Dynamic heterogeneity in COVID-19: Insights from a mathematical model.

Critical illness, such as severe COVID-19, is heterogenous in presentation and treatment response. However, it remains possible that clinical course may be influenced by dynamic and/or random events such that similar patients subject to similar injuries may yet follow different trajectories. We deployed a mechanistic mathematical model of COVID-19 to determine the range of possible clinical courses after SARS-CoV-2 infection, which may follow from specific changes in viral properties, immune properties, treatment modality and random external factors such as initial viral load.

In silico clinical studies for optimal COVID-19 vaccination schedules in patients with cancer.

This study introduces a tailored COVID-19 model for patients with cancer, incorporating viral variants and immune-response dynamics. The model aims to optimize vaccination strategies, contributing to personalized healthcare for vulnerable groups.

Multi-ancestry meta-analysis of host genetic susceptibility to tuberculosis identifies shared genetic architecture.

The heritability of susceptibility to tuberculosis (TB) disease has been well recognized. Over 100 genes have been studied as candidates for TB susceptibility, and several variants were identified by genome-wide association studies (GWAS), but few replicate. We established the International Tuberculosis Host Genetics Consortium to perform a multi-ancestry meta-analysis of GWAS, including 14,153 cases and 19,536 controls of African, Asian, and European ancestry.

T cell responses to SARS-CoV-2 infection and vaccination are elevated in B cell deficiency and reduce risk of severe COVID-19.

Individuals with primary and pharmacologic B cell deficiencies have high rates of severe disease and mortality from coronavirus disease 2019 (COVID-19), but the immune responses and clinical outcomes after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination have yet to be fully defined. Here, we evaluate the cellular immune responses after both SARS-CoV-2 infection and vaccination in patients receiving the anti-CD20 therapy rituximab (RTX) and those with low B cell counts due to common variable immune deficiency (CVID) disease. Assessment of effector and memory CD4 and CD8 T cell responses to SARS-CoV-2 revealed elevated reactivity and proliferative capacity after both infection and vaccination in B cell-deficient individuals, particularly within the CD8 T cell compartment, in comparison with healthy controls.

Ratios from full blood count as markers for TB diagnosis, treatment, prognosis: a systematic review.

The monocyte-to-lymphocyte (MLR) and neutrophil-to-lymphocyte (NLR) ratio are calculated from routine full blood counts. The aim of this study was to systematically review MLR and NLR as biomarkers for diagnosis, treatment response monitoring and prognostic biomarker for TB infection or disease. A systematic literature search was conducted in Medline, Embase and the Cochrane Library on 12 January 2022.

HLA class I signal peptide polymorphism determines the level of CD94/NKG2-HLA-E-mediated regulation of effector cell responses.

Human leukocyte antigen (HLA)-E binds epitopes derived from HLA-A, HLA-B, HLA-C and HLA-G signal peptides (SPs) and serves as a ligand for CD94/NKG2A and CD94/NKG2C receptors expressed on natural killer and T cell subsets. We show that among 16 common classical HLA class I SP variants, only 6 can be efficiently processed to generate epitopes that enable CD94/NKG2 engagement, which we term 'functional SPs'. The single functional HLA-B SP, known as HLA-B/-21M, induced high HLA-E expression, but conferred the lowest receptor recognition.

Genomic and transcriptomic analysis of checkpoint blockade response in advanced non-small cell lung cancer.

Anti-PD-1/PD-L1 agents have transformed the treatment landscape of advanced non-small cell lung cancer (NSCLC). To expand our understanding of the molecular features underlying response to checkpoint inhibitors in NSCLC, we describe here the first joint analysis of the Stand Up To Cancer-Mark Foundation cohort, a resource of whole exome and/or RNA sequencing from 393 patients with NSCLC treated with anti-PD-(L)1 therapy, along with matched clinical response annotation. We identify a number of associations between molecular features and outcome, including (1) favorable (for example, ATM altered) and unfavorable (for example, TERT amplified) genomic subgroups, (2) a prominent association between expression of inducible components of the immunoproteasome and response and (3) a dedifferentiated tumor-intrinsic subtype with enhanced response to checkpoint blockade.

Monocyte, Lymphocyte and Neutrophil Ratios - Easy-to-Use Biomarkers for the Diagnosis of Pediatric Tuberculosis.

Background: The neutrophil-to-lymphocyte-ratio (NLR), neutrophil-to-monocyte-plus-lymphocyte-ratio (NMLR) and monocyte-to-lymphocyte-ratio (MLR) may have diagnostic potential for tuberculosis (TB).

Methods: Data of two prospective multicenter studies in Switzerland were used, which included children <18 years with TB exposure, infection or disease or with febrile non-TB lower-respiratory-tract infection (nTB-LRTI).

