Tens of millions of people in the U.S. have struggled with long COVID: a suite of symptoms that can persist long after an initial COVID infection and impact one’s day-to-day life. Typically, these “long haulers” experience fatigue, difficulty concentrating and joint pain. At its worst, however, the syndrome can leave them bedridden.
Now studies suggest the rates of long COVID may be dropping. Although the investigations were not designed to assess the reason for this trend, scientists suspect the downturn is a result of increased immunity to SARS-CoV-2 (the virus that causes COVID), milder variants of that pathogen and improved treatments. It is a welcome reprieve, but the decline does not help the millions of people who are already suffering from long COVID. Moreover experts warn that the risk is still not zero. And without a clear explanation for the downward trend, it is unclear whether it will continue.
“You have to be vigilant,” says Paul Elliott, an epidemiologist at Imperial College London’s School of Public Health. “You can’t just relax these days and be done.”
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There is reason for hope, however. Elliott and his team recently reported that people infected during the pandemic’s Omicron wave were 88 percent less likely to develop long COVID, compared with those infected with the original strain that emerged in Wuhan, China. The research, published in October in Nature Communications, is the latest in a growing number of studies that point to a downswing in the debilitating condition. This summer, the U.S. Centers for Disease Control and Prevention noted that the proportion of people infected with SARS-CoV-2 who went on to develop long COVID dropped from 18.9 percent in June 2022 to 11 percent in January 2023. And just a few months before that European researchers found that the risk of long COVID among cancer patients fell from 19.1 percent in 2020 to 6.2 percent in early 2022. Other studiesshow similar findings.
Although the studies disagree on absolute numbers, experts argue that the downhill trend is real—that the likelihood of any individual developing long COVID has fallen since the beginning of the pandemic. The question is why.
To start, greater population immunity—whether from infection, vaccination or both—has likely provided protection against lingering symptoms. There is no question that vaccines have provided a strong defense against the virus over the past three years. And multiplestudiessuggest that vaccination also reduces the chances of developing long COVID—especially for those who stay up-to-date on their shots. The study on cancer patients, for example, found that the risk of developing long COVID was highest before vaccines against the disease were available and that participants who had received a booster were less likely to develop long COVID than those who were only partially vaccinated. Moreover a study published just last week found that three or more doses of a COVID vaccine reduced the risk of long COVID by 73 percent, compared with 21 percent after just one dose. And while research is inconclusive on whether repeat infections confer protection, a single infection mixed with vaccination—otherwise known as hybrid immunity—likely reduces future infections and disease.
“At the population level, we are developing immune responses to the virus,” says Akiko Iwasaki, an immunologist at the Yale School of Medicine. “The baseline immunity is different from when the pandemic first started.”
We are also dealing with different viral variants. Many scientists believe that the intrinsic features of the different SARS-CoV-2 strains make them more or less likely to cause long COVID. Thus, many long COVID studies broke their data down not by infection date but by the dominant variant at the time. And some suggested that the severity of long COVID was far worse for those infected at the very start of the pandemic. One investigation compared Swiss hospital workers in May 2022—roughly six months after the Omicron variant first appeared—with workers who had been infected with the original strain in 2020. It found that the latter had far more lingering symptoms than those who were infected more recently. “I really think there is something to this variant, to Omicron, that makes it less aggressive,” says Philipp Kohler, an infectious disease specialist at St. Gallen Cantonal Hospital in Switzerland and co-senior author of the study.
In some ways, the findings are not a surprise. During acute illness, Omicron is much less likely than earlier strains to land patients in the hospital with severe symptoms, which researchers know is a major risk factor for long COVID. Mild cases can also lead to long COVID, however, causing scientists to argue that another factor is at play. One hypothesis suggested in animal studies is that Omicron targets cells in the upper respiratory tract—causing coldlike symptoms in the nose and throat—whereas earlier forms of the virus targeted the lower respiratory tract and even involved other organs, where they continued to replicate and cause long-term symptoms.
Finally, treatments may have chipped away at long COVID incidence as well. Antivirals can now help to corral the virus early in an infection, thus reducing both its acute severity and its long-term impacts. In March 2023 a study involving more than 280,000 veterans with COVID found that those who were given the drug Paxlovid in the first five days of symptoms had an about 25 percent lower risk of developing long COVID than a control group. And a more recent study found that people who were overweight who received another drug called metformin, which also has antiviral properties, were 41 percent less likely to develop long COVID than those who received a placebo. Yale Medicine cardiologist Erica Spatz, who was not involved in the metformin study, was so impressed by the results that she now prescribes it to any COVID patients concerned about long COVID.
Yet for the most part, doctors are not widely ordering these drugs, meaning that they are probably not the main culprit behind the society-wide long COVID decline. And disentangling the two other hypotheses—population-level immunity and an intrinsic change to the virus—will be a challenge. Ziyad Al-Aly, a clinical epidemiologist at Washington University in St. Louis, who has led several studies of long COVID and was senior author of the metformin paper, would like to see an investigation that would cover the entire pandemic—one that enrolls patients who suffered long COVID following infections with every variant and thoroughly documents their vaccination, infection and antiviral history to tease out the actual reason behind this change. He notes that such a study would not be easy, particularly because COVID testing and tracking have recently slowed, so long COVID patients are likely being undercounted. (Many of the previously mentioned papers avoided this issue because they stopped collecting data before the slowdown in testing.) But Al-Aly argues that such a study is feasible. It is also crucial if we want to know whether the long COVID downswing will continue.
Many argue that if population immunity is key, then long COVID cases could continue to drop. That is assuming vaccination uptake does not deteriorate further, however. “We cannot have our cake and eat it, too,” Al-Aly says. “We cannot say vaccinations reduce the risk of long COVID by some percent and then abandon them—as is looking very likely—and expect long COVID to continue to decline.”
But if the variant is more important, the future of long COVID will be the result of evolutionary chance. The virus will continue to mutate, and the next variant could be far more severe than Omicron and thus drive long COVID rates—not to mention deaths and hospitalizations—up again. Yet even in this dire case, Iwasaki says there is promise. If you are vaccinated, she says, you might be able to withstand a more dangerous variant. “That is my hope,” Iwasaki says. “Currently there is nothing to go against that hope. But we can’t be too comfortable. We can’t assume that the future variants will be very mild.”
And even if we are lucky, many experts argue that a dwindling risk is still a very real one. Nicole Ford, a senior health scientist at the CDC, who led the agency’s investigation of long COVID earlier this year, notes that at the end of the study period in June 2023, roughly one in 10 adults who previously reported a COVID infection were still suffering from persistent symptoms. Of those, one in four had difficulty performing day-to-day activities—an alarming find, given that treatment is still lacking, and some patients have yet to fully recover. “The take-home from this study is that long COVID is common,” Ford says. “It can impact absolutely anyone.”