An international team of scientists has found distinct changes in the blood of people with long COVID, suggesting a potential strategy to diagnose and perhaps treat a mysterious condition that takes many forms.
The study, published Thursday in the journal Science, adds to our understanding of long COVID, the lingering and often debilitating symptoms experienced by some people, by revealing shifts in proteins that the body produces in response to inflammation that may persist months after infection.
“We identified common patterns in long COVID patients not recovered at six months after acute infection,” compared to healthy patients, wrote the team, a collaboration of scientists from New York City’s Icahn School of Medicine at Mount Sinai, Switzerland, Sweden and London.
There is tremendous need to diagnose and find effective ways to treat long COVID, a constellation of symptoms that include exhaustion, migraines, brain fog and nausea.
Although its prevalence is difficult to estimate, surveys suggest that long COVID may afflict 5.3 percent to 7.5 percent of people infected by the virus. The more vaccines you get, the less likely you are to get the disease. One dose of vaccine reduces risk by 21 percent, two doses reduces risk by 59 percent, and three or more doses reduces risk by 73 percent, according to a recent study.
What causes long COVID? Long after the initial infection, the immune response doesn’t stop fighting.
Experts don’t know why, but University of California San Francisco research has revealed tiny pieces of the SARS-CoV-2 virus, perhaps hidden in tissue, that persists long after infection. There is mixed evidence for the effectiveness of the antiviral drug Paxlovid in preventing long COVID.
Currently, doctors are treating the symptoms, rather than the underlying cause, of long COVID.
The new findings are important because “they demonstrate dysfunction, which is important to patients,” said Jaime Seltzer, director of scientific and medical outreach at the advocacy group MEAction, which advocates for patients with long COVID and myalgic encephalomyelitis/chronic fatigue syndrome, or ME/CFS, which is caused by other viral infections.
“Secondly, they point the way to potential treatments and even possibly mechanisms” of disease, she said.
This paper builds on our understanding of long COVID by connecting the changes that occur during an acute infection to longer-term abnormalities in markers of blood cell function, said Dr. Michael Peluso, an infectious disease physician at Zuckerberg San Francisco General Hospital, who is studying the biological mechanisms that drive long COVID and the infection’s long-term impact on health.
“It suggests that there is a relationship between the virus, its immune effects and changes in certain blood coagulation pathways,” he said.
No immediate changes
Although the study represents another step forward for understanding the science of long COVID, it will not immediately change the approach to diagnosing or treating the condition, said Peluso.
“We need more investment in larger studies to build upon these findings, as well as clinical trials to test whether altering some of the abnormalities that have been found here could result in symptomatic benefit,” he said.
In the new study, scientists analyzed changes in the blood of 113 patients who either fully recovered from COVID-19 or developed long COVID, as well as healthy people.
Specifically, they measured levels of 6,596 different proteins in study participants over a year, then sampled the blood again six months and one year later. Proteins act like keys that fit in multiple locks on the surface of cells. Changes in proteins mean that cellular processes have been altered.
The team found that patients with long COVID showed changes in the system of proteins that combats pathogens, like viruses. Dysregulation of these proteins could be contributing to the tiny “microclots” sometimes seen in long COVID patients.
This type of dysregulation has also been seen in people with other persistent infection-related illnesses, such as chronic fatigue syndrome, said Seltzer. It’s the body’s way of adapting, she said.
There are caveats. With only 113 patients, the study was relatively small. Many participants were so sick that they needed hospitalization, which could have influenced results. Finally, it studied changes only within a year of infection; three to five years later, there may be different markers in the blood, said Seltzer.
These features suggest potential interventions, Wolfram Ruf of the Center for Thrombosis and Hemostasis in Germany wrote in a commentary that accompanied the report. Perhaps anti-inflammatory drugs would help, he noted, and anti-coagulants might reduce the risk of dangerous blood clots.
“Eventually, the hope is that some of these findings can translate into the clinic, but we are still a ways away from that,” said Peluso. “We need to keep up the momentum to get answers for the tens of millions of people with this disabling condition.”
