Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Human isotopic ecology at its core aims to study humans as a part of their environments, as animals within an ecosystem. We are complex animals with complicated foodways and mobility patterns that are hard to address without large multifaceted data sets. As biomolecular data from archaeological remains proliferates scientists are now at the stage where we are able to collate large bodies of data and undertake complex meta‐analyses and address the complexities of human ecology and past socioenvironmental dynamics. Here we present a data set of 862 entries of new primary isotopic data (37 faunal bone, 235 human enamel carbonate with a subset of 18 for 87/86Sr, 347 human bone, 243 human bulk dentine) within a larger data set compiled from available legacy data. It contains a total of 8,910 isotopic entries from ancient humans and animals relating to diet and mobility from the late Roman period into the Middle Ages (c. 400–1200 AD). It includes carbon, nitrogen, oxygen, and strontium isotope ratios from human bone, human dentine, faunal bone, and human bioapatite from thousands of individuals, and hundreds of sites found across 26 modern countries in western Europe. Studies have previously focused on only one of these aspects, compiling data sets for one tissue, or common isotopic pairing, or focusing on a particular site or region at a smaller scale for multi‐isotope multitissue studies. This is the largest and first multitissue, multi‐isotope, multiproxy data set of its kind from premodern populations. In publishing this data set, we hope to inspire more synthetic and meta‐analytical work on human isotopic ecology. Insights from these data should lead to greater understanding of diet, agriculture, climate change, human–animal interactions, mobility/migration, and much more in the past. It is hoped that these insights into past socioenvironmental dynamics will help inform current discourse on human–environmental interactions. There are no copyright or proprietary restrictions on the data; these data papers should be cited when these data are used in publications. Additionally, we would like to hear from other researchers who use these data sets in teaching or for their own research.

Debate over migrations to Britain during the fifth and sixth centuries AD is still rampant in archaeological discourse. Stable carbon, nitrogen and oxygen isotope values from multiple tissues in individuals buried at Finglesham in Kent during the first millennium AD demonstrate not only migration of individuals to the region but also highlight community integration through foodways and refute previous models of ‘invasion’ and replacement. This case study community suggests gendered differences in mobility into early medieval England, with males more likely to be migrants from cooler regions than women. It also challenges traditional narratives of social status in these furnished cemeteries being linked to diet or migrant status with no clear correlations found between funerary treatment and isotopic signatures. This multi-tissue and multi-isotope study tracks dietary changes in this multi-origin community throughout their lives and shows that they may have even changed their diets to adapt to Christianising influences in the region.