According to a recent study, the virus that causes COVID-19 may be growing resistant to antiviral medications. But ought we to worry?
It is advised to use the antiviral medications redeliver and nirmatrelvir against mild to moderate SARS-CoV-2 infections to lower the likelihood of hospitalization and the development of more severe symptoms in high-risk patients. On the other hand, prolonged exposure to these therapies may cause the virus to develop new mutations that enable it to avoid these drugs.
Immunocompromised individuals need antiviral therapy for a longer duration and have a greater risk of developing antiviral resistance because they clear infections more slowly. Consequently, viruses that are resistant to drugs have more time to develop in immunocompromised or other high-risk individuals.
Two investigations on the emergence of drug-resistant strains of SARS-CoV-2 were released this week. The research teams from both studies discovered drug-resistant mutations in immunosuppressed patients receiving treatment with nirmatrelvir or redeliver. The first study also discovered that these resistant mutations could be transmitted from patient to patient, which would present a significant future challenge to the management and control of the disease.
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This study examined the effect of antiviral therapy on the emergence of resistant SARS-CoV-2 mutations in 15 immunocompromised patients. It was carried out by researchers at Cornell University and the National Institutes of Health (NIH) and was published in the journal Nature Communications on September 18. Remdesivir was given to every patient; three received nirmatrelvir, and four received monoclonal antibodies.
By sequencing the virus’s DNA, researchers discovered that most patients harboured viruses with protective mutations against these antivirals. Through in vitro studies, the researchers validated the viruses’ decreased susceptibility to redeliver and nirmatrelvir therapy. Additionally, they showed that, at least in hamsters, these resistant mutations may be efficiently passed from one person to another. However, a combination of antiviral medications was able to overcome this resistance.
The second study evaluated a cohort of 165 patients with COVID-19 infections between 2021 and 2023. It was carried out by researchers from Stanford University, Harvard University, Brigham and Women’s Hospital, and the University of Pittsburgh and published in the journal JAMA Network Open. There were two groups of participants: those who got antiviral treatment and those who did not.
The group discovered that individuals who had taken antivirals were more likely to develop antiviral-resistant mutations than those who had not. This was especially noticeable in immunocompromised individuals and those who were given nirmatrelvir instead of remdesivir.
However, the majority of these alterations were only seen at low concentrations before going back to normal.
“In this cohort study of 156 participants, treatment-emergent nirmatrelvir resistance mutations were commonly detected, especially in individuals who were immunosuppressed,” the investigators noted. “However, these mutations were generally present at low frequencies and were transient in nature.”
They came to the conclusion that it was implausible for these resistant variations to disseminate over the broader population at this time. They did, however, emphasize that we ought to keep an eye on these alterations and drug-use trends.
