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A genome-wide association study highlights a variant in DOCK2, which is common in East Asian populations but rare in Europeans, as a host genetic risk factor for severe COVID-19.

Genetic mechanisms influencing COVID-19 susceptibility are not well understood. Here, the authors analyzed whole blood RNA-seq data of 465 Japanese individuals with COVID-19, highlighting thousands of fine-mapped variants affecting expression and splicing of genes, as well as the presence of COVID-19 severity-interaction eQTLs.

A single-cell multiomic immune cell atlas from 235 Japanese, including patients with COVID-19 and healthy individuals, linked with host genetics including germline and somatic mutation, plasma proteomics and metagenomics data reveals that immune cells are dynamically regulated in a cell state-dependent manner.

Analysis of the blood DNA virome in patients with COVID-19 and autoimmune disease associates endogenous HHV-6 (eHHV-6) and high anellovirus load with increased disease risk, most notably for systemic lupus erythematosus. eHHV-6 carriers show a distinct immune response.

SARS-CoV-2 Omicron XEC variant, a recombinant of JN.1 progeny, shows increased viral fitness and pathogenicity. Here, the authors show that the nucleocapsid mutation R204P enhances inflammation and suggest a growing role of non-spike mutations in viral evolution.

Neuronal micronuclei are transferred to microglia during the early postnatal period, which leads to altered microglial morphology and transcriptomic signatures, suggesting that these micronuclei may act as mediators that control microglial characteristics.

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.

Peripheral blood mononuclear cells from 73 Japanese patients with coronavirus disease 2019 (COVID-19) and 75 healthy controls were analyzed using single-cell transcriptomics. Combining these data with genotyping data highlights the interplay between host genetics and the immune response in modulating disease severity.

XBB.1.5 of SARS-CoV-2 is a descendant of XBB.1 and has mutations in spike and ORF8, making it more infectious to humans. Here, the authors examined in detail the differences in virological properties of the two variants.

XBB is the first recombinant, globally dominant variant of SARS-CoV-2. Here, the authors examine the variant’s origins and virological properties, showing it is the first example of SARS-CoV-2 improving its fitness through recombination.

In vitro studies in human cell lines and in vivo studies in a hamster model show that the SARS-CoV-2 Omicron variant is less pathogenic than both the Delta variant and an ancestral strain of SARS-CoV-2.

A newly discovered control system regulates the eliminations of meiosis-specific transcripts during mitosis, but allows their expression in meiosis.

A member of the vacuolar H⁺-ATPase family, ATP6V0A1 is involved in lysosomal activity. Here, the authors report that ATP6V0A1 variants identified in individuals with developmental and epileptic encephalopathy are associated with impairment of lysosomal acidification, autophagy and mTORC1 signaling, suggesting an essential role of ATP6V0A1 in brain development.

Plasma eMTBR-tau243 is a specific biomarker of tau tangles in Alzheimer’s disease and enables the detecting and tracking of Alzheimer’s clinical impairment.

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.

Genetically grafting macrocyclic peptides into the structural loops of fragment crystallizable regions can make them surrogate receptor agonists with longer half-lives in circulation and enhanced penetration of the blood–brain barrier.

Ito et al. present CoVFit, an AI model that predicts variant fitness (transmissibility) from spike protein sequences alone. They further demonstrate its utility in forecasting viral evolution via single amino acid mutations.

Using more than 100 independent iPSC lines derived from patients with Alzheimer’s disease, the authors discovered loci associated with the neuronal production of amyloid β and confirmed their influence using RNA interference.

Conventional actuators cannot exhibit high performance at cryogenic temperatures. Shunsuke Sato and colleagues demonstrated that Cu-Al-Mn shape memory alloys can provide high work output from 50 K, showing their potential for use in low-temperature technology fields.

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.

Cerebrospinal fluid measures of isoform-specific tau species from the microtubule-binding region serve as the first fluid biomarkers of primary tauopathy.

CSF MTBR-tau243 is more related to tau tangles and clinical cognitive impairment in Alzheimer’s disease than phospho-tau biomarkers, which are more related to amyloid plaques.

JN.1 lineage is a globally dominant variant of SARS-CoV-2. Here, the authors examine structural insights into the BA.2.86 and JN.1 spike dynamics to help understand the mechanisms underlying SARS-CoV-2 infection and its neutralizing-antibody evasion.

Mutations in the spike of SARS-CoV-2 can result in the escape of the neutralising antibody response but may retain susceptibility to the cellular immune response. Here the authors show the G446S mutation in the spike protein of Omicron BA.1 is associated with altered antigen presentation and potentiates activation of specific T cell immunity.

Site-specific hyperphosphorylations of tau in the cerebrospinal fluid change with disease course, and correlate with pathology and cognitive decline in dominantly inherited Alzheimer’s disease.

The dopamine D₂ receptor (D₂R) is a GPCR and an important drug target for schizophrenia treatment. Here, the authors present the crystal structure of human D₂R in complex with the antipsychotic drug spiperone, which is of interest for designing antipsychotics with improved receptor selectivity.

Appropriate processing of value information is essential for survival. Here the authors show that in mice, serotonergic activations originating from the median raphe nucleus facilitated aversion in a pathway-dependent manner, while silencing this pathway was rewarding.

Zebrafish is a popular system for studying the molecular basis of glycan-related human diseases. Here, the authors present glycomic profiles of eight zebrafish organs and establish the organ-specific expression patterns of related biosynthetic enzymes.

Poly(ADP-ribose) polymerases participate in many biological and pathological processes. Takaoka and co-workers show that the short isoform of PARP-13 (ZAPS) is selectively induced by 5'-triphosphate–modified RNA and regulates signaling mediated by the RNA helicase RIG-I.

Recent Omicron SARS-CoV-2 subvariants independently acquire 5 key Spike mutations. Here, the authors evaluate the evolutionary importance of the 5 mutations and characterize the virological properties of variant BQ.1.1 harboring all 5 mutations.

Cerebrospinal fluid (CSF) tests are used in the clinical diagnosis of Alzheimer’s disease. This study found that CSF tau phosphorylation at two sites (T217 and T205) is a better test for Alzheimer’s disease pathology than currently available tests.