Study: Major Steroid Treatment for Severe COVID Only Benefits Male Patients

A new study from the University of Calgary suggests that a main treatment for severe COVID-19 patients may only help male patients by altering the function of immune cells, but it has little benefit for female patients.

Dexamethasone is a steroid that has been used to treat ICU patients with COVID-related acute respiratory distress syndrome.

Frank J. Contacessa, MD, an internist at Northwell Health Physician Partners, told Verywell that dexamethasone is most commonly used to suppress the immune system, but the mechanism behind this treatment has been unclear.

Researchers discovered that before dexamethasone was used to treat severe COVID, the male mortality rate was over 25%, while female mortality was lower at around 15–16%. With the introduction of dexamethasone, male mortality went down to about 20%, but there was no improvement to the mortality rate among female patients.

Bryan Yipp, MD, an associate professor at the Cumming School of Medicine and a co-author of the study, said that the findings about how dexamethasone didn’t seem to have any benefit for female COVID-19 patients were buried in the previous literature.

In a viral infection like COVID-19, infected cells release proteins called interferons that trigger an immune response. But persistent interferon response in COVID-19 ends up driving inflammation that can damage the lungs, Yipp said.

Yipp’s team found that dexamethasone can activate neutrophils, a type of white blood cells that can downregulate interferon-stimulated genes, i.e., suppress their activity. When male patients received the steroid treatment, the dysregulated interferon signals went away within a week, Yipp said. But in female patients, the proportions of neutrophils were not as high and they did not react to the steroids in the same way.

“We think that what the steroids are doing is bringing the male immune system back into check, which improves their mortality,” Yipp said. “But in females, that dysregulation is not so apparent.”

Although researchers don’t have clear explanation for this phenomenon yet, these findings are useful in determining whether certain COVID-19 treatments are useful. If female patients are not deriving any benefit from steroid treatment, then healthcare providers may have to reconsider the risk of administering this drug.

Dexamethasone does come with a number of risks, including an increased risk of infection as well as longer-term side effects with the immune system and the metabolic system.

“As a physician, you never want to subject a patient to all risk, no benefit, so that’s obviously a huge problem,” Yipp said, adding that researchers should look into all the immune drugs that are being used for COVID-19 treatment.

Yipp added it’s “relatively disconcerting” that scientists don’t actually know much about the differences between male and female immune systems. In the future, he said, medical research may have to adopt personalized therapies rather than a blanket approach.

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