Remdesivir-resistant version of COVID-19 detected in organ transplant recipients
Recent studies have shown that patients with weakened immune systems — which enables the virus that causes COVID-19 to remain longer in the body, copy itself, and continually change — may enable the development of new, slightly different versions of the virus (variants). These patients include those treated with drugs that suppress the immune system to keep it from rejecting a newly transplanted organ.
A new study, led by researchers at NYU Grossman School of Medicine and NYU Long Island School of Medicine, shows that two kidney transplant patients treated with immunosuppressive drugs, and who later had a lengthy COVID-19 infection, developed a version of the virus with a genetic change (mutation) that made it resistant to the antiviral therapy remdesivir.
This treatment is among the first antiviral drugs approved for use in the pandemic and remains an important weapon against the pandemic coronavirus. Remdesivir is especially important for treating transplant recipients since the more recently developed Paxlovid (a combination of nirmatrelvir and ritonavir) can interfere with immunosuppressants sometimes used in these patients, say the study authors.
The study results reflect a standard problem in antiviral medicine, in which the rapid and error-prone reproductive process of viruses continuously creates slightly different genetic versions of themselves. Some randomly develop the qualities needed to resist the drug treatment. In the case of SARS-CoV-2, the pandemic virus, remdesivir is thought to work by interfering with the virus’s ability to create copies of itself through the action of a polymerase, a viral enzyme.
According to the findings, both patients were initially infected with a version of the coronavirus that did not carry the mutation that provides resistance to remdesivir. However, following treatment with the antiviral agent, the virus developed the V7921 RNA-dependent polymerase (V7921) gene mutation, which has previously been shown in laboratory settings to make the virus more resistant to remdesivir.
“Our findings may help explain how the coronavirus continues to develop resistance to treatment,” says study lead author John Hogan, MD, 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.”
Despite the availability of vaccines and several drug therapies for COVID-19, experts say people with compromised immune systems, such as transplant patients and those with cancer or untreated HIV, remain at high risk for the disease. The new study, publishing online Sept. 26 in the journal Clinical Infectious Diseases, is the first to identify the remdesivir-resistant V7921 mutation in organ-transplant patients treated with the antiviral drug, according to Hogan.
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