COVID-19 and thrombosis: repurposing old drugs and finding new targets

Australia has thankfully not had the level of exposure to COVID-19 as many other countries but our researchers will be in the mix in finding treatments to offset the thrombotic complications in severe COVID-19 disease.

According to haematologist Dr James McFadyen, from the Atherothrombosis and Vascular Biology Program at the Baker Heart and Diabetes Institute, Australia punches above its weight internationally in haematology and thrombosis research.

“Australia has world leading labs investigating thrombosis and quite a few labs in the country have been at the forefront developing novel antithrombotic agents as well, so that, partnered with industry leaders such as CSL puts us in a pretty good place to try and hopefully develop new therapeutics.”

Dr McFadyen, his haematology colleague Dr Hannah Stevens and cardiologist Professor Karlheinz Peter have coauthored a review of thrombosis in COVID-19 in a paper in Circulation Research.

The paper outlines some of the likely mechanisms at play and highlights potential therapies including anticoagulants such as heparin, FXII inhibition, fibrinolytic agents and antiplatelet therapies.

Dr McFadyen, also from the Alfred Hospital and Monash University, told the limbic the pathway to thrombosis in COVID-19 was a complicated process.

He said it had been demonstrated a few months ago that the COVID spike protein that allows the virus to latch on to cells appeared to be associated with inflammation in the endothelium.

“Only very recently we have evidence coming out that platelet function is altered in patients with COVID.”

“And the formation of NETs [neutrophil extracellular traps] – part of the immune response – that looks like it is also a prominent feature in patients with COVID as well.”

He said despite the many steps and pathways to thrombosis, the focus currently was on blocking the final step.

“The reasons why that is the current focus is that principally, all of our current therapeutic target that final step and it’s a case of trying to repurpose current therapies that we have and adopt them in the setting of COVID.”

“There are a number of clinical trials underway at the moment looking at different doses of blood thinning medications in different patient groups with COVID to see if that will improve outcomes.”

He said some antithrombotic drugs may also have beneficial “off target” effects.

“So the heparins used commonly as anticoagulants may have other properties e.g. anti inflammatory effects and there is some data they may be able to inhibit viral entry into the cells as well. That’s yet to fully play out but there are a couple of potential other benefits that may be derived from anticoagulants in COVID.”

He said research to understand the fundamental biology of thrombosis in COVID-19 had to run in parallel with the high priority research around repurposing of currently available therapeutics.

“Across North America and Europe, those trials are now getting up and running and unless they happen we won’t have definitive answers; we just ended up with low grade evidence.”

“And without understanding the basic biology or the pathophysiology of what is underpinning the mechanisms that lead to thrombosis, then we won’t know what new targets to develop.”

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