Routes of importation and spatial dynamics of SARS-CoV-2 variants during localised interventions in Chile (preprint)

South America suffered large SARS-CoV-2 epidemics between 2020 and 2022 caused by multiple variants of interest and concern, some causing substantial morbidity and mortality. However, their transmission dynamics are poorly characterised. The epidemic situation in Chile enables us to investigate differences in the distribution and spread of variants Alpha, Gamma, Lambda, Mu and Delta. Chile implemented non-pharmaceutical interventions and an integrated genomic and epidemiological surveillance system that included airport and community surveillance to track SARS-CoV-2 variants. Here we combine viral genomic data and anonymised human mobility data from mobile phones to characterise the routes of importation of different variants into Chile, the relative contributions of airport-based importations to viral diversity versus land border crossings and test the impact of the mobility network on the diffusion of viral lineages within the country. We find that Alpha, Lambda and Mu were identified in Chile via airport surveillance six, four and five weeks ahead of their detection via community surveillance, respectively. Further, some variants that originated in South America were imported into Chile via land rather than international air travel, most notably Gamma. Different variants exhibited similar trends of viral dissemination throughout the country following their importation, and we show that the mobility network predicts the time of arrival of imported lineages to different Chilean comunas. Higher stringency of local NPIs was also associated with fewer domestic viral importations. Our results show how genomic surveillance combined with high resolution mobility data can help predict the multi-scale geographic expansion of emerging infectious diseases. Significance statementGlobal preparedness for pandemic threats requires an understanding of the global variations of spatiotemporal transmission dynamics. Regional differences are important because the local context sets the conditions for the unfolding of local epidemics, which in turn affect transmission dynamics at a broader scale. Knowledge gaps from the SARS-CoV-2 pandemic remain for regions like South America, where distinct sets of viral variants emerged and spread from late 2020 onwards, and where changes in human behaviour resulted in epidemics which differed from those observed in other regions. Our interdisciplinary analysis of the SARS-CoV-2 epidemic in Chile provides insights into the spatiotemporal trends of viral diffusion in the region which shed light on the drivers that can influence future epidemic waves and pandemics.

COVID-19 pandemic re-shaped the global dispersal of seasonal influenza viruses (preprint)

Understanding how the global dispersal patterns of seasonal influenza viruses were perturbed during and after the COVID-19 pandemic is needed to inform influenza intervention and vaccination strategies in the post-pandemic period. Although global human mobility has been identified as a key driver of influenza dispersal1, alongside climatic and evolutionary factors2,3, the impact of international travel restrictions on global influenza transmission and recovery remains unknown. Here we combine molecular, epidemiological, climatic, and international travel data within a phylodynamic framework to show that, despite human mobility remaining the principal driver of global influenza virus dissemination, the pandemics onset led to a shift in the international population structure and migration network of seasonal influenza lineages. We find that South Asia and Africa played important roles as exporters and phylogenetic trunk locations of influenza in 2020 and 2021, and we highlight the association between population movement, antigenic drift and persistence during the intensive non-pharmaceutical interventions (NPIs) phase. The influenza B/Yamagata lineage disappeared in a context of reduced relative genetic diversity, moderate lineage turnover, and lower positive selection pressure. Our results demonstrate that mobility perturbations reshaped the global dispersal dynamics of influenza viruses, with potential implications for vaccine design and genomic surveillance programmes. As the risk of future pandemics persists, our study provides an opportunity to assess the impact of NPIs during the pandemic on respiratory infectious diseases beyond the interplay between SARS-CoV-2 and influenza viruses.

Understanding COVID-19 testing behaviour in England through a sociodemographic lens (preprint)

BackgroundUnderstanding underlying mechanisms of heterogeneity in test-seeking and reporting behaviour can help to protect the vulnerable and guide equity-driven interventions. Using COVID-19 testing data for England and data from community prevalence surveillance surveys (REACT-1 and ONS-CIS) from October 2020 to March 2022, we investigated the relationship between sociodemographic factors and testing behaviours in England. MethodsWe used mass testing data for lateral flow device (LFD; data for 290 million tests performed and reported) and polymerase chain reaction (PCR) (data for 107 million tests performed and returned from the laboratory) tests made available for the general public, provided by date, self-reported age and ethnicity at lower tier local authority (LTLA) level. Using a mechanistic causal model to debias the PCR testing data, we obtained estimates of weekly SARS-CoV-2 prevalence by self-reported ethnic groups and age groups for LTLAs in England. This approach to debiasing the PCR (or LFD) testing data also estimated a testing bias parameter defined as the odds of testing in infected versus not infected individuals, which would be close to zero if the likelihood of test seeking (or seeking and reporting) was the same regardless of infection status. Using confirmatory PCR data, we estimated false positivity rates, sensitivity, specificity, and the rate of decline in detection probability by PCR by sociodemographic groups. We also estimated the daily incidence allowing us to determine the fraction of cases captured by the testing programme. FindingsFrom March 2021 onwards, individuals in the most deprived regions reported approximately half as many LFD tests per-capita than those in the least deprived areas (Median ratio [Inter quartile range, IQR]: 0{middle dot}50 [0{middle dot}44, 0{middle dot}54]). During October 2020 - June 2021, PCR testing patterns were in the opposite direction (Median ratio [IQR]: 1{middle dot}8 [1{middle dot}7, 1{middle dot}9]). Infection prevalences in Asian or Asian British communities were considerably higher than those of other ethnic groups during the Alpha and Omicron BA.1 waves. Our estimates indicate that the England COVID-19 testing program detected 26% - 40% of all cases (including asymptomatic cases) over the study period with no consistent differences by deprivation levels or ethnic groups. PCR testing biases were generally higher than for LFDs, which was in line with the general policy of symptomatic and asymptomatic use of these tests. During the invasion phases of the Delta and Omicron variants of concern, the PCR testing bias in the most deprived populations was roughly double (ratio: 2{middle dot}2 and 2{middle dot}7 respectively) that in the least. We also determined that ethnic minorities and older individuals were less likely to use confirmatory PCR tests through most of the pandemic and that there was possibly a longer delay in reporting a positive LFD test in the Black populations. InterpretationDifferences in testing behaviours across sociodemographic groups may be reflective of the relatively higher costs of self-isolation to vulnerable populations, differences in test accessibility, digital literacy, and differing perception about the utility of tests and risks posed by infection. Our work shows how mass testing data can be used in conjunction with surveillance surveys to identify gaps in the uptake of public health interventions at fine scale levels and by sociodemographic groups. It provides a framework for monitoring local interventions and yields valuable lessons for policy makers in ensuring an equitable response to future pandemics. FundingUK Health Security Agency.

