Genetics of symptom remission in outpatients with COVID-19

Dubé, Marie-Pierre; Lemaçon, Audrey; Barhdadi, Amina; Lemieux Perreault, Louis-Philippe; Oussaïd, Essaïd; Asselin, Géraldine; Provost, Sylvie; Sun, Maxine; Sandoval, Johanna; Legault, Marc-André; Mongrain, Ian; Dubois, Anick; Valois, Diane; Dedelis, Emma; Lousky, Jennifer; Choi, Julie; Goulet, Elisabeth; Savard, Christiane; Chicoine, Lea-Mei; Cossette, Mariève; Chabot-Blanchet, Malorie; Guertin, Marie-Claude; de Denus, Simon; Bouabdallaoui, Nadia; Marchand, Richard; Bassevitch, Zohar; Nozza, Anna; Gaudet, Daniel; L’Allier, Philippe L.; Hussin, Julie; Boivin, Guy; Busseuil, David; Tardif, Jean-Claude

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.