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In many regions of the world, the Alpha, Beta and Gamma SARS-CoV-2 Variants of Concern (VOCs) co-circulated during 2020-21 and fueled waves of infections. During 2021, these variants were almost completely displaced by the Delta variant, causing a third wave of infections worldwide. This phenomenon of global viral lineage displacement was observed again in late 2021, when the Omicron variant disseminated globally. In this study, we use phylogenetic and phylogeographic methods to reconstruct the dispersal patterns of SARS-CoV-2 VOCs worldwide. We find that the source-sink dynamics of SARS-CoV-2 varied substantially by VOC, and identify countries that acted as global hubs of variant dissemination, while other countries became regional contributors to the export of specific variants. We demonstrate a declining role of presumed origin countries of VOCs to their global dispersal: we estimate that India contributed <15% of all global exports of Delta to other countries and South Africa <1-2% of all global Omicron exports globally. We further estimate that >80 countries had received introductions of Omicron BA.1 100 days after its inferred date of emergence, compared to just over 25 countries for the Alpha variant. This increased speed of global dissemination was associated with a rebound in air travel volume prior to Omicron emergence in addition to the higher transmissibility of Omicron relative to Alpha. Our study highlights the importance of global and regional hubs in VOC dispersal, and the speed at which highly transmissible variants disseminate through these hubs, even before their detection and characterization through genomic surveillance. HighlightsO_LIGlobal phylogenetic analysis reveals relationship between air travel and speed of dispersal of SARS-CoV-2 variants of concern (VOCs) C_LIO_LIOmicron VOC spread to 5x more countries within 100 days of its emergence compared to all other VOCs C_LIO_LIOnward transmission and dissemination of VOCs Delta and Omicron was primarily from secondary hubs rather than initial country of detection during a time of increased global air travel C_LIO_LIAnalysis highlights highly connected countries identified as major global and regional exporters of VOCs C_LI
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Up to November 2021, over 200 different SARS-CoV-2 lineages circulated in Mexico. To investigate lineage replacement dynamics, we applied a phylodynamic approach to explore the evolutionary trajectories of five dominant lineages that circulated during the first year of the local epidemic. For most lineages, peaks in sampling frequencies coincided with different epidemiological waves of infection in the country. Lineages B.1.1.222 and B.1.1.519 showed comparable dynamics, represented by clades likely originating in Mexico and persisting for over a year. Lineages B.1.1.7, P.1 and B.1.617.2 also displayed similar dynamics, characterized by multiple introduction events leading to a few successful extended local transmission chains that persisted for several months. We further explored viral movements across the country, applied within the largest clades identified (belonging to lineage B.1.617.2). Many clades were located within the south region of the country, suggesting that this area played a key role in the spread of SARS-CoV-2 in Mexico.
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BackgroundWhilst timely clinical characterisation of infections caused by novel SARS-CoV-2 variants is necessary for evidence-based policy response, individual-level data on infecting variants are typically only available for a minority of patients and settings. MethodsHere, we propose an innovative approach to study changes in COVID-19 hospital presentation and outcomes after the Omicron variant emergence using publicly available population-level data on variant relative frequency to infer SARS-CoV-2 variants likely responsible for clinical cases. We apply this method to data collected by a large international clinical consortium before and after the emergence of the Omicron variant in different countries. ResultsOur analysis, that includes more than 100,000 patients from 28 countries, suggests that in many settings patients hospitalised with Omicron variant infection less often presented with commonly reported symptoms compared to patients infected with pre-Omicron variants. Patients with COVID-19 admitted to hospital after Omicron variant emergence had lower mortality compared to patients admitted during the period when Omicron variant was responsible for only a minority of infections (odds ratio in a mixed-effects logistic regression adjusted for likely confounders, 0.67 [95% confidence interval 0.61 - 0.75]). Qualitatively similar findings were observed in sensitivity analyses with different assumptions on population-level Omicron variant relative frequencies, and in analyses using available individual-level data on infecting variant for a subset of the study population. ConclusionsAlthough clinical studies with matching viral genomic information should remain a priority, our approach combining publicly available data on variant frequency and a multi-country clinical characterisation dataset with more than 100,000 records allowed analysis of data from a wide range of settings and novel insights on real-world heterogeneity of COVID-19 presentation and clinical outcome.
