Evidence map›Paper›PMID 39363910›Full record

ArticleJournal of clinical and translational pathology2023

Androgen Drives the Expression of SARS-CoV-2 Entry Proteins in Sinonasal Tissue.

Rong Rong Huang, Jenna M Giafaglione, Takao Hashimoto, Liying Zhang, Weibo Yu, Jianyu Rao, Joshua W Russo, Steven P Balk, Nicholas G Nickols, Mathew B Rettig and 2 more

Abstract read
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In one paragraph

Article in Journal of clinical and translational pathology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Rong Rong HuangDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, CA, USA.ORCID https://orcid.org/0000-0001-5308-8024
Jenna M GiafaglioneDepartment of Molecular, Cell & Developmental Biology, University of California, Los Angeles, CA, USA.
Takao HashimotoDepartment of Molecular, Cell & Developmental Biology, University of California, Los Angeles, CA, USA.
Liying ZhangDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, CA, USA.
Weibo YuDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, CA, USA.
Jianyu RaoDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, CA, USA.
Joshua W RussoHematology-Oncology Division, Department of Medicine and Cancer Center, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Steven P BalkHematology-Oncology Division, Department of Medicine and Cancer Center, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Nicholas G NickolsDepartment of Radiation Oncology, University of California, Los Angeles, CA, USA.
Mathew B RettigDivision of Hematology-Oncology, Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
Andrew GoldsteinDepartment of Molecular, Cell & Developmental Biology, University of California, Los Angeles, CA, USA.
Huihui YeDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, CA, USA.ORCID https://orcid.org/0000-0002-8307-9492

Funding

UCLA SPORE IN PROSTATE CANCERP50CA092131 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REITER, ROBERT E · 2002 to 2023
$42.6M
Steroid Metabolism in Castration-Resistant Prostate CancerP01CA163227 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI PETER S NELSON · 2013 to 2026
$25.0M
The Origins of Metabolic Reprogramming in Prostate CancerR01CA237191 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GOLDSTEIN, ANDREW S · 2019 to 2023
$2.0M
NCI NIH HHS P01 CA163227NCI NIH HHS P50 CA092131NCI NIH HHS R01 CA237191
6 · The paper itself

Abstract

Background and objectives: Men have higher morbidity and mortality from COVID-19 than women, possibly due to androgen receptor-regulated viral entry protein expression. This led to a clinical trial of androgen deprivation therapy (ADT), which has not shown a significant benefit in the outcomes among hospitalized male COVID-19 patients. The aim of this study was to explore biological explanations for the failure of ADT to mitigate clinical outcomes in men with severe COVID-19 by assessing the role of androgen in regulating viral entry protein expression in the upper and lower respiratory tract. Methods: Immunohistochemistry was used to assess the expression of transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2) and how it correlated to androgen receptor expression in the sinonasal epithelium, minor salivary glands of the sinus, lacrimal glands, and lungs from mice pretreated with and without castration and ADT as well as the sinonasal epithelium obtained from healthy human donors and hospitalized COVID-19 patients. Results: In murine models, castration and ADT treatment downregulated the expression of TMPRSS2 and ACE2 in the sinonasal epithelium, minor salivary glands of the sinus, and lacrimal glands, but not in the lungs. Correlative analyses using human tissue also showed a potential role of ADT in men during the early sinonasal phase but not in the later lung phase of SARS-CoV-2 infection. Conclusions: Our study suggests a potential benefit of ADT in male patients with early COVID-19 when the virus enters the nasopharynx, but not in those with advanced disease. The downregulation of viral entry proteins in the upper respiratory system following androgen blockade may be a key mechanism for this effect.

Indexed as

ACE2Androgen deprivation therapyAndrogen receptorCOVID-19SARS-CoV-2TMPRSS2Viral entry proteins

Identifiers

PMID39363910
PMCPMC11449218

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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 OpenQuestion graph.