2,805 research outputs found
Novel genes and sex differences in COVID-19 severity.
No full textHere we describe the results of a genome-wide study conducted in 11 939 COVID-19 positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (p < 5x10-8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (p = 1.3x10-22 and p = 8.1x10-12, respectively), and for variants in 9q21.32 near TLE1 only among females (p = 4.4x10-8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (p = 2.7x10-8) and ARHGAP33 (p = 1.3x10-8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, p = 4.1x10-8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥ 60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided
Novel risk loci for COVID-19 hospitalization among admixed American populations
No full textPublisher Copyright: © 2024, Diz-de Almeida, Cruz et al.The genetic basis of severe COVID-19 has been thoroughly studied, and many genetic risk factors shared between populations have been identified. However, reduced sample sizes from non-European groups have limited the discovery of population-specific common risk loci. In this second study nested in the SCOURGE consortium, we conducted a genome-wide association study (GWAS) for COVID-19 hospitalization in admixed Americans, comprising a total of 4702 hospitalized cases recruited by SCOURGE and seven other participating studies in the COVID-19 Host Genetic Initiative. We identified four genome-wide significant associations, two of which constitute novel loci and were first discovered in Latin American populations (BAZ2B and DDIAS). A trans-ethnic meta-analysis revealed another novel cross-population risk locus in CREBBP. Finally, we assessed the performance of a cross-ancestry polygenic risk score in the SCOURGE admixed American cohort. This study constitutes the largest GWAS for COVID-19 hospitalization in admixed Latin Americans conducted to date. This allowed to reveal novel risk loci and emphasize the need of considering the diversity of populations in genomic research.Peer reviewe
Novel genes and sex differences in COVID-19 severity
No full textHere, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.Instituto de Salud Carlos III (COV20_00622 to A.C., COV20/00792 to M.B., COV20_00181 to C.A., COV20_1144 to M.A.J.S., PI20/00876 to C.F.); European Union (ERDF) ‘A way of making Europe’. Fundación Amancio Ortega, Banco de Santander (to A.C.), Estrella de Levante S.A. and Colabora Mujer Association (to E.G.-N.) and Obra Social La Caixa (to R.B.); Agencia Estatal de Investigación (RTC-2017-6471-1 to C.F.), Cabildo Insular de Tenerife (CGIEU0000219140 ‘Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19’ to C.F.) and Fundación Canaria Instituto de Investigación Sanitaria de Canarias (PIFIISC20/57 to C.F.)
Shaping current European mitochondrial haplogroup frequency in response to infection : the case of SARS-CoV-2 severity
No full textPublisher Copyright: © The Author(s) 2025.The frequency of mitochondrial DNA haplogroups (mtDNA-HG) in humans is known to be shaped by migration and repopulation. Mounting evidence indicates that mtDNA-HG are not phenotypically neutral, and selection may contribute to its distribution. Haplogroup H, the most abundant in Europe, improved survival in sepsis. Here we developed a random forest trained model for mitochondrial haplogroup calling using data procured from GWAS arrays. Our results reveal that in the context of the SARS-CoV-2 pandemic, HV branch were found to represent protective factors against the development of critical SARS-CoV-2 in an analysis of 14,349 patients. These results highlight the role of mtDNA in the response to infectious diseases and support the proposal that its expansion and population proportion has been influenced by selection through successive pandemics.Peer reviewe
Pulse oximetry adoption and oxygen orders at paediatric admission over 7 years in Kenya: a multihospital retrospective cohort study
No full textObjectives To characterise adoption and explore specific clinical and patient factors that might influence pulse oximetry and oxygen use in low-income and middle-income countries (LMICs) over time; to highlight useful considerations for entities working on programmes to improve access to pulse oximetry and oxygen.
Design A multihospital retrospective cohort study.
Settings All admissions (n=132 737) to paediatric wards of 18 purposely selected public hospitals in Kenya that joined a Clinical Information Network (CIN) between March 2014 and December 2020.
