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In a prospective study enrolling 1,222 patients from 22 emergency departments, a device using a machine-learning-based signature of blood mRNAs demonstrated clinically acceptable performance to diagnose bacterial and viral infections and to predict the all-cause need for critical care interventions within 7 days, with benchmark to established biomarkers and risk scores.

Joelle Pineau is leading an effort to encourage artificial-intelligence researchers to open up their code.

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).

Using data from the CoVPN 3008 study, the authors show that the neutralizing antibody correlate of risk holds in people living with HIV. However, the nAb correlate was weaker and shorter-lived in a vaccine-immunity versus hybrid-immunity population.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

A report from the first 2,000 newborns enrolled in the Early Check program, which offered genome screening covering 198 genes associated with early-onset diseases, shows the feasibility and potential clinical utility of the approach, leading to 28 true positive results.

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.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

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.

Hypoimmune gene editing in human pluripotent stem cells (hPSCs) provides a promising platform for cellular therapies. Here, the authors report that CRISPR mediated deletion of ICAM-1 in hPSC-derived grafts reduces immune cell adhesion, dampens T cell activation, and protects against immune rejection.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Lipid particles loaded with RNA coding for tumour-unspecific antigens can enhance early responses of type-I interferons, mediating the success of immune checkpoint inhibitors as well as epitope spreading.

Severe febrile illnesses in children may be various in presentation and aetiology but involve immune dysfunction amenable to immunomodulation. Here, the authors identify shared neutrophil and T cell dysfunction and a distinct interferon signature in critically ill children with severe febrile illness.

Clinical management of COVID-19 in resource-poor settings has distinct challenges and detailed patient characterisation is needed. Here, the authors describe the clinical and immunological profiles of patients at a hospital in Malawi with confirmed and suspected COVID-19.

To evaluate the effects of implementing the WHO Labour Care Guide on cesarean section rates, as compared to routine intrapartum care, a pilot trial conducted in India generated preliminary evidence around the effectiveness of the strategy that can inform larger definitive trials.

Pearse et al. use whole genome sequencing to describe the antigenic and overall diversity of 169 Escherichia coli isolates causing invasive infections in neonates in a single hospital in Malawi. High levels of O-antigen diversity are found, highlighting the difficulty of developing a vaccine for this patient population.

Antibiotic-resistant bacteria are an urgent threat to human health. Here, Roberts et al. characterise and monitor an ongoing hospital outbreak of carbapenemase-producing Enterobacter hormaechei by integrating several technologies for whole-genome sequencing and shotgun metagenomics.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

Analysis of bronchoalveolar lavage fluid samples from patients with SARS-CoV-2-induced respiratory failure suggests that SARS-CoV-2 infects alveolar macrophages to cause release of T cell chemoattractants, thereby inducing local inflammatory cytokine release and further T cell activation, ultimately resulting in a positive feedback loop that drives alveolar inflammation.

Swanton and colleagues present a clonal expression signature, ORACLE, which, in combination with clinicopathological and molecular risk factors, can predict survival of patients with lung adenocarcinoma, and they prospectively validate its prognostic value.

A clinical review of all pediatric deaths in England from March 2020 to February 2021 attributes 25 deaths to SARS-CoV-2 infection and identifies risk factors to guide interventions.

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.

Lymphocyte development is regulated by Ikaros transcription factors. Georgopoulos and colleagues show that Ikaros tethers the nucleosome-remodeling factor Mi-2β and restrains its ability to act at nonlymphoid gene sites.

Scientific disagreements are not just a matter of using different methods or having conflicting data. Sulik et al. surveyed psychological scientists and found that disagreements are also associated with differences in researchers’ cognitive traits.

Here, Brotherton and colleagues sequence 39 mitochondrial genomes from ancient human remains. They track population changes across Central Europe and find that the foundations of the European mitochondrial DNA pool were formed during the Neolithic rather than the post-glacial period.

The influence of pregnancy on Long COVID is not well understood. Here, the authors use electronic health record data from the United States to compare the incidence of Long COVID in females after infection in pregnancy with matched non-pregnant females of reproductive age.

Mitochondrial electron transport chain activity provides ATP, generates superoxide, regulates apoptosis and provides the biosynthetic building blocks for growing cells. Here Steinert et al. genetically dissect these functions and find that, in the absence of mitochondrial complex III function, acute stimulation results in CD8⁺ T cell exhaustion and that mitochondrial complex III reactive oxygen species are required for establishment of naive and memory populations.

Maternal and perinatal morbidity and mortality remain high in Malawi, partially due to gaps in the coverage and quality of health services. Here the authors develop an individual-based simulation model of maternal and perinatal health and healthcare in Malawi, situated in the Thanzi La Onse ‘whole health system, all-disease’ framework, and apply it to estimate the impact of current and improved coverage and quality of maternity services on health in Malawi between 2023 and 2030.

Solid organ transplant recipients are at increased risk of infectious disease and have unique molecular pathophysiology. Here the authors use host-microbe profiling to assess SARS-CoV-2 infection and immunity in solid organ transplant recipients, showing enhanced viral abundance, impaired clearance, and increased expression of innate immunity genes.

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.

Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.