Immune system causes lung damage in COVID patients

Inflammatory agent Interleukin-6 fires up complement system

Ghent, 24/08/2023 – Researchers at the Center for Inflammation Research, Ghent University Hospital, Ghent University and the Université Libre de Bruxelles have figured out how SARS-CoV-2, the virus that causes COVID-19, causes severe lung damage. The complement system, part of our innate defenses, is to blame. The breakthrough could potentially lead to new treatment options.

Respiratory infections have a huge impact on health and health care. The majority of respiratory tract infections are caused by viruses such as the influenza virus, RSV or SARS-CoV-2. Newborns, the elderly or individuals with weakened immune systems are particularly susceptible to becoming seriously ill from viral respiratory tract infections. 

Complement system

In a study published in the reputable journal Science Translational Medicine, Belgian researchers describe how the complement system, a part of our innate immune system, leads to lung damage in critically ill COVID-19 patients. The complement system normally ensures that pathogens and dead cells are efficiently removed from our bodies. But in severe COVID-19, that system is dysregulated and actually contributes to lung damage.

Damaged pulmonary alveoli

Complement - a group of proteins - is produced in the liver, entering the bloodstream as part of the innate immune system that protects us in the first hours of an infection. ​ 

Bart Lambrecht, Director of the VIB-UGent Center for Inflammation Research"We noticed that the lungs themselves also started making a lot of complement system proteins. Their sustained and uncontrolled activity in the lungs damages the alveoli during COVID-19 infection, making oxygen uptake difficult. Our discoveries open the door for studies with existing drugs that block the complement system."
Lung tissue with scarring, bleeds and signs of a clean-up following a severe COVID infection. Credits Prof. Jo Van Dorpe and Prof. Amélie Dendooven, Pathologic Anatomy, Ghent Universitary Hospital.
Lung tissue with scarring, bleeds and signs of a clean-up following a severe COVID infection. Credits Prof. Jo Van Dorpe and Prof. Amélie Dendooven, Pathologic Anatomy, Ghent Universitary Hospital.

500 patients studied

The research team reached the conclusions by analyzing samples from three large clinical studies conducted in Belgium under the coordination of UZ Gent, in collaboration with the Federal Knowledge Center for Health Care (KCE) and Belgian pharmaceutical company UCB. "By 2020, we have treated and included more than 500 COVID-19 patients in these three studies," says physician-researcher Karel Van Damme. "We examined the samples of all these patients with state-of-the-art protein analyses. These show that the inflammatory substance interleukin-6 is the culprit driving the complement system."

Rheumatoid medication

It had long been known that the inflammatory substance interleukin-6 (IL-6) plays a crucial role in inflammatory responses. Drugs targeting IL-6 are used in the treatment of rheumatoid arthritis. "These drugs are also effective in COVID-19, as shown in research we participated in," Bart Lambrecht says. "Our new results show that when you inhibit IL-6, the complement system cools down." ​ 

More research is needed to determine whether blocking the complement system directly can also benefit. ​ "Our initial results with UCB's complement inhibitor zilucoplan were promising, but the study was too small to draw any conclusions."

Data available for further research

While traditionally a publication is enough, the researchers have also made all the data publicly available through a website. "The most sophisticated - and expensive - biological techniques easily yield thousands of measurement points. These data are buried somewhere in the publication as addendum, but are often not viewed, which is a shame," explains Karel Van Damme. 

Karel Van Damme, "Via a user-friendly website, other researchers can now make maximum use of all our data to answer new scientific questions more quickly. After all, we think that a disrupted complement system also plays a role in other diseases such as influenza (flu) and sepsis, which cause millions of deaths worldwide every year. Because we looked at a lot of organs at different stages of infection, our studies provide an atlas for figuring out exactly where and when the complement system does damage, and when we need to intervene."
Joran Lauwers

Joran Lauwers

Science & Business Communications Expert, VIB

About VIB

VIB’s core mission is to generate disruptive insights in the molecular underpinning of life and to translate these actively into impactful innovations for patients and society. VIB is an independent research institute where some 1,800 top scientists from Belgium and abroad conduct pioneering basic research. As such, they are pushing the boundaries of what we know about molecular mechanisms and how they rule living organisms such as human beings, animals, plants, and microorganisms. Based on a close partnership with five Flemish universities – Ghent University, KU Leuven, University of Antwerp, Vrije Universiteit Brussel, and Hasselt University – and supported by a solid funding program, VIB unites the expertise of all its collaborators and research groups in a single institute. VIB’s technology transfer activities translate research results into concrete benefits for society such as new diagnostics and therapies and agricultural innovations. These applications are often developed by young start-ups from VIB or through collaborations with other companies. This also leads to additional employment and bridges the gap between scientific research and entrepreneurship. VIB also engages actively in the public debate on biotechnology by developing and disseminating a wide range of science-based information. 

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