Outcomes Pulse oximetry use and oxygen prescription on admission; we performed growth-curve modelling to investigate the association of patient factors with study outcomes over time while adjusting for hospital factors.
Results Overall, pulse oximetry was used in 48.8% (64 722/132 737) of all admission cases. Use rose on average with each month of participation in the CIN (OR: 1.11, 95% CI 1.05 to 1.18) but patterns of adoption were highly variable across hospitals suggesting important factors at hospital level influence use of pulse oximetry. Of those with pulse oximetry measurement, 7% (4510/64 722) had hypoxaemia (SpO2 <90%). Across the same period, 8.6% (11 428/132 737) had oxygen prescribed but in 87%, pulse oximetry was either not done or the hypoxaemia threshold (SpO2 <90%) was not met. Lower chest-wall indrawing and other respiratory symptoms were associated with pulse oximetry use at admission and were also associated with oxygen prescription in the absence of pulse oximetry or hypoxaemia.
Conclusion The adoption of pulse oximetry recommended in international guidelines for assessing children with severe illness has been slow and erratic, reflecting system and organisational weaknesses. Most oxygen orders at admission seem driven by clinical and situational factors other than the presence of hypoxaemia. Programmes aiming to implement pulse oximetry and oxygen systems will likely need a long-term vision to promote adoption, guideline development and adherence and continuously examine impact
The Warwick Hip Trauma Evaluation – an abridged protocol for the WHiTE Study : a multiple embedded randomised controlled trial cohort study
No full textFractures of the proximal femur are one of the greatest challenges facing the medical community, constituting a heavy socioeconomic burden worldwide. The National Hip Fracture Audit currently provides a framework for service evaluation. This evaluation is based upon the assessment of process rather than assessment of patient-centred outcome and therefore it fails to provide meaningful data regarding the clinical effectiveness of treatments. This study aims to capture data from the cohort of patients who present with a fracture of the proximal femur at a single United Kingdom Major Trauma Centre. Patient-centred outcomes will be recorded and provide a baseline cohort within which to test the clinical effectiveness of experimental interventions
Addressing geographical variation in the progression of non-communicable diseases in Peru: the CRONICAS cohort study protocol.
No full textBackground The rise in non-communicable diseases in developing countries has gained increased attention. Given that around 80% of deaths related to non-communicable diseases occur in low- and middle-income countries, there is a need for local knowledge to address such problems. Longitudinal studies can provide valuable information about disease burden of non-communicable diseases in Latin America to inform both public health and clinical settings. Methods The CRONICAS cohort is a longitudinal study performed in three Peruvian settings that differ by degree of urbanisation, level of outdoor and indoor pollution and altitude. The author sought to enrol an age- and sex-stratified random sample of 1000 participants at each site. Study procedures include questionnaires on socio-demographics and well-known risk factors for cardiopulmonary disease, blood draw, anthropometry and body composition, blood pressure and spirometry before and after bronchodilators. All participants will be visited at baseline, at 20 and 40 months. A random sample of 100 households at each site will be assessed for 24 h particulate matter concentration. Primary outcomes include prevalence of risk factors for cardiopulmonary diseases, changes in blood pressure and blood glucose over time and decline in lung function. Discussion There is an urgent need to characterise the prevalence and burden of non-communicable diseases in low- and middle-income countries. Peru is a middle-income country currently undergoing a rapid epidemiological transition. This longitudinal study will provide valuable information on cardiopulmonary outcomes in three different settings and will provide a platform to address potential interventions that are locally relevant or applicable to other similar settings in Latin America
Evolution of Growth following Anti-Tumor Necrosis Factor-α Therapy in Paediatric Crohn's Disease: Data from the Swiss IBD Cohort Study
No full textUp to 85% of pediatric patients affected by Crohn's disease experience growth failure. This study aims to elucidate the effects of anti-tumor necrosis factor (TNF) biologics on patient growth.
