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).

This study investigated disparities in residential exposure to carcinogenic air pollutants among Asian Americans, including Asian ancestry subgroups, in four US metro areas with high proportions of Asians, i.e., Honolulu, Los Angeles, San Francisco Bay Area, and Seattle. Generalized estimating equations adjusting for socioeconomic status, population density and clustering show that a greater proportion of Asian Americans in census tracts was associated with significantly greater health risk in all four metro areas. Intracategorical disparities were uncovered for Asian ancestry. A greater proportion Korean was positively associated with risk in four metro areas; greater proportion Chinese and Filipino were positively associated with risk in three of the four metro areas. While Asian Americans are infrequently examined in environmental justice research, these results demonstrate that Asian Americans experience substantial distributional environmental injustices in these four metro areas and that ancestry is an important dimension of intracategorical complexity.

Glucose variations have a bidirectional relationship with the sleep/wake and circadian systems in type 1 diabetes (T1D); however, the mechanisms remain unclear. The aim of this study was to describe the coupling between glucose and unstructured physical activity over 168 h in young adults with T1D. We hypothesized that there would be differences in sleep and wake characteristics and circadian variations. Glucose was measured with a continuous glucose monitoring device every 5 min and activity with a non-dominant wrist-worn actigraph in 30-s epochs over 6–14 days. There was substantial glucose and unstructured physical activity coupling during sleep and wake, along with circadian variation based on the wavelet coherence analysis. The extent to which glucose fluctuations result in disrupted sleep over longer than one week should be examined considering the harmful effects on achieving glycemic targets. Further studies are needed to delineate the respective roles of glucose production and utilization and the potential for improved meal and insulin timing to optimize glucose and sleep in this population reliant on exogenous insulin.

This article draws on two decades of media representations of HIV, ethnographic research among people living with HIV, and an analysis of global health programms in Bolivia. In doing so, we chart the evolution of media representations in relation to the global health context and the implications of these representations for people living with HIV. Our overarching argument is that media discourses on HIV in Bolivia have consistently been produced in a context of an unequal balance of power between global health bodies and local actors. This power imbalance has enabled global health bodies operating in Bolivia to maintain authority in producing local narratives about HIV, even when these narratives do not adequately capture the particularities of the Bolivian context. The mismatch between dominant global health narratives that have infiltrated the Bolivian media and ethnographic realities can have deleterious effects on people living with HIV. We draw on the concept communicative inequities to highlight how global health bodies shape dominant media narratives and the ways these dominant narratives at times misrepresent ethnographic realities. Thus, a media analysis informed by ethnographic experiences offers a unique lens for interrogating the implications of global health interventions.

In the version of this article initially published, the name of Ana Margarita Baldión-Elorza, of the SCOURGE Consortium, appeared incorrectly (as Ana María Baldion) and has now been amended in the HTML and PDF versions of the article.