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Intractable COVID-19 and Prolonged SARS-CoV-2 Replication in a CAR-T-cell Therapy Recipient: A Case Study

Hensley, Matthew K. and Bain, William G. and Jacobs, Jana and Nambulli, Sham and Parikh, Urvi and Cillo, Anthony and Staines, Brittany and Heaps, Amy and Sobolewski, Michele D. and Rennick, Linda J. and Macatangay, Bernard J. C. and Klamar-Blain, Cynthia and Kitsios, Georgios D. and Methé, Barbara and Somasundaram, Ashwin and Bruno, Tullia and Cardello, Carly and Shan, Feng and Workman, Creg and Ray, Prabir and Ray, Anuradha and Lee, Janet and Sethi, Rahil and Schwarzmann, William E. and Ladinsky, Mark S. and Bjorkman, Pamela J. and Vignali, Dario A. and Duprex, W. Paul and Agha, Mounzer E. and Mellors, John W. and McCormick, Kevin D. and Morris, Alison and Haidar, Ghady (2021) Intractable COVID-19 and Prolonged SARS-CoV-2 Replication in a CAR-T-cell Therapy Recipient: A Case Study. Clinical Infectious Diseases . ISSN 1058-4838. (In Press)

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A CAR-T-cell recipient developed severe COVID-19, intractable RNAemia, and viral replication lasting >2 months. Pre-mortem endotracheal aspirate contained 2x10¹⁰ SARS-CoV-2 RNA copies/mL and infectious virus. Deep sequencing revealed multiple sequence variants consistent with intra-host virus evolution. SARS-CoV-2 humoral and cell-mediated immunity were minimal. Prolonged transmission from immunosuppressed patients is possible.

Item Type:Article
Related URLs:
URLURL TypeDescription
Bain, William G.0000-0001-8506-0552
Jacobs, Jana0000-0002-0322-585X
Nambulli, Sham0000-0002-9781-9703
Parikh, Urvi0000-0002-4016-0629
Cillo, Anthony0000-0002-3213-3129
Heaps, Amy0000-0003-4410-4007
Macatangay, Bernard J. C.0000-0002-0405-0991
Methé, Barbara0000-0001-8711-1448
Somasundaram, Ashwin0000-0003-3167-406X
Workman, Creg0000-0002-9964-9509
Ray, Prabir0000-0002-0430-5114
Ray, Anuradha0000-0001-6844-8918
Ladinsky, Mark S.0000-0002-1036-3513
Bjorkman, Pamela J.0000-0002-2277-3990
Vignali, Dario A.0000-0002-2771-5992
Duprex, W. Paul0000-0003-1716-6376
McCormick, Kevin D.0000-0003-1544-319X
Morris, Alison0000-0002-7290-6536
Haidar, Ghady0000-0003-0634-8211
Additional Information:© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model ( Received: 23 November 2020; Published: 28 January 2021. The authors would like to thank Dr. Rima Abdel-Massih, Luann Borowski, Michelle Busch, Dr. Jennifer McComb, Dr. Bryan McVerry, Heather Michael, Dr. Stephanie Mitchell, Asma Naqvi, John Ries, Dr. Charles Rinaldo, Caitlin Schaefer, Dr. Michael Shurin, Dr. Alan Wells, and Dr. Sarah Wheeler. Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number KL2TR001856 awarded to G.H., Career Development Award Number IK2 BX004886 from the United States Department of Veterans Affairs Biomedical Laboratory R&D (BLRD) Service awarded to W.B., NIH grant P50 8 P50 AI150464-13 (P.J.B.), George Mason University Fast Grants (P.J.B.), Center for Vaccine Research/University of Pittsburgh, P01HL114453 (P.R, J.S.L.), R01 HL136143 (J.S.L.), and by the University of Pittsburgh Medical Center (UPMC) awarded to D.A.A.V. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Author contributions: Drs. Hensley and Bain contributed equally to this article. Drs. Jacobs and Nambulli contributed equally to this article. All authors have seen and approved the manuscript and contributed significantly to the work. The manuscript has not been previously published nor is it being considered for publication elsewhere. Disclosures: GH receives research funds from Karius, Inc. JWM is a consultant to Gilead Sciences and Merck, and owns shares in Co-Crystal Pharmaceuticals, Infectious Disease Connect, and Abound Bio. GDK has received research funds from Karius, Inc. DAAV: cofounder and stock holder – Novasenta, Tizona and Potenza; stock holder – Oncorus and Werewolf; patents licensed and royalties - Astellas, BMS; scientific advisory board member - Tizona, Werewolf and F-Star; consultant - Astellas, BMS, Almirall, Incyte; research funding – BMS and Novasenta. The rest of the authors have no disclosures.
Funding AgencyGrant Number
Department of Veterans AffairsIK2 BX004886
NIHP50 8 P50 AI150464-13
George Mason UniversityUNSPECIFIED
University of PittsburghUNSPECIFIED
NIHR01 HL136143
Subject Keywords:COVID-19, SARS-CoV-2 immune responses, SARS-CoV-2 RNAemia, SARS-CoV-2 intra-host variation, SARS-CoV-2 infectivity, Severe Acute Respiratory Syndrome Coronavirus-2
Record Number:CaltechAUTHORS:20210201-145608486
Persistent URL:
Official Citation:Matthew K Hensley, William G Bain, Jana Jacobs, Sham Nambulli, Urvi Parikh, Anthony Cillo, Brittany Staines, Amy Heaps, Michele D Sobolewski, Linda J Rennick, Bernard J C Macatangay, Cynthia Klamar-Blain, Georgios D Kitsios, Barbara Methé, Ashwin Somasundaram, Tullia Bruno, Carly Cardello, Feng Shan, Creg Workman, Prabir Ray, Anuradha Ray, Janet Lee, Rahil Sethi, William E Schwarzmann, Mark S Ladinsky, Pamela J Bjorkman, Dario A Vignali, W Paul Duprex, Mounzer E Agha, John W Mellors, Kevin D McCormick, Alison Morris, Ghady Haidar, Intractable COVID-19 and Prolonged SARS-CoV-2 Replication in a CAR-T-cell Therapy Recipient: A Case Study, Clinical Infectious Diseases, 2021;, ciab072,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:107841
Deposited By: Tony Diaz
Deposited On:01 Feb 2021 23:30
Last Modified:02 Feb 2021 20:53

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