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For each of the COVID-19 pandemic waves, hospitals have had to plan for deploying surge capacity and resources to manage large but transient increases in COVID-19 admissions. While a lot of effort has gone into predicting regional trends in COVID-19 cases and hospitalizations, there are far fewer successful tools for creating accurate hospital-level forecasts. At the same time, anonymized phone-collected mobility data proved to correlate well with the number of cases for the first two waves of the pandemic (spring 2020, and fall-winter 2021). In this work, we show how mobility data could bolster hospital-specific COVID-19 admission forecasts for five hospitals in Massachusetts during the initial COVID-19 surge. The high predictive capability of the model was achieved by combining anonymized, aggregated mobile device data about users contact patterns, commuting volume, and mobility range with COVID hospitalizations and test-positivity data. We conclude that mobility-informed forecasting models can increase the lead-time of accurate predictions for individual hospitals, giving managers valuable time to strategize how best to allocate resources to manage forthcoming surges.
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The Delta variant of concern of SARS-CoV-2 has spread globally causing large outbreaks and resurgences of COVID-19 cases1-3. The emergence of Delta in the UK occurred on the background of a heterogeneous landscape of immunity and relaxation of non-pharmaceutical interventions4,5. Here we analyse 52,992 Delta genomes from England in combination with 93,649 global genomes to reconstruct the emergence of Delta, and quantify its introduction to and regional dissemination across England, in the context of changing travel and social restrictions. Through analysis of human movement, contact tracing, and virus genomic data, we find that the focus of geographic expansion of Delta shifted from India to a more global pattern in early May 2021. In England, Delta lineages were introduced >1,000 times and spread nationally as non-pharmaceutical interventions were relaxed. We find that hotel quarantine for travellers from India reduced onward transmission from importations; however the transmission chains that later dominated the Delta wave in England had been already seeded before restrictions were introduced. In England, increasing inter-regional travel drove Deltas nationwide dissemination, with some cities receiving >2,000 observable lineage introductions from other regions. Subsequently, increased levels of local population mixing, not the number of importations, was associated with faster relative growth of Delta. Among US states, we find that regions that previously experienced large waves also had faster Delta growth rates, and a model including interactions between immunity and human behaviour could accurately predict the rise of Delta there. Deltas invasion dynamics depended on fine scale spatial heterogeneity in immunity and contact patterns and our findings will inform optimal spatial interventions to reduce transmission of current and future VOCs such as Omicron.
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Characterisation of SARS-CoV-2 genetic diversity through space and time can reveal trends in virus importation and domestic circulation, and permit the exploration of questions regarding the early transmission dynamics. Here we present a detailed description of SARS-CoV-2 genomic epidemiology in Ecuador, one of the hardest hit countries during the early stages of the COVID-19 pandemic. We generate and analyse 160 whole genome sequences sampled from all provinces of Ecuador in 2020. Molecular clock and phylgeographic analysis of these sequences in the context of global SARS-CoV-2 diversity enable us to identify and characterise individual transmission lineages within Ecuador, explore their spatiotemporal distributions, and consider their introduction and domestic circulation. Our results reveal a pattern of multiple international importations across the country, with apparent differences between key provinces. Transmission lineages were mostly introduced before the implementation of non-pharmaceutical interventions (NPIs), with differential degrees of persistence and national dissemination.
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Nonpharmaceutical interventions, such as contact tracing and quarantine, are currently the primary means of controlling the spread of SARS-CoV-2; however, it remains uncertain which interventions are most effective at reducing transmission at the population level. Using serial interval data from before and after the rollout of nonpharmaceutical interventions in China, we estimate that the relative frequency of presymptomatic transmission increased from 34% before the rollout to 71% afterward. The shift touward earlier transmission indicates a disproportionate reduction in transmission post-symptom onset. We estimate that, following the rollout of nonpharmaceutical interventions, transmission post-symptom onset was reduced by 82% whereas presymptomatic transmission decreased by only 16%. These findings suggest that interventions which limit opportunities for transmission in the later stages of infection, such as contact tracing and isolation, may have been particularly effective at reducing transmission of SARS-CoV-2.
