Emerging SARS-CoV-2 Resistance After Antiviral Treatment.

Emerging SARS-CoV-2 Resistance After Antiviral Treatment.

Publication date: Sep 03, 2024

Previous studies have identified mutations in SARS-CoV-2 strains that confer resistance to nirmatrelvir, yet how often this resistance arises and its association with posttreatment virologic rebound is not well understood. To examine the prevalence of emergent antiviral resistance after nirmatrelvir treatment and its association with virologic rebound. This cohort study enrolled outpatient adults with acute COVID-19 infection from May 2021 to October 2023. Participants were divided into those who received antiviral therapy and those who did not. The study was conducted at a multicenter health care system in Boston, Massachusetts. Treatment regimen, including none, nirmatrelvir, and remdesivir. The primary outcome was emergent SARS-CoV-2 antiviral resistance, defined as the detection of antiviral resistance mutations, which were not present at baseline, were previously associated with decreased antiviral efficacy, and emerged during or after completion of a participant’s treatment. Next-generation sequencing was used to detect low frequency mutations down to 1% of the total viral population. Overall, 156 participants (114 female [73. 1%]; median [IQR] age, 56 [38-69] years) were included. Compared with 63 untreated individuals, the 79 who received nirmatrelvir were older and more commonly immunosuppressed. After sequencing viral RNA from participants’ anterior nasal swabs, nirmatrelvir resistance mutations were detected in 9 individuals who received nirmatrelvir (11. 4%) compared with 2 of those who did not (3. 2%) (P = . 09). Among the individuals treated with nirmatrelvir, those who were immunosuppressed had the highest frequency of resistance emergence (5 of 22 [22. 7%]), significantly greater than untreated individuals (2 of 63 [3. 1%]) (P = . 01). Similar rates of nirmatrelvir resistance were found in those who had virologic rebound (3 of 23 [13. 0%]) vs those who did not (6 of 56 [10. 7%]) (P = . 86). Most of these mutations (10 of 11 [90. 9%]) were detected at low frequencies (

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Concepts Keywords
Massachusetts Adenosine Monophosphate
Nirmatrelvir Adenosine Monophosphate
Outpatient Adult
Viral Aged
Alanine
Alanine
Antiviral Agents
Antiviral Agents
Cohort Studies
COVID-19
COVID-19 Drug Treatment
Drug Resistance, Viral
Female
Humans
Male
Middle Aged
Mutation
remdesivir
SARS-CoV-2

Semantics

Type Source Name
disease MESH COVID-19
disease MESH infection
disease MESH Infectious Diseases
drug DRUGBANK Methylphenidate
drug DRUGBANK Adenosine phosphate
drug DRUGBANK L-Alanine

Original Article

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