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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.

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.

A genome-wide study by the Long COVID Host Genetics Initiative identifies an association between the FOXP4 locus and long COVID, implicating altered lung function in its pathophysiology.

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.

Human lens clarity and function depends on well-organized cell junctions. Here, the authors used MicroED to reveal the 3.5 Å structure of MP20, showing that MP20 tetramers form adhesive junctions essential for maintaining lens transparency

Over half the world’s rivers dry periodically, yet little is known about the biological communities in dry riverbeds. This study examines biodiversity across 84 non-perennial rivers in 19 countries using DNA metabarcoding. It finds that nutrient availability, climate and biotic interactions influence the biodiversity of these dry environments.

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

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.

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.

Bacterial cultures experiencing changes in environmental conditions accumulate mutator strains, presumably to enhance their capability for adaptive evolution. The presence of bacterial viruses is demonstrated to have a similar effect, as during co-evolution of Pseudomonas fluorescens and its lytic DNA phage, bacterial mutation rates significantly increase, resulting in a higher probability of phage extinction.

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.

The rapid rise in brightness of a tidal disruption event is attributed to the destruction of a main sequence star by a black hole of intermediate mass in a dwarf galaxy. Such events are rare, and non-accreting intermediate-mass black holes are challenging to find.

Many genetic variants have been associated with human traits, but the mechanism is often unknown. Here, the authors integrate local and distal genetic associations with multi-omics datasets to provide a roadmap to understand the underlying mechanisms of GWAS variants on complex traits.

Mechanisms explaining the milder clinical syndrome that is observed in children with SARS-CoV-2 infection.

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

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.

Developmental disorders (DDs) are more prevalent in males, thought to be due to X-linked genetic variation. Here, the authors investigate the burden of X-linked coding variants in 11,044 DD patients, showing that this contributes to ~6% of both male and female cases and therefore does not solely explain male bias in DDs.

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.

Chromodomain Helicase DNA-binding (CHD) proteins have been implicated in neurodevelopmental processes. Here, the authors identify missense variants in CHD3 that disturb its chromatin remodeling activities and cause a neurodevelopmental disorder with macrocephaly and speech and language impairment.

Clinical multi-omics data are integrated and analyzed using a generative deep-learning model.

The efficacy of carbapenem antibiotics can be compromised by metallo-β-lactamases, but a high-throughput screen followed by optimization has now enabled the discovery of indole-2-carboxylates (InCs) as potent broad-spectrum metallo-β-lactamase inhibitors. The results highlight the potential of InC–carbapenem combinations for clinical use as well as mechanism-guided approaches to combatting globally disseminated antibiotic resistant mechanisms.

By integrating healthcare and exome-sequencing data from parent–offspring trios of patients with developmental disorders, 28 genes that had not previously been associated with developmental disorders were identified.

The authors of this Case Study demonstrate the substantial impact of molecular genetic testing in the improvement of diagnostics and patient treatment on the basis of the case of a 17-year-old patient who was diagnosed as having type 1 diabetes mellitus in early infancy, but after reassessment was found to have neonatal diabetes mellitus owing to a Kir6.2 mutation.

A prespecified secondary endpoint from the TriMaster study demonstrates that after trying three different classes of diabetes medications most patients preferentially selected the drug that was associated with the best glycemic control on an individual level.

Using a randomized three-way crossover design and stratification approaches based on obesity and renal function in people with type 2 diabetes, the TriMaster study demonstrated that patients with obesity were more likely to have greater glycemic control with pioglitazone (a thiazolidinedione) than with sitagliptin (a DPP4 inhibitor) and that patients with eGFR 60–90 ml/min/1.73 m² were more likely to achieve lower HbA1c levels on sitagliptin than on canagliflozin (an SGLT2 inhibitor).

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

Whole-exome analysis of individuals with developmental disorders shows that de novo mutations can equally cause loss or altered protein function, but that most mutations causing altered protein function have not yet been described.

This Brain Somatic Mosaicism Network analysis of 283 cases of malformations of cortical development identifies 69 candidate and known genes in 76 patients. Single-nucleus RNA sequencing and mouse modeling implicate radial glia and daughter excitatory neurons.

A phase I dose-escalation trial of GD2-CAR T cells in children and young adults with diffuse midline gliomas to assess the feasibility of manufacturing, safety and tolerability, and to preliminarily assess efficacy.

Typhoid toxin is not essential for the pathogenesis of typhoid fever in healthy humans challenged with Salmonella Typhi.

The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

A single dose of the ChAdOx1 nCoV-19 vaccine elicits antibodies and cytokine-producing T cells that might help control or prevent SARS-CoV-2 infection.

Grieger, Takele, Vesco, et al. perform a systematic review and meta-analysis of gestational weight gain interventions. Findings indicate lifestyle interventions that reduce excessive gestational weight gain provide greater benefits for women with a normal BMI and higher HDL cholesterol levels at the initiation of interventions.