Swiss scientists have identified immune system abnormalities in patients with long COVID that might open the door to new diagnostic tests and treatments.
The researchers found that a group of proteins in the blood that are part of the body’s immune response called the “complement system” are not working properly in patients with long COVID.
Blood samples turned up important differences between those who recovered from COVID and those who did not. These differences might be used as biomarkers to diagnose long COVID and might even point the way to new treatments for the condition, the researchers said.
By testing for 6500 blood proteins in about 300 patients, the Swiss researchers found that dysfunctional complement system proteins could possibly explain fatigue and “smoldering inflammation,” said Onur Boyman, MD, a professor of immunology from University Hospital Zurich in Zurich, Switzerland.
Long COVID has been linked to hundreds of symptoms including brain fog, chronic fatigue, pain, and digestive issues. Various factors drive the condition and likely work with one another other, said David Putrino, PhD, from the Icahn School of Medicine at Mount Sinai in New York City. The Swiss study is useful because “we’re trying to best understand how we can explain all of this far-reaching pathobiology,” he said.
Testing Across Continents
Dr. Boyman’s team collected blood samples from people with COVID in Europe and New York and tracked them. They compared those who developed long COVID with those who did not. One protein that was most unique to patients with long COVID is a blood complement that activates the immune system, Dr. Boyman said. But in people with long COVID, the immune response stays activated after the virus is gone. He described the response as “smoldering inflammation” in multiple organs, including the lungs and the gastrointestinal system.
The complement system also plays a role in clearing the body of dead cells. If the cells “lie around too much,” they can trigger an immune response, he said.
That may explain exercise intolerance in people with long COVID, Dr. Boyman said. Some people with long COVID have inflammation in the epithelium — the inner layer of their blood vessels. This would make it harder for the circulatory systems to recover from exercise, Dr. Boyman said.
“We think this regulated complement system is actually quite a central piece of the puzzle,” he said.
The Microclot Connection
The findings also support past research linking blood clots to long COVID. He suggested that clinicians and researchers consider testing drugs that regulate or inhibit the complementary system as a treatment of long COVID. Dr. Boyman said they are currently used for rare immune diseases.
Resia Pretorius, PhD, a professor of physiological sciences at Stellenbosch University in Stellenbosch, South Africa, said scientists studying the role of microclots in patients with long COVID often see complementary proteins inside the clots, so it has already been associated with long COVID. But she likened this clotting process to a garbage can that “just rolls along and collects everything that gets in its way. I think they are actively driving inflammation and disease.”
One factor complicating long COVID diagnosis and treatment is that it is a complex condition that involves multiple organ systems. That’s why the latest research suggests an underlying driver for the multiple symptoms of long COVID, Dr. Putrino said.
“Not every person has every symptom; not every person has every organ system affected,” Dr. Putrino said. “Whatever is happening is decided across the whole body.”