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Intractable Coronavirus Disease 2019 (COVID-19) and Prolonged Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Replication in a Chimeric Antigen Receptor-Modified 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 C. 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 Coronavirus Disease 2019 (COVID-19) and Prolonged Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Replication in a Chimeric Antigen Receptor-Modified T-Cell Therapy Recipient: A Case Study. Clinical Infectious Diseases, 73 (3). e815-e821. ISSN 1058-4838. PMCID PMC7929077. doi:10.1093/cid/ciab072.

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A chimeric antigen receptor-modified T-cell therapy recipient developed severe coronavirus disease 2019, intractable RNAemia, and viral replication lasting >2 months. Premortem endotracheal aspirate contained >2 × 10¹⁰ severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA copies/mL and infectious virus. Deep sequencing revealed multiple sequence variants consistent with intrahost 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 CentralArticle
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
Bruno, Tullia C.0000-0002-6433-0207
Cardello, Carly0000-0002-2810-7681
Shan, Feng0000-0003-3660-8475
Workman, Creg0000-0002-9964-9509
Ray, Prabir0000-0002-0430-5114
Ray, Anuradha0000-0001-6844-8918
Lee, Janet0000-0002-6812-6043
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
Agha, Mounzer E.0000-0002-2275-7544
Mellors, John W.0000-0002-3737-9742
McCormick, Kevin D.0000-0003-1544-319X
Morris, Alison0000-0002-7290-6536
Haidar, Ghady0000-0003-0634-8211
Alternate Title:Intractable COVID-19 and Prolonged SARS-CoV-2 Replication in a CAR-T-cell Therapy Recipient: A Case Study
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; Editorial decision: 20 January 2021; Published: 28 January 2021; Corrected and typeset: 27 February 2021. The authors 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. Financial support. Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) (award number KL2TR001856 to G. H.); the United States Department of Veterans Affairs Biomedical Laboratory R&D Service (career development award number IK2 BX004886 to W. B.); the NIH (grant number P50 8 P50 AI150464–13 to P. J. B.); George Mason University Fast Grants (to P. J. B.); the Center for Vaccine Research/University of Pittsburgh (grant numbers P01HL114453 to P. R. and J. S. L. and R01 HL136143 to J. S. L.); and the University of Pittsburgh Medical Center P01 AI108545, P50 CA097190 & R01s CA203689, DK089125, AI129893, and AI144422 (to D. A. V.). Author contributions. M. K. H. and W. G. B. contributed equally to this work as co-first authors. J. J. and S. N. contributed equally to this work. All authors have seen and approved the manuscript and contributed significantly to this work. Disclaimer. The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Potential conflicts of interest. G. H. and G. D. K. have received research funds from Karius, Inc. J. W. M. is a consultant to Gilead Sciences and Merck and owns shares in Co-Crystal Pharmaceuticals, Infectious Disease Connect, and Abound Bio. D. A. V. is a cofounder and stock holder of Novasenta, Tizona, and Potenza; is a stock holder of Oncorus and Werewolf; holds patents and receives royalties from Astellas and BMS; is a scientific advisory board member for Tizona, Werewolf, and F-Star; is a consultant to Astellas, BMS, Almirall, and Incyte; and receives research funding from BMS and Novasenta. All other authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
Funding AgencyGrant Number
Department of Veterans AffairsIK2 BX004886
NIHP50 8 P50 AI150464-13
George Mason UniversityUNSPECIFIED
University of PittsburghUNSPECIFIED
NIHR01 HL136143
NIHP01 AI108545
NIHP50 CA097190
NIHR01 CA203689
NIHR01 DK089125
NIHR01 AI129893
NIHR01 AI144422
Subject Keywords:COVID-19, SARS-CoV-2 immune responses, SARS-CoV-2 RNAemia, SARS-CoV-2 intrahost variation, SARS-CoV-2 infectivity, severe acute respiratory syndrome coronavirus 2
Issue or Number:3
PubMed Central ID:PMC7929077
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 C 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 Coronavirus Disease 2019 (COVID-19) and Prolonged Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Replication in a Chimeric Antigen Receptor-Modified T-Cell Therapy Recipient: A Case Study, Clinical Infectious Diseases, Volume 73, Issue 3, 1 August 2021, Pages e815–e821,
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:11 Aug 2021 17:22

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