Nature Medicine

BackgroundOlder age is widely considered a risk factor for post-acute sequelae of SARS-CoV-2 infection (PASC), typically attributed to immunosenescence and inflammaging. However, whether this association reflects intrinsic biological ageing or accumulated comorbidity burden remains unclear, with implications for clinical risk stratification. MethodsWe conducted a retrospective cohort study using the Precision PASC Research Cohort (P2RC) from Mass General Brigham, comprising 133,792 COVID-19 pat...

In November 2024, a highly divergent BA.3-related SARS-CoV-2 lineage, designated BA.3.2, was detected in South Africa, marking the first appearance of a BA.3-derived lineage in over two years. Phylogenetic reconstruction places BA.3.2 on an extended branch descending from ancestral BA.3, with no intermediate genomes detected, consistent with a prolonged period of unsampled or isolated evolution. Molecular clock analyses indicate accelerated divergence characteristic of a saltation event, while p...

The adoption of artificial intelligence in dermatology promises democratized access to healthcare, but model reliability depends on the quality and comprehensiveness of the data fueling these models. Despite rapid growth in publicly available dermatology images, the field lacks quantitative key performance indicators to measure whether new datasets expand clinical coverage or merely replicate what is already known. Here we present SkinMap, a multi-modal framework for the first comprehensive audi...

Strengthening in-country sequencing capacity generated 28 Lassa virus genomes from human clinical cases, expanding our knowledge of Lassa fever in Guinea. Phylogeographic analysis revealed cross-border exchange between Liberia and the NZerekore region, and a Sierra Leone introduction into the Gueckedou area. Enhanced genomic surveillance is crucial to guide future public health actions.

Background. Early identification of risk for hospitalisation is crucial to reducing public health burden. Immune and endocrine-related markers are robust indicators of disease in epidemiological studies, but their value has not been consistently established with severe disorders requiring hospitalisation. Patterning of biomarker expression through latent profile analysis (LPA), may improve predictive accuracy for clinical outcomes above individual biomarkers alone. Method. Four biomarkers (C-rea...

BACKGROUNDOn 14 August 2024, WHO Director-General declared a public health emergency of international concern (PHEIC) following a sharp increase in mpox cases linked to the emergence of monkeypox virus (MPXV) clade Ib. We characterise imported and autochthonous cases of MPXV clade I reported in the WHO European Region since August 2024. METHODSBetween 14 August 2024 and 23 November 2025, we collected key information of MPXV clade I infections reported by member states of the WHO European Region...

Why do some individuals develop mild COVID-19 while others progress to severe disease remains a central challenge in SARS-CoV-2 immunology. In this study, we leveraged the BACO Cohort - a unique historical cohort of immunologically naive, hospitalized COVID-19 patients from the first pandemic wave - to investigate early immune determinants of clinical disease trajectories. Integrating bulk RNA-seq, Olink proteomics, and systems serology, we identified two fundamentally distinct immune trajectori...

We examined whether the recent emergence of influenza A(H3N2) subclade K, associated with an unusually early influenza season in the Northern hemisphere, was accompanied by a reduction in human population immunity. Using virus neutralisation assays on pre-epidemic human sera collected in May 2025, we found evidence of moderate antigenic drift. Further, vaccines used in the 2024/2025 season induced cross-neutralising immunity. These findings provide timely insight for interpreting recent influenz...

BackgroundRapid emergence and replacement of SARS-CoV-2 variants underscore the need for early and reliable indicators of variant dominance to guide timely public health response. However, early genomic trajectories are typically short, sparse, and noisy, with strong fluctuations and substantial cross-country heterogeneity in sequencing intensity and reporting. MethodsWe develop a scalable forecasting framework that predicts whether new variants will reach high prevalence and how long they will...

Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common and life-threatening complication of chimeric antigen receptor (CAR) T-cell therapy, with early detection being critical for timely intervention and improved outcomes. Cytokines such as interleukin-6 (IL-6) are key mediators of the inflammatory cascade underlying ICANS pathogenesis, but prospective clinical evidence for their predictive value is limited. Here we quantify IL-6 levels in a prospective cohort of 40 CAR-T pat...

