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An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in 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).

TCR-TRANSLATE, a deep learning framework adapting machine translation to immune design, demonstrates the successful generation of a functional T cell receptor sequence for a cancer epitope from the target sequence alone.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

An Omicron investigator, a Mars explorer and an AI ethics pioneer are some of the people behind the year’s big research stories.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Steam generation from solar energy is currently inefficient because of costly high optical concentration and large heat losses involved. Ghasemi et al. develop an efficient approach with internal efficiency up to 85% at low water temperature using a carbon-based material with a double-layer structure.

High ambient temperatures are associated with reduced sleep duration and quality, and increased obstructive sleep apnoea (OSA). Here the authors quantify the effect of 24 h ambient temperature on nightly OSA severity and report projected in losses of healthy life years and workplace productivity due to OSA in scenarios of projected temperatures ≥1.8° C above pre-industrial levels by 2100.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

The oceanic heat transport is traditionally believed to be determined by the large-scale ocean circulation. New findings suggest that the energetic mesoscale processes in the Iceland Basin profoundly modulate the oceanic heat transport variability on time scales from intra-seasonal to interannual.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Modeling analysis from the Global Dietary Database estimated that 70% of new global cases of type 2 diabetes are attributable to suboptimal intake of 11 dietary factors, with substantial differences in dietary risks across world regions and nations.

Different functional variants in ADH1B (and elsewhere) in Europeans and Africans strongly affect risk for alcohol dependence. Dependence only partly genetically correlates with consumption, with strong correlations to other psychiatric disorders.

Archived patient-derived tissue specimens play a central role in understanding disease and developing therapies. Here authors present DropBlot, a microfluidic platform that integrates droplet-based antigen retrieval with single-cell immunoblotting, enabling efficient protein retrieval and proteoform separation from fixed human specimens.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

This study presents a predictive equation for total energy expenditure derived from doubly labelled water measurements. Applying this equation to two large datasets (the National Diet and Nutrition Survey and National Health and Nutrition Examination Survey) shows that the misreporting of total energy intake is greater than 50%, with important implications for macronutrient availability.

Cities are renowned for catalyzing human interactions, but their effects on urban species are less clear. This Perspective argues for such a focus, and proposes a framework for studying interactions between urban species.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Mosaic chromosomal alterations (mCAs) in peripheral blood leukocytes are associated with an increased risk of malignancy. Here, the authors use genome-wide genotyping array data to investigate the prevalence of mCAs in sub-Saharan African children with versus those without Burkitt lymphoma.

A genome-wide association study performed in 1,126,563 individuals identifies seven new loci associated with Alzheimer’s disease and implicates microglia and immune cells in late-onset disease.

Mutations in the RyR1 channel cause core myopathies. Here the authors show that ER stress and the unfolded protein response underlie the pathology caused by a common RyR1 channel mutation, and show that treatment with a chemical chaperone restores muscle function in mice.

Vaccination is effective in protecting from COVID-19. Here the authors report immune responses and breakthrough infections in twice-vaccinated patients receiving anti-TNF treatments for inflammatory bowel disease, and find dampened vaccine responses that implicate the need of adapted vaccination schedules for these patients.

Low total energy expenditure (TEE) has been a hypothesized risk factor for weight gain, but longitudinal repeatability of TEE is incompletely understood. Here the authors report that TEE is repeatable for adults, but not for children, and increases in TEE (adjusted for fat-free mass, fat mass, age and sex) are not associated with body composition changes in short-term longitudinal analyses.

This study finds that sST2 is a disease-causing factor for Alzheimer’s disease. Higher sST2 levels impair microglial Aβ clearance in APOE4⁺ female individuals. A genetic variant, rs1921622, is associated with a reduction in sST2 level and protects against AD in APOE4⁺ female individuals.

Lechat et al. examines the severity of obstructive sleep apnea (OSA) using a large global dataset of users of an FDA-validated under-the-mattress sensor. These results demonstrate a seasonal component in the severity of OSA and show that this effect is partially explained by ambient temperature and variations in sleep duration.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

Radio and X-ray observations of the jet emission from M81^∗, the nearest low-luminosity supermassive black hole, reveal a knot structure. The knot is unexpected, as models generally assume a continuous and compact jet.

Ruth Loos and colleagues report results of a large genome-wide association study for body mass index. They identify 18 new loci associated with this trait, some of which map near key hypothalamic regulators of energy balance.

The impact of the DART spacecraft on the asteroid Dimorphos is reported and reconstructed, demonstrating that kinetic impactor technology is a viable technique to potentially defend Earth from asteroids.

A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.

Flow cytometry allows high-throughput analysis of multiple proteins in individual cells, but relies on availability of antibodies. Here Porichis et al.report a sensitive method for multi-parameter flow cytometric and imaging detection of proteins together with mRNA or miRNA at the single-cell level.

A chemical screen identified BET bromodomain inhibitors as promoters of keratinocyte regenerative function and skin wound healing. Specifically, low-dose transient treatment with BET inhibitors imposes an activated, migratory state in keratinocytes.

Results from a phase 3, double-blind, randomized, placebo-controlled trial demonstrate that MDMA-assisted therapy is safe and effective in treating severe post-traumatic stress disorder.

Cecilia Lindgren and colleagues report results of a large-scale genome-wide association study for waist-to-hip ratio, a measure of body fat distribution. They identify 13 new loci associated with this trait, several of which show stronger effects in women than in men.

Erik Ingelsson and colleagues report a large-scale genome-wide meta-analysis for associations to the extremes of anthropometric traits, including body mass index, height, waist-to-hip ratio and clinical obesity. They identify four loci newly associated with height and seven loci newly associated with clinical obesity and find overlap in the genetic structure and distribution of variants identified for these extremes of the trait distributions and for the general population.

RNA-sequencing analysis of cells in the human cortex enabled identification of diverse cell types, revealing well-conserved architecture and homologous cell types as well as extensive differences when compared with datasets covering the analogous region of the mouse brain.