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No one knows for sure why COVID-19 is linked to male sexual woes, but growing evidence, including a new study in monkeys, has suggested that the SARS-CoV-2 virus directly infects the male reproductive system -- just like other viruses such as mumps and Zika.

Thomas J. Hope, PhD, a cell biologist at Northwestern University in Chicago, who co-authored the monkey study published as a preprint on , told MedPage Today that his team saw "the same pathology [in monkeys] that we've seen recorded in human studies. To an extent, we feel comfortable in saying it's probably direct infection that's causing all these problems."

Hope and co-authors hadn't intended to break ground on COVID-19 and male sexual health research. They launched their study in rhesus macaques inoculated with the virus to determine if a scanning technology known as immunoPET, which is used in cancer and simian immunodeficiency virus research, could detect signs of SARS-CoV-2.

They used an intravenously injected probe to light up areas that showed signs of infection and conducted PET/CT scans at necropsy to take a closer look. This strategy works because it points the researcher toward elusive antibodies that are akin to needles in haystacks, Hope said.

"If we just take random samples, we can't learn anything. But if I can make the needle glow, I can grab a handful of hay, hold it up, and open my hand to see if I captured the needle. If not, then I go grab another handful. Through this kind of approach, I can find a tiny little piece of tissue," he explained.

The technology worked, but not in the way that the researchers anticipated. Unexpectedly, they didn't find much infection in the lungs, but they did discover a "robust and dynamic signal" of infection in the penises, testicles, and prostates of all three monkeys examined.

These findings suggest that COVID-linked erectile dysfunction, swollen testicles, and semen dysfunction in humans are "likely a consequence of the direct viral infection of the tissues" in the male reproductive tract, they wrote.

Hope said that this study confirms previous research that has found signs of the virus in the male reproductive system. At least two studies, published in and , have suggested COVID-19 lurks in the testicles.

As a whole, the findings challenge the idea that the male sexual problems linked to COVID-19 could be caused solely by systemic inflammation or symptoms such as fever. "This is all valuable information because we know so little right now, and this virus is hard to follow," Hope said. "Once we know where the virus is in the body, we can use the appropriate therapy that will get to that spot."

Why study the virus in the male reproductive system of monkeys instead of humans? "We can't get access to these tissues except for cadavers," Hope explained. In vivo tissues are ideal, he added, but men are unlikely to agree to allow a researcher to poke around their privates for research purposes.

Research like this in animals also offers a benefit because scientists can better track how long it takes for cells to become infected with COVID-19, Hope noted. In human cadavers, "the pathology associated with a specific organ could have happened 6 months ago, or 6 weeks ago. It's variable."

T. Mike Hsieh, MD, a urologist at the University of California San Diego, told MedPage Today that it will be helpful to understand whether COVID-19 causes male sexual problems via direct infection of reproductive organs or by some other route such as systemic inflammation.

He pointed out that other viruses -- most famously, mumps -- can target the testicles. An estimated who get mumps develop swollen testicles, and their sperm count may also drop. More rarely, women can develop swollen ovaries.

Hsieh said that while he has seen cases of erectile dysfunction in patients after COVID-19, "I haven't seen any convincing long-term, chronic sexual problems from COVID-19."

What's next on the research front? While funding is running out, Hope said that his team expects to explore the effects of COVID-19 on the female reproductive system. "I'm optimistic that by the end of the spring, we'll have multiple female animals that will provide us insights into what's happening in women," he added.

Previous research has linked COVID-19 in women to and higher rates of .

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