Protracted coronavirus disease 2019 after chimeric antigen receptor-T cell therapy successfully treated with sequential multidrug therapy

A 56-year-old woman who received CD19 chimeric antigen receptor-T cell therapy for refractory diffuse large B-cell lymphoma developed severe coronavirus disease 2019 (COVID-19) and was treated with nirmatrelvir/ritonavir in April 2022. However, she experienced persistent fatigue and cough and fever in June. Computed tomography revealed bilateral ground-glass opacities (GGO), and the patient was treated with corticosteroids for organizing pneumonia after COVID-19. Partial improvement was observed, but new GGO appeared despite corticosteroid therapy. Genome analysis of severe acute respiratory syndrome coronavirus 2 detected Omicron variant BA.1.1.2, which was prevalent at the time of initial infection. The patient was diagnosed with protracted COVID-19 and was treated with remdesivir, molnupiravir, nirmatrelvir/ritonavir, and tixagevimab/cilgavimab. These treatments appeared to contribute to the improvement of protracted COVID-19. •B-cell depletion by CAR-T cell therapy, hematopoietic stem cell transplantation, and anti-CD20 monoclonal antibodies is the risk factors for protracted COVID-19.•Sequential multidrug therapy including remdesivir, molnupiravir, nirmatrelvir/ritonavir, and tixagevimab/cilgavimab improved protracted COVID-19 after CAR-T cell therapy.•Multiple and long-term use of antiviral drugs is a reasonable treatment option.