A new study from the University of Calgary shows how dexamethasone, the main treatment for serious COVID-19 lung infections, alters the way immune cells work, which may help male patients, but has little or no effect. no benefits for women.
These remarkable results are the result of a multidisciplinary study published in Natural medicine, led by Dr. Jeff Biernaskie, PhD, Professor, Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine (UCVM) and Dr. Bryan Yipp, MD, Associate Professor, Department of Critical Care Medicine, Cumming School of Medicine.
âWe found that men got benefits from steroids and women, both at the cellular and population level, got limited benefits,â says Yipp, Tier II Canada Research Chair in pulmonary immunology, inflammation and host defense. âRight now, the basic treatment for severe COVID-19 that we give everyone may only benefit half of the population. It’s a big deal.â
How does our body fight infection with COVID-19?
At the start of the pandemic, hospital treatments for seriously ill people were not yet informed by research on the effectiveness of drugs in COVID-19 conditions. Steroids were the first drugs identified with proven benefit, but they were only moderately successful in reducing deaths, and exactly what they did was not understood.
Additionally, when the study began, no one knew exactly how immune cells would respond to COVID-19 infection at the cellular level. Why do some people really get sick while others don’t? Why did some drugs help some but not others?
âTo be able to develop new treatments, we wanted to study how different people respond to SARS-CoV2 infection and how different immune responses dictate the severity of their disease,â says Biernaskie, president of the Calgary Firefighters Burn Treatment Society in Regeneration. skin and wounds. Healing.
Yipp and Biernaskie sought to better understand how steroids help and, at the same time, assess why a clinical trial of steroids in COVID-19 showed they only help some men, but not women.
When Yipp accessed the provincial eCRITICAL database of all ICU admissions during the pandemic, he found that the introduction of dexamethasone treatment in Alberta was reducing the number of male deaths but had no effect. on the female population. “It was a disturbing observation.”
Analyze thousands of immune cells from intensive care patients
Blood has been drawn from COVID-19 and non-COVID-19 patients who have been admitted to intensive care units in Calgary with severe respiratory distress. Researchers at the Biernaskie lab used state-of-the-art single-cell RNA sequencing and bioinformatics techniques to simultaneously analyze the functional states of thousands of immune cells in each patient. This allowed them to document cellular behaviors at different stages of the disease (COVID-19 infections or not COVID) and to measure the effects of treatment.
“We sampled as many patients as possible, not just at one point in time, but at one point in time so that we could get a feel for the course of the disease and the course of the immune response,” explains Biernaskie.
In most viral infections, proteins called interferons work to quickly clear the virus. But with COVID-19, rather than working quickly, “the response to the interferon flows out, which actually fuels the fire of inflammation and then the organ damage worsens,” Yipp explains.
âWhat we found is that, specifically in men, we observe an exaggerated response to neutrophil interferon, which is significantly restricted when a patient is given dexamethasone,â Biernaskie explains. “But with women, compared to men, their response to neutrophil interferon was much more tempered, so dexamethasone had little effect.”
Find therapies that benefit more people
After identifying the reasons why there is a sexual bias in how dexamethasone works, Yipp believes the way forward is for researchers to figure out how to create therapies that benefit more people, or individualized therapies, also known as the name of precision or personalized medicine, so that a holistic approach is not used.
Biernaskie and Yipp credit the significant contributions of interns and junior scientists involved in the research, including Dr Nicole Rosin and Sarthak Sinha who spent countless hours managing the project and analyzing the results.
The project was supported by a grant Biernaskie and Yipp received from the Thistledown Foundation and the Calgary Firefighters Burn Treatment Society, “which enthusiastically supported my request to divert some of the funds from the CFBTS chair to support this initiative at the start of the pandemic, âBiernaski said.