2021

2021. triplicates. Download FIG?S3, PDF file, 0.1 MB. Copyright ? 2022 Mathema et al. This content is distributed under the terms of the Creative Commons Attribution 4.0 International license. FIG?S4. Neutralization of WT and NJ4 (R.1) variant by vaccine sera. Data represent the mean SEM of results of technical triplicates. Download FIG?S4, PDF file, 0.2 MB. Copyright ? 2022 Mathema et al. This Penciclovir content is distributed under the terms of the Creative Commons Attribution 4.0 International license. FIG?S5. Prevalence of E484K/Q, N501Y/T, L452R, and T478K mutants among SARS-Cov-2 samples from January 2021 to October 2021. Download FIG?S5, PDF file, 0.1 MB. Copyright ? 2022 Mathema et al. This content is distributed under the terms of the Creative Commons Attribution 4.0 International license. Data Availability StatementThe SARS-CoV-2 genomes sequenced in this study were deposited in GISAID (https://www.gisaid.org). Sequences can be accessed by searching records from both the originating lab at Hackensack Medical Center and the submitting lab at the New York Genome Center. ABSTRACT Examining the neutralizing capacity of monoclonal antibodies (MAbs) used to treat COVID-19, as well as antibodies recovered from unvaccinated, previously vaccinated, and infected individuals, against Penciclovir severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) remains critical to study. Here, we report on a SARS-CoV-2 nosocomial outbreak caused by the SARS-CoV-2 R.1 variant harboring the E484K mutation in a 281-bed psychiatric facility in New Jersey among unvaccinated inpatients and health care professionals (HCPs). A total of 81 inpatients and HCPs tested positive for SARS-Cov-2 by reverse transcription (RT)-PCR from 29 October 9 to 30 November 2020. The R.1 variant exhibits partial or complete resistance to two MAbs in clinical use, as well as 2 receptor binding domain name MAbs and 4 N-terminal domain name (NTD) MAbs. NTD MAbs against pseudovirus harboring single characteristic R.1 mutations highlight the role of S255F in loss of activity. Additionally, we note dampened Penciclovir neutralization capacity by plasma from individuals with previous SARS-CoV-2 contamination or sera from vaccinated individuals. The relative resistance of the R.1 variant is likely lower than that of B.1.351 and closer to that of P.1 and B.1.526. The R.1 lineage has been reported in 47 says in the United States and 40 countries. Although high proportions exhibited symptoms (26% and 61% among patients and HCPs, respectively) and relative antibody resistance, we detected only 10 R.1 variants from over 2,900 samples (~0.34%) collected from January to October 2021. Among 3 vaccinated individuals previously infected with R.1, we observed robust neutralizing antibody responses against SARS-CoV-2 wild type and VOCs. KEYWORDS: SARS-CoV-2, variants of concern, spike protein, vaccine INTRODUCTION Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC), mutants that exhibit increased transmission, immune evasion, or both, have been reported in different global regions, and predominate lineages have been genotyped. Three VOCs, B.1.1.7 (Alpha) (1), B1.351 (Beta) (2), P.1 (Gamma) (3), and B.617.2 (Delta) (4), containing extensive mutations in the spike protein, emerged in the United Kingdom, South Africa, Brazil, and India, respectively, and have spread globally. Most recently, B.1.1.529 (Omicron) has dominated worldwide incident infections at an alarming pace (5, 6). The Penciclovir mapping of specific mutations in the spike protein has revealed strong evidence of convergent evolution, and in particular, the E484K change (or L452R and T478K in the case of Delta and S371L, N440K, G446S, and Q493R in the case of Omicron) (5, 7, 8), which enables evasion of monoclonal therapy and neutralizing antibodies, has been identified in discrete lineages in different geographic locations and associated with variant clones with increased transmission. Mouse monoclonal to AXL The extent to which these VOC mutants diminish the efficacy of monoclonal therapy used to treat COVID-19 and the neutralizing capacity of antibodies recovered from unvaccinated, previously infected, and vaccinated individuals remains critical to study. In this study, we report on a SARS-CoV-2 nosocomial outbreak caused by the SARS-CoV-2 R.1 variant harboring the E484K mutation in a 281-bed psychiatric facility in New Jersey among unvaccinated inpatients and.