A new study from the University of Zurich (UZH) has revealed that the complement system plays an important role in Long Covid, a common sequela of SARS-CoV-2 infection. The findings, published in Science, show that the complement system ends up damaging tissue and blood cells even after the original infection has ended.
A significant proportion of individuals infected with SARS-CoV-2 develop long-lasting symptoms with a wide range of manifestations. The causes and disease mechanisms of Long Covid are still unknown, and there are no diagnostic tests or targeted treatments.
Part of the immune system active for too long
A team of researchers led by Onur Boyman, professor of immunology at UZH and Director of the Department of Immunology at the University Hospital Zurich (USZ), has implicated the complement system. It is part of the innate immune system and normally helps to fight infections and eliminate damaged and infected body cells.
“In patients with Long Covid, the complement system no longer returns to its basal state, but remains activated and, thus, also damages healthy body cells,” says Boyman.
Continued activation of complement system damages tissue and blood cells
The researchers followed 113 COVID patients for up to one year after their acute SARS-CoV-2 infection and compared them with 39 healthy controls.
After six months, 40 patients had active Long Covid disease.
More than 6500 proteins in the blood of the study participants were analysed both during the acute infection and six months later.
“The analyses of which proteins were altered in Long Covid confirmed the excessive activity of the complement system. Patients with active Long Covid disease also had elevated blood levels indicating damage to various body cells, including red blood cells, platelets and blood vessels,” explains Carlo Cervia-Hasler, a postdoctoral researcher in Boyman’s team and first author of the study.
Bioinformatics recognises protein patterns
The measurable changes in blood proteins in active Long Covid indicate an interaction between proteins of the complement system, which are involved in blood clotting and the repair of tissue damage and inflammation.
In contrast, the blood levels of Long Covid patients who recovered from the disease returned to normal within six months.
Active Long Covid is therefore characterised by the protein pattern in the blood.
The blood markers were discovered using bioinformatics methods in collaboration with Karsten Borgwardt during his time as a professor at ETH Zurich.
“Our work not only lays the foundation for better diagnosis, but also supports clinical research into substances that could be used to regulate the complement system. This opens up new avenues for the development of more targeted therapies for patients with Long Covid,” Onur Boyman said.
Source: University of Zurich