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The UKs COVID-19 epidemic during early 2020 was one of worlds largest and unusually well represented by virus genomic sampling. Here we reveal the fine-scale genetic lineage structure of this epidemic through analysis of 50,887 SARS-CoV-2 genomes, including 26,181 from the UK sampled throughout the countrys first wave of infection. Using large-scale phylogenetic analyses, combined with epidemiological and travel data, we quantify the size, spatio-temporal origins and persistence of genetically-distinct UK transmission lineages. Rapid fluctuations in virus importation rates resulted in >1000 lineages; those introduced prior to national lockdown were larger and more dispersed. Lineage importation and regional lineage diversity declined after lockdown, whilst lineage elimination was size-dependent. We discuss the implications of our genetic perspective on transmission dynamics for COVID-19 epidemiology and control.
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ImportanceAccess to testing is key to a successful response to the COVID-19 pandemic. ObjectiveTo determine the geographic accessibility to SARS-CoV-2 testing sites in the United States, as quantified by travel time. DesignCross-sectional analysis of SARS-CoV-2 testing sites as of April 7, 2020 in relation to travel time. SettingUnited States COVID-19 pandemic. ParticipantsThe United States, including the 48 contiguous states and the District of Columbia. ExposuresPopulation density, percent minority, percent uninsured, and median income by county from the 2018 American Community Survey demographic data. Main OutcomeSARS-CoV-2 testing sites identified in two national databases (Carbon Health and CodersAgainstCovid), geocoded by address. Median county 1 km2 gridded friction surface of travel times, as a measure of geographic accessibility to SARS-CoV-2 testing sites. Results6,236 unique SARS-CoV-2 testing sites in 3,108 United States counties were identified. Thirty percent of the U.S. population live in a county (N = 1,920) with a median travel time over 20 minutes. This was geographically heterogeneous; 86% of the Mountain division population versus 5% of the Middle Atlantic population lived in counties with median travel times over 20 min. Generalized Linear Models showed population density, percent minority, percent uninsured and median income were predictors of median travel time to testing sites. For example, higher percent uninsured was associated with longer travel time ({beta} = 0.41 min/percent, 95% confidence interval 0.3-0.53, p = 1.2x10-12), adjusting for population density. Conclusions and RelevanceGeographic accessibility to SARS-Cov-2 testing sites is reduced in counties with lower population density and higher percent of minority and uninsured, which are also risk factors for worse healthcare access and outcomes. Geographic barriers to SARS-Cov-2 testing may exacerbate health inequalities and bias county-specific transmission estimates. Geographic accessibility should be considered when planning the location of future testing sites and interpreting epidemiological data. Key PointsO_LISARS-CoV-2 testing sites are distributed unevenly in the US geography and population. C_LIO_LIMedian county-level travel time to SARS-CoV-2 testing sites is longer in less densely populated areas, and in areas with a higher percentage of minority or uninsured populations. C_LIO_LIImproved geographic accessibility to testing sites is imperative to manage the COVID-19 pandemic in the United States. C_LI
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BackgroundThe first case of COVID-19 was detected in Brazil on February 25, 2020. We report the epidemiological, demographic, and clinical findings for confirmed COVID-19 cases during the first month of the epidemic in Brazil. MethodsIndividual-level and aggregated COVID-19 data were analysed to investigate demographic profiles, socioeconomic drivers and age-sex structure of COVID-19 tested cases. Basic reproduction numbers (R0) were investigated for Sao Paulo and Rio de Janeiro. Multivariate logistic regression analyses were used to identify symptoms associated with confirmed cases and risk factors associated with hospitalization. Laboratory diagnosis for eight respiratory viruses were obtained for 2,429 cases. FindingsBy March 25, 1,468 confirmed cases were notified in Brazil, of whom 10% (147 of 1,468) were hospitalised. Of the cases acquired locally (77{middle dot}8%), two thirds (66{middle dot}9% of 5,746) were confirmed in private laboratories. Overall, positive association between higher per capita income and COVID-19 diagnosis was identified. The median age of detected cases was 39 years (IQR 30-53). The median R0 was 2{middle dot}9 for Sao Paulo and Rio de Janeiro. Cardiovascular disease/hypertension were associated with hospitalization. Co-circulation of six respiratory viruses, including influenza A and B and human rhinovirus was detected in low levels. InterpretationSocioeconomic disparity determines access to SARS-CoV-2 testing in Brazil. The lower median age of infection and hospitalization compared to other countries is expected due to a younger population structure. Enhanced surveillance of respiratory pathogens across socioeconomic statuses is essential to better understand and halt SARS-CoV-2 transmission. FundingSao Paulo Research Foundation, Medical Research Council, Wellcome Trust and Royal Society.
