@article{144eaf368af14cb992fdb449d20ccea7,
title = "Increased viral variants in children and young adults with impaired humoral immunity and persistent SARS-CoV-2 infection: A consecutive case series",
abstract = "Background: There is increasing concern that persistent infection of SARS-CoV-2 within immunocompromised hosts could serve as a reservoir for mutation accumulation and subsequent emergence of novel strains with the potential to evade immune responses. Methods: We describe three patients with acute lymphoblastic leukemia who were persistently positive for SARS-CoV-2 by real-time polymerase chain reaction. Viral viability from longitudinally-collected specimens was assessed. Whole-genome sequencing and serological studies were performed to measure viral evolution and evidence of immune escape. Findings: We found compelling evidence of ongoing replication and infectivity for up to 162 days from initial positive by subgenomic RNA, single-stranded RNA, and viral culture analysis. Our results reveal a broad spectrum of infectivity, host immune responses, and accumulation of mutations, some with the potential for immune escape. Interpretation: Our results highlight the potential need to reassess infection control precautions in the management and care of immunocompromised patients. Routine surveillance of mutations and evaluation of their potential impact on viral transmission and immune escape should be considered.",
keywords = "SARS-CoV-2, case report, immunocompromised, pediatric, persistent infection, variants",
author = "Truong, {Thao T.} and Alex Ryutov and Utsav Pandey and Rebecca Yee and Lior Goldberg and Deepa Bhojwani and Paibel Aguayo-Hiraldo and Pinsky, {Benjamin A.} and Andrew Pekosz and Lishuang Shen and Boyd, {Scott D.} and Wirz, {Oliver F.} and Katharina R{\"o}ltgen and Moiz Bootwalla and Maglinte, {Dennis T.} and Dejerianne Ostrow and David Ruble and Han, {Jennifer H.} and Biegel, {Jaclyn A.} and Maggie Li and Huang, {Chun Hong} and Sahoo, {Malaya K.} and Pannaraj, {Pia S.} and Maurice O'Gorman and Judkins, {Alexander R.} and Xiaowu Gai and {Dien Bard}, Jennifer",
note = "Funding Information: The work was partially funded by The Saban Research Institute at Children's Hospital Los Angeles intramural support for COVID-19 Directed Research (X.G. and J.D.B.), the Johns Hopkins Center of Excellence in Influenza Research and Surveillance HHSN272201400007C (A.P.), NIH/NIAID R01AI127877 (S.D.B.), NIH/NIAID R01AI130398 (S.D.B.), NIH 1U54CA260517 (S.D.B.), an endowment to S.D.B. from the Crown Family Foundation, an Early Postdoc.Mobility Fellowship Stipend to O.F.W. from the Swiss National Science Foundation (SNSF), and a Coulter COVID-19 Rapid Response Award to S.D.B. L.G. is a SHARE Research Fellow in Pediatric Hematology-Oncology. Funding Information: The work was partially funded by The Saban Research Institute at Children's Hospital Los Angeles intramural support for COVID-19 Directed Research (X.G. and J.D.B.), the Johns Hopkins Center of Excellence in Influenza Research and Surveillance HHSN272201400007C (A.P.), NIH/NIAID R01AI127877 (S.D.B.), NIH/NIAID R01AI130398 (S.D.B.), NIH 1U54CA260517 (S.D.B.), an endowment to S.D.B. from the Crown Family Foundation, an Early Postdoc.Mobility Fellowship Stipend to O.F.W. from the Swiss National Science Foundation (SNSF), and a Coulter COVID-19 Rapid Response Award to S.D.B. L.G. is a SHARE Research Fellow in Pediatric Hematology-Oncology. The authors thank the ATUM Bio team for optimization, production, and sharing of antigens used in this study. We thank the National Institute of Infectious Diseases, Japan, for providing VeroE6TMPRSS2 cells. All genomic data were uploaded to GISAID. The corresponding accessions are available upon request from the corresponding author. The work was partially funded by The Saban Research Institute at Children's Hospital Los Angeles intramural support for COVID-19 Directed Research (X.G. and J.D.B.), the Johns Hopkins Center of Excellence in Influenza Research and Surveillance HHSN272201400007C (A.P.), NIH/NIAID R01AI127877 (S.D.B.), NIH/NIAID R01AI130398 (S.D.B.), NIH 1U54CA260517 (S.D.B.), an endowment to S.D.B. from the Crown Family Foundation, an Early Postdoc.Mobility Fellowship Stipend to O.F.W. from the Swiss National Science Foundation (SNSF), and a Coulter COVID-19 Rapid Response Award to S.D.B. L.G. is a SHARE Research Fellow in Pediatric Hematology-Oncology. Funding Information: The work was partially funded by The Saban Research Institute at Children's Hospital Los Angeles intramural support for COVID-19 Directed Research (X.G. and J.D.B.), the Johns Hopkins Center of Excellence in Influenza Research and Surveillance HHSN272201400007C (A.P.), NIH/NIAID R01AI127877 (S.D.B.), NIH/NIAID R01AI130398 (S.D.B.), NIH 1U54CA260517 (S.D.B.), an endowment to S.D.B. from the Crown Family Foundation, an Early Postdoc.Mobility Fellowship Stipend to O.F.W. from the Swiss National Science Foundation (SNSF), and a Coulter COVID-19 Rapid Response Award to S.D.B. L.G. is a SHARE Research Fellow in Pediatric Hematology-Oncology. The authors thank the ATUM Bio team for optimization, production, and sharing of antigens used in this study. We thank the National Institute of Infectious Diseases, Japan, for providing VeroE6TMPRSS2 cells. Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = may,
doi = "10.1016/j.ebiom.2021.103355",
language = "English (US)",
volume = "67",
journal = "EBioMedicine",
issn = "2352-3964",
publisher = "Elsevier BV",
}