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...

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.

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...

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...

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...

BackgroundThe hyperpolymorphic nature and structural complexity of the human leukocyte antigen (HLA) genomic region present challenges for accurate and scalable typing across diverse sample types. While wholegenome sequencing (WGS) offers the opportunity to infer HLA genotypes without targeted enrichment, systematic benchmarks across sequencing platforms, biospecimens and coverage levels remain limited. ResultsWe assembled a multi-platform resource of WGS datasets derived from short-read (Illum...

Immune imprinting, also known as immune history, is a core aspect of adaptive immunity that influences antibody responses to future antigen exposures. Nevertheless, the impact of sequential flavivirus vaccinations on epitope targeting and antibody activity in humans remains incompletely understood. This question is particularly important in regions where the inactivated Japanese encephalitis virus (JEV) vaccines and the live-attenuated dengue virus (DENV) vaccines are used, as both have been ass...

An H3N2 variant, named subclade K, continues to circulate widely during the 2025-2026 influenza season. This virus possesses a hemagglutinin (HA) protein that has eleven substitutions relative to the HA of the Northern Hemisphere 2025-2026 H3N2 vaccine strain. Many of these substitutions are in epitopes in well-characterized HA antigenic sites. Despite this, interim vaccine effectiveness studies indicate that the 2025-2026 influenza vaccine provides moderate protection against H3N2 subclade K in...

Clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) viruses continue to expand geographically and across mammalian hosts, raising concern about pandemic potential. The degree and specificity of pre-existing immunity in humans are key determinants of this risk. We analyzed hemagglutinin (HA)-and neuraminidase (NA)-specific antibody responses in 300 sera collected from adults in New York City. While HA directed binding antibodies to clade 2.3.4.4b H5 were low and hemagglutination-inhibiting a...

BackgroundTuberculosis (TB) and HIV co-infection cause profound immune dysregulation. Understanding how these infections alter immune cell distribution across systemic and tissue compartments is critical for improving therapeutic and vaccine strategies. MethodsFlow cytometry was used to quantify CD4 and CD8 T cells, B cells, and tissue-resident memory (TRM) T and B cells in peripheral blood mononuclear cells (PBMCs), lung tissue, bronchoalveolar lavage (BAL), spleen, and lung-draining hilar lym...

ObjectiveThis study investigates the prevalence of human pegivirus (HPgV) in SARS-CoV-2-positive patients within the context of viral co-infections that may modulate COVID-19 outcomes and assesses whether HPgV co-infection is associated with COVID-19 severity. HPgV is a widely circulating but rarely monitored human virus with documented immunomodulatory effects in other viral infections, including HIV and Ebola. While HPgV prevalence is low in the general U.S. population (1-2%), it rises markedl...

BackgroundStrikingly low allocation of SARS-CoV-2 vaccine to the African Continent limits its capacity to control transmission. Characterizing the trajectory of vaccination efforts and their impact on the expected burden of SARS-CoV-2 will help planning vaccine delivery strategies, and public health interventions more broadly. As the burden is strongly age-dependent, this requires an understanding of the age-structured dynamics of susceptible individuals, accounting for the combined effects of v...

Newly emerging influenza virus strains pose a constant threat as they encounter a population lacking neutralizing antibodies against the new strain. However, cross-reactive non-neutralizing antibodies (nnABs) may be present and assist in mitigating disease symptoms via various effector mechanisms, including antibody-dependent cellular cytotoxicity (ADCC). Although nnABs to influenza virus have received more attention lately, little information is available on their age-related prevalence, steady...

Infection with pnuemococcus bacteria is generally mild but can be more severe in the young and elderly, causing invasive pneumococcal disease (IPD) and community-acquired pneumonia (CAP). Although paediatric pneumococcal conjugate vaccine (PCV) programmes and elderly pneumococcal polysaccharide vaccine (PPV) programmes have reduced cases, we estimate that pneumococcal infection still leads to direct health care costs of around {pound}68M and approximately 16 thousand QALY losses in England per y...