Drug used in organ transplants can reduce deaths from severe COVID-19, research suggests

A new study suggests an immune-suppressing drug called cyclosporine may reduce the risk of death in severe COVID-19 patients.

Published this month in EClinicalMedicine, the study is far from conclusive. A team at a hospital in Madrid, Spain, looked back at the records of 607 severe COVID-19 patients admitted in March and April. They were treated with one or more drugs thought to help in critical cases, including steroids, HIV antivirals, a rheumatoid arthritis drug, and hydroxychloroquine, the antimalarial touted by President Donald Trump.

Cyclosporine, long used to prevent organ rejection in transplant patients, was the only drug that clearly reduced deaths. Of the 253 patients who received cyclosporine, 36 (14%) died. In a closely matched comparison group of 354 patients who did not get the drug, 105 (almost 30%) died. Overall, nearly a quarter of the 607 patients died.

The Spanish researchers, led by physician Pablo Guisado-Vasco, noted that cyclosporine is “a unique immune inhibitory drug” because of the biochemical pathway it blocks. That pathway is involved in a devastating immune overreaction, called a cytokine storm, that can occur in the worst COVID-19 cases.

» READ MORE: Temple study helps predict which COVID-19 patients develop dangerous ‘cytokine storm’

“This mechanism might interfere with the initial step in the cytokine storm release," the researchers wrote.

Cyclosporine has numerous advantages. It is off patent, relatively inexpensive, and supplies are ample. But that also means it will not make huge profits, so pharmaceutical companies are not eager to sponsor rigorous clinical trials that would definitely show whether it works. And unlike hydroxychloroquine — another old, affordable drug — cyclosporine has not had a high-profile champion. President Trump tweeted support for the antimalarial as late as July, ignoring study after study that showed it was not effective in treating COVID-19.

Cyclosporine can have side effects such as high blood pressure and impaired kidney function. It must be used carefully in seriously ill COVID-19 patients, who tend to be older and have chronic illnesses. In the Madrid study, for example, half the patients were over age 69; hypertension, heart disease, diabetes, and respiratory diseases were common.

» READ MORE: COVID-19 patients can be overwhelmed with inflammation. Doctors are learning to calm that ‘storm.’

Two U.S. medical centers, the University of Pennsylvania and Baylor College of Medicine in Houston, are conducting clinical studies of cyclosporine.

The Penn effort is a small pilot study designed to assess the safety of the drug in patients hospitalized with moderately severe COVID-19. The trial launched in June with a goal of enrolling 20 patients; so far, only three have been treated.

The leader is Carl June, the Penn Medicine researcher whose lab pioneered T-cell immune therapy for blood cancer patients. T-cell therapy can trigger the cytokine storm, and June’s team discovered that the rheumatoid arthritis drug Actemra can work as an antidote, calming the immune response. In contrast, Actemra did not benefit the Madrid coronavirus patients.

On Monday, June emailed the status of the cyclosporine trial: "The first two patients had no complications and were discharged safely; the third patient is in the hospital. We have had a problem (fortunately) with very few patients requiring hospitalization in Philly since June 2020. Maybe with a second wave, we’ll get more patients.”

Baylor’s trial, posted in July on the government’s clinical trials list, aims to enroll 75 patients who are hospitalized but don’t need intensive care. Two-thirds of them will be randomly assigned to get cyclosporine for seven days, and the rest will get standard care without the drug.

The trial has not yet begun recruiting. The leader, Baylor thoracic surgeon Bryan Burt, did not respond this week to an Inquirer email asking why. .