Evidence map›Paper›PMID 34980495›Full record

Trial reportEuropean urology2022

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.

Karin Welén, Ebba Rosendal, Magnus Gisslén, Annasara Lenman, Eva Freyhult, Osvaldo Fonseca-Rodríguez, Daniel Bremell, Johan Stranne, Åse Östholm Balkhed, Katarina Niward and 17 more

Open access · hybridAbstract readClinical Trial, Phase IIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in European urology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 4 pooled it
3.4field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

39 citing papers in PubMed, 4 syntheses or guidelines pooled it, 57 citations in OpenAlex.

  1. Association of the androgens with COVID-19 prognostic outcomes: a systematic review.Archives of public health = Archives belges de sante publique · 2023
    Pooled it
  2. [Prostate cancer, androgen deprivation, and risk of COVID-19 infection : A systematic review and meta-analysis].Progres en urologie : journal de l'Association francaise d'urologie et de la Societe francaise d'urologie · 2022
    Pooled it
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  9. Effect of Pituitary-Target Gland Axis on RAAS in the Context of COVID-19.International journal of medical sciences · 2025
    Review
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  12. COVID-19 therapeutics.Clinical microbiology reviews · 2024
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  15. Proxalutamide reduces SARS-CoV-2 infection and associated inflammatory response.Proceedings of the National Academy of Sciences of the United States of America · 2023
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

27 authors at 7 institutions in 1 country.

Karin WelénInstitute of Clinical Sciences, Department of Urology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Ebba RosendalDepartment of Clinical Microbiology, Section of Virology, Umeå University, Umeå, Sweden; The Laboratory for Molecular Infection Medicine Sweden, Umeå, Sweden.
Magnus GisslénInstitute of Biomedicine, Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Infectious Diseases, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.
Annasara LenmanDepartment of Clinical Microbiology, Section of Virology, Umeå University, Umeå, Sweden.
Eva FreyhultDepartment of Medical Sciences, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Osvaldo Fonseca-RodríguezDepartment of Clinical Microbiology, Umeå University, Umeå, Sweden.
Daniel BremellInstitute of Biomedicine, Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Johan StranneInstitute of Clinical Sciences, Department of Urology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Åse Östholm BalkhedDepartment of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
Katarina NiwardDepartment of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
Johanna RepoDepartment of Clinical Microbiology, Umeå University, Umeå, Sweden.
David RobinssonDepartment of Urology, Region of Jönköping, Jönköping, Sweden.
Anna J HenningssonDepartment of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Department of Clinical Microbiology, Region Jönköping County, Jönköping, Sweden.
Johan StyrkeDepartment of Surgical and Perioperative Sciences, Urology & Andrology, Umeå University, Umeå, Sweden.
Martin AngelinDepartment of Clinical Microbiology, Umeå University, Umeå, Sweden.
Elisabeth LindquistDepartment of Clinical Microbiology, Umeå University, Umeå, Sweden.
Annika AllardDepartment of Clinical Microbiology, Section of Virology, Umeå University, Umeå, Sweden.
Miriam BeckerDepartment of Clinical Microbiology, Section of Virology, Umeå University, Umeå, Sweden.
Stina RudolfssonDepartment of Surgical and Perioperative Sciences, Urology & Andrology, Umeå University, Umeå, Sweden.
Robert BucklandDepartment of Surgical and Perioperative Sciences, Urology & Andrology, Umeå University, Umeå, Sweden.
Camilla Thellenberg CarlssonDepartment of Radiation Sciences, Umeå University, Umeå, Sweden.
Anders BjartellDivision of Urological Cancers, Department of Translational Medicine, Lund University, Malmö, Sweden.
Anna C NilssonDepartment of Translational Medicine, Infectious Diseases Research Unit, Lund University, Malmö, Sweden.
Clas AhlmDepartment of Clinical Microbiology, Umeå University, Umeå, Sweden.
Anne-Marie Fors ConnollyThe Laboratory for Molecular Infection Medicine Sweden, Umeå, Sweden; Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
Anna K ÖverbyThe Laboratory for Molecular Infection Medicine Sweden, Umeå, Sweden; Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
Andreas JosefssonInstitute of Clinical Sciences, Department of Urology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Surgical and Perioperative Sciences, Urology & Andrology, Umeå University, Umeå, Sweden; Wallenberg Center for Molecular Medicine (WCMM), Umeå University, Umeå, Sweden. Electronic address: andreas.josefsson@umu.se.
Umeå University · SEUniversity of Gothenburg · SELinköping University · SELund University · SERegion Jönköpings län · SERegion Västra Götaland · SEScience for Life Laboratory · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMen are more severely affected by COVID-19. Testosterone may influence SARS-CoV-2 infection and the immune response.

objectiveTo clinically, epidemiologically, and experimentally evaluate the effect of antiandrogens on SARS-CoV-2 infection. DESIGNS, SETTINGS, AND

participantsA 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.

interventionIn 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.

conclusionsThe 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.

Indexed as

COVID-19 Drug TreatmentAgedAged, 80 and overAndrogen AntagonistsAndrogensAnilidesBenzamidesCOVID-19COVID-19 Nucleic Acid TestingFemaleHospitalizationHumansMaleMiddle AgedNitrilesPhenylthiohydantoinAndrogen AntagonistsAndrogensAnilidesBenzamidesbicalutamideenzalutamideNitrilesPhenylthiohydantoinTestosteroneTosyl CompoundsAndrogen deprivation therapyAntiandrogenBicalutamideCOVID-19EnzalutamideRandomized trialSARS-CoV-2

Identifiers

PMID34980495
PMCPMC8673828
OpenAlexW4200176034

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.