Infecting large portions of the global population, seasonal influenza is a major burden on societies around the globe. While the global source sink dynamics of the different seasonal influenza viruses have been studied intensively, its local spread remains less clear. In order to improve our understanding of how influenza is transmitted on a city scale, we collected an extremely densely sampled set of influenza sequences alongside patient metadata. To do so, we sequenced influenza viruses isolated from patients of two different hospitals, as well as private practitioners in Basel, Switzerland during the 2016/2017 influenza season. The genetic sequences reveal that repeated introductions into the city drove the influenza season. We then reconstruct how the effective reproduction number changed over the course of the season. While we did not find that transmission dynamics in Basel correlate with humidity or school closures, we did find some evidence that it may positively correlated with temperature. Alongside the genetic sequence data that allows us to see how individual cases are connected, we gathered patient information, such as the age or household status. Zooming into the local transmission outbreaks suggests that the elderly were to a large extent infected within their own transmission network. In the remaining transmission network, our analyses suggest that school-aged children likely play a more central role than pre-school aged children. These patterns will be valuable to plan interventions combating the spread of respiratory diseases within cities given that similar patterns are observed for other influenza seasons and cities.

IntroductionUrban transmission patterns of influenza viruses are complex and poorly understood, and multiple factors may play a critical role in modifying transmission. Whole genome sequencing (WGS) allows the description of patient-to-patient transmissions at highest resolution. The aim of this study is to explore urban transmission patterns of influenza viruses in high detail by combining geographical, epidemiological and immunological data with WGS data.Methods and analysisThe study is performed at the University Hospital Basel, University Children’s Hospital Basel and a network of paediatricians and family doctors in the Canton of Basel-City, Switzerland. The retrospective study part includes an analysis of PCR-confirmed influenza cases from 2013 to 2018. The prospective study parts include (1) a household survey regarding influenza-like illness (ILI) and vaccination against influenza during the 2015/2016 season; (2) an analysis of influenza viruses collected during the 2016/2017 season using WGS—viral genomic sequences are compared with determine genetic relatedness and transmissions; and (3) measurement of influenza-specific antibody titres against all vaccinated and circulated strains during the 2016/2017 season from healthy individuals, allowing to monitor herd immunity across urban quarters. Survey data and PCR-confirmed cases are linked to data from the Statistics Office of the Canton Basel-City and visualised using geo-information system mapping. WGS data will be analysed in the context of patient epidemiological data using phylodynamic analyses, and the obtained herd immunity for each quarter. Profound knowledge on the key geographical, epidemiological and immunological factors influencing urban influenza transmission will help to develop effective counter measurements.Ethics and disseminationThe study is registered and approved by the regional ethics committee as an observational study (EKNZ project ID 2015–363 and 2016–01735). It is planned to present the results at conferences and publish the data in scientific journals.Trial registration numberNCT03010007.

Infecting large portions of the global population, seasonal influenza is a major burden on societies around the globe. While the global source sink dynamics of the different seasonal influenza viruses have been studied intensively, it's local spread remains less clear. In order to improve our understanding of how influenza is transmitted on a city scale, we collected an extremely densely sampled set of influenza sequences alongside patient metadata. To do so, we sequenced influenza viruses isolated from patients of two different hospitals, as well as private practitioners in Basel, Switzerland during the 2016/2017 influenza season. The genetic sequences reveal that repeated introductions into the city drove the influenza season. We then reconstruct how the effective reproduction number changed over the course of the season. We find trends in transmission dynamics correlated positively with trends in temperature, but not relative humidity nor school holidays. Alongside the genetic sequence data that allows us to see how individual cases are connected, we gathered patient information, such as the age or household status. Zooming into the local transmission outbreaks suggests that the April 26, 2020 1/23 Author summaryAs shown with the current SARS-CoV-2 pandemic, respiratory diseases can quickly spread around the globe. While it can be hugely important to understand how diseases spread around the globe, local spread is most often the main driver of novel infections of respiratory diseases such as SARS-CoV-2 or influenza. We here use genetic sequence data alongside patient information to better understand what the drives the local spread of influenza by looking at the 2016/2017 influenza season in Basel, Switzerland as an example. The genetic sequence data allows us to reconstruct the how the transmission dynamics changed over the course of the season, which we correlate to changes, but not humidity or school holidays. Additionally, the genetic sequence data allows us to see how individual cases are connected. Using patient information, such as age and household status our analyses suggest that the elderly mainly transmit within their own transmission network. Additionally, they suggest that school aged children, but not pre-school aged children are important drivers of the local spread of influenza. 12Phylogenetics allows us to see how individual cases are epidemiologically connected. 13 This is done by reconstructing the evolutionary relationship between temporally spaced 14 samples of genetic sequence data, isolated from different infected individuals. The 15 resulting phylogenetic tree displays how samples are related to each other, and branch 16 lengths in calendar time display the elapsed time. The phylogenetic tree can therefore 17 be interpreted as an approximation of the transmission chain of the sampled cases. Such 18 a view on part of the influenza transmission chain allows to further quantify the 19 epidemiological dynamics which gave rise to the observed phylogenetic tree using 20 phylodynamic methods [...

162/150) 39 40With two-thirds of the global population projected to be living in urban areas by 2050, 41 understanding the transmission patterns of viral pathogens within cities is crucial for effective 42 prevention strategies. Here, in unprecedented spatial resolution, we analysed the socioeconomic 43 determinants of influenza transmission in a European city. We combined geographical and 44 epidemiological data with whole genome sequencing of influenza viruses at the scale of urban 45 quarters and statistical blocks, the smallest geographic subdivisions within a city. We observed 46 annually re-occurring geographic clusters of influenza incidences, mainly associated with net Introduction: 54Transmission of influenza is influenced by extensive but poorly understood interactions between 55 various viral, host and environmental factors 1-3 . Influenza may serve as a model for pandemic 56 threats including the most recent COVID-19 pandemic. Whole viral genome sequencing has 57 enabled reconstruction of phylogenetic relatedness at high resolution. Using these approaches, 58the interactions and dynamics of influenza transmission events have been described across a 59 range of scales: globally 4-6 , across continents 1,7 , in university campuses 8 , or within households 9-60 12 . With two-thirds of the global population projected to be living in urban areas by 2050, 61 understanding the transmission patterns of influenza within cities is crucial for effective prevention 62 strategies and may help to prepare for pandemic threats. Previous work identified cities as 63 containing critical chains of transmission outside of peak climatic conditions (Dalziel, B. D. et al 64 Science 2019), but the resolution to look at these critical intra-city transmission chains in detail 65 has until now been lacking. Very few studies have explored transmission events and dynamics of 66 influenza viruses at the scale of a city 13-17 . Cities are heterogeneous with remarkably different 67 neighbourhoods based on the socioeconomic position of the individuals living there. 68Consequently, a high spatial resolution of the urban space and built environment is crucial to fully 69 understanding the impact of factors linked to health and disease 18,19 . 71In this study we combine epidemiologic, geographical and demographical factors at the 72 unprecedented resolution of urban quarters (i.e. neighbourhood/area) and statistical blocks (i.e. 73city block/street) levels, the smallest statistical enumeration areas within a city. Basel, 74Switzerland, serving as our model city, we explored the local patterns of influenza distribution and 75 transmission from 2013 to 2018. Basel has urban quarters that differ substantially in 76 socioeconomic indicators and housing structure. By using information at the level of statistical 77 blocks, we were able to construct a detailed picture of influenza transmission within the city. We 78 visualized kernel density estimates of influenza cases (reflecting the clustering of cases), a 79 fundamental data smoothing me...