A common allele of HLA is associated with asymptomatic SARS-CoV-2 infection

Nature, Год журнала: 2023, Номер 620(7972), С. 128 - 136

Опубликована: Июль 19, 2023

Abstract Studies have demonstrated that at least 20% of individuals infected with SARS-CoV-2 remain asymptomatic 1–4 . Although most global efforts focused on severe illness in COVID-19, examining infection provides a unique opportunity to consider early immunological features promote rapid viral clearance. Here, postulating variation the human leukocyte antigen ( HLA ) loci may underly processes mediating infection, we enrolled 29,947 individuals, for whom high-resolution genotyping data were available, smartphone-based study designed track COVID-19 symptoms and outcomes. Our discovery cohort n = 1,428) comprised unvaccinated who reported positive test result SARS-CoV-2. We tested association five disease course identified strong between HLA-B*15:01 observed two independent cohorts. Suggesting this genetic is due pre-existing T cell immunity, show cells from pre-pandemic samples carrying reactive immunodominant S-derived peptide NQKLIANQF. The majority displayed memory phenotype, highly polyfunctional cross-reactive derived seasonal coronaviruses. crystal structure HLA-B*15:01–peptide complexes demonstrates peptides NQKLIANQF NQKLIANAF (from OC43-CoV HKU1-CoV) share similar ability be stabilized presented by HLA-B*15:01. Finally, structural similarity underpins cross-reactivity high-affinity public receptors, providing molecular basis -mediated immunity.

Язык: Английский

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HLA-DQB1*05:03 is associated with an increased risk of COVID-19 progression in the Bulgarian population

Human Immunology, Год журнала: 2025, Номер 86(1), С. 111228 - 111228

Опубликована: Янв. 1, 2025

Язык: Английский

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Association between HLA genetics and SARS-CoV-2 infection in a large real-world cohort

Genes and Immunity, Год журнала: 2025, Номер unknown

Опубликована: Апрель 24, 2025

Genetic variation in the human leukocyte antigen (HLA) region is thought to influence susceptibility and severity of a variety infectious diseases. Several studies have explored possible relationship between HLA genetics SARS-CoV-2 infection, although mixed results, small sample sizes, difficulty controlling for exposure risk made it difficult draw firm conclusions. Here, dataset 419,234 subjects with genotype data COVID-19 PCR test results was studied. A baseline analysis performed examine association non-HLA factors on positivity. Then, multivariate logistic regressions, incorporating single paired alleles, were then corrected significant from analysis. Proxies socioeconomic status significantly associated positivity across all ancestry groups Forty-one alleles displayed positivity; after risk, only eight associations remained. Additionally, two allele pairs correction. Of variables, showed greatest effect size. The this study suggest that many, if not all, reported infection may be spurious, owing confounding factors.

Язык: Английский

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A Hybrid Framework of Blockchain and IoT Technology in the Pharmaceutical Industry: A Comprehensive Study

Mobile Information Systems, Год журнала: 2023, Номер 2023, С. 1 - 14

Опубликована: Апрель 20, 2023

The pharmaceutical company is key to having a strong healthcare system, and excellent essential for every society economy. However, there are significant concerns with medication safety security as result of fake inferior medical items, which constitute hazard harm consumers’ health. Globally, drug counterfeiting severe problem that endangers the public’s health well consumers. global business manufacturing medications generates enormous annual revenue. To have quality industry great importance plays vital role in medicine supplies. With emerging computer technologies like blockchain IoT cutting across several industries sectors revolutionizing world, systematic literature review various articles chosen from different databases was carried out this study analyze evaluate application areas technology existing frameworks been proposed solve problems faced industry. outcome showed hybrid framework can assist reducing counterfeit provide solutions most This also addressed drawbacks

Язык: Английский

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HLA‐DPB1*13:01 associates with enhanced, and KIR2DS4*001 with diminished protection from developing severe COVID‐19

HLA, Год журнала: 2023, Номер 103(1)

Опубликована: Окт. 18, 2023

Extreme polymorphism of HLA and killer‐cell immunoglobulin‐like receptors (KIR) differentiates immune responses across individuals. Additional to T cell receptor interactions, subsets class I act as ligands for inhibitory activating KIR, allowing natural killer (NK) cells detect kill infected cells. We investigated the impact KIR on severity COVID‐19. High resolution II genotypes were determined from 403 non‐hospitalized 1575 hospitalized SARS‐CoV‐2 patients Italy collected in 2020. observed that possession KIR2DS4*001 allotype is associated with severe disease, requiring hospitalization (OR = 1.48, 95% CI 1.20–1.85, p c 0.017), this effect greater individuals homozygous 3.74, 1.75–9.29, 0.003). also allotype, HLA‐DPB1*13:01 protects disease 0.49, 0.33–0.74, 0.019). These association analyses replicated using logistic regression sex age covariates. Autoantibodies against IFN‐α COVID‐19 detected 26% 156 tested. HLA‐C*08:02 was more frequent autoantibodies than those without, KIR3DL1*01502 only present lacking antibodies. findings suggest integral determining clinical outcome following infection, by influencing course both innate adaptive immunity.

