bims-covirf 2021-10-03 papers

on COVID19 risk factors

Issue of 2021–10–03
two papers selected by
Catherine Rycroft, BresMed

Explaining ethnic differentials in COVID-19 mortality: cohort study.
Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality.

Am J Epidemiol. 2021 Sep 29. pii: kwab237. [Epub ahead of print]

Explaining ethnic differentials in COVID-19 mortality: cohort study.

G David Batty, Bamba Gaye, Catharine R Gale, Mark Hamer, Camille Lassale.

  Ethnic inequalities in coronavirus disease 2019 (COVID-19) hospitalizations and mortality have been widely reported but there is scant understanding of how they are embodied. The UK Biobank prospective cohort study comprises around half a million people who were aged 40-69 years at study induction between 2006 and 2010 when information on ethnic background and potential explanatory factors was captured. Study members were prospectively linked to a national mortality registry. In an analytical sample of 448,664 individuals (248,820 women), 705 deaths were ascribed to COVID-19 between 5th March, 2020 and 24th January, 2021. In age- and sex-adjusted analyses, relative to White participants, Black study members experienced around five times the risk of COVID-19 mortality (odds ratio; 95% confidence interval: 4.81; 3.28, 7.05), while there was a doubling in the South Asian group (2.05; 1.30, 3.25). Controlling for baseline comorbidities, social factors (including socioeconomic circumstances), and lifestyle indices attenuated this risk differential by 34% in Black study members (2.84; 1.91, 4.23) and 37% in South Asian individuals (1.57; 0.97, 2.55). The residual risk of COVID-19 deaths in ethnic minority groups may be ascribed to a range of unmeasured characteristics and requires further exploration.

Keywords:  COVID-19; UK Biobank; cohort study; ethnicity

DOI:  https://doi.org/10.1093/aje/kwab237
J Clin Invest. 2021 Oct 01. pii: e152386. [Epub ahead of print]

Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality.

Tomoko Nakanishi, Sara Pigazzini, Frauke Degenhardt, Mattia Cordioli, Guillaume Butler-Laporte, Douglas Maya-Miles, Luis Bujanda, Youssef Bouysran, Mari Ek Niemi, Adriana Palom, David Ellinghaus, Atlas Khan, Manuel Martínez-Bueno, Selina Rolker, Sara Amitrano, Luisa Roade Tato, Francesca Fava, Christoph D Spinner, Daniele Prati, David Bernardo, Federico Garcia, Gilles Darcis, Israel Fernandez-Cadenas, Jan Cato Holter, Jesus M Banales, Robert Frithiof, Krzysztof Kiryluk, Stefano Duga, Rosanna Asselta, Alexandre C Pereira, Manuel Romero-Gómez, Beatriz Nafría-Jiménez, Johannes R Hov, Isabelle Migeotte, Alessandra Renieri, Anna M Planas, Kerstin U Ludwig, Maria Buti, Souad Rahmouni, Marta E Alarcón-Riquelme, Eva C Schulte, Andre Franke, Tom H Karlsen, Luca Valenti, Hugo Zeberg, J Brent Richards, Andrea Ganna.

   BACKGROUND: There is considerable variability in COVID-19 outcomes amongst younger adults-and some of this variation may be due to genetic predisposition.
METHODS: We combined individual level data from 13,888 COVID-19 patients (N=7,185 hospitalized) from 17 cohorts in nine countries to assess the association of the major common COVID-19 genetic risk factor (chromosome 3 locus tagged by rs10490770) with mortality, COVID-19-related complications and laboratory values. We next performed meta-analyses using FinnGen and the Columbia University COVID-19 Biobank.
RESULTS: We found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (HR 1.4, 95%CI 1.2-1.7). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (OR 2.1, 95%CI 1.6-2.6), venous thromboembolism (OR 1.7, 95%CI 1.2-2.4), and hepatic injury (OR 1.5, 95%CI 1.2-2.0). Risk allele carriers ≤60 years had higher odds of death or severe respiratory failure (OR 2.7, 95%CI 1.8-3.9) compared to those >60 years (OR 1.5, 95%CI 1.2-1.8, interaction-p=0.038). Amongst individuals ≤60 years who died or experienced severe respiratory failure, 32.3% were risk variant carriers, compared to 13.9% of those not experiencing these outcomes. The genetic risk improved the prediction of death or severe respiratory failure similarly to, or better than, most established clinical risk factors.
CONCLUSIONS: The major common COVID-19 genetic risk factor is associated with increased risks of morbidity and mortality, which are more pronounced amongst individuals ≤60 years. The effect was similar in magnitude and more common than most established clinical risk factors, suggesting potential implications for future clinical risk management.

Keywords:  COVID-19; Genetic variation; Genetics

DOI:  https://doi.org/10.1172/JCI152386