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People with chronic obstructive pulmonary disease, cardiovascular disease or hypertension have a high risk of severe coronavirus disease 2019 (COVID-19). Long-term exposure to air pollution, especially PM2.5, has also been associated with COVID-19 mortality. We collated individual-level data of confirmed COVID-19 cases during the first wave of the epidemic in mainland China. We fitted a generalized linear model using city-level COVID-19 cases and severe cases as the outcome, and long-term average levels of air pollutants as the exposure. Our analysis was adjusted using several variables, including a mobile phone dataset, covering human movement from Wuhan before the travel ban and movements within each city during the time of emergency response. Other variables included census, smoking prevalence, climate, and socio-economic data from 324 cities in China. We adjusted for human mobility and socio-economic factors, and found that an increase in long-term NO2 or PM2.5 may correspond to an increase in the number of COVID-19 cases and severe infections. However, the linkage might also be affected by the confounding factor of population size because of the predefined correlation between population size and air pollution. The results are derived from a large, newly compiled and geocoded repository of population and epidemiological data relevant to COVID-19. The findings of this paper (and other previous studies that have given ambiguous results) indicate that a more definitive analysis is needed of the link between COVID-19 and air pollution.
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The COVID-19 pandemic is straining public health systems worldwide and major non-pharmaceutical interventions have been implemented to slow its spread1-4. During the initial phase of the outbreak the spread was primarily determined by human mobility5,6. Yet empirical evidence on the effect of key geographic factors on local epidemic spread is lacking7. We analyse highly-resolved spatial variables for cities in China together with case count data in order to investigate the role of climate, urbanization, and variation in interventions across China. Here we show that the epidemic intensity of COVID-19 is strongly shaped by crowding, such that epidemics in dense cities are more spread out through time, and denser cities have larger total incidence. Observed differences in epidemic intensity are well captured by a metapopulation model of COVID-19 that explicitly accounts for spatial hierarchies. Densely-populated cities worldwide may experience more prolonged epidemics. Whilst stringent interventions can shorten the time length of these local epidemics, although these may be difficult to implement in many affected settings.
