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 on Thursday in the journal Science, adds to our understanding of long COVID, the lingering and often debilitating symptoms experienced by some people. One significant finding revealed shifts in proteins the body produces in response to inflammation that may persist months after infection. Another detected blood clots and tissue injury.

“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 that are not explainable using conventional lab tests.

At a hearing in Washington D.C. this week, senators at the Senate Committee on Health, Education, Labor and Pension agreed that the government must become more involved in long COVID research and support. Sen. Tim Kaine, D-Va., said he has been struggling with symptoms of long COVID for four years.

On March 15, a demonstration is planned at Lincoln Memorial to raise awareness and urge greater funding, preventative measures, research, and treatment strategies.

Although long COVID’s prevalence is difficult to estimate, surveys suggest it may afflict 5.3% to 7.5% of people infected by the virus.  It’s not known why some people develop long COVID and others don’t. But vaccines offer protection. One dose of vaccine reduces risk by 21%, two doses reduce risk by 59%, and three or more doses reduce risk by 73%, according to a recent study.

What causes long COVID? One possibility is that, long after it fends off infection, the immune system is still fighting. It turns on — but doesn’t turn off.

Experts don’t know why. UC San Francisco research suggests that viral genetic material remains embedded in tissues, long after infection. Or perhaps COVID triggers an autoimmune response when the body mistakenly attacks itself. There is mixed evidence for the effectiveness of the antiviral drug Paxlovid in preventing long COVID.

There is a desperate need for a diagnostic test and treatment for long COVID. Currently, doctors are treating the symptoms, rather than the underlying cause.

The new findings are important because “they demonstrate dysfunction, which is important to patients,” said Jaime Seltzer, scientific director at the nonprofit MEAction, which advocates for patients with long COVID and myalgic encephalomyelitis/chronic fatigue syndrome, or ME/CFS.

“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.

Although the study represents another step forward in 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 a year later.  Proteins act like keys that fit in multiple locks on the surface of cells. Changes in proteins mean that cellular processes are altered.

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The team found that patients with long COVID suffer from disruption in the system of proteins that combats viruses and other pathogens. This change could be contributing to the tiny “microclots” sometimes seen in long COVID patients, as well as other symptoms.

Immune dysfunction is also suspected to be driving the symptoms in those with other persistent infection-linked illnesses, such as ME/CFS and Lyme Disease, 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 only studied changes within a year of infection; three to five years later, there may be different markers in the blood, said Seltzer. Patients’ immune systems may not be able to stay overactive indefinitely.

These features suggest potential interventions, wrote Wolfram Ruf of the Center for Thrombosis and Hemostasis in Germany, in a commentary that accompanied the report. Perhaps anti-inflammatory drugs would help. 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.”