NYU study of kidney transplant patients shows how COVID-19 treatment may trigger mutations
A bottle containing the anti-viral drug Remdesivir. Credit: AP/Zsolt Czegledi
Two kidney transplant recipients treated with immunosuppressive drugs who later had severe COVID-19 infections developed a genetically mutated version of the virus resistant to the antiviral treatment remdesivir, according to a new study.
In 2020, remdesivir became the first Food and Drug Administration-approved therapy for COVID-19 and has been shown to shorten the recovery time in hospitalized adults.
The drug is considered particularly important for transplant recipients because Paxlovid, another more recently developed antiviral treatment, can interfere with immunosuppressants often used for these patients, said Dr. Adriana Heguy, a genomicist and senior author of the study by the NYU Grossman School of Medicine in Manhattan and NYU Long Island School of Medicine in Mineola.
"This plants a red flag that people who are immunosuppressed … have to be followed up very quickly and to continue doing tests to make sure they're testing negative," said Heguy, who also serves as professor in the department of Pathology at NYU Langone. She added that future studies must examine whether antivirus treatments themselves trigger such virus mutations.
The study, published online Monday in the journal Clinical Infectious Diseases, is the first to identify the remdesivir-resistant mutation in people with organ transplants treated with the antiviral drug.
“Our findings may help explain how the coronavirus continues to develop resistance to treatment,” said Dr. John Hogan, the study's lead author and an assistant professor in the Department of Medicine at NYU Langone Health. “It is possible that the antiviral treatment itself, combined with the patients’ weakened immune systems, may have driven the evolution of this concerning mutation.”
The report examined two NYU Langone patients — one in their 50s and another in their 60s from Long Island — who were taking immunosuppressant drugs after receiving a kidney transplant. Despite being vaccinated against COVID-19 before the transplant, both patients contracted the virus and developed symptoms such as fatigue, cough, and fever that lingered for several months.
While both individuals were treated for the virus with remdesivir, they were later readmitted to the hospital weeks later as their symptoms worsened. Both patients survived their illnesses.
When researchers reanalyzed the virus, they confirmed the presence of a new omicron mutation not previously present in the transplant recipients who received the remdesivir treatment, researchers said.
Researchers later checked an international database and found this rare gene mutation in about 300 patients treated with remdesivir across the globe, Heguy said.
Other recent studies have shown that new virus variants may develop in transplant patients with weakened immune systems who get COVID-19, including those treated with drugs to keep their systems from rejecting the new organ, researchers said. These patients, including those with cancer and HIV, are at high risk of developing severe cases of COVID, even if they are fully vaccinated.
Transplant patients should continue to take remdesivir, Heguy said, but doctors must carefully monitor those individuals for new mutations.
“In the future, physicians might also screen for such mutations before making treatment decisions for their most vulnerable patients," said Heguy, adding that the study's authors plan to begin tracking immunosuppressed patients at NYU Langone treated for protracted COVID infections.
Heguy said the emergence of treatment-resistant COVID mutations could require the development of additional antiviral therapies or the development of medications to control infection.
Robert Brodsky is a breaking news reporter who has worked at Newsday since 2011. He is a Queens College and American University alum.
