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