Shifting Trend in Outcomes of Respiratory Viral Infections Among Hematopoietic Cell Transplant and Cellular Therapy Recipients during 2023-2024 Respiratory Viral Season

Respiratory viral infections (RVI) represent a critical challenge to the health and survival of hematopoietic cell transplantation (HCