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MUMC+ unravels Covid-19 complex immune response mechanism

Patients with severe Covid-19 suffer life-threatening complications such as thrombosis, blood clots, in the blood vessels of mainly the lungs but also in other organs. Dutch researchers are showing that, and also how, immune cells trigger the body to cause thrombosis and how a still experimental medicine can help keep these cells in check.

The immune system tries to clear the virus that causes Covid-19 and Sars-CoV-2 from the start of the infection. This battle usually ends in the patient's favour. However, neutrophils, important cells of the immune system, sometimes get to work too zealously, Maastricht UMC+ researchers discovered. The cells literally throw out a net of DNA fibres to catch pathogens. If they are successful, the body cleans up the neutrophils with the pathogens caught. Now this DNA fishing appears to have a disadvantage: it activates blood clotting, which in turn can lead to thrombosis and damage to the blood vessels. The researchers demonstrated this step by step with tests developed in #Maastricht. The researchers saw these nets almost exclusively in the seriously ill people with COVID-19 and pulmonary thrombosis.

Drug development

Together with colleagues from Amsterdam UMC and Charité-Universitätsmedizin in Berlin, Maastricht researchers then tested a still experimental medicine in people with severe Covid-19. The drug, an antibody directed against protein C5a, prevents neutrophil cells from becoming too active and casting their net. The drug appears safe and seems to be effective; the risk of death appeared to be halved in the treated patients. Follow-up research will have to confirm the effectiveness of the antibody against protein C5a in a larger group of patients. The preliminary findings were recently published in two leading medical journals. Once again, it becomes clear that research into the underlying mechanism forms the basis for the logical deployment of new medicines in Covid-19. This integrated approach with advanced research techniques to directly link the immune system to clotting and changes in blood vessels offers many more opportunities to provide more targeted treatment for this vulnerable patient group.

"This can save lives, but also limit the feared long-term problems with COVID-19,"

says immunologist and research leader Pieter van Paassen.

Photo: Pieter van Paassen, Immunologist and Research team leader, Maastricht UMC+

Maastricht UMC+ is characterised by its multidisciplinary and problem-based approach. The Maastricht University Hospital has approximately 7500 employees and 5000 students. Maastricht UMC+ is affiliated with the de Nederlandse Federatie van Universitair Medische Centra – NFU.

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