Popular COVID drug dexamethasone may not help women

Dexamethasone is a powerful steroid that’s reportedly worked wonders in some people who get severe lung inflammation from COVID-19. It was the first drug that showed promise in saving severely ill patients during the summer of 2020, when COVID-19 treatment was still sort of a grab bag. A common generic drug, it can cost as little as $1 a dose, and it’s become standard of care in many hospitals. Oh, and it also may…not work on women.

That’s what University of Calgary researchers argue in a paper published this week in Nature Medicine. Doctors have been treating COVID patients with steroids like dexamethasone for months, but they admit there’s a knowledge gap explaining why they work when they do, and for whom. The University of Calgary team was aware of trials showing dexamethasone only helped some males, but not females. So authors Jeff Biernaskie and Bryan Yipp examined patients at an Alberta hospital, and discovered that the treatment reduced male deaths, but had effectively no benefit for sick females. They call it an “unsettling observation.”

They took blood from COVID patients treated with dexamethasone, and from other hospital patients who didn’t have COVID, for a control group. Complicated lab tests using RNA sequencing and bioinformatics analyzed the patients’ immune responses, and the team says they documented one reaction in men and another in women. When the body gets a viral infection, proteins known as interferons typically attack the virus. But against COVID-19, the interferons slow down, fueling more inflammation and leading to worse organ damage. In a statement, Biernaskie said that “specifically in males, we see an exaggerated neutrophil interferon response that is significantly restrained when a patient is given dexamethasone.” But with females, “their neutrophil interferon response was much more tempered, so dexamethasone had little effect.”

“Males derived benefit from the steroids, and the females, at both the cellular level and at the population level, received limited benefit,” his colleague Yipp said. Their conclusion: “Currently, it’s possible the mainstay therapy for severe COVID-19 that we’re giving everybody is only benefiting half the population. This is a big problem.”

More research is needed to get to the bottom of why, medically, the drug appears to work differently in men and women, they say. As for ridding sex bias from treatments themselves, their solution is for researchers to make developing more personalized medicines a priority, rather than taking a “blanket approach” to therapy.

Today, the Biden Administration ordered 10 million courses of another treatment for COVID-19, Pfizer’s antiviral Paxlovid pill.