Epidemiology of respiratory viral infections among hematopoietic cellular therapy and chimeric antigen receptor T-cell therapy recipients in the post COVID-19 era

Abstract

Respiratory viral infections (RVIs) remain a source of morbidity among hematopoietic cell transplant (HCT) or chimeric antigen receptor (CAR) T-cell therapy recipients. This study aims to understand the post-pandemic RVI epidemiology in cellular therapy recipients. IRB-approved retrospective study of consecutive HCT and CAR T-cell therapy recipients diagnosed with RVI within 100 days of cellular therapy in a single academic center from January 1, 2022, to August 2, 2024.

Among 2072 HCTs and 545 CAR T-cell treatments, 194 RVIs were identified within the first 100 days (cumulative incidence of 7.4%). The incidence of RVI was 12.7% in CAR T (n=70), 7.8% in allogeneic HCT (n=69), and 4.7% in autologous HCT (n=55) recipients. SARS-CoV-2 was the most common pathogen (43%), followed by parainfluenza virus (21%) and RSV (16%). Most RVIs (79%) were community-acquired with a median onset of 54 days post-infusion. Among the194 episodes, 151 (78%) were upper respiratory tract infections, and 43 (22%) were lower respiratory tract infections (LRTIs); 49% (21/43) of LRTIs were severe. In multivariate analysis, severe RVI was associated with the use of tocilizumab within 30 days of RVI (OR 4.84 95% CI 1.12-20.96, p=0.035), low ALC (<200 cells/microL; OR 6.82 (95%CI 1.89-24.67, p=0.003), and infection with non-SARS-CoV-2 viruses (OR 10.26, 95% CI 2.37-44.43, p=0.002).

Early RVIs occurred most frequently in CAR T recipients, and SARS-CoV-2 was the most common pathogen. Approximately one quarter of medically attended RVI involves the lower respiratory tract. Severe disease is associated with infections with non-SARSCoV- 2 viruses and profound lymphopenia.