which individuals defined by different attributes related to their susceptibility, infectiousness and social interactions transmit the pathogen to each other given rise to heterogeneous transmission patterns. Irrespective of their complexity, the accuracy of these models is constrained by the validity of the epidemiological parameters that underpin them. For example, the model parameters controlling the risk of infection together with the social contact between infectious and susceptible individuals determine the transmission rate, which in turns influences the peak and duration of the epidemics. By manipulating these parameters, modelers can represent the impact of public health measures such as social distancing (lowering the contact rate) or wearing protective masks (lowering the risk of infection). This study evaluates the effectiveness of initial public health interventions globally by estimating the effective repro- duction number (the expected number of secondary infections resulting from an infectious individual) on a daily basis and highlights the importance of using updated reproduction numbers for outbreak forecast. In section 2, we describe the methods. In section 3, we first present the patterns of initial public health interventions and effective reproduction numbers for a fixed temporal window across countries. Then we look into temporal patterns of number of public health interventions, effective reproduction number and incidence counts using a time lagged cross correlation analy- sis. Lastly, future outbreaks are predicted to illustrate how the currency of epidemiological parameters can influence the forecasting of expected infection counts. We end with a discussion. ∗Corresponding author. Email addresses: [email protected] (Jie Zhu), [email protected] (Blanca Gallego) 2 2 Method 2.1 Data Sources By 15 May 2020, there were 188 countries with recorded incidence of the infection of SARS-COV-2 and 101 of them had implemented at least one public health intervention to contain the spread of the virus and had at least one death 8. We modeled the transmission dynamics of SARS-COV-2 between 22 Jan to 15 May 2020 via fitting a stochastic SEIRD model 9 (illustrated in Figure 1) to three available time series: 1) Daily number of incident cases, 2) Daily number of deaths, and 3) Daily number of recoveries, as recorded, for each country, by the Johns Hopkins Coronavirus Resource Center 10. Figure 1. Simulation model structure. The population is divided into the following five classes: susceptible, exposed (non-infectious and asymptomatic), infectious (asymptomatic and symptomatic), removed (i.e., isolated, recovered, or otherwise non-infectious) and dead. The reported data is modeled with four classes: observed positive tests, reported infections, removed and deaths. To monitor public health interventions, we captured government stringent policies using the Oxford Covid-19 gov- ernment response tracker 8, which contains 17 policies organized into three groups: containment and closure policies, economic policies and health system policies. We explored 12 of these policies, namely those that have a more imme- diate and direct impact on individual’s lifestyle and well-being.