At first, Dr. Eunice Yu didn’t think much of the fact that a majority of her patients coming in with long COVID symptoms were middle aged women. After all, women are more likely to seek medical treatment for health issues in general. Maybe that explained why so many of them were pouring in with similar stories: how before COVID, they had been healthy, productive, even athletic women with kids and jobs and a million responsibilities.
“They were working, they were very active, often running, swimming and engaged in their family life,” said Yu, the medical director of COVID-19 Recovery Care at Henry Ford Health. “And they find all of a sudden, after an infection that was supposed to get better within a couple of weeks, [it’s] suddenly lingering now months and [even] years.”
Now, the women's lives looked very different. Plagued with debilitating fatigue, brain fog, muscle aches, and respiratory problems, some were unable to do basic activities like fold laundry, walk up the stairs, or get out of bed.
“They're struggling to do very basic things like take a shower without having to rest,” she said. “They are struggling to preserve their energy for the very most important things that they need to do for the day, like hugging their kids and sending them off to school. Or logging in for two out of the four meetings that they need to do that day.”
Desperate to understand what was happening, Yu started combing the mounting research about post-COVID conditions, also known as long COVID. What she found convinced her it was no coincidence the majority of her patients were female: a growing body of published studies suggest female sex is a risk factor for long COVID. In fact, being female may be a “significant predictor” of whether someone will go on to experience persistent symptoms like exertion intolerance, breathlessness, muscle pain, and the other issues Yu’s patients are experiencing.
“It does seem like it's a pretty reliable signal that there are more women than men who are likely to get long COVID, and that the middle-aged age group is more likely as well,” she said. “There are still millions of men who have experienced long COVID symptoms, or symptoms lasting longer than three months. But far more women have experienced it than men.”
Dr. Salim Hayek, co-director of the University of Michigan post COVID-19 clinic, agreed.
“The vast majority of people that we see in our clinic for long COVID symptoms are women who are experiencing this, what we call dysautonomia,” he said. (Dysautonomia is a problem with the part of the nervous system that regulates things like heartbeat, breathing, and digestion.)
“So essentially they're experiencing lightheadedness when standing. They're experiencing rapid heart rate palpitations and shortness of breath. And it is clearly predominant in women. … I can safely say that at least 75% of patients coming in with long COVID symptoms have been women rather than men.”
At first, some patients told “there’s nothing wrong with you”
Almost immediately after opening the long COVID clinic, Hayek said they were overwhelmed by the sheer number of patients seeking treatment.
“That clinic was the busiest we’ve ever had,” he said. “We’ve had 400 people on the waiting list at all times. And we had a lot of trouble getting people [in for treatment], just by the sheer volume of patients complaining of symptoms that they attributed to long COVID."
"It was a really busy clinic. We didn't have enough physicians staffing it and the waitlist was long,” said Hayek.
So long, in fact, that the U of M health system is moving away from having a standalone post-COVID clinic, he said. Logistically, it’s easier to send patients “to the specialty that fits their symptoms,” rather than “having everybody come to one point.”
That’s the approach Yu has taken at Henry Ford Health. There’s just no way to have the roughly 3,000 long COVID patients in their system, all funnel into a single clinic. Rather, she said, you need to build the ability to recognize and treat long COVID into the overall primary care system, because too often, these patients are being told that there’s either nothing wrong with them, or that there’s nothing that can be done to help them.
“One thing I've seen is how a lot of these folks have been struggling to get care, and really desperate to find answers,” Yu said. “And [they] have gone to every specialist [and] have done a lot of testing. And when doctors tell them, ‘I'm sorry, I don't understand what's happening to you, and there's not anything else that I can figure out,’ they have to go on to the next person.
“And it's just an incredibly frustrating experience. A lot of folks are telling me how dismissed they feel by the health care system, as well as how discouraged they feel that there is not sort of an answer. And that uncertainty is just crushing.”
Hayek said that’s why he reassures patients that they’re not crazy. “A lot of people feel frustrated that they're not understood, or people are dismissing these symptoms. These are real symptoms. These are not these are not made up. And they are treatable.”
Long COVID’s “remarkable similarities” to other syndromes
The chief reason Hayek’s so confident about treating long COVID is that he’s seen this before: women coming in with similar symptoms, weeks or even months after having an acute illness. And he’s not alone. Many researchers think long COVID may share characteristics with other prolonged, debilitating syndromes that have also been linked to acute infectious diseases — and are also diagnosed disproportionately in women.