Results: Of the 389 children included 25 (6.

Altered IL-6 signalling and risk of tuberculosis disease: a meta-analysis and Mendelian randomisation study.

IL-6 responses are ubiquitous in () infections, but their role in determining human tuberculosis (TB) disease risk is unknown. We used single nucleotide polymorphisms (SNPs) in and near the IL-6 receptor () gene, focusing on the non-synonymous variant, rs2228145, associated with reduced classical IL-6 signalling, to assess the effect of altered IL-6 activity on TB disease risk. We identified 16 genome wide association studies (GWAS) of TB disease collating 17,982 cases of TB disease and 972,389 controls across 4 continents.

Brief Report: Declining Rates of SARS-CoV-2 Vaccine Uptake Among Patients With Thoracic Malignancies.

• Patients with primary thoracic malignancies are at increased risk of complications and death from COVID-19. Multiple studies have demonstrated humoral immune responses to SARS-CoV-2 vaccinations in patients with cancer, though the degree of immunogenicity varies. Over the last year the United States CDC has issued recommendations for multiple additional ‘booster’ vaccine doses for patients with cancer for protection against severe disease.

Mechanistic model for booster doses effectiveness in healthy, cancer, and immunosuppressed patients infected with SARS-CoV-2.

SARS-CoV-2 vaccines are effective at limiting disease severity, but effectiveness is lower among patients with cancer or immunosuppression. Effectiveness wanes with time and varies by vaccine type. Moreover, previously prescribed vaccines were based on the ancestral SARS-CoV-2 spike-protein that emerging variants may evade.

Germline variants associated with toxicity to immune checkpoint blockade.

Immune checkpoint inhibitors (ICIs) have yielded remarkable responses but often lead to immune-related adverse events (irAEs). Although germline causes for irAEs have been hypothesized, no individual variant associated with developing irAEs has been identified. We carried out a genome-wide association study of 1,751 patients on ICIs across 12 cancer types.

IL7 genetic variation and toxicity to immune checkpoint blockade in patients with melanoma.

Treatment with immune checkpoint blockade (ICB) frequently triggers immune-related adverse events (irAEs), causing considerable morbidity. In 214 patients receiving ICB for melanoma, we observed increased severe irAE risk in minor allele carriers of rs16906115, intronic to IL7. We found that rs16906115 forms a B cell-specific expression quantitative trait locus (eQTL) to IL7 in patients.

Genome-wide association study of leprosy in Malawi and Mali.

Leprosy is a chronic infection of the skin and peripheral nerves caused by Mycobacterium leprae. Despite recent improvements in disease control, leprosy remains an important cause of infectious disability globally. Large-scale genetic association studies in Chinese, Vietnamese and Indian populations have identified over 30 susceptibility loci for leprosy.

Immunogenicity of SARS-CoV-2 vaccines in patients with breast cancer.

Purpose: To explore the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with breast cancer based on type of anticancer treatment.

Methods: Patients with breast cancer had anti-spike antibody concentrations measured ⩾14 days after receiving a full SARS-CoV-2 vaccination series. The primary endpoint was IgA/G/M anti-spike antibody concentration.

Natural Killer cells demonstrate distinct eQTL and transcriptome-wide disease associations, highlighting their role in autoimmunity.

Natural Killer cells are innate lymphocytes with central roles in immunosurveillance and are implicated in autoimmune pathogenesis. The degree to which regulatory variants affect Natural Killer cell gene expression is poorly understood. Here we perform expression quantitative trait locus mapping of negatively selected Natural Killer cells from a population of healthy Europeans (n = 245).

Cutaneous Toxicities Associated with Immune Checkpoint Inhibitors: An Observational, Pharmacovigilance Study.

Cutaneous immune-related adverse events (cirAEs) are the most prevalent complication to arise from immunotherapy and cause significant morbidity. We aimed to determine the spectrum, timing, clinical features, and outcomes of cirAEs by conducting an observational pharmacovigilance study using VigiBase, the World Health Organization's global database of individual case safety reports from over 130 member countries (ClinicalTrials.gov, number NCT04898751).

Repertoires of SARS-CoV-2 epitopes targeted by antibodies vary according to severity of COVID-19.

Antibodies to SARS-CoV-2 are central to recovery and immunity from COVID-19. However, the relationship between disease severity and the repertoire of antibodies against specific SARS-CoV-2 epitopes an individual develops following exposure remains incompletely understood. Here, we studied seroprevalence of antibodies to specific SARS-CoV-2 and other betacoronavirus antigens in a well-annotated, community sample of convalescent and never-infected individuals obtained in August 2020.

T cell reactivity to the SARS-CoV-2 Omicron variant is preserved in most but not all individuals.

The SARS-CoV-2 Omicron variant (B.1.1.