Genomic assessment of invasion dynamics of SARS-CoV-2 Omicron BA.1 (preprint)

SARS-CoV-2 variants of concern (VOCs) arise against the backdrop of increasingly heterogeneous human connectivity and population immunity. Through a large-scale phylodynamic analysis of 115,622 Omicron genomes, we identified >6,000 independent introductions of the antigenically distinct virus into England and reconstructed the dispersal history of resulting local transmission. Travel restrictions on southern Africa did not reduce BA.1 importation intensity as secondary hubs became major exporters. We explored potential drivers of BA.1 spread across England and discovered an early period during which viral lineage movements mainly occurred between larger cities, followed by a multi-focal spatial expansion shaped by shorter distance mobility patterns. We also found evidence that disease incidence impacted human commuting behaviours around major travel hubs. Our results offer a detailed characterisation of processes that drive the invasion of an emerging VOC across multiple spatial scales and provide unique insights on the interplay between disease spread and human mobility.

Context-specific emergence and growth of the SARS-CoV-2 Delta variant (preprint)

The Delta variant of concern of SARS-CoV-2 has spread globally causing large outbreaks and resurgences of COVID-19 cases. The emergence of Delta in the UK occurred on the background of a heterogeneous landscape of immunity and relaxation of non-pharmaceutical interventions. 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 Delta's 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. Delta's 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.

Context-specific emergence and growth of the SARS-CoV-2 Delta variant (preprint)

The Delta variant of concern of SARS-CoV-2 has spread globally causing large outbreaks and resurgences of COVID-19 cases. The emergence of Delta in the UK occurred on the background of a heterogeneous landscape of immunity and relaxation of non-pharmaceutical interventions. 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 Delta's 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. Delta’s 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.

The costs of keeping schools open during the COVID-19 pandemic (preprint)

There is a trade-off between restrictions on the education sector and other economic sectors in the control of SARS-CoV-2 transmission. Here we integrate a dynamic model of SARS-CoV-2 transmission with a 63-sector economic model reflecting sectoral heterogeneity in transmission and economic interdependence between sectors. We identify control strategies which optimize economic production while keeping schools and universities operational, and constraining infections such that emergency hospital capacity is not exceeded. We estimate an economic gain of between £163bn (24%) and £205bn (31%) for the United Kingdom compared to a blanket lockdown of non-essential activities over six months, depending on hospital capacity. Sectors identified as priorities for closures are contact-intensive, produce few crucial inputs for other sectors and/or are less economically productive. Partial closures over some months are required for retail trade, hospitality, accommodation, creative activities, arts, entertainment, and personal services including hairdressing and beauty treatments under most scenarios.

Modelling the impact of COVID-19-related control programme interruptions on progress towards the WHO 2030 target for soil-transmitted helminths (preprint)

Background On the 1st of April 2020, the World Health Organization (WHO) recommended an interruption of all neglected tropical disease control programmes, including soil-transmitted helminths (STH), in response to the COVID-19 pandemic. This paper investigates the impact of this disruption on the achieved progress towards the WHO 2030 target for STH. Methods We used two stochastic individual-based models to simulate the impact of missing one or more preventive chemotherapy (PC) rounds in different endemicity settings. We also investigate the extent to which the impact can be lessened by mitigation strategies, such as semi-annual or community-wide PC. Results Both models show that even without a mitigation strategy, control programmes will catch up by 2030. The catch-up time is limited to a maximum of 4.5 years after the interruption. Mitigations strategies may reduce this catch-up time by up to two years and can even increase the probability of achieving the 2030 target. Conclusions Though a PC interruption will only temporarily impact the progress towards the WHO 2030 target, programmes are encouraged to restart as soon as possible to minimise the impact on morbidity. The implementation of suitable mitigation strategies can turn the interruption into an opportunity to accelerate the progress toward reaching the target.