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2.
Eur Urol ; 81(3): 285-293, 2022 03.
Article in English | MEDLINE | ID: covidwho-1568696

ABSTRACT

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.


Subject(s)
Androgen Antagonists/therapeutic use , Anilides/therapeutic use , Benzamides/therapeutic use , COVID-19/drug therapy , Nitriles/therapeutic use , Phenylthiohydantoin/therapeutic use , SARS-CoV-2/isolation & purification , Tosyl Compounds/therapeutic use , Aged , Aged, 80 and over , Androgens/therapeutic use , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19 Nucleic Acid Testing , Female , Hospitalization , Humans , Male , Middle Aged , Retrospective Studies , Sweden/epidemiology , Testosterone , Treatment Outcome
4.
BMJ Glob Health ; 6(7)2021 07.
Article in English | MEDLINE | ID: covidwho-1331811

ABSTRACT

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.


Subject(s)
COVID-19 , Cluster Analysis , Hospitalization , Humans , Retrospective Studies , SARS-CoV-2 , Spatial Analysis , Sweden/epidemiology
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