Journal
EBIOMEDICINE
Volume 67, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ebiom.2021.103355
Keywords
SARS-CoV-2; immunocompromised; persistent infection; variants; case report; pediatric
Funding
- Saban Research Institute at Children's Hospital Los Angeles
- Johns Hopkins Center of Excellence in Influenza Research and Surveillance [HHSN272201400007C]
- NIH/NIAID [R01AI127877, R01AI130398]
- NIH [1U54CA260517]
- Crown Family Foundation
- Swiss National Science Foundation (SNSF)
- Coulter COVID-19 Rapid Response Award
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The study highlights the concern that persistent infection of SARS-CoV-2 in immunocompromised hosts may lead to mutation accumulation and emergence of strains that evade immune responses. There is a need to reassess infection control precautions and consider routine surveillance of mutations for their potential impact on viral transmission and immune escape.
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. (C) 2021 The Authors. Published by Elsevier B.V.
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