By David ,November 25, 2023 10:59 Newsday

When Andrea Maione caught COVID-19 in 2020, the Huntington woman already had sarcoidosis, an immune-system disease.

COVID made symptoms such as fatigue, shortness of breath, brain fog and joint pain much worse, and added new ones, including dizziness and an inability to taste some foods. More than three years later, Maione, 50, is still struggling.

She’s among millions of Americans with long COVID, which, like sarcoidosis, is more common in women than men.

Scientists are examining cases such as Maione’s to answer one of the many mysteries about long COVID: Why are women more likely than men to have sometimes debilitating symptoms of the virus that linger for weeks, months or years?

WHAT TO KNOW

• Women are significantly more likely to have long COVID, which is the continuing effects of COVID-19 at least four weeks after infection.
• An October federal survey found that more than 17% of adult U.S. women reported ever having experienced long COVID, compared with about 11% of men.
• Experts say possible causes of the sex differences include women’s stronger immune response to the virus, leading to long-term problems, and connections with immune-related diseases that are more common in women.

The answers could lie in differences in how men’s and women’s immune systems react to viruses and function generally, and in similarities between COVID-19 and immune-system diseases such as sarcoidosis, experts say.

Studies vary in estimates as to how many Americans have long COVID, which is defined by federal health authorities as effects from the virus at least four weeks after initial infection, but the gap between men and women is consistent.

More than 17% of adult U.S. women reported having had COVID-19 symptoms at least three months after infection in a Census Bureau survey from Oct. 18 to 30, compared with about 11% of men.

Nearly 7% of women and 4% of men said they currently had long COVID symptoms, and of those, more than 28% had “significant activity limitations.”

A 2022 Centers for Disease Control and Prevention survey, released in September, found lower levels of long COVID but a similar gap: 8.5% of women said they’d had long COVID, compared with 5.2% of men.

No cause determined yet

Scientists have not yet determined the causes of long COVID, which affects people in different ways. The most common symptoms include fatigue, dizziness, brain fog and gastrointestinal problems, studies show.

When COVID-19 infects someone, the body’s immune system kicks into gear, but too strong an immune response can damage the body, said Dr. Sabra Klein, a professor of molecular microbiology and immunology at Johns Hopkins University in Baltimore who studies sex differences in immune responses to COVID-19 and other viruses.

“Generally speaking, women mount greater immune responses” to viruses, and that stronger response could be one reason why women are more likely to endure effects of a COVID-19 infection long term, Klein said.

“If you keep stimulating an inflammatory immune response, you’re going to get side effects of inflammatory diseases,” she said. “So depending on which tissues [get inflamed], that can lead to shortness of breath, tightness of your chest, if that’s happening in your lungs. That can lead to inflammation of your heart, and contribute to some heart disease, if it’s in your heart.”

The prolonged immune response could be because pieces of the virus may remain in some people’s cells long after infection, for unknown reasons, Klein said.

Women’s more robust immunological reaction could be why men are more likely to get seriously ill from COVID-19 initially, said Dr. Alan Bulbin, director of infectious diseases at St. Francis Hospital & Heart Center in Flower Hill. But that also could harm some women long term, he said.

“For women, it’s their benefit turning against them,” he said.

At the Stony Brook Medicine Post-COVID Clinic in Lake Grove, more than twice as many of the roughly 1,400 patients are female as are male, said Dr. Sritha Rajupet, the center’s medical director.

She has noticed that women at the clinic are more likely than men to have fatigue, muscle and joint pain and mood-related changes such as anxiety or depression.

Some diseases, such as fibromyalgia, have similar symptoms and also affect women more than men, leading Rajupet and other experts to wonder if there’s a link between the illnesses and long COVID.

Autoimmune diseases such as lupus and multiple sclerosis — in which the immune system attacks and destroys healthy body tissue — also are more common in women, “And there is a hypothesis that auto-reactive immune responses might underlie long COVID,” Klein said. Some autoimmune diseases are caused by an initial viral infection, she said.

Different factors could cause long COVID in different people, she said.

Higher levels of long COVID in women also could stem from differences in men’s and women’s hormonal cycles, said David Putrino, a professor of rehabilitation medicine at the Icahn School of Medicine at Mount Sinai in Manhattan who researches long COVID.

Women experience greater hormonal changes, “and with these changes bring extreme surges in inflammation and immune functioning,” he said.

These spikes in immune response and inflammation could combine with inflammation spurred by a COVID-19 infection to cause long-term problems, he said.

Putrino is co-author of a study, now being finalized, that examines links between hormonal changes and long COVID, and how long COVID is more likely to be severe in women than in men. Findings will be released upon publication; a preprint version is expected within the next several weeks, he said. 

‘Become tired of trying to fight’

Maione has had COVID-19 three times: in May and December 2020, and in October 2022. She has been a long-distance runner for years, and she said doctors told her that is why she survived two bouts of COVID-related pneumonia in 2020.

Maione endured fatigue, shortness of breath, brain fog and other symptoms after 2020, but “some days were better than others,” and she was able to recover enough to run a half-marathon in March 2022, although at a slower speed than previous ones.

Yet her October 2022 infection reversed her progress, and her recovery since has been less strong, she said.

“A little bit here and there, but not as much as I would have hoped,” Maione said. “Mentally, I’ve become tired of trying to fight.”

The pain she had just from sarcoidosis was mild, with occasional flare-ups, but today it can sometimes be almost unbearable, she said.

“Some days I’ve been in so much pain I haven’t been able to get out of bed,” she said.

Maione had to leave four jobs because brain fog or fatigue made it difficult for her to work. She recently filed for Social Security disability.

Maione recently went back on the treadmill and was able to go two miles at a slow pace. But she worries she won’t get better.

“I’m anxious because I think, ‘What if this is it? What if my body isn’t going to cooperate?’ It’s scary,” she said.

Elizabeth Medina, 41, of Levittown, got COVID-19 in March 2020 and still has severe fatigue and frequent pain and numbness. She has food allergies, but because COVID-19 robbed her of her ability to taste or smell food, she can’t tell if she’s inadvertently eating something that is harmful. She now carries an EpiPen with her in case of a severe allergic reaction.

She’s seen little improvement in the past 3½ years.

“It almost feels hopeless,” she said.

Medina worries about getting in an accident — because of fatigue and brain fog — when she drives to and from her job as a school guidance counselor in the Bronx. At work, typing and writing can be painful.

Her doctors have told her that people with other diseases sometimes have a stall in improvements and later recover. But she’s had her hopes dashed too many times to be too optimistic.

“I’ve accepted this is what it’s going to be,” she said.