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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).

Krisai et al. compare brain structure and cognitive function in elderly patients with and without atrial fibrillation using brain MRI and cognitive testing. They find that atrial fibrillation is associated with more brain lesions and lower cognitive function, but the cognitive impairment occurs primarily through direct effects of the arrhythmia rather than through brain damage.

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.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

¹³⁴Ce and ¹³⁴La have great potential as companion diagnostic isotopes for radiotherapeutics labelled with α-emitting ²²⁵Ac and ²²⁷Th. Now, by controlling the Ce^III/Ce^IV redox couple, the large-scale production, purification and characterization of ¹³⁴Ce- and ¹³⁴La-based radiolabels has been achieved and their use for in vivo positron emission tomography is demonstrated.

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.

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.

Hundreds of genetic loci associated with age at menopause, combined with experimental evidence in mice, highlight mechanisms of reproductive ageing across the lifespan.

The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease.

Stepwise evolution of invasive Salmonella Typhimurium in Africa is defined using genotypic and phenotypic analyses of isolates collected over a 50-yr period.

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 impact of antiparasitic treatment on local tissue responses in the case of chronic Chagas disease (caused by Trypanosoma cruzi infection) is not well understood. Authors provide insight into clinical treatment failure and drivers of post-infectious conditions.

Sampling the viromes of vertebrates, arthropods and plants on an island ecosystem shows that viral transmission between species is strongly affected by phylogeny but less affected by predator–prey relationships and that generalist viruses pose the greatest zoonotic risk.

Radionuclide pairs 44Sc/47Sc and 86Y/90Y possess great promise in the development of theranostic agents, but realizing the full potential of these isotopes necessitates improving rare-earth chelation chemistry. Here the authors show that a hydroxypyridinone-based ligand is a promising candidate for applications in this arena.

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

Defective DNA interstrand crosslink repair in Fanconi anaemia drives extensive genomic rearrangements, thereby substantially increasing the risk of cancer development.

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.

An examination of motor cortex in humans, marmosets and mice reveals a generally conserved cellular makeup that is likely to extend to many mammalian species, but also differences in gene expression, DNA methylation and chromatin state that lead to species-dependent specializations.

The microbiota promotes resistance to respiratory infection through unclear mechanisms. Here, the authors identify members of the gut and upper airway microbiota that protect against respiratory infection by Streptococcus pneumoniae and Klebsiella pneumoniae by activating GM-CSF signaling.

Strontium isotope analysis can be applied to animal and plant tissues to help determine their provenance. Here, the authors generate a strontium isoscape of sub-Saharan Africa using data from 2266 environmental samples and demonstrate its efficacy by tracing the African roots of individuals from historic slavery contexts.

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.

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.

In this study, the authors report that a bat influenza A (H9N2) virus shows receptor binding features similar to avian influenza viruses, efficiently infects ex-vivo human respiratory cells and replicates in the lungs of mice and upper respiratory tract of ferrets following airborne transmission.

One reason for the high failure rate of experimental cancer therapies is that mouse tumor models do not accurately predict the behavior of human cancers. Zhou et al. provide more realistic models by generating chimeric mice bearing drug-inducible, tissue-specific oncogenes.

Transcriptomic and proteomic profiling of blood samples from individuals with COVID-19 reveals immune cell and hematopoietic progenitor cell alterations that are differentially associated with disease severity.

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.

Sex differences in fasting glucose and insulin have been identified, but the genetic loci underlying these differences have not. Here, the authors perform a meta-analysis of genome-wide association studies to detect sex-specific and sex-dimorphic loci associated with fasting glucose and insulin.

A study of SARS-CoV-2 variants examining their transmission, infectivity, and potential resistance to therapies provides insights into the biology of the Delta variant and its role in the global pandemic.

Colorectal cancer cells can acquire resistance to MEK inhibition due to BRAF or KRAS amplification. Here, the authors show that while MEK inhibitor withdrawal in BRAF mutant cells restores sensitivity to the inhibitor through the loss of BRAF amplification mediated by a p57-dependent mechanism, drug withdrawal from KRAS mutant cells does not restore sensitivity but results in EMT and chemoresistance.

Changes in the microenvironment of the aged lung relative to younger lung tissue can lead to the reactivation of dormant melanoma cells through a mechanism that involves a decrease in WNT5A and AXL signalling and an increase in MERTK.

Efforts to treat heart failure with antioxidants have failed. Here, authors reveal a robust sex-dependent endogenous defense against oxidative damage and demonstrate antioxidative treatment’s efficacy solely in subjects with inadequate redox capacity.

Variably methylated intracisternal A particle (VM-IAP) retrotransposons are stable across the murine lifespan. VM-IAP retrotransposons are unaffected by maternal exposure to the endocrine disruptor bisphenol A, an obesogenic diet or methyl donor supplementation.

The spike protein of the Omicron variant of SARS-CoV-2 has a higher affinity for ACE2 than Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic and vaccine-elicited neutralizing antibodies.

A critical period for social reward learning in mice, which closes at maturity, can be reopened by MDMA-mediated upregulation of oxytocin-dependent plasticity.

Neuraminidase inhibitors offer a line of defence against flu infections, but resistance can occur even in the absence of prior exposure. Here Wan et al. describe the mode of action of CD6, a monoclonal antibody that protects against a common influenza strain, as a new therapeutic intervention model.

Authenticity is promoted by cultural norms, institutions and folk wisdom, but there is disagreement about what exactly authenticity is. In this Review, Sedikides and Schlegel describe major conceptualizations of the subjective experience of authenticity and discuss its relevance for psychological functioning.

Dysregulation of ribonucleoprotein complex granules, previously implicated in neuromuscular disease, can drive pathogenesis in a genetic form of dilated cardiomyopathy, as shown in gene-edited pigs and patient-derived cardiomyocytes.

Individuals over eighty years of age are less likely to mount a good immune response against SARS-CoV-2 (measured by neutralization titres) after the first dose of the BNT162b2 mRNA vaccine, but achieve good neutralization after the second dose.