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- Nakanishi, T, et al.
(author)
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Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality
- 2021
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In: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory.
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Journal article (other academic/artistic)abstract
- BackgroundThere is considerable variability in COVID-19 outcomes amongst younger adults—and some of this variation may be due to genetic predisposition. We characterized the clinical implications of the major genetic risk factor for COVID-19 severity, and its age-dependent effect, using individual-level data in a large international multi-centre consortium.MethodThe major common COVID-19 genetic risk factor is a chromosome 3 locus, tagged by the marker rs10490770. We combined individual level data for 13,424 COVID-19 positive patients (N=6,689 hospitalized) from 17 cohorts in nine countries to assess the association of this genetic marker with mortality, COVID-19-related complications and laboratory values. We next examined if the magnitude of these associations varied by age and were independent from known clinical COVID-19 risk factors.FindingsWe found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (hazard ratio [HR] 1·4, 95% confidence interval [CI] 1·2–1·6) and COVID-19 related mortality (HR 1·5, 95%CI 1·3–1·8). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (odds ratio [OR] 2·0, 95%CI 1·6-2·6), venous thromboembolism (OR 1·7, 95%CI 1·2-2·4), and hepatic injury (OR 1·6, 95%CI 1·2-2·0). Risk allele carriers ≤ 60 years had higher odds of death or severe respiratory failure (OR 2·6, 95%CI 1·8-3·9) compared to those > 60 years OR 1·5 (95%CI 1·3-1·9, interaction p-value=0·04). Amongst individuals ≤ 60 years who died or experienced severe respiratory COVID-19 outcome, we found that 31·8% (95%CI 27·6-36·2) were risk variant carriers, compared to 13·9% (95%CI 12·6-15·2%) of those not experiencing these outcomes. Prediction of death or severe respiratory failure among those ≤ 60 years improved when including the risk allele (AUC 0·82 vs 0·84, p=0·016) and the prediction ability of rs10490770 risk allele was similar to, or better than, most established clinical risk factors.InterpretationThe major common COVID-19 risk locus on chromosome 3 is associated with increased risks of morbidity and mortality—and these are more pronounced amongst individuals ≤ 60 years. The effect on COVID-19 severity was similar to, or larger than most established risk factors, suggesting potential implications for clinical risk management.FundingFunding was obtained by each of the participating cohorts individually.
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- Bemmerer, D., et al.
(author)
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Feasibility of low-energy radiative-capture experiments at the LUNA underground accelerator facility
- 2005
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In: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 24:2, s. 313-319
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Journal article (peer-reviewed)abstract
- The LUNA (Laboratory Underground for Nuclear Astrophysics) facility has been designed to study nuclear reactions of astrophysical interest. It is located deep underground in the Gran Sasso National Laboratory, Italy. Two electrostatic accelerators, with 50 and 400 kV maximum voltage, in combination with solid and gas target setups allowed to measure the total cross-sections of the radiative-capture reactions 2H2H(p, γ) 3He3Heand 14N14N(p, γ) 15O15Owithin their relevant Gamow peaks. We report on the gamma background in the Gran Sasso laboratory measured by germanium and bismuth germanate detectors, with and without an incident proton beam. A method to localize the sources of beam-induced background using the Doppler shift of emitted gamma rays is presented. The feasibility of radiative-capture studies at energies of astrophysical interest is discussed for several experimental scenarios. © Società Italiana di Fisica/Springer-Verlag 2005.
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