Increased viral variants in children and young adults with impaired humoral immunity and persistent SARS-CoV-2 infection: A consecutive case series
Thao T Truong, Alex Ryutov, Utsav Pandey, Rebecca Yee, Lior Goldberg, Deepa Bhojwani, Paibel Aguayo-Hiraldo, Benjamin A Pinsky, Andrew Pekosz, Lishuang Shen, Scott D Boyd, Oliver F Wirz, Katharina Röltgen, Moiz Bootwalla, Dennis T Maglinte, Dejerianne Ostrow, David Ruble, Jennifer H Han, Jaclyn A Biegel, Maggie Li, ChunHong Huang, Malaya K Sahoo, Pia S Pannaraj, Maurice O'Gorman, Alexander R Judkins, Xiaowu Gai, Jennifer Dien Bard, Thao T Truong, Alex Ryutov, Utsav Pandey, Rebecca Yee, Lior Goldberg, Deepa Bhojwani, Paibel Aguayo-Hiraldo, Benjamin A Pinsky, Andrew Pekosz, Lishuang Shen, Scott D Boyd, Oliver F Wirz, Katharina Röltgen, Moiz Bootwalla, Dennis T Maglinte, Dejerianne Ostrow, David Ruble, Jennifer H Han, Jaclyn A Biegel, Maggie Li, ChunHong Huang, Malaya K Sahoo, Pia S Pannaraj, Maurice O'Gorman, Alexander R Judkins, Xiaowu Gai, Jennifer Dien Bard
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.
Conflict of interest statement
Declaration of Competing Interests S.D.B. has consulted for Regeneron, Sanofi, and Novartis on topics unrelated to this study. S.D.B., and K.R. have filed provisional patent applications related to serological tests for SARS-CoV-2 antibodies. All other authors have no competing interests.
Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.
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Source: PubMed