Similar post-infection syndromes were observed in people who contracted the Ebola or chikungunya viruses. And chronic Lyme disease, chronic fatigue syndrome, fibromyalgia and postural orthostatic tachycardia syndrome (POTS — a condition that affects blood flow) are all more frequently diagnosed in women than in men, have many of the same symptoms, and share “remarkable similarities” with long COVID.
In fact, Hayek said a lot of his long COVID patients present just like his POTS patients. (Other researchers have noted the similarity between POTS and long COVID patients, too.)
POTS is a blood circulation disorder that causes fatigue and a feeling of lightheadedness brought on by standing or sitting up. Even the smallest exertion can make a patient’s heart race and leave them feeling breathless.
Like long COVID, POTS is often experienced after a viral illness. And women experience POTS at roughly five times the rate of men, Hayek said.
“This is less of a mystery than it’s sometimes portrayed to be,” he said. “Because millions and millions and millions of people are infected with COVID, now we suddenly see this much more frequently than we ever had before. But it doesn't mean that this is something that we haven't seen before, or this is something that we don't understand. This is something that we do understand, and that we have seen before, even in the post-viral setting.”
The good news, he said, is that the vast majority of these long COVID patients at the clinic do well. “Yes, you will have some patients that will have prolonged symptoms, but the vast majority will resolve within six months,” Hayek said. “And that's the first thing I tell patients. I reassure them, this is not something you're going to have to live with forever. We have treatments. We have strategies that really help. And that is a major source of relief.”
A “blind spot in the field of medicine”
But we still don’t understand what causes many of these similar post-infectious syndromes, or why they seem to happen predominantly to women. For years, they’ve been lumped under the umbrella of “enigmatic chronic illnesses” that “represent a substantial healthcare burden, but there is a lack of understanding of the underlying mechanisms, representing a significant blind spot in the field of medicine,” scientists wrote in this month’s Nature Medicine.
“For some reason, more women than men have been getting all of these different conditions, and [it] may be related to a stronger immune response in women,” Yu said. That’s one theory: that women may have a heightened immune response to pathogens like COVID.
“So the body’s trying to defend itself … and essentially the body starts injuring itself in the effort of fighting the virus off,” which can lead to heightened inflammation, Hayek said. “When that inflammation goes unchecked after some time, that's when we start noticing tissue damage that not just occurs at the level of the nerves, but at the level of different organs. Why specifically it happens in women, we don't know.”
Another theory: latent reservoirs of the COVID virus could hide out in the body, and either get reactivated or keep generating that hyperactive immune response in female patients. (Something similar may happen with Lyme disease, too.)
“Fragments of SARS-CoV-2 could remain hidden in reservoirs such as the kidneys or brain, igniting some chronic inflammation ... giving rise to symptoms such as pain or brain fog experienced by patients with long COVID,” researchers in the European Respiratory Journal wrote earlier this year.
But with millions of men and women now experiencing long COVID, and a growing push to invest in research, there may finally be some more answers.
“With the just the urgency of so many folks being disabled so quickly, there is a lot of attention and a lot of money for research, in particular on these underlying mechanisms,” Yu said. “I hope [this] will help us better understand these conditions, no matter who gets them.”
The long term cost
Given that as many as 1 in 5 adults who get COVID may go on to experience long term symptoms, experts are trying to calculate the full cost of millions of Americans dealing with chronic disease.
“We could possibly approach a million, and even higher than a million, long COVID cases in Michigan,” said Jonathan Tsao, a biostatistics expert at U of M's Center for Healthcare and Research Transformation, which just published a small, statewide survey on long COVID. One in three respondents who’d contracted COVID said they went on to have long term symptoms. And women were nearly four times as likely as men to report experiencing long COVID.
Across the board, “long haulers are more likely to be in a worse financial situation than a year ago compared to those who recovered from COVID and those who never got COVID,” the survey found.
“[With] all these long term chronic conditions, it is very debilitating for individuals to function at their full working capacity,” Tsao said.
“Those who've experienced these symptoms, they were more likely to either work reduced hours, or decide to voluntarily quit, or even get laid off from their jobs due to the demands of their jobs as well.”
He’s hoping employers are paying attention, and make accommodations just “like any other disability that might happen in the workplace.” But women will likely be most impacted — not just because they experience more long COVID, but because they already were more likely to work in sectors that saw COVID-related job cuts, or have to take on caregiving responsibilities during the pandemic.
“What we want them to take away from this … is basically that they're not alone,” Tsao said. “There's a lot of people who are going through what they're going through.”
