This report, drawn from the ARF-RSV prospective multicenter observational cohort (NCT06197152), documents the detection of a nirsevimab-resistant respiratory syncytial virus (RSV-B) variant in an immunocompromised adult who required intensive care.
The finding originates from the ongoing ARF-RSV study, a prospective, multicenter observational cohort (ClinicalTrials.gov identifier NCT06197152). The analysis reported in the abstract is based on routine virologic sampling and genetic sequencing of clinical respiratory specimens obtained during the patient’s ICU admission. Details on full laboratory methods, sequencing platforms, or additional cohort-wide sampling were not provided in the abstract.
The subject was a 64-year-old man with a history of aggressive mantle cell lymphoma under active treatment. He was admitted to the intensive care unit for severe sepsis during an episode of febrile aplasia. According to the abstract, his clinical course was rapidly favorable with resolution of hemodynamic failure within a few days. The abstract does not provide additional details on antimicrobial or antiviral treatments, supportive care measures, ventilatory status, duration of ICU stay, or long-term outcomes.
Two nasopharyngeal samples collected 7 days apart tested positive for RSV-B. Genetic analysis assigned the virus to lineage B.D.E.1 in both samples. Both specimens harbored a dominant F:K68Q substitution in the RSV fusion (F) protein. Sequencing metrics reported in the abstract indicate a mean depth of coverage above 180× in the first sample, with the F:K68Q substitution detected at an allele frequency of 99%. The second sample had a mean coverage of 170× and the same substitution detected at an allele frequency of 97%, consistent with persistence of the variant as the dominant viral population over the week between samples.
The authors note that the F:K68Q substitution has previously been associated with high-level resistance to nirsevimab, a monoclonal antibody that targets the prefusion conformation of the RSV F protein. Detection of this substitution at near-fixation levels in sequential samples from an immunocompromised adult demonstrates within-host persistence of a resistant variant during a severe RSV infection.
This observation is clinically relevant because monoclonal antibodies against the prefusion F protein, including nirsevimab, are being developed and deployed for prevention of RSV-associated morbidity. The detection of an F:K68Q variant in an adult ICU patient suggests the potential for antibody escape mutations to arise or persist in vulnerable hosts, which may have implications for prophylaxis or therapeutic strategies that rely on single epitope-targeting antibodies.
If you would like, I can summarize the likely clinical implications for ICU management of immunocompromised patients with RSV, or outline what additional laboratory and surveillance data would be useful to assess the public-health significance of F:K68Q. All statements above are limited to information reported in the PubMed abstract.