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Genetics of symptom remission in outpatients with COVID-19.

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.

SUBMITTER: Dube MP

PROVIDER: S-EPMC8149390 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Genetics of symptom remission in outpatients with COVID-19.

Dubé Marie-Pierre MP Lemaçon Audrey A Barhdadi Amina A Lemieux Perreault Louis-Philippe LP Oussaïd Essaïd E Asselin Géraldine G Provost Sylvie S Sun Maxine M Sandoval Johanna J Legault Marc-André MA Mongrain Ian I Dubois Anick A Valois Diane D Dedelis Emma E Lousky Jennifer J Choi Julie J Goulet Elisabeth E Savard Christiane C Chicoine Lea-Mei LM Cossette Mariève M Chabot-Blanchet Malorie M Guertin Marie-Claude MC de Denus Simon S Bouabdallaoui Nadia N Marchand Richard R Bassevitch Zohar Z Nozza Anna A Gaudet Daniel D L'Allier Philippe L PL Hussin Julie J Boivin Guy G Busseuil David D Tardif Jean-Claude JC

Scientific reports 20210525 1

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<sup>-8</sup>) 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 ...[more]

PMID: 34035401

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Project description:IntroductionWith the emergence of new SARS-CoV-2 variants has come significant variations in disease manifestation, severity, and duration in non-hospitalized infected patients. To characterize symptom patterns and risk factors associated with symptom severity and duration, COVID-19 and influenza-like illness (ILI) outpatients and their contacts were enrolled at two sites in the United States of America and one site in Thailand.MethodsCOVID-19 infection was confirmed at enrollment with a positive antigen or PCR test. Baseline demographics and medical histories were collected from participants at enrollment and daily self-reported symptom questionnaires were obtained to assess symptom severity and duration. Risk factors associated with symptom severity and duration were determined by multivariate logistic regression and Cox proportional hazards model.ResultsTwo hundred and forty one participants meeting the eligibility criteria were enrolled, including 174 confirmed COVID-19 cases (9% Delta and 90% Omicron), 33 ILI cases, and 34 healthy contacts. COVID-19 participants had a shorter median symptom duration of 9.0 (95% CI, 8.0-11.0) days than ILI participants. Infection with the Delta variant resulted in a longer symptom alleviation period compared to infection with the Omicron variant. The most commonly reported symptoms among COVID-19 participants were reported in the nasal and chest/respiratory domains of the FLU-PRO Plus. Participants infected with the Delta variant reported more symptoms overall, with significantly more symptoms affecting eyes and senses reported. 55% of SARS-CoV-2-positive participants reached a negative N1 Ct value by the day 14 study time point. No risk factors for moderate to severe symptoms were identified in this outpatient cohort. Male sex was associated with a shorter symptom duration.ConclusionSymptom manifestation varied among Delta and Omicron variants. Few risk factors were identified for increased symptom severity or duration.

Project description:BackgroundAfter mild COVID-19, some outpatients experience persistent symptoms. However, data are scarce and prospective studies are urgently needed.ObjectivesTo characterize the post-COVID-19 syndrome after mild COVID-19 and identify predictors.ParticipantsOutpatients with symptoms suggestive of COVID-19 with (1) PCR-confirmed COVID-19 (COVID-positive) or (2) SARS-CoV-2 negative PCR (COVID-negative).DesignMonocentric cohort study with prospective phone interview between more than 3 months to 10 months after initial visit to the emergency department and outpatient clinics.Main measuresData of the initial visits were extracted from the electronic medical file. Predefined persistent symptoms were assessed through a structured phone interview. Associations between long-term symptoms and PCR results, as well as predictors of persistent symptoms among COVID-positive, were evaluated by multivariate logistic regression adjusted for age, gender, smoking, comorbidities, and timing of the survey.Key resultsThe study population consisted of 418 COVID-positive and 89 COVID-negative patients, mostly young adults (median age of 41 versus 36 years in COVID-positive and COVID-negative, respectively; p = 0.020) and healthcare workers (67% versus 82%; p = 0.006). Median time between the initial visit and the phone survey was 150 days in COVID-positive and 242 days in COVID-negative patients. Persistent symptoms were reported by 223 (53%) COVID-positive and 33 (37%) COVID-negative patients (p = 0.006) and proportions were stable among the periods of the phone interviews. Overall, 21% COVID-positive and 15% COVID-negative patients (p = 0.182) attended care for this purpose. Four surveyed symptoms were independently associated with COVID-19: fatigue (adjusted odds ratio 2.14, 95% CI 1.04-4.41), smell/taste disorder (26.5, 3.46-202), dyspnea (2.81, 1.10-7.16), and memory impairment (5.71, 1.53-21.3). Among COVID-positive, female gender (1.67, 1.09-2.56) and overweight/obesity (1.67, 1.10-2.56) were predictors of persistent symptoms.ConclusionsMore than half of COVID-positive outpatients report persistent symptoms up to 10 months after a mild disease. Only 4 of 14 symptoms were associated with COVID-19 status. The symptoms and predictors of the post-COVID-19 syndrome need further characterization as this condition places a significant burden on society.

Project description:Research objective was to detail COVID-19's natural trajectory in relation to the Czech population's viral load. Our prospective detailed daily questionnaire-based telemonitoring study evaluated COVID-19's impact among 105 outpatients. In accordance with government quarantine requirements, outpatients were divided into a cohort with two negative tests at the end of the disease (40 patients) and a cohort with a new algorithm (65 patients) following a 14-day quarantine. Median follow-up differed significantly between the 2 groups (23 days vs. 16 days). Only 6% of patients were asymptomatic during the entire telemonitoring period. Another 13% of patients were diagnosed asymptomatic, as suspected contacts, yet later developed symptoms, while the remaining 81% were diagnosed as symptomatic on average 6 days following symptom onset. Telemonitoring enabled precise symptom status chronicling. The most frequently reported complaints were fevers, respiratory issues, and anosmia. Six patients were eventually hospitalized for complications detected early after routine telemonitoring. During the extended follow-up (median 181 days), anosmia persisted in 26% of patients. 79% of patients in the new quarantine algorithm cohort reported no symptoms on day 11 compared to just 56% of patients in the two negative test cohort upon first testing negative (median-19 days). The highest viral load occurred within 0-2 days of initial symptom onset. Both the PCR viral load and two consecutive PCR negative sample realizations indicated high interindividual variability with a surprisingly fluctuating pattern among 43% of patients. No definitive COVID-19 symptoms or set of symptoms excepting anosmia (59%) and/or ageusia (47%) were identified. No preexisting medical conditions specifically foreshadowed disease trajectory in a given patient. Without a PCR negativity requirement for quarantine cessation, patients could exhibit fewer symptoms. Our study therefore highlights the urgent need for routine ambulatory patient telemedicine monitoring, early complication detection, intensive mass education connecting disease demeanor with subsequent swift diagnostics, and, notably, the need to reevaluate and modify quarantine regulations for better control of SARS-CoV-2 proliferation.

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Genetics of symptom remission in outpatients with COVID-19.

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Genetics of symptom remission in outpatients with COVID-19.

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