EBioMedicine (May 2021)
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
Affiliations
- Thao T. Truong
- Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, United States
- Alex Ryutov
- Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, United States
- Utsav Pandey
- Department of Pathology, Westchester Medical Center/New York Medical College, Valhalla, NY, United States
- Rebecca Yee
- Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, United States
- Lior Goldberg
- Department of Pediatrics, Cancer and Blood Disease Institute, Division of Hematology-Oncology, Children's Hospital Los Angeles, Los Angeles, CA, United States; Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- Deepa Bhojwani
- Department of Pediatrics, Cancer and Blood Disease Institute, Division of Hematology-Oncology, Children's Hospital Los Angeles, Los Angeles, CA, United States; Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- Paibel Aguayo-Hiraldo
- Department of Pediatrics, Cancer and Blood Disease Institute, Division of Hematology-Oncology, Children's Hospital Los Angeles, Los Angeles, CA, United States; Keck School of Medicine, University of Southern California, Los Angeles, CA, United States; Department of Pediatrics, Cancer and Blood Disorder Institute, Transplant and Cellular Therapy Section, Children's Hospital Los Angeles, CA, United States
- Benjamin A. Pinsky
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, United States; Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States
- Andrew Pekosz
- W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
- Lishuang Shen
- Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, United States
- Scott D. Boyd
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, United States; Sean N. Parker Center for Allergy and Asthma Research, Stanford, CA, United States
- Oliver F. Wirz
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, United States
- Katharina Röltgen
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, United States
- Moiz Bootwalla
- Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, United States
- Dennis T. Maglinte
- Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, United States
- Dejerianne Ostrow
- Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, United States
- David Ruble
- Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, United States
- Jennifer H. Han
- Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, United States
- Jaclyn A. Biegel
- Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, United States; Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- Maggie Li
- W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
- ChunHong Huang
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, United States
- Malaya K. Sahoo
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, United States
- Pia S. Pannaraj
- Keck School of Medicine, University of Southern California, Los Angeles, CA, United States; Department of Pediatrics, Division of Infectious Diseases, Children's Hospital Los Angeles, Los Angeles, CA, United States
- Maurice O'Gorman
- Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, United States; Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- Alexander R. Judkins
- Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, United States; Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- Xiaowu Gai
- Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, United States; Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- Jennifer Dien Bard
- Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, United States; Keck School of Medicine, University of Southern California, Los Angeles, CA, United States; Corresponding author at: Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, United States.
- Journal volume & issue
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Vol. 67
p. 103355
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.
