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Genomic Epidemiology and Serology Associated with a SARS-CoV-2 R.1 Variant Outbreak in New Jersey.
Mathema, Barun; Chen, Liang; Wang, Pengfei; Cunningham, Marcus H; Mediavilla, Jose R; Chow, Kar Fai; Luo, Yang; Zhao, Yanan; Composto, Kaelea; Zuckerman, Jerry; Zody, Michael C; Wilson, Nancy; Lee, Annie; Oschwald, Dayna M; Liu, Lihong; Iketani, Sho; Germer, Soren; Fennessey, Samantha; Wang, Maple; Kramer, Yael; Toole, Patricia; Maniatis, Tom; Ho, David D; Perlin, David S; Kreiswirth, Barry N.
  • Mathema B; Department of Epidemiology, Mailman School of Public Health, Columbia Universitygrid.21729.3fgrid.239585.0 Irving Medical Center, New York, New York, USA.
  • Chen L; Hackensack Meridian Health Center for Discovery and Innovation, Nutley, New Jersey, USA.
  • Wang P; Hackensack Meridian School of Medicine, Nutley, New Jersey, USA.
  • Cunningham MH; Aaron Diamond AIDS Research Center, Columbia Universitygrid.21729.3fgrid.239585.0 Vagelos College of Physicians and Surgeons, New York, New York, USA.
  • Mediavilla JR; Hackensack Meridian Health Center for Discovery and Innovation, Nutley, New Jersey, USA.
  • Chow KF; Hackensack Meridian Health Center for Discovery and Innovation, Nutley, New Jersey, USA.
  • Luo Y; Hackensack Meridian Health Biorepository, Hackensack, New Jersey, USA.
  • Zhao Y; Aaron Diamond AIDS Research Center, Columbia Universitygrid.21729.3fgrid.239585.0 Vagelos College of Physicians and Surgeons, New York, New York, USA.
  • Composto K; Hackensack Meridian Health Center for Discovery and Innovation, Nutley, New Jersey, USA.
  • Zuckerman J; Hackensack Meridian School of Medicine, Nutley, New Jersey, USA.
  • Zody MC; Hackensack Meridian Health Center for Discovery and Innovation, Nutley, New Jersey, USA.
  • Wilson N; Hackensack University Medical Centergrid.239835.6, Hackensack, New Jersey, USA.
  • Lee A; New York Genome Centergrid.429884.b, New York, New York, USA.
  • Oschwald DM; Hackensack Meridian Health, Carrier Clinic, Belle Mead, New Jersey, USA.
  • Liu L; Hackensack Meridian Health Center for Discovery and Innovation, Nutley, New Jersey, USA.
  • Iketani S; New York Genome Centergrid.429884.b, New York, New York, USA.
  • Germer S; Aaron Diamond AIDS Research Center, Columbia Universitygrid.21729.3fgrid.239585.0 Vagelos College of Physicians and Surgeons, New York, New York, USA.
  • Fennessey S; Department of Microbiology and Immunology, Columbia Universitygrid.21729.3fgrid.239585.0 Irving Medical Center, New York, New York, USA.
  • Wang M; New York Genome Centergrid.429884.b, New York, New York, USA.
  • Kramer Y; New York Genome Centergrid.429884.b, New York, New York, USA.
  • Toole P; Aaron Diamond AIDS Research Center, Columbia Universitygrid.21729.3fgrid.239585.0 Vagelos College of Physicians and Surgeons, New York, New York, USA.
  • Maniatis T; Hackensack Meridian Health Biorepository, Hackensack, New Jersey, USA.
  • Ho DD; Hackensack Meridian Health, Carrier Clinic, Belle Mead, New Jersey, USA.
  • Perlin DS; New York Genome Centergrid.429884.b, New York, New York, USA.
  • Kreiswirth BN; Aaron Diamond AIDS Research Center, Columbia Universitygrid.21729.3fgrid.239585.0 Vagelos College of Physicians and Surgeons, New York, New York, USA.
mBio ; 13(5): e0214122, 2022 Oct 26.
Article in English | MEDLINE | ID: covidwho-2001782
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 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 MAbs and 4 N-terminal domain (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 neutralization capacity by plasma from individuals with previous SARS-CoV-2 infection 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 states 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. IMPORTANCE The neutralizing capacities of monoclonal antibodies used to treat COVID-19 and of those recovered from previously infected and vaccinated individuals against SARS-CoV-2 variants of concern (VOCs) remain important questions. We report on a nosocomial outbreak caused by a SARS-CoV-2 R.1 variant harboring an E484K mutation among 81 unvaccinated inpatients and health care professionals. We note high attack rates with symptoms in nearly 50% of infected individuals, in sharp contrast to an unrelated institutional outbreak caused by the R.1 variant among a vaccinated population. We found little evidence of significant community spillover. This variant exhibits partial or complete resistance to two monoclonal antibodies in clinical use and dampened the neutralization capacity of convalescent-phase plasma from individuals with previous infection or sera from vaccinated individuals. Among three vaccinated individuals previously infected with R.1, we observed robust neutralizing antibody responses against SARS-CoV-2 wild type and VOCs. These findings underscore the importance of vaccination for prevention of symptomatic COVID-19 disease.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Cross Infection / COVID-19 Type of study: Observational study / Prognostic study / Randomized controlled trials Topics: Vaccines / Variants Limits: Humans Country/Region as subject: North America Language: English Journal: MBio Year: 2022 Document Type: Article Affiliation country: Mbio.02141-22

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Cross Infection / COVID-19 Type of study: Observational study / Prognostic study / Randomized controlled trials Topics: Vaccines / Variants Limits: Humans Country/Region as subject: North America Language: English Journal: MBio Year: 2022 Document Type: Article Affiliation country: Mbio.02141-22