Genetics of symptom remission in outpatients with COVID-19

Dube, M.-P.; Lemacon, A.; Barhdadi, A.; Lemieux Perreault, L.-P.; Oussaid, E.; Asselin, G.; Provost, S.; Sun, M.; Sandoval, J.; Legault, M.-A.; Mongrain, I.; Dubois, A.; Valois, D.; Dedelis, E.; Lousky, J.; Choi, J.; Goulet, E.; Savard, C.; Chicoine, L.-M.; Cossette, M.; Chabot-Blanchet, M.; Guertin, M.-C.; de Denus, S.; Bouabdallaoui, N.; Marchand, R.; Bassevitch, Z.; Nozza, A.; Gaudet, D.; L'Allier, P. L.; Hussin, J.; Boivin, G.; Busseuil, D.; Tardif, J.-C.

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 x 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 x 10-8) in interaction with colchicine (P = 1.19 x 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.