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

Creators: Hensley, Matthew K.; Bain, William G.; Jacobs, Jana; Nambulli, Sham; Parikh, Urvi; Cillo, Anthony; Staines, Brittany; Heaps, Amy; Sobolewski, Michele D.; Rennick, Linda J.; Macatangay, Bernard J. C.; Klamar-Blain, Cynthia; Kitsios, Georgios D.; Methé, Barbara; Somasundaram, Ashwin; Bruno, Tullia C.; Cardello, Carly; Shan, Feng; Workman, Creg; Ray, Prabir; Ray, Anuradha; Lee, Janet; Sethi, Rahil; Schwarzmann, William E.; Ladinsky, Mark S.; Bjorkman, Pamela J.; Vignali, Dario A.; Duprex, W. Paul; Agha, Mounzer E.; Mellors, John W.; McCormick, Kevin D.; Morris, Alison; Haidar, Ghady

Abstract

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.

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 (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_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.

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Resource type: Journal Article
Publisher: Oxford University Press
Published in: Clinical Infectious Diseases, 73(3), e815-e821, ISSN: 1058-4838.