In a new study, researchers found that the rheumatoid arthritis drug baricitinib can block viral entry and reduce mortality in patients with moderate to severe COVID-19.
They found a 71% reduction in mortality for the group receiving baricitinib in addition to standard care.
These results are especially encouraging seeing as the study included a large group of elderly patients, a group that is often excluded in other trials.
The research was conducted by a team at Karolinska Institutet in Sweden and elsewhere.
In the study, 83 patients hospitalized with COVID-19 pneumonia in Italy and Spain were treated with baricitinib in addition to standard care.
Of these, 17% suffered an adverse outcome that resulted in death or invasive mechanical ventilation.
This compared to 35% in the matched control group of 83 patients who received standard care only. The patients had a median age of 81 years.
The drug was generally well tolerated with a reduction in the inflammation from the first treatment days, according to the researchers.
However, some adverse events including bacterial infections and gut and heart complications were noted, although these were also observed in the control group so it is unclear what, if anything, can be ascribed to baricitinib.
In a prior study, the same team reported how they used artificial intelligence (AI) to identify baricitinib as a promising repurposing candidate for COVID-19.
That study also showed how the drug inhibited inflammation and reduced the viral load of SARS-CoV-2.
In this study, the researchers elaborated on those findings by demonstrating that interferons, cytokines made and released by host cells in response to viruses, strongly increases the expression of the ACE2 receptor, which acts as an entry point for SARS-CoV-2 into human cells.
While the liver injury is commonly observed in severe COVID-19, mechanisms and dynamics of SARS-CoV-2 infections had not been investigated in this organ.
By combining 3-D mini-organs of human liver cells, RNA sequencing and super-resolution microscopy, the scientists were able to show that barcitinib reversed ACE2 gene expression changes triggered by interferons and reduced SARS-CoV-2 infectivity.
Interestingly, interferons did not have the same effect on the ACE2 receptor in lung organoids, suggesting that these signaling proteins affect pulmonary and liver organs differently.
These findings explain the dual anti-cytokine and anti-viral actions of baricitinib and support further evaluation in randomized control trials.
One author of the study is Volker Lauschke, an associate professor of personalized medicine and drug development.
The study is published in the journal Science Advances.
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