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COVID-19 is caused by the SARS-CoV-2 coronavirus and was first reported in central China in December 2019. Extensive molecular surveillance in Guangdong, Chinas most populous province, during early 2020 resulted in 1,388 reported RNA positive cases from 1.6 million tests. In order to understand the molecular epidemiology and genetic diversity of SARS-CoV-2 in China we generated 53 genomes from infected individuals in Guangdong using a combination of metagenomic sequencing and tiling amplicon approaches. Combined epidemiological and phylogenetic analyses indicate multiple independent introductions to Guangdong, although phylogenetic clustering is uncertain due to low virus genetic variation early in the pandemic. Our results illustrate how the timing, size and duration of putative local transmission chains were constrained by national travel restrictions and by the provinces large-scale intensive surveillance and intervention measures. Despite these successes, COVID-19 surveillance in Guangdong is still required as the number of cases imported from other countries is increasing. HighlightsO_LI1.6 million molecular diagnostic tests identified 1,388 SARS-CoV-2 infections in Guangdong Province, China, by 19th March 2020 C_LIO_LIVirus genomes can be recovered using a variety of sequencing approaches from a range of patient samples. C_LIO_LIGenomic analyses reveal multiple virus importations into Guangdong Province, resulting in genetically distinct clusters that require careful interpretation. C_LIO_LILarge-scale epidemiological surveillance and intervention measures were effective in interrupting community transmission in Guangdong C_LI
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The ongoing COVID-19 outbreak has expanded rapidly throughout China. Major behavioral, clinical, and state interventions are underway currently to mitigate the epidemic and prevent the persistence of the virus in human populations in China and worldwide. It remains unclear how these unprecedented interventions, including travel restrictions, have affected COVID-19 spread in China. We use real-time mobility data from Wuhan and detailed case data including travel history to elucidate the role of case importation on transmission in cities across China and ascertain the impact of control measures. Early on, the spatial distribution of COVID-19 cases in China was well explained by human mobility data. Following the implementation of control measures, this correlation dropped and growth rates became negative in most locations, although shifts in the demographics of reported cases are still indicative of local chains of transmission outside Wuhan. This study shows that the drastic control measures implemented in China have substantially mitigated the spread of COVID-19.
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BackgroundThe novel coronavirus (2019-nCoV) epidemic has spread to 23 countries from China. Local cycles of transmission already occurred in 7 countries following case importation. No African country has reported cases yet. The management and control of 2019-nCoV introductions heavily relies on countrys health capacity. Here we evaluate the preparedness and vulnerability of African countries against their risk of importation of 2019-nCoV. MethodsWe used data on air travel volumes departing from airports in the infected provinces in China and directed to Africa to estimate the risk of introduction per country. We determined the countrys capacity to detect and respond to cases with two indicators: preparedness, using the WHO International Health Regulation Monitoring and Evaluation Framework; and vulnerability, with the Infectious Disease Vulnerability Index. Countries were clustered according to the Chinese regions contributing the most to their risk. FindingsCountries at the highest importation risk (Egypt, Algeria, Republic of South Africa) have moderate to high capacity to respond to outbreaks. Countries at moderate risk (Nigeria, Ethiopia, Sudan, Angola, Tanzania, Ghana, Kenya) have variable capacity and high vulnerability. Three clusters of countries are identified that share the same exposure to the risk originating from the provinces of Guangdong, Fujian, and Beijing, respectively. InterpretationSeveral countries in Africa are stepping up their preparedness to detect and cope with 2019-nCoV importations. Resources and intensified surveillance and capacity capacity should be urgently prioritized towards countries at moderate risk that may be ill-prepared to face the importation and to limit onward transmission. FundingThis study was partially supported by the ANR project DATAREDUX (ANR-19-CE46-0008-03) to VC; the EU grant MOOD (H2020-874850) to MG, CP, MK, PYB, VC.
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Respiratory illness caused by a novel coronavirus (COVID-19) appeared in China during December 2019. Attempting to contain infection, China banned travel to and from Wuhan city on 23 January and implemented a national emergency response. Here we evaluate the spread and control of the epidemic based on a unique synthesis of data including case reports, human movement and public health interventions. The Wuhan shutdown slowed the dispersal of infection to other cities by an estimated 2.91 days (95%CI: 2.54-3.29), delaying epidemic growth elsewhere in China. Other cities that implemented control measures pre-emptively reported 33.3% (11.1-44.4%) fewer cases in the first week of their outbreaks (13.0; 7.1-18.8) compared with cities that started control later (20.6; 14.5-26.8). Among interventions investigated here, the most effective were suspending intra-city public transport, closing entertainment venues and banning public gatherings. The national emergency response delayed the growth and limited the size of the COVID-19 epidemic and, by 19 February (day 50), had averted hundreds of thousands of cases across China. One sentence summaryTravel restrictions and the national emergency response delayed the growth and limited the size of the COVID-19 epidemic in China.