Genetics of symptom remission in outpatients with COVID-19
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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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SciScore for 10.1101/2021.02.24.21252396: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources Of the 2249 samples genotyped, 20 were excluded due to <98% genotyping completion rate, 3 samples with discordant sex between clinical and genetic data sets were excluded, one contaminated sample was removed, 16 genetically-determined related family members were excluded and we excluded 232 outliers from the cluster based on 1000 Genomes CEU reference samples (Utah Residents with Northern and Western European Ancestry) according to multidimensional scaling. 1000 Genomessuggested: (1000 Genomes Project and AWS, RRID:SCR_008801)Plink files were produced by the iaap-cli tool (version … SciScore for 10.1101/2021.02.24.21252396: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources Of the 2249 samples genotyped, 20 were excluded due to <98% genotyping completion rate, 3 samples with discordant sex between clinical and genetic data sets were excluded, one contaminated sample was removed, 16 genetically-determined related family members were excluded and we excluded 232 outliers from the cluster based on 1000 Genomes CEU reference samples (Utah Residents with Northern and Western European Ancestry) according to multidimensional scaling. 1000 Genomessuggested: (1000 Genomes Project and AWS, RRID:SCR_008801)Plink files were produced by the iaap-cli tool (version 1.1.0-80d7e5b). Plinksuggested: (PLINK, RRID:SCR_001757)The coordinates of the first two MDS components of each subject were plotted including the genotypes of HapMap CEU, JPT-CHB, and YRI data (unrelated individuals). HapMapsuggested: None12 Genome-wide imputation was performed on the TOPMed Imputation Server (version 1.5.7)13 using Eagle (version 2.4)14 for phasing and Minimac4 (version 1.0.2)13 for imputation. Eaglesuggested: (Eagle, RRID:SCR_017262)We tested the colocalization between the COLCORONA GWAS signals and clinically relevant phenotypes using the COLOC R package v3.2-1.23 Network analysis of selected candidate genes was conducted using GeneMANIA. GeneMANIAsuggested: (GeneMANIA, RRID:SCR_005709)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Limitations: Our study had some limitations. Notably, we had limited power to study the more severe outcomes of death or hospitalisation for COVID-19 due in part to a healthy volunteer bias. The invitation and consent to the genetic substudy occurred after the randomisation visit, and very ill patients may have been less likely to agree to the additional interview or may have already died or been hospitalised by the time of recontact. We made all efforts to rapidly reach all participants and persisted recontact attempts even after the end of the 30-day follow-up period on treatment. Healthy volunteer bias is frequent in optional pharmacogenomic studies of clinical trials. To diminish this bias, a simultaneous consent process with the main study and the collection of genetic material at the randomisation visit is recommended. In practice, however, the additional consent for the genetic study adds time to the recruitment process and can be a deterrent to overall participation, particularly for a disease with acute onset such as COVID-19. Information on symptom types was not collected in this study. Because analyses were conducted with individuals of European genetic ancestry, validation of the genetic associations in other populations will be necessary. Importantly, the results have not yet been replicated in an independent population sample, and we cannot exclude the possibility that the results may be chance findings. Conclusion: This is the first study to report a GWAS for t...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04322682 Completed Colchicine Coronavirus SARS-CoV2 Trial (COLCORONA) Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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