Язык: Английский

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Narrative Review Explaining the Role of HLA-A, -B, and -C Molecules in COVID-19 Disease in and around Africa

Infectious Disease Reports, Год журнала: 2024, Номер 16(2), С. 380 - 406

Опубликована: Апрель 18, 2024

The coronavirus disease 2019 (COVID-19) has left a devasting effect on various regions globally. Africa exceptionally high rates of other infectious diseases, such as tuberculosis (TB), human immunodeficiency virus (HIV), and malaria, was not impacted by COVID-19 to the extent continents Globally, caused approximately 7 million deaths 700 infections thus far. severity susceptibility vary among individuals populations, which could be attributed factors, including viral strain, host genetics, environment, lifespan, co-existing conditions. Host genetics play substantial part in individuals. Human leukocyte antigen (HLA) previously been shown very important across immune responses against viruses. HLA widely studied gene region for associations that have identified. proteins present peptides cytotoxic lymphocytes, causes an response kill infected cells. molecule serves central association; therefore, we expect association with COVID-19. Therefore, this narrative review, look at region, particularly, class I, understand its role disease.

Язык: Английский

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The subdued post-boost spike-directed secondary IgG antibody response in Ugandan recipients of the Pfizer-BioNTech BNT162b2 vaccine has implications for local vaccination policies

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Фев. 16, 2024

This study aimed to delineate longitudinal antibody responses the Pfizer-BioNTech BNT162b2 COVID-19 vaccine within Ugandan subset of Sub-Saharan African (SSA) demographic, filling a significant gap in global datasets. We enrolled 48 participants and collected 320 specimens over 12 months after primary vaccination dose. A validated enzyme-linked immunosorbent assay (ELISA) was used quantify SARS-CoV-2-specific IgG, IgM, IgA concentrations (ng/ml) optical densities (ODs). Statistical analyses included box plots, diverging bar graphs, Wilcoxon test with Bonferroni correction. noted robust S-IgG response 14 days dose, which consistent data. There no surge levels booster contrasting trends other populations. The S-IgM transient predominantly below established thresholds for this population, reflects its typical early emergence rapid decline. S-IgA rose initial dose then decreased six months, aligning temporal patterns mucosal immunity. Eleven breakthrough infections were noted, all asymptomatic, regardless participants' serostatus, suggests protective effect from vaccination. elicited strong SSA demographic. dynamics distinctly differed data highlighting significance region-specific research necessity customised strategies.

Язык: Английский

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Dynamics of T-cell Responses Following COVID-19 mRNA Vaccination and Breakthrough Infection in Older Adults

Pathogens and Immunity, Год журнала: 2023, Номер 8(1), С. 117 - 135

Опубликована: Ноя. 17, 2023

Introduction: While older adults generally mount weaker antibody responses to a primary COVID-19 vaccine series, T-cell remain less well characterized in this population. We compared SARS-CoV-2 spike-specific after 2- and 3-dose mRNA vaccination subsequent breakthrough infection younger adults. Methods: quantified CD4+ CD8+ T-cells reactive overlapping peptides spanning the ancestral spike protein 40 (median age 79) 50 health care workers 39), all naive, using an activation-induced marker assay. were further assessed 24 participants, including 8 adults, who subsequently experienced their first infection. Results: A third dose significantly boosted frequencies above 2-dose levels did not differ between either dose. Multivariable analyses adjusting for sociodemographic, health, vaccine-related variables confirmed that was associated with impaired cellular responses. Instead, strongest predictors of post-third-dose corresponding post-second-dose frequencies. Breakthrough increased both frequencies, comparable Exploratory revealed association HLA-A*02:03 higher post-vaccination which may be attributable numerous strong-binding HLA-A*02:03-specific epitopes protein. Conclusion: Older robust vaccination, are following

Язык: Английский

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Strong humoral response after Covid‐19 vaccination correlates with the common HLA allele A*03:01 and protection from breakthrough infection

HLA, Год журнала: 2024, Номер 103(3)

Опубликована: Март 1, 2024

Few data exist on the role of genetic factors involving HLA system response to Covid‐19 vaccines. Moving from suggestions a previous study investigating association some alleles with humoral BNT162b2, we here compared allele frequencies among weak ( n = 111) and strong 123) responders, defined as those healthcare workers lowest highest anti‐Spike antibody levels after vaccination. Individuals clinical history or positive anti‐nucleocapside antibodies were excluded. We found common HLA‐A*03:01 an independent predictor (OR 12.46, 95% CI: 4.41–35.21, p < 0.0001), together younger age vaccines 0.004). Correlation between protection breakthrough infection has been observed, 2‐year cumulative incidence 42% 63% respectively 0.03). Due high frequency need for seasonal vaccinations against SARS‐CoV‐2 mutants, our findings provide useful information about inter‐individual differences observed in vaccine might support further studies next

Язык: Английский

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HLA-DQ2/8 and COVID-19 in celiac disease: Boon or Bane

Опубликована: Ноя. 17, 2023

The SARS-CoV-2 pandemic continues to pose a global threat. While its virulence has subsided, it persisted due the continual emergence of new mutations. Although many high-risk conditions related COVID-19 have been identified, understanding protective factors remains limited. Intriguingly, epidemiological evidence suggests low incidence COVID-19-infected CD patients. present study explores whether their genetic background, namely associated HLA-DQs, offers protection against severe outcomes. We hypothesize that HLA-DQ 2/8 alleles may shield patients from and subsequent effects, possibly memory CD4 T cells primed by previous exposure human-associated common cold coronaviruses (CCC) higher affinity those allele&#039;s groove. In this context, we examined potential cross-reactivity between epitopes CCC assessed binding (BA) these 2/8. Using computational methods, analyzed sequence similarity four distinct CCC. Of 924 unique immunodominant 15-mer with at least 67% identity, 37 exhibited significant BA 2/8, suggesting effect. various mechanisms might explain role HLA-DQ2/8 in COVID-19-afflicted If substantiated, insights could enhance our gene-environment enigma viral-host relationship, guiding therapeutic innovations ongoing pandemic.

Язык: Английский

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