Background & AimsLiver cancer primarily develops in patients with chronic liver disease (CLD), yet most cases are diagnosed at an advanced stage with poor prognosis. While clinical surveillance of patients with CLD generates extensive longitudinal data, its unstructured free-text nature hinders large-scale research. To unlock this real-world evidence, we developed a scalable framework using open-source Large Language Models (LLMs) to transform unstructured clinical text into structured data. Me...

Pathology faces persistent challenges including a global shortage of specialists, uneven access to expertise, increasing diagnostic complexity, and a growing need for second-opinion consultations. While digital and telepathology platforms address parts of this problem, existing solutions often trade accessibility for structured, workflow-aware clinical integration. At the same time, multimodal medical AI shows promise for diagnostic support but raises concerns regarding transparency, automation ...

BackgroundArtemisinin-based combination therapies (ACTs) are the most widely used treatment for Plasmodium falciparum malaria. Kelch 13 mutations associated with artemisinin partial resistance (ART-R) have emerged in Sub-Saharan Africa (SSA) and are now reported in an increasing number of countries. ACT treatment failure rates are at risk of unprecedented increase. To summarise existing surveillance data and guide future surveillance, we produce modelled estimates of the spatiotemporal distribut...

Large language models (LLMs) are evolving into diagnostic co-pilots, yet current benchmarks fail to test the integrated, stepwise reasoning required in diagnostic pathology. Here, we present Pathologys Last Exam (PLE), a curated, highly detailed, text-based benchmark of 100 complex cases spanning organ systems, enriched for rare/challenging entities, plus 20 adversarial cases designed to stress-test model safety. Each case provides structured blocks (Primary, Clinical, Histopathology, IHC/Specia...

Proactive identification of systemic vulnerability for disease(s) before clinical onset in healthy individuals is an ultimate goal of preventive and precision medicine, yet current tools remain largely disease-specific and fail to quantify latent vulnerability, an integrative measure of underlying health status, for early prevention and risk-stratified intervention. To address this, we developed the Risk Score for Disease Vulnerability (RS4DV) based on 85 accessible biopsychosocial measures, whi...

AO_SCPLOWBSTRACTC_SCPLOWInfluenza A subclade K viruses caused high infection rates in the 2025/2026 Northern Hemisphere season, raising concerns about antigenic drift and reduced vaccine effectiveness. We measured antibody responses in matched human pre- and post-vaccination sera against a vaccine-like as well as subclade K isolates. Pre-existing immunity to subclade K variants was noted with seasonal influenza vaccination boosting titers two-fold against subclade K and three-fold against the va...

Acute kidney injury (AKI) and chronic kidney disease (CKD) are two interconnected clinical conditions, both defined by degree of functional impairment, but with heterogeneous clinical trajectories. Using new transcriptomic technologies, recent studies have described the cellular diversity in the healthy and injured kidney at the single cell level. Here, we used single nucleus transcriptomics to investigate the molecular diversity and commonalities in kidney biopsies from over 150 participants wi...

BackgroundInfluenza vaccination and bacterial colonization both shape immunity in the respiratory tract, yet their combined impact on the human lung mucosa remains poorly understood. Secondary bacterial pneumonia following influenza infection is a leading cause of mortality, underscoring the need to define how vaccines and microbes intersect at the airway interface. MethodsUsing the Experimental Human Pneumococcal Challenge (EHPC) model, we examined how intramuscular inactivated (TIV) and nasal...

Cutaneous leishmaniasis (CL) is a skin disease caused by Leishmania infection, for which no licensed human vaccine exists. Protective immunity is largely T cell-mediated and depends on antigen presentation by MHC molecules, yet the naturally presented epitopes during human disease remain poorly defined. To address this gap, we performed mass spectrometry-based immunopeptidomics on lesional biopsies from 27 Ethiopian CL patients spanning the full clinical spectrum. We newly identified 333 MHC-I a...

The exposome factors, such as diet, lifestyle, microbiome, chemical exposures and social exposome, shapes human health beyond genetic influences, but the mechanisms remain only partially understood. Leveraging the Area Deprivation Index (ADI) of Neighborhood Atlas, a validated measure of the US social exposome, we derive molecular insights on how adverse social exposome (ASE) may impact cardiometabolic and brain health. Using complementary metabolomics platforms, we measured blood metabolome as ...