Coronavirus disease 2019 (COVID-19) research agenda for healthcare epidemiology

This SHEA white paper identifies knowledge gaps and challenges in healthcare epidemiology research related to coronavirus disease 2019 (COVID-19) with a focus on core principles of healthcare epidemiology. These gaps, revealed during the worst phases of the COVID-19 pandemic, are described in 10 sections: epidemiology, outbreak investigation, surveillance, isolation precaution practices, personal protective equipment (PPE), environmental contamination and disinfection, drug and supply shortages, antimicrobial stewardship, healthcare personnel (HCP) occupational safety, and return to work policies. Each section highlights three critical healthcare epidemiology research questions with detailed description provided in supplementary materials. This research agenda calls for translational studies from laboratory-based basic science research to well-designed, large-scale studies and health outcomes research. Research gaps and challenges related to nursing homes and social disparities are included. Collaborations across various disciplines, expertise and across diverse geographic locations will be critical

100 ancient genomes show repeated population turnovers in Neolithic Denmark.

Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales <sup>1-4</sup> . However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution <sup>5-7</sup> . Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet ( <sup>13</sup> C and <sup>15</sup> N content), mobility ( <sup>87</sup> Sr/ <sup>86</sup> Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use

Population genomics of post-glacial western Eurasia.

Western Eurasia witnessed several large-scale human migrations during the Holocene <sup>1-5</sup> . Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes-mainly from the Mesolithic and Neolithic periods-from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a 'great divide' genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 BP, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 BP, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a 'Neolithic steppe' cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations