Ryan Chiao, Photo Editor

A team of researchers at the Yale School of Medicine have figured out a promising treatment strategy for COVID-19, further elucidating the disease’s pathway and uncovering a potentially lifesaving piece to the pandemic puzzle.

As COVID-19 cases spiked in hospitals, it quickly became clear that one of the symptoms was inflammation of the cells lining blood vessels, or thrombosis. A research team of pharmacists, hematology experts and other clinical researchers were prompted to investigate treatments for this complication, hoping to lower COVID-19 death rates due to thrombosis. Lead author Matthew Meizlish, a resident at Yale New Haven Hospital, and senior authors Alfred Lee, associate professor of hematology, and Kent Owusu, a critical care pharmacist at Yale New Haven, oversaw the research. The results were published in The American Journal of Hematology on Jan. 21.

“Everyone on the clinical side [of the research team] was trying to figure out, how can we treat this?” Meizlish said. “What can we do clinically to address this problem?” 

Since the beginning of the pandemic, hospitals have taken different approaches to patient care. According to Angela Rogers, an expert in pulmonary and critical care medicine at Stanford University, this is because carefully controlled, rigorous research trials have not been conducted on most treatments. Some medical professionals have administered anticoagulant or blood-thinning drugs, which prevent blood clotting, and aspirin, an antiplatelet drug, but this treatment has been controversial due to the lack of robust evidence surrounding it. 

Administering high-intensity anticoagulation drugs may be dangerous because in the process of reducing blood clotting, they elevate the risk of uncontrollable bleeding, William Schaffner ’57, professor of preventive medicine and infectious diseases at Vanderbilt University, explained. It became difficult to find the suitable level of anticoagulants that would reduce in-hospital COVID-19 deaths from thrombosis without posing an additional danger to the patients.

The Yale scientists sought to address this significant lack of research. Their study was retrospective, using data from previously treated COVID-19 hospital patients. Yale New Haven had been implementing an algorithm to treat thrombosis with differing anticoagulation levels. 

As Meizlish explained, most patients were simply given a prophylactic, or relatively low, dose of blood thinners to reduce blood clots as a starting preventative measure. An intermediate dose of anticoagulation was administered to patients with high levels of D-dimers, a protein fragment whose presence in a person’s blood is a definitive indication of clotting. The study analyzed the differences in COVID-19 survival rates between groups who were given each level of anticoagulants. 

“The central challenge here was that we wanted to use this as an opportunity to ask whether intermediate dose anticoagulation has any effect on patient outcomes,” Meizlish said. 

The research team found that there was a higher COVID-19 survival rate among those who received the intermediate dose anticoagulation than those who received the lower prophylactic dose. Furthermore, administering aspirin to the patients also significantly lowered COVID-19 deaths relative to those who did not receive any antiplatelet treatment.

For the research team, obtaining the data was a significant hurdle. 

“There was a lot of rigor that went into ensuring that we were able to present the data in its most absolute best form,” Owusu said. “It was challenging to get to that.” 

Also, since the study was retrospective, the team had to ensure that patients in each group, receiving either intermediate dose or prophylactic dose anticoagulation, were randomized as much as possible.

What ultimately set this study apart from other research in the field was the usage of certain statistical tools such as propensity score matching and multivariable regression analysis to increase the randomization of the participants between the groups. 

According to Meizlish, another statistical tool, the Rothman Index, “was a particularly good predictor of mortality … that helped us to identify patients’ disease severity” along with other factors such as age, weight and previous comorbidities.

The study was also the first large-scale investigation into the differences between intermediate and prophylactic dose anticoagulation in COVID-19 patients, since intermediate dose anticoagulation has not been a typical treatment.

“If we don’t suspect that someone has a clot but they have evidence of an increase in D-dimer, we are going to use intermediate dose anticoagulation,” Meizlish said.

The findings of the research are greatly influential and promising in the field of COVID-19 treatment. Other researchers across the country have already lauded the research, including Schaffner.

“I think that a lot of people are going to be looking at the aspirin part of the study and trying to figure out … what patient characteristics would qualify for the initiation of treatment with aspirin,” Schaffner said. 

Rogers agreed, and said that she thinks more studies should be investigating these topics and that “this study looks exciting.”

However, both experts as well as the Yale researchers cautioned against taking aspirin for COVID-19 treatment at home because there has not been enough data published for less severe cases of the disease.

According to the Centers for Disease Control and Prevention, there have been almost 500,000 deaths in the U.S. from COVID-19 as of Feb. 17.

Lucy Sun | lucy.sun@yale.edu