ABSTRACT
The availability of millions of SARS-CoV-2 sequences in public databases such as GISAID and EMBL-EBI (UK) allows a detailed study of the evolution, genomic diversity and dynamics of a virus like never before. Here we identify novel variants and sub-types of SARS-CoV-2 by clustering sequences in adapting methods originally designed for haplotyping intra-host viral populations. We asses our results using clustering entropy -- the first time it has been used in this context. Our clustering approach reaches lower entropies compared to other methods, and we are able to boost this even further through gap filling and Monte Carlo based entropy minimization. Moreover, our method clearly identifies the well-known Alpha variant in the UK and GISAID datasets, but is also able to detect the much less represented (< 1% of the sequences) Beta (South Africa), Epsilon (California), Gamma and Zeta (Brazil) variants in the GISAID dataset. Finally, we show that each variant identified has high selective fitness, based on the growth rate of its cluster over time. This demonstrates that our clustering approach is a viable alternative for detecting even rare subtypes in very large datasets.
ABSTRACT
Colombia announced the first case of severe acute respiratory syndrome coronavirus 2 on March 6, 2020. Since then, the country has reported a total of 4,240,982 cases and 106,544 deaths as of June 30, 2021. This motivates an investigation of the SARS-CoV-2 transmission dynamics at the national and regional level using case incidence data. Mathematical models are employed to estimate the transmission potential and perform short-term forecasts of the COVID-19 epidemic trajectory in Colombia. Furthermore, geographic heterogeneity of COVID-19 in Colombia is examined along with the analysis of mobility and social media trends, showing that the increase in mobility in July 2020 and January 2021 were correlated with surges in case incidence. The estimation of national and regional reproduction numbers shows sustained disease transmission during the early phase of the pandemic, exhibiting sub-exponential growth dynamics. Moreover, most recent estimates of reproduction number are >1.0 at the national and regional levels as of May 30, 2021. Further, the 30-day ahead short-term forecasts obtained from Richards model present a sustained decline in case counts in contrast to the sub-epidemic and GLM model. Nevertheless, our spatial analysis in Colombia shows distinct variations in incidence rate patterns across different departments that can be grouped into four distinct clusters. Lastly, the correlation of social media trends and adherence to social distancing measures is observed by the fact that a spike in the number of tweets indicating the stay-at-home orders was observed in November 2020 when the case incidence had already plateaued. Author summaryAs the COVID-19 pandemic continues to spread across Colombia, studies highlighting the intensity of the pandemic become imperative for appropriate resource allocation and informing public health policies. In this study we utilize mathematical models to infer the transmission dynamics of SARS-CoV-2 at the regional and national level as well as short-term forecast the COVID-19 epidemic trajectory. Moreover, we examine the geographic heterogeneity of the COVID-19 case incidence in Colombia along with the analysis of mobility and social media trends in relation to the observed COVID-19 case incidence in the country. The estimates of reproduction numbers at the national and regional level show sustained disease transmission as of May 30, 2021. Moreover, the 30-day ahead short-term forecasts for the most recent time-period (June 1-June 30, 2021) generated from the mathematical models needs to be interpreted with caution as the Richards model point towards a sustained decline in case incidence contrary to the GLM and sub-epidemic wave model. Nevertheless, the spatial analysis in Colombia shows distinct variations in incidence rate patterns across different departments that can be grouped into four distinct clusters. Lastly, the social media and mobility trends explain the occurrence of case resurgences over the time.
ABSTRACT
Since the emergence of COVID-19, a series of non-pharmaceutical interventions (NPIs) has been implemented by governments and public health authorities world-wide to control and curb the ongoing pandemic spread. From that perspective, Belarus is one of a few countries with a relatively modern healthcare system, where much narrower NPIs have been put in place. Given the uniqueness of this Belarusian experience, the understanding its COVID-19 epidemiological dynamics is essential not only for the local assessment, but also for a better insight into the impact of different NPI strategies globally. In this work, we integrate genomic epidemiology and surveillance methods to investigate the emergence and spread of SARS-CoV-2 in the country. The observed Belarusian SARS-CoV-2 genetic diversity originated from at least eighteen separate introductions, at least five of which resulted in on-going domestic transmissions. The introduction sources represent a wide variety of regions, although the proportion of regional virus introductions and exports from/to geographical neighbors appears to be higher than for other European countries. Phylodynamic analysis indicates a moderate reduction in the effective reproductive number [R]e after the introduction of limited NPIs, with the reduction magnitude generally being lower than for countries with large-scale NPIs. On the other hand, the estimate of the Belarusian [R]e at the early epidemic stage is comparable with this number for the neighboring ex-USSR country of Ukraine, where much broader NPIs have been implemented. The actual number of cases by the end of May, 2020 was predicted to be 2-9 times higher than the detected number of cases.
ABSTRACT
The novel coronavirus SARS-CoV-2 was first detected in China in December 2019 and has rapidly spread around the globe. The World Health Organization declared COVID-19 a pandemic in March 2020 just three months after the introduction of the virus. Individual nations have implemented and enforced a variety of social distancing interventions to slow the virus spread, that had different degrees of success. Understanding the role of non-pharmaceutical interventions (NPIs) on COVID-19 transmission in different settings is highly important. While most such studies have focused on China, neighboring Asian counties, Western Europe, and North America, there is a scarcity of studies for Eastern Europe. The aim of this study is to contribute to filling this gap by analyzing the characteristics of the first months of the epidemic in Ukraine using agent-based modelling and phylodynamics. Specifically, first we studied the dynamics of COVID-19 incidence and mortality and explored the impact of epidemic NPIs. Our stochastic model suggests, that even a small delay of weeks could have increased the number of cases by up to 50%, with the potential to overwhelm hospital systems. Second, the genomic data analysis suggests that there have been multiple introductions of SARS-CoV-2 into Ukraine during the early stages of the epidemic. Our findings support the conclusion that the implemented travel restrictions may have had limited impact on the epidemic spread. Third, the basic reproduction number for the epidemic that has been estimated independently from case counts data and from genomic data suggest sustained intra-country transmissions.
