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Randomized Controlled Trial
. 2021 May 25;11(1):10847.
doi: 10.1038/s41598-021-90365-6.

Genetics of symptom remission in outpatients with COVID-19

Marie-Pierre Dubé  1   2   3 , Audrey Lemaçon  4   5   6 , Amina Barhdadi  4   5 , Louis-Philippe Lemieux Perreault  4   5 , Essaïd Oussaïd  4   5 , Géraldine Asselin  4   5 , Sylvie Provost  4   5 , Maxine Sun  4   5   6 , Johanna Sandoval  4   5 , Marc-André Legault  4   5   7 , Ian Mongrain  4   5 , Anick Dubois  4   5 , Diane Valois  4   5 , Emma Dedelis  4   5 , Jennifer Lousky  4   5 , Julie Choi  4   5 , Elisabeth Goulet  4 , Christiane Savard  4 , Lea-Mei Chicoine  4 , Mariève Cossette  4   8 , Malorie Chabot-Blanchet  4   8 , Marie-Claude Guertin  4   8 , Simon de Denus  4   5   9 , Nadia Bouabdallaoui  4 , Richard Marchand  4 , Zohar Bassevitch  4   8 , Anna Nozza  4   8 , Daniel Gaudet  10 , Philippe L L'Allier  4 , Julie Hussin  4   6   7 , Guy Boivin  11 , David Busseuil  4 , Jean-Claude Tardif  12   13
Affiliations
Randomized Controlled Trial

Genetics of symptom remission in outpatients with COVID-19

Marie-Pierre Dubé et al. Sci Rep. .

Abstract

We conducted a genome-wide association study of time to remission of COVID-19 symptoms in 1723 outpatients with at least one risk factor for disease severity from the COLCORONA clinical trial. We found a significant association at 5p13.3 (rs1173773; P = 4.94 × 10-8) near the natriuretic peptide receptor 3 gene (NPR3). By day 15 of the study, 44%, 54% and 59% of participants with 0, 1, or 2 copies of the effect allele respectively, had symptom remission. In 851 participants not treated with colchicine (placebo), there was a significant association at 9q33.1 (rs62575331; P = 2.95 × 10-8) in interaction with colchicine (P = 1.19 × 10-5) without impact on risk of hospitalisations, highlighting a possibly shared mechanistic pathway. By day 15 of the study, 46%, 62% and 64% of those with 0, 1, or 2 copies of the effect allele respectively, had symptom remission. The findings need to be replicated and could contribute to the biological understanding of COVID-19 symptom remission.

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Conflict of interest statement

MPD reports personal fees and minor equity interest from Dalcor Pharmaceuticals and personal fees from GlaxoSmithKline, other from AstraZeneca, Pfizer, Servier, Sanofi. MPD and JCT have a patent “Methods for Treating or Preventing Cardiovascular Disorders and Lowering Risk of Cardiovascular Events” issued to Dalcor, no royalties received, a patent “Genetic Markers for Predicting Responsiveness to Therapy with HDL-Raising or HDL Mimicking Agent” issued to Dalcor, no royalties received, and a patent “Methods for using low dose colchicine after myocardial infarction” with royalties paid to the Montreal Heart Institute. JCT reports grants from the Government of Quebec, the Montreal Heart Institute Foundation, the Bill and Melinda Gates Foundation, Amarin, AstraZeneca, Ceapro, DalCor Pharmaceuticals, Esperion, Ionis, Pfizer, RegenXBio and Sanofi; personal fees from AstraZeneca, DalCor Pharmaceuticals, HLS Pharmaceuticals, Pfizer, Pharmascience, Sanofi and Servier; and minor equity interest from Dalcor Pharmaceuticals. In addition, JCT’s institution has submitted a patent “Methods of treating a coronavirus infection using Colchicine” pending and a patent “Early administration of low-dose colchicine after myocardial infarction” pending. JCT has waived his rights in all patents related to colchicine and does not stand to benefit financially if colchicine becomes used as a treatment for COVID-19. NB reports personal fees from AstraZeneca outside of the present work. SdD was supported through grants from AstraZeneca, Pfizer, Roche Molecular Science, Dalcor Pharmaceuticals outside of the present work. JH is funded by an IVADO COVID-19 fast response grant with co-applicant MPD and JCT (CVD19-030). Other authors have nothing to declare.

Figures

Figure 1
Figure 1
Manhattan plots for the GWAS of time to remission of COVID-19 symptoms. (a) Using a Cox proportional hazards regression with 1723 subjects from the colchicine and placebo arms of the COLCORONA study, controlling for study arm, sex, age, and 10 principal components for genetic ancestry, with 6,392,715 genetic variants of minor allele frequency ≥ 5%. (b) Using a Cox proportional hazards regression with 851 subjects from the placebo arm of the COLCORONA study, controlling for sex, age, and 10 principal components for genetic ancestry, with 6,390,776 genetic variants of minor allele frequency ≥ 5%.
Figure 2
Figure 2
Cumulative incidence curves for COVID-19 symptom remission.
See this image and copyright information in PMC

References

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