Researchers to study methylprednisolone’s impact on COVID-19

Nov. 2, 2020

Researchers at the University of Alabama at Birmingham (UAB) have launched a study into the impact of methylprednisolone, a corticosteroid, on patients with severe cases of COVID-19, according to a press release.

Early results from the United Kingdom's RECOVERY trial this summer found that critically ill COVID-19 patients on ventilators who received dexamethasone, a corticosteroid drug, were at a one-third lower risk of dying than those who did not receive the drug. Patients receiving oxygen therapy, but not on ventilators, had a 20 percent lower risk of dying.

 But dexamethasone is in short supply, according to Randy Cron, MD, PhD, Professor of Pediatrics and Medicine at UAB. That is why Cron and Winn Chatham, MD, Professor of Medicine at UAB, are conducting a pilot study of methylprednisolone. Outside of COVID-19, oncologists often use dexamethasone to treat hemophagocytic lymphohistiocytosis, a cytokine storm syndrome seen in patients with blood cancers such as leukemias and lymphomas. Rheumatologists treat cytokine storm syndrome (where it is commonly called macrophage activation syndrome) in patients with lupus and rheumatoid arthritis using methylprednisolone.

Anyone battling a serious infection, regardless of cause, may experience a cytokine storm, Cron said. In addition to blood cancers and rheumatic diseases, cytokine storm syndrome is seen in herpes virus family member infections, and case reports have noted nearly 100 different infectious agents that can cause cytokine storms. In patients with COVID-19, clinicians increasingly see cytokine storm syndrome as a major factor in poor outcomes. Cytokine storm syndrome develops in a large percentage of COVID-19 patients who are ill enough to require hospitalization, Cron said.

Glucocorticoids, such as dexamethasone and methylprednisolone, are both "used to calm the cytokine storm," Cron said. "They have very broad-ranging effects on the immune system," including decreasing production of pro-inflammatory proteins and "decreasing function of multiple immune cell types."

Cron and Chatham plan to enroll at least 30 patients hospitalized with COVID-19 pneumonia who have features of cytokine storm syndrome.

Patients in the study will be randomized to receive either 6mg daily of dexamethasone or 32 mg daily of methylprednisolone. The goal is to reduce the need for invasive mechanical ventilation and ICU care. "We believe methylprednisolone will minimize ICU admissions and enhance survival," wrote Cron and Chatham in their project proposal. 

Patients will receive the drugs at the doses listed above for seven days or until they show stable improvement in oxygen saturation and lower levels of markers of cytokine storm syndrome, including serum ferritin, D-dimer and C-reactive protein.

 The researchers also plan to explore genetic risk factors that may be shared by COVID-19 patients who develop cytokine storm syndrome. Cron and colleagues have identified genetic risk factors in other cytokine storm syndromes, including those triggered by H1N1 influenza. This earlier work suggests that as much as 15 percent of the general population carries genetic mutations putting them at higher risk for developing cytokine storm syndrome. Finding such risk factors in COVID-19 patients would allow clinicians to target treatments to patients with the highest potential for success on those therapies.

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