Prolonged SARS-CoV-2 Infection in a CAR T-Cell Therapy Recipient | Hematology | JAMA | JAMA Network
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March 9, 2021

Prolonged SARS-CoV-2 Infection in a CAR T-Cell Therapy Recipient

JAMA. 2021;325(10):924. doi:10.1001/jama.2021.2493

In a recent case report, a team of physicians described an immunosuppressed patient with severe coronavirus disease 2019 (COVID-19) who was contagious for more than 2 months. Infectious virus was present in the patient’s endotracheal aspirate (ETA) 72 days after his COVID-19 diagnosis and 2 days before he died from the massive lung infection. The findings from the 73-year-old man, who had recently undergone chimeric antigen receptor T-cell (CAR-T) therapy, suggest that patients with COVID-19 who are severely immunosuppressed may need isolation for longer than the currently recommended 20 days.

The patient with treatment–resistant multiple myeloma was first admitted to the intensive care unit (ICU) for COVID-19 symptoms 25 days after a CAR-T–cell infusion, which was preceded by lymphodepletion. As a result, the patient had a diminished T-cell response and an almost nonexistent antibody response.

Despite receiving convalescent plasma and the antiviral remdesivir, the patient had high plasma levels of viral RNA throughout his illness, which required 2 ICU stays. He also had persistent positive results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on repeat nasopharyngeal swab polymerase chain reaction testing.

Genetic sequencing at day 4 detected viral sequences compatible with the type of virus then circulating in Pittsburgh, where he was hospitalized. Between days 13 and 72, however, the researchers found several additional viral genetic changes from the patient’s plasma and ETA, including some present in variants now widely circulating in the UK and South Africa.

The timing and number of genetic changes indicate that the virus evolved within the patient, arguing against reinfection or superinfection, the researchers said. Although still speculative, the findings raise the possibility that the concerning SARS-CoV-2 variants now widely circulating may have originated in patients with protracted infections, the team wrote in Clinical Infectious Diseases.

“For patients with a high risk of prolonged infectivity, a ‘test-based’ strategy will help guide the duration of transmission-based precautions,” study senior author Ghady Haidar, MD, of the University of Pittsburgh School of Medicine, said in an email. “This is something we are actively working on, and I suspect we and other centers will continue to refine our strategies as data about this phenomenon emerge.”

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