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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).

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.

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.

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.

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.

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.

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.

In this Consensus Statement, the authors describe the details of the evolution of the risk-based treatment of favourable-histology Wilms tumour (FHWT) and outline the rationale for the new risk stratification that will be used in the now open Children’s Oncology Group therapeutic trial for FHWT, AREN2231.

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.

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

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.

A comprehensive single-cell RNA sequencing study delineates cell-type-specific transcriptomic changes in the brain associated with normal ageing that will inform the investigation into functional changes and the interaction of ageing and disease.

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.

An integrated analysis of de novo and inherited coding variants in 42,607 individuals with autism spectrum disorder identifies 60 risk genes of which five have not previously been associated with neurodevelopmental disorders.

Although immune checkpoint blockade is a standard treatment for patients with malignant mesothelioma, only a minority of patients exhibit radiological response. In a phase II clinical trial (MIST4) investigating the efficacy, safety and molecular correlates of response following treatment with atezolizumab and bevacizumab, the authors demonstrate that the gut microbiota may modulate responsiveness to treatment.

AmpG is an MFS importer of bacterial cell wall fragments. Here, authors present a cryoEM structure and supporting mutagenesis to illuminate AmpG’s essential role in bacterial fitness and derepression of broad-spectrum β-lactam antibiotic resistance.

The affected cellular populations during Alzheimer’s disease progression remain understudied. Here the authors use a cohort of 84 donors, quantitative neuropathology and multimodal datasets from the BRAIN Initiative. Their pseudoprogression analysis revealed two disease phases.

Estimates from the Global Dietary Database indicated that 2.2 million new type 2 diabetes and 1.2 million new cardiovascular disease cases were attributable to sugar-sweetened beverages worldwide in 2020, with the highest burdens in sub-Saharan Africa, Latin America and the Caribbean.

Combined patch clamp recording, biocytin staining and single-cell RNA-sequencing of human neurocortical neurons shows an expansion of glutamatergic neuron types relative to mouse that characterizes the greater complexity of the human neocortex.

Circulating tumour DNA profiling in early-stage non-small-cell lung cancer can be used to track single-nucleotide variants in plasma to predict lung cancer relapse and identify tumour subclones involved in the metastatic process.

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

Markov, Ren, Senkow and colleagues report that in patients with severe SARS-CoV-2 pneumonia, alveolar T cell interferon responses targeting structural SARS-CoV-2 proteins characterized patients who recovered, whereas responses against nonstructural proteins and activation of NF-κB were associated with poor outcomes.

Segal and colleagues identify a population of immature neutrophils as having regenerative properties on injured neurons and being capable of inducing axon regeneration. These findings suggest potential strategies for restoring lost neurological functions in central nervous system disorders.

Two doses of the coronavirus disease 2019 vaccine ChAdOx1 nCoV-19 boost antibody responses and functions in phase 1/2 trial participants.

This Resource describes data, code and tools developed for the Human Reference Atlas and the Human BioMolecular Atlas Program for building and navigating a multiscale human atlas.

 A transcriptomic cell-type atlas of the whole adult mouse brain with ~5,300 clusters built from single-cell and spatial transcriptomic datasets with more than eight million cells reveals remarkable cell type diversity across the brain and unique cell type characteristics of different brain regions. 

TSPO PET imaging is widely used to quantify microglial activation. Here, the authors show that TSPO expression increases in activated rodent but not human microglia, implying that in humans TSPO informs on microglial density rather than activation status.

As phase 1 of the Earth Microbiome Project, analysis of 16S ribosomal RNA sequences from more than 27,000 environmental samples delivers a global picture of the basic structure and drivers of microbial distribution.

The immune response to SARS-CoV-2 infection is variable but has been linked to prognosis and the development of severe immunopathology. Here the authors assess a range of immune parameters in both peripheral blood and respiratory samples, providing a comparative assessment of the immune response between these compartments and their potential impact on immune-pathogenesis.

More than 1 in 10 babies born in the UK are suspected of having an infection. Here the authors show that newborn babies with signs of infection (raised C-Reactive Protein levels) have exaggerated leg reflexes and pain-related brain activity following a heel prick blood test, suggesting they may be more sensitive to pain.

Comparison of intermittent fasting plus early time-restricted eating (iTRE) to calorie restriction, as well as standard care, in adults at risk of type 2 diabetes in a three-arm randomized controlled study demonstrated that iTRE was associated with greater improvements in postprandial glucose metabolism at 6 months.

Compared to other apes, humans live longer, reproduce faster and have larger brains; here, total energy expenditure is studied in humans and all species of great ape, and is shown to be significantly higher in humans, demonstrating that the human lineage has experienced an energy-boosting acceleration in metabolic rate.

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.

Dietary quality is reported at the global, regional and national level across 185 countries. Though diet quality increased modestly since 1990 at the global level, in South Asia and Sub-Saharan Africa it did not improve. In some regions, children’s dietary quality is lower than that of adults.

The engagement of immunological memory is a key component to the protective anti-SARS-CoV-2 B and T cell responses. Here the authors assess the B and T cells of a cohort of UK healthcare workers in response to infection and longitudinally track the compartment showing distinct trajectories following early priming.

A large, open dataset containing parallel recordings from six visual cortical and two thalamic areas of the mouse brain is presented, from which the relative timing of activity in response to visual stimuli and behaviour is used to construct a hierarchy scheme that corresponds to anatomical connectivity data.

In this immunological ancillary study of the PREVAC trial, the authors show that approved Ebola virus vaccines induce memory T-cell responses that persist during the five year follow-up after initial vaccination.

Human populations in the southern Africa interior were collecting non-utilitarian objects at around 105,000 years ago, suggesting that the development of this innovative behaviour did not depend on exploiting coastal resources.

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.

Here, using amplicon sequencing and metabolomics in a large multi-country cohort, the authors find that adiposity-related microbiota differences differ between low-to-middle-income compared to high-income countries.

Obtaining data on antimicrobial resistance (AMR) from healthy human populations is difficult. Here, Hendriksen et al. use metagenomic analysis to obtain AMR data from untreated sewage from 79 sites in 60 countries, finding correlations with socio-economic, health and environmental factors.