Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.

Aims: COVID-19 increases the risk of cardiovascular disease, especially thrombotic complications. There is less knowledge on the risk of arrhythmias after COVID-19. In this study, we aimed to quantify the risk of arrhythmias following COVID-19. Methods and results: This study was based on national register data on all individuals in Sweden who tested positive for SARS-CoV-2 between 1 February 2020 and 25 May 2021. The outcome was incident cardiac arrhythmias, defined as international classification of diseases (10th revision) codes in the registers as follows: atrial arrhythmias; paroxysmal supraventricular tachycardias; bradyarrhythmias; and ventricular arrhythmias. A self-controlled case series study and a matched cohort study, using conditional Poisson regression, were performed to determine the incidence rate ratio and risk ratio, respectively, for an arrhythmia event following COVID-19.A total of 1 057 174 exposed (COVID-19) individuals were included in the study as well as 4 074 844 matched unexposed individuals. The incidence rate ratio of atrial tachycardias, paroxysmal supraventricular tachycardias, and bradyarrhythmias was significantly increased up to 60, 180, and 14 days after COVID-19, respectively. In the matched cohort study, the risk ratio during Days 1-30 following COVID-19/index date was 12.28 (10.79-13.96), 5.26 (3.74-7.42), and 3.36 (2.42-4.68), respectively, for the three outcomes. The risks were generally higher in older individuals, in unvaccinated individuals, and in individuals with more severe COVID-19. The risk of ventricular arrhythmias was not increased. Conclusion: There is an increased risk of cardiac arrhythmias following COVID-19, and particularly increased in elderly vulnerable individuals, as well as in individuals with severe COVID-19.

A Phase 2 Trial of the Effect of Antiandrogen Therapy on COVID-19 Outcome: No Evidence of Benefit, Supported by Epidemiology and In Vitro Data.

BACKGROUND: Men are more severely affected by COVID-19. Testosterone may influence SARS-CoV-2 infection and the immune response. OBJECTIVE: To clinically, epidemiologically, and experimentally evaluate the effect of antiandrogens on SARS-CoV-2 infection. DESIGNS, SETTINGS, AND PARTICIPANTS: A randomized phase 2 clinical trial (COVIDENZA) enrolled 42 hospitalized COVID-19 patients before safety evaluation. We also conducted a population-based retrospective study of 7894 SARS-CoV-2-positive prostate cancer patients and an experimental study using an air-liquid interface three-dimensional culture model of primary lung cells. INTERVENTION: In COVIDENZA, patients were randomized 2:1 to 5 d of enzalutamide or standard of care. OUTCOME MEASUREMENTS: The primary outcomes in COVIDENZA were the time to mechanical ventilation or discharge from hospital. The population-based study investigated risk of hospitalization, intensive care, and death from COVID-19 after androgen inhibition. RESULTS AND LIMITATIONS: Enzalutamide-treated patients required longer hospitalization (hazard ratio [HR] for discharge from hospital 0.43, 95% confidence interval [CI] 0.20-0.93) and the trial was terminated early. In the epidemiological study, no preventive effects were observed. The frail population of patients treated with androgen deprivation therapy (ADT) in combination with abiraterone acetate or enzalutamide had a higher risk of dying from COVID-19 (HR 2.51, 95% CI 1.52-4.16). In vitro data showed no effect of enzalutamide on virus replication. The epidemiological study has limitations that include residual confounders. CONCLUSIONS: The results do not support a therapeutic effect of enzalutamide or preventive effects of bicalutamide or ADT in COVID-19. Thus, these antiandrogens should not be used for hospitalized COVID-19 patients or as prevention for COVID-19. Further research on these therapeutics in this setting are not warranted. PATIENT SUMMARY: We studied whether inhibition of testosterone could diminish COVID-19 symptoms. We found no evidence of an effect in a clinical study or in epidemiological or experimental investigations. We conclude that androgen inhibition should not be used for prevention or treatment of COVID-19.

Spatial clustering and contextual factors associated with hospitalisation and deaths due to COVID-19 in Sweden: a geospatial nationwide ecological study.

INTRODUCTION: In Sweden, thousands of hospitalisations and deaths due to COVID-19 were reported since the pandemic started. Considering the uneven spatial distribution of those severe outcomes at the municipality level, the objective of this study was, first, to identify high-risk areas for COVID-19 hospitalisations and deaths, and second, to determine the associated contextual factors with the uneven spatial distribution of both study outcomes in Sweden. METHODS: The existences of spatial autocorrelation of the standardised incidence (hospitalisations) ratio and standardised mortality ratio were investigated using Global Moran's I test. Furthermore, we applied the retrospective Poisson spatial scan statistics to identify high-risk spatial clusters. The association between the contextual demographic and socioeconomic factors and the number of hospitalisations and deaths was estimated using a quasi-Poisson generalised additive regression model. RESULTS: Ten high-risk spatial clusters of hospitalisations and six high-risk clusters of mortality were identified in Sweden from February 2020 to October 2020. The hospitalisations and deaths were associated with three contextual variables in a multivariate model: population density (inhabitants/km2) and the proportion of immigrants (%) showed a positive association with both outcomes, while the proportion of the population aged 65+ years (%) showed a negative association. CONCLUSIONS: Our study identified high-risk spatial clusters for hospitalisations and deaths due to COVID-19 and the association of population density, the proportion of immigrants and the proportion of people aged 65+ years with those severe outcomes. Results indicate where public health measures must be reinforced to improve sustained and future disease control and optimise the distribution of resources.