Genetic characteristics involved in COVID-19 severity. The CARGENCORS case-control study and meta-analysis.

Pre-existing coronary artery disease (CAD), and thrombotic, inflammatory, or virus infectivity response phenomena have been associated with COVID-19 disease severity. However, the association of candidate single nucleotide variants (SNVs) related to mechanisms of COVID-19 complications has been seldom analysed. Our aim was to test and validate the effect of candidate SNVs on COVID-19 severity. CARGENCORS (CARdiovascular GENetic risk score for Risk Stratification of patients positive for SARS-CoV-2 [COVID-19] virus) is an age- and sex-matched case-control study with 818 COVID-19 cases hospitalized with hypoxemia, and 1636 controls with COVID-19 treated at home. The association between severity and SNVs related to CAD (n = 32), inflammation (n = 19), thrombosis (n = 14), virus infectivity (n = 11), and two published to be related to COVID-19 severity was tested with adjusted logistic regression models. Two external independent cohorts were used for meta-analysis (SCOURGE and UK Biobank). After adjustment for potential confounders, 14 new SNVs were associated with COVID-19 severity in the CARGENCORS Study. These SNVs were related to CAD (n = 10), thrombosis (n = 2), and inflammation (n = 2). We also confirmed eight SNVs previously related to severe COVID-19 and virus infectivity. The meta-analysis showed five SNVs associated with severe COVID-19 in adjusted analyses (rs11385942, rs1561198, rs6632704, rs6629110, and rs12329760). We identified 14 novel SNVs and confirmed eight previously related to COVID-19 severity in the CARGENCORS data. In the meta-analysis, five SNVs were significantly associated to COVID-19 severity, one of them previously related to CAD.

The natural history of QTc interval and its clinical impact in coronavirus disease 2019 survivors after 1 year.

Background and objective: Prolonged QTc interval on admission and a higher risk of death in SARS-CoV-2 patients have been reported. The long-term clinical impact of prolonged QTc interval is unknown. This study examined the relationship in COVID-19 survivors of a prolonged QTc on admission with long-term adverse events, changes in QTc duration and its impact on 1-year prognosis, and factors associated with a prolonged QTc at follow-up. Methods: We conducted a single-center prospective cohort study of 523 SARS-CoV-2-positive patients who were alive on discharge. An electrocardiogram was taken on these patients within the first 48 h after diagnosis and before the administration of any medication with a known effect on QT interval and repeated in 421 patients 7 months after discharge. Mortality, hospital readmission, and new arrhythmia rates 1 year after discharge were reviewed. Results: Thirty-one (6.3%) survivors had a baseline prolonged QTc. They were older, had more cardiovascular risk factors, cardiac disease, and comorbidities, and higher levels of terminal pro-brain natriuretic peptide. There was no relationship between prolonged QTc on admission and the 1-year endpoint (9.8% vs. 5.5%, p = 0.212). In 84% of survivors with prolonged baseline QTc, it normalized at 7.9 ± 2.2 months. Of the survivors, 2.4% had prolonged QTc at follow-up, and this was independently associated with obesity, ischemic cardiomyopathy, chronic obstructive pulmonary disease, and cancer. Prolonged baseline QTc was not independently associated with the composite adverse event at 1 year. Conclusions: Prolonged QTc in the acute phase normalized in most COVID-19 survivors and had no clinical long-term impact. Prolonged QTc at follow-up was related to the presence of obesity and previously acquired chronic diseases and was not related to 1-year prognosis.

Myocardial Injury as a Prognostic Factor in Mid- and Long-Term Follow-Up of COVID-19 Survivors.

Myocardial injury, which is present in >20% of patients hospitalized for COVID-19, is associated with increased short-term mortality, but little is known about its mid- and long-term consequences. We evaluated the association between myocardial injury with one-year mortality and readmission in 172 COVID-19 patients discharged alive. Patients were grouped according to the presence or absence of myocardial injury (defined by hs-cTn levels) on admission and matched by age and sex. We report mortality and hospital readmission at one year after admission in all patients and echocardiographic, laboratory and clinical data at six months in a subset of 86 patients. Patients with myocardial injury had a higher prevalence of hypertension (73.3% vs. 50.0%, p = 0.003), chronic kidney disease (10.5% vs. 2.35%, p = 0.06) and chronic heart failure (9.3% vs. 1.16%, p = 0.03) on admission. They also had higher mortality or hospital readmissions at one year (11.6% vs. 1.16%, p = 0.01). Additionally, echocardiograms showed thicker walls in these patients (10 mm vs. 8 mm, p = 0.002) but without functional disorder. Myocardial injury in COVID-19 survivors is associated with poor clinical prognosis at one year, independent of age and sex, but not with echocardiographic functional abnormalities at six months.