Notes from the Field: Mpox Cluster Caused by Tecovirimat-Resistant Monkeypox Virus - Five States, October 2023-February 2024.

The antiviral drug tecovirimat* has been used extensively to treat U.S. mpox cases since the start of a global outbreak in 2022. Mutations in the mpox viral protein target (F13 or VP37) that occur during treatment can result in resistance to tecovirimat† (1,2). CDC and public health partners have conducted genetic surveillance of monkeypox virus (MPXV) for F13 mutations through sequencing and monitoring of public databases. MPXV F13 mutations associated with resistance have been reported since 2022, typically among severely immunocompromised mpox patients who required prolonged courses of tecovirimat (3-5). A majority of patients with infections caused by MPXV with resistant mutations had a history of tecovirimat treatment; however, spread of tecovirimat-resistant MPXV was reported in California during late 2022 to early 2023 among persons with no previous tecovirimat treatment (3). This report describes a second, unrelated cluster of tecovirimat-resistant MPXV among 18 persons with no previous history of tecovirimat treatment in multiple states.

Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant.

We identified an emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant by viral whole-genome sequencing of 2,172 nasal/nasopharyngeal swab samples from 44 counties in California, a state in the western United States. Named B.1.427/B.1.429 to denote its two lineages, the variant emerged in May 2020 and increased from 0% to >50% of sequenced cases from September 2020 to January 2021, showing 18.6%-24% increased transmissibility relative to wild-type circulating strains. The variant carries three mutations in the spike protein, including an L452R substitution. We found 2-fold increased B.1.427/B.1.429 viral shedding in vivo and increased L452R pseudovirus infection of cell cultures and lung organoids, albeit decreased relative to pseudoviruses carrying the N501Y mutation common to variants B.1.1.7, B.1.351, and P.1. Antibody neutralization assays revealed 4.0- to 6.7-fold and 2.0-fold decreases in neutralizing titers from convalescent patients and vaccine recipients, respectively. The increased prevalence of a more transmissible variant in California exhibiting decreased antibody neutralization warrants further investigation.

Transmission, infectivity, and antibody neutralization of an emerging SARS-CoV-2 variant in California carrying a L452R spike protein mutation.

We identified a novel SARS-CoV-2 variant by viral whole-genome sequencing of 2,172 nasal/nasopharyngeal swab samples from 44 counties in California. Named B.1.427/B.1.429 to denote its 2 lineages, the variant emerged around May 2020 and increased from 0% to >50% of sequenced cases from September 1, 2020 to January 29, 2021, exhibiting an 18.6-24% increase in transmissibility relative to wild-type circulating strains. The variant carries 3 mutations in the spike protein, including an L452R substitution. Our analyses revealed 2-fold increased B.1.427/B.1.429 viral shedding in vivo and increased L452R pseudovirus infection of cell cultures and lung organoids, albeit decreased relative to pseudoviruses carrying the N501Y mutation found in the B.1.1.7, B.1.351, and P.1 variants. Antibody neutralization assays showed 4.0 to 6.7-fold and 2.0-fold decreases in neutralizing titers from convalescent patients and vaccine recipients, respectively. The increased prevalence of a more transmissible variant in California associated with decreased antibody neutralization warrants further investigation.