Almost 20 percent of all U.S. adults who have had COVID-19 were experiencing long COVID as of June 2022. Nearly three years into the pandemic, the millions of people experiencing the illness are still facing highly debilitating, life-altering symptoms like brain fog; muscle and joint pain; loss of smell or taste; difficulty breathing; and a worsening of symptoms after physical or mental effort (including daily chores such as washing dishes) known as post-exertional malaise. But some patients and advocates say funding for research on what causes long COVID and how it can be treated has been notably slow.
“The infrastructure to build on the existing research really isn’t there, [nor the] resources for the kind of large-scale clinical funding that we’re going to require to solve this,” Hannah Davis, co-founder of the Patient-Led Research Collaborative and a long COVID patient since 2020, tells PGN. The good news is that there’s been a lot of progress on research over the past six months, which has given patients a glimmer of hope. “Now that it is very clear that millions of people in the U.S. are sick, and it’s affecting the economy,” Davis adds, “something’s starting to be done about it.”
To help you understand the latest on long COVID—who is most likely to be affected, theories on how the illness develops, and possible ways to treat it—we’ve rounded up some of the most important recent research findings.
Women may be most at risk
Globally, a recent study found that women make up 63 percent of long COVID patients, while another study focused on the U.S. also found that women could be more at risk for experiencing the illness. A CDC survey found that among U.S. adults, women were more likely than men to have long COVID.
Though there’s no clear answer about why women may be more likely to experience long COVID, a few studies have suggested it may be because women have a more robust immune system response compared to men. And while that’s beneficial when fighting COVID-19, Dr. Dean Blumberg of UC Davis Health told Healthline that it can “go overboard” and “result in immune dysregulation following COVID, resulting in the symptoms of long COVID.” The authors of one literature review wrote that the same immune differences that make women more vulnerable than men to autoimmune diseases may also make them more susceptible to long COVID.
How long COVID develops
There are several theories about what causes long COVID, including the idea that the virus remains in a person’s system for longer than expected after infection.
“Many people had thought that the virus would be eliminated from the body after the initial illness,” Dr. Anthony Komaroff, professor at Harvard Medical School and senior physician at Brigham and Women’s Hospital, tells PGN. “However, there now is increasing evidence that the virus—or at least pieces of the virus—can remain in the body for a long time, at least in some people, and that this happens more often in people with long COVID. That could be causing the immune system to be chronically activated, as it recognizes and reacts to the residual virus. And the chronically activated immune system, in turn, could be causing the symptoms of the illness. This is a plausible, but unproven, theory.”
Another theory that researchers are currently studying is the possibility that microclots, or tiny blood clots, could be blocking blood vessels and preventing oxygen from flowing properly through the body. Some non-peer-reviewed research has suggested that systemic inflammation in long COVID patients could lead to the formation of microclots.
Researchers have also found several similarities between long COVID and other illnesses like myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Komaroff said the two illnesses share many symptoms, including brain fog, fatigue, disrupted sleep, and abnormalities of heart rate and blood pressure on standing up. “Loss of smell and taste are much more common in long COVID than in ME/CFS, but otherwise the symptoms of the two illnesses are very similar,” Komaroff says. He added that “as more research is reported, it’s becoming clear that the two illnesses also share similar underlying biological abnormalities. These abnormalities involve the immune system, the brain and autonomic nervous system, energy metabolism, and abnormalities in the types of bacteria that live in the gut.”
Another recent analysis that studied data from 22 countries found that 90 percent of people living with long COVID initially experienced mild COVID-19 illness—which means that even if a person’s COVID-19 case is mild, they could be at risk of developing long COVID.
COVID-19 reinfections can increase the risk of developing long COVID
A recent study found that people who were infected with COVID-19 more than once were more likely to experience long COVID symptoms. The study, conducted with data from the Department of Veterans Affairs, also found that reinfections overall can increase the risk of hospitalization and death. This study is a particularly important one, according to Dr. Alba Azola, assistant professor at Johns Hopkins University School of Medicine and co-director of the Johns Hopkins Post-Acute COVID-19 Team, who was not involved in the study. Not only does it indicate that reinfection is linked to long COVID risk, but “people are starting to take their guards down and not continue common sense, social distancing, masking, all those types of measures,” she says. And as COVID-19 cases continue to rise again, “it’s important for people to understand the risks that they’re putting themselves in” if they stop taking precautions. But the study has its limitations: Its participants were mostly older males, who are not representative of the general population.
Possible prevention and treatments
A recent Cambridge University meta-analysis found that vaccination (primarily mRNA vaccines) both before and after a COVID-19 infection decreased the risk of long COVID. “COVID-19 vaccination before and after having COVID-19 provided a low but statistically significant decrease in post-COVID-19 conditions for the variants circulating during the study period,” the authors of the analysis wrote. They also acknowledged that more research is needed into vaccine effectiveness against long COVID, including for non-mRNA COVID-19 vaccines.
Each of the many long COVID symptoms—including respiratory, neurological, and digestive symptoms—has its own set of research on treatments, some of which are currently being offered at long COVID clinics. For instance, Dr. Zara Patel, director of endoscopic skull base surgery and professor of otolaryngology at Stanford University, tells PGN there are some research-backed treatments already being offered to patients with anosmia, or smell loss, including olfactory trainings, steroid irrigations, high-dose omega-3, and platelet-rich plasma.
A recent large Veterans Affairs study found that Paxlovid, the antiviral used to treat COVID-19, may reduce the risk of developing long COVID. The study, which is not yet peer reviewed and included over 56,000 veterans with a positive COVID-19 test, found that the patients who received Paxlovid within the first five days of being infected had a 25 percent lower risk of developing long COVID, including symptoms like liver disease, neurocognitive impairment, blood disorders, and fatigue.
According to Dr. Francesca Beaudoin, Brown University professor and director of the Long COVID Initiative, this study is particularly important as some long COVID patients seek alternative treatments that may not be proven effective or may even be harmful. “People have been trying a lot of off-label therapies, off-label therapeutics,” Beaudoin tells PGN. “Ivermectin is probably the one that I’ve most heard about recently, but also people getting blood tests and immunology profiles, paying out of pocket.” So, Beaudoin added, “the more that we have evidence around what works and doesn’t work, [the more that] will equip people to make more informed decisions.”