Existing drugs could prevent blood clots in severe COVID-19 cases

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New findings that COVID-19-related blood clots may be caused by an abnormal antibody response could help to identify preventative treatments.

Researchers have demonstrated how antibodies produced as a protective response against COVID-19 are triggering increased function of platelets, which may be leading to fatal blood clots in severe cases of the infection. Platelets are small cells in the blood which form clots to stop or prevent bleeding, but this can have life-threatening consequences if the platelets do not function properly.

The study has been published in the journal Blood.

To investigate COVID-19’s impact on the body, researchers took antibodies from people with a severe form of the infection and cloned them in a lab to study. The study revealed that the small sugars found on these antibodies were different to antibodies from healthy individuals, and, when those cloned antibodies were introduced to blood cells taken from healthy donors, there was an observed increase in platelet activity.

The research team also discovered that it was possible to reduce or stop platelets from responding in this way by treating blood with active ingredients from different medication known to either inhibit platelet function or immune responses. From this, they suggest that it may be possible to reduce or stop the cells from producing an exaggerated platelet response by using drugs that are currently used to treat immune system problems.

MATIS trial: testing existing drugs

In a trial – called MATIS – led by Imperial College London and Imperial College Healthcare NHS Trust, researchers are already testing these drugs in patients at hospital sites across the UK to see if they can reduce serious clotting for hospitalised COVID-19 patients.

The lab-based study of human cells provides key evidence to support the scientific basis for the MATIS trial and, while there are yet to be any results reported from this clinical trial, the two teams will continue to work closely together as the trial develops.

Abnormal immune response

Professor Jon Gibbins, Director of the Institute for Cardiovascular and Metabolic Research at the University of Reading, said: “Until now, we have only had assumptions about why platelets involved in clotting were being activated during COVID-19 infection.

“One way to think of what happens is that the immune response that is designed to protect you from the infection, in some cases, particularly in severely ill patients, actually causes more damage. In this case, the antibodies that are produced to stop COVID-19 from spreading trigger infected cells to induce platelet activity which causes clotting even though there is no wound that needs healing.

“We are particularly excited because our studies of platelets in the laboratory establishes important mechanisms that explain how and why dangerous blood clots may occur in severely ill COVID-19 patients and, importantly, also provides clues as to how this may be prevented.”

Co-author Nichola Cooper, Reader at Imperial College London and Consultant Haematologist at Imperial College Healthcare NHS Trust, who also designed and leads the MATIS trial, said: “Early on in the COVID-19 pandemic, it was clear that the infection was causing an overwhelming immune response, including blood clotting, and that many of the more severe cases and deaths were related to this.

“Having been involved in early research around blood clotting related to inflammation, it occurred to me that the drugs we already use for other disorders could be easily accessible treatments for COVID-19. We are yet to see results from the MATIS trial so we do not yet know how these drugs will work in patients, but our hope is that we can both inhibit the inflammatory response and prevent severe disease and blood clots. It is exciting to see our collaboration with Reading backing our theory already and providing a solid scientific basis for clinical trials.”



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