CIDRAP – A report published yesterday in Clinical Infectious Diseases describes a new SARS-CoV-2 mutation that confers resistance to the COVID-19 antiviral drug remdesivir in two persistently infected kidney transplant recipients treated with immunosuppressive drugs.
NYU researchers identified the V792I RNA-dependent 25 RNA polymerase mutation in the transplant patients, who were hospitalized and experienced life-threatening COVID-19 complications from reinfection after receiving remdesivir.
“Ineffective immune clearance contributes to persistent viral replication in immunocompromised hosts and increased opportunities for mutation,” the researchers wrote. “The failure to appropriately identify, treat, and control the spread of mutated SARS-CoV-2 isolates could have far-reaching consequences.”
One patient was in his or her 60s and had received two doses of the Pfizer/BioNTech COVID-19 vaccine before being infected with the Omicron subvariant BA.1.1 6 months after transplant and receiving a 5-day course of remdesivir. Twenty-four days later, the patient was readmitted to the hospital and given remdesivir. After 3.5 months, the patient was reinfected but had mild symptoms, so no treatment was given.
The other patient was in his or her 50s and had received two doses of the Moderna COVID-19 vaccine before becoming infected 14 months after transplant. The patient improved after receiving a 3-day course of remdesivir but was readmitted 18 days later because of worsening symptoms. After receiving a 5-day course of remdesivir, the patient improved.
Remdesivir is thought to work by disrupting SARS-CoV-2’s ability to replicate. The authors noted that the drug is important for treating COVID-19 in transplant recipients because Paxlovid, another antiviral, can interfere with immunosuppressant drugs used to prevent organ rejection in these high-risk patients.
“Our results highlight the importance of continuing to monitor how the coronavirus changes over time and keeping on the lookout for genetic mutations that allow the virus to overcome the medical community’s efforts to thwart it,” senior author Adriana Heguy, PhD, said in an NYU news release. “In the future, physicians might also screen for such mutations before making treatment decisions for their most vulnerable patients.”