ABSTRACT
Mexico has experienced one of the highest COVID-19 death rates in the world. A delayed response towards implementation of social distancing interventions until late March 2020 and a phased reopening of the country in June 2020 has facilitated sustained disease transmission in the region. Here, we systematically generate and compare 30-day ahead forecasts using previously validated growth models based on mortality trends from the Institute for Health Metrics and Evaluation for Mexico and Mexico City in near real-time. Moreover, we estimate reproduction numbers for SARS-CoV-2 based on methods that rely on genomic data as well as case incidence data. Subsequently, functional data analysis techniques are utilized to analyze the shapes of COVID-19 growth rate curves at the state level to characterize the spatial-temporal transmission patterns. The early estimates of reproduction number for Mexico were estimated between R[~]1.1-from genomic and case incidence data. Moreover, the mean estimate of R has fluctuated [~]1.0 from late July till end of September 2020. The spatial analysis characterizes the state-level dynamics of COVID-19 into four groups with distinct epidemic trajectories. We found that the sequential mortality forecasts from the GLM and Richards model predict downward trends in the number of deaths for all thirteen forecasts periods for Mexico and Mexico City. The sub-epidemic and IHME models predict more realistic stable trajectory of COVID-19 mortality trends for the last three forecast periods (09/21-10/21 - 09/28-10/27) for Mexico and Mexico City. Our findings support the view that phenomenological models are useful tools for short-term epidemic forecasting albeit forecasts need to be interpreted with caution given the dynamic implementation and lifting of social distancing measures.
ABSTRACT
Since its discovery in the Hubei province of China, the global spread of the novel coronavirus SARS-CoV-2 has resulted in millions of COVID-19 cases and hundreds of thousands of deaths. The spread throughout Asia, Europe, and the Americas has presented one of the greatest infectious disease threats in recent history and has tested the capacity of global health infrastructures. Since no effective vaccine is available, isolation techniques to prevent infection such as home quarantine and social distancing while in public have remained the cornerstone of public health interventions. While government and health officials were charged with implementing stay-at-home strategies, many of which had little guidance as to the consequences of how quickly to begin them. Moreover, as the local epidemic curves have been flattened, the same officials must wrestle with when to ease or cease such restrictions as to not impose economic turmoil. To evaluate the effects of quarantine strategies during the initial epidemic, an agent based modeling framework was created to take into account local spread based on geographic and population data with a corresponding interactive desktop and web-based application. Using the state of Massachusetts in the United States of America, we have illustrated the consequences of implementing quarantines at different time points after the initial seeding of the state with COVID-19 cases. Furthermore, we suggest that this application can be adapted to other states, small countries, or regions within a country to provide decision makers with critical information necessary to best protect human health. Author summaryIn this work we presented a local agent-based geographic model for the epidemic spread of COVID-19 with and without quarantine measures. The model is implemented as an interactive Microsoft Windows application, as a web tool online (summaries only), and the source code is freely available at GitHub. In this article, the model is presented for the state of Massachusetts (United States), but can be easily adopted to other administrative districts, areas and territories where the demographics and population characteristics of the reported cases are known. After calibration, the model predicts the morbidity and mortality of the epidemic as it spreads with different quarantine parameters, which lead to reduction of social contact probabilities between individuals. The model outputs for different quarantine start dates and durations are then summarized and compared to actual disease incidence. These summaries demonstrate the effectiveness of the early quarantine measures on the reduction of the number of new infections and deaths. The model framework can also be adopted for use in future decision making process for government and health officials as plans to cease or ease quarantines continue to evolve using the interactive application.
ABSTRACT
BackgroundThe COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is straining health systems around the world. Although the Chinese government implemented a number of severe restrictions on peoples movement in an attempt to contain its local and international spread, the virus had already reached many areas of the world in part due to its potent transmissibility and the fact that a substantial fraction of infected individuals develop little or no symptoms at all. Following its emergence, the virus started to generate sustained transmission in neighboring countries in Asia, Western Europe, Australia, Canada and the United States, and finally in South America and Africa. As the virus continues its global spread, a clear and evidence-based understanding of properties and dynamics of the global transmission network of SARS-CoV-2 is essential to design and put in place efficient and globally coordinated interventions. MethodsWe employ molecular surveillance data of SARS-CoV-2 epidemics for inference and comprehensive analysis of its global transmission network before the pandemic declaration. Our goal was to characterize the spatial-temporal transmission pathways that led to the establishment of the pandemic. We exploited a network-based approach specifically tailored to emerging outbreak settings. Specifically, it traces the accumulation of mutations in viral genomic variants via mutation trees, which are then used to infer transmission networks, revealing an up-to-date picture of the spread of SARS-CoV-2 between and within countries and geographic regions. Results and ConclusionsThe analysis suggest multiple introductions of SARS-CoV-2 into the majority of world regions by means of heterogeneous transmission pathways. The transmission network is scale-free, with a few genomic variants responsible for the majority of possible transmissions. The network structure is in line with the available temporal information represented by sample collection times and suggest the expected sampling time difference of few days between potential transmission pairs. The inferred network structural properties, transmission clusters and pathways and virus introduction routes emphasize the extent of the global epidemiological linkage and demonstrate the importance of internationally coordinated public health measures.
