Science - USA (2020-06-05)

sciencemag.org SCIENCE

CREDITS: (PHOTO) VYACHESLAV PROKOFYEV/TASS VIA GETTY IMAGES; (DATA) MONTOPOLI

ET AL

.,

ANNALS OF ONCOLOGY

, HTTPS://DOI.ORG/10.1016/J.ANNONC.2020.04.479 (2020)

I

n January, one of the first publications

on those sickened by the novel corona-

virus in Wuhan, China, reported that

three out of every four hospitalized pa-

tients were male. Data from around the

world have since confirmed that men

face a greater risk of severe illness and

death from COVID-19 than women, and

that children are largely spared. Now, sci-

entists investigating how the virus does its

deadly work have zeroed in on a possible

reason: Androgens—male hormones such

as testosterone—appear to boost the virus’

ability to get inside cells.

A constellation of emerging data supports

this idea, including COVID-19 outcomes in

men with prostate cancer and lab studies

of how androgens regulate key genes. And

preliminary observations from Spain sug-

gest that a disproportionate number of men

with male pattern baldness—which is linked

to a powerful androgen—end up in hospitals

with COVID-19. Researchers are rushing to

test already approved drugs that block an-

drogens’ effects, deploying them early in

infection in hopes of slowing the virus and

buying time for the immune system to beat

it back.

“Everybody is chasing a link between an-

drogens ... and the outcome of COVID-19,”

says Howard Soule, executive vice president

at the Prostate Cancer Foundation, who

on 13 May ran a Zoom call presenting the

newest research that drew 600 scientists

and physicians. A second call scheduled for

3 June will discuss incipient clinical trials.

Epidemiological data from around the

world have confirmed the early reports of

male vulnerability. In Lombardy in Italy, for

example, men comprised 82% of 1591 pa-

tients admitted to intensive care units (ICUs)

from 20 February to 18 March, according to

a JAMA paper. And male mortality exceeded

that of women in every adult age group in

another JAMA study of 5700 New York City

patients hospitalized with COVID-19.

Now, researchers are on the trail of a

mechanism for this male bias—an effort

led by prostate cancer researchers, who

have a deep acquaintance with androgens.

Christina Jamieson of the University of

California (UC), San Diego, who has devel-

oped organoids to study prostate cancer,

recalls that she was in a Zoom meeting

honing ideas on how to link her research to

COVID-19 when her sister, also a UC San

Diego scientist, sent her a one-word text. It

read: “TMPRSS2.”

It was 16 April, and within minutes

Jamieson had found the publication that

prompted the text: a Cell paper by Markus

Hoffmann of the Leibniz Institute for Pri-

mate Research and colleagues. The paper

sent a lightning bolt through the prostate

research community, because it showed

that infection with SARS-CoV-2, the virus

that causes COVID-19, relies in part on TM-

PRSS2, a membrane-bound enzyme. The

enzyme cleaves the “spike” protein on the

coronavirus’ surface, allowing the virus to

fuse with the host cell’s membrane and get

inside the cell.

Jamieson and other prostate cancer re-

searchers were familiar with the enzyme,

because in about half of all prostate can-

cers, a TMPRSS2 mutation revs up an onco-

gene that kicks cell growth into overdrive.

In the prostate, TMPRSS2 is produced when

male hormones bind to the androgen recep-

tor. “Doing research, it’s like you’re trying

to throw an anchor into the vast ocean of

By Meredith Wadman

COVID-

Sex hormones signal why virus hits men harder

Emerging role of androgens suggests potential therapies to suppress infection

IN DEPTH

Men, like this one being

carried into a medical

center for COVID-

patients in Moscow, tend

to get sicker from the

coronavirus than women.

A protective treatment?

In one Italian study, men with prostate cancer who

received drugs that suppress androgens were much

less likely to be infected with SARS-CoV-2.

MEN ON

ANDROGEN-

DEPRIVATION

THERAPY (ADT)

MEN NOT

ON ADT

Total men with

prostate cancer

5273 3 7, 1 6 1

Number infected

with SARS-CoV-

4 114

Estimated cases

per 10,

8 31

1038 5 JUNE 2020 • VOL 368 ISSUE 6495

Published by AAAS