This retrospective analysis examined height, height velocity and weight in pediatric patients with Crohn's disease from the Swiss Inflammatory Bowel Disease Cohort Study between 2007 and 2020 (n = 97). Z-scores were determined according to age and gender of a healthy pediatric population. Growth of patients treated with anti-TNF biologics and immunomodulators was analyzed by linear regression over 5 years and compared within each subgroup by paired Student t tests 1 year (T1), 2 years (T2), and 5 years (T5) after treatment initiation.
Mean height and weight z-scores at diagnosis were -0.3 ± 1.3 and -1.0 ± 1.6, respectively (age at diagnosis 11.1 ± 2.7 years, 52.0% male). Initial treatment was led by azathioprine (58.3%) and infliximab (19.8%). Patients treated with biologics exhibited significant height increase at T1 (p = 0.022), with an overall flat height evolution (y = 0.00x - 0.31), whereas significant weight increase was maintained at T5 (p = 0.0005, y = 0.13x - 0.50). Patients on immunomodulators showed a height increase (y = 0.15x - 0.20) and a significant weight increase at T2 (p = 0.0047, y = 0.10x - 0.41). Height velocity z-scores showed a significant increase across both genders. Factors contributing to a decreased height z-score included male sex, age 10 and below at diagnosis, a concomitant corticosteroid treatment and a top-down treatment strategy.
Our findings indicate that anti-TNF biologics are associated with significant short-term height and long-term weight gains in pediatric patients with Crohn's disease, similar to those observed with immunomodulators.
© 2025 The Author(s). Published by S. Karger AG, Basel
Academic authorship: who, why and in what order?
No full textWe are frequently asked by our colleagues and students for advice on authorship for scientific articles. This short paper outlines some of the issues that we have experienced and the advice we usually provide. This editorial follows on from our work on submitting a paper1 and also on writing an academic paper for publication.2 We should like to start by noting that, in our view, there exist two separate, but related issues: (a) authorship and (b) order of authors. The issue of authorship centres on the notion of who can be an author, who should be an author and who definitely should not be an author, and this is partly discipline specific. The second issue, the order of authors, is usually dictated by the academic tradition from which the work comes. One can immediately envisage disagreements within a multi-disciplinary team of researchers where members of the team may have different approaches to authorship order
HIV status, breastfeeding modality at 5 months and postpartum maternal weight changes over 24 months in rural South Africa
No full textObjective:
To determine the effect of infant feeding practices on postpartum weight change among HIV-infected and -uninfected women in South Africa.<p></p>
Methods:
In a non-randomised intervention cohort study of antiretroviral therapy-naïve women in South Africa, infants were classified as exclusive (EBF), mixed (MF) or non-breastfed (NBF) at each visit. We analysed infant feeding cumulatively from birth to 5 months using 24-hour feeding history (collected weekly for each of the preceding 7 days). Using generalised estimating equation mixed models, allowing for repeated measures, we compared postpartum weight change (kg) from the first maternal postpartum weight within the first 6 weeks (baseline weight) to each subsequent visit through 24 months among 2340 HIV-infected and -uninfected women with live births and at least two postpartum weight measurements.<p></p>
Results:
HIV-infected (−0.2 kg CI: −1.7 to 1.3 kg; P = 0.81) and -uninfected women (−0.5 kg; 95% CI: −2.1 to 1.2 kg; P = 0.58) had marginal non-significant weight loss from baseline to 24 months postpartum. Adjusting for HIV status, socio-demographic, pregnancy-related and infant factors, 5-month feeding modality was not significantly associated with postpartum weight change: weight change by 24 months postpartum, compared to the change in the reference EBF group, was 0.03 kg in NBF (95% CI: −2.5 to +2.5 kg; P = 0.90) and 0.1 kg in MF (95% CI: −3.0 to +3.2 kg; P = 0.78).<p></p>
Conclusion:
HIV-infected and -uninfected women experienced similar weight loss over 24 months. Weight change postpartum was not associated with 5-month breastfeeding modality among HIV-infected and -uninfected women
- …
