Long-COVID patients have clear hormonal and immune differences, research shows, raising hope for treatments  

The findings clearly show that “the biology of people with long COVID has changed and is observably different from people who do not have long COVID, so we know what we’re looking at is a physiological condition,” David Putrino, co-author of the study and director of the Cohen Center for Recovery from Complex Chronic Illness at Mount Sinai, told MarketWatch. 

Based on the findings, Putrino said, “we’re able to give clinicians who are treating long COVID a trail of breadcrumbs” to follow to identify individual differences in hormones, immune function and other factors and more effectively treat their patients. 

Long COVID refers to a broad group of health problems that continue four weeks or more after an initial COVID infection, with common symptoms including severe fatigue, heart palpitations, difficulty thinking and shortness of breath. About 6% of U.S. adults had long COVID as of June, according to the Centers for Disease Control and Prevention.

The new research comes as COVID hospitalizations are once again on the rise, climbing 7.7% in the week ending Sept. 9, according to the CDC. Putrino, who runs a long-COVID clinic at Mount Sinai, said his “whole team is drowning in long-COVID cases,” with many of those cases triggered by COVID infections from just this year. The clinic’s waiting list is months long, he said.   

Since it was first recognized early in the pandemic, long COVID has stirred debate in some circles about whether it might be driven largely by psychological factors. But “every day we’re compiling evidence that this is in fact a biological condition and a complex chronic illness, not a psychosomatic one,” Putrino said. “The good science is finally starting to emerge that refutes the bad science that was being published early in the pandemic that minimized or gaslit people with this terrible illness.” 

That new evidence is crucial in part, Putrino said, because long-COVID patients are frequently refused accommodations, such as the ability to work remotely or reduce their work hours, that they have a legal right to under the Americans with Disabilities Act. The research on long-COVID biomarkers, he said, can provide those patients “with hard evidence of their condition so they can access the accommodations that are due to them, and even hold people accountable who have refused them in the past.” 

One in 10 adults with long COVID say they stopped working because of their symptoms, according to a recent Urban Institute study, and only about six in 10 long-COVID patients reported having access to paid sick leave at work. 

The Mount Sinai and Yale researchers studied more than 270 patients between January and 2021 and June 2022, including those with no prior COVID infection, those who had fully recovered from COVID and those with active long-COVID symptoms lasting four months or more. Each patient completed questionnaires about their symptoms, medical history and quality of life. Researchers analyzed the blood biomarker similarities and differences among the groups and used machine learning to assess which biomarkers most effectively helped the algorithm identify patients with long COVID. Ultimately, the algorithm was 96% accurate in differentiating long-COVID patients from those without the condition.  

The study provides new evidence about the potential causes of common long-COVID symptoms, and the researchers are working to correlate specific biomarkers with specific symptoms, Putrino said. For example, long-COVID patients often have lower morning levels of cortisol, a hormone produced by the adrenal glands, which is “potentially very pertinent to fatigue,” Putrino said. That helps build the evidence against long COVID being driven by psychological factors, he notes, because people with anxiety and depression often have higher, not lower, cortisol levels.     

The research also helps illustrate how the long-COVID disease process can vary widely from one person to the next. “Your own medical history and genetic history matters in terms of what goes wrong when you get long COVID,” Putrino said. While “there’s no silver bullet, no one magic cure for every single long-COVID patient,” he said, the research offers guideposts for clinicians on which tests to run so they can treat the dysfunction they see in the individual. The research, he said, “is a stepping stone toward therapies, a stepping stone toward understanding and addressing the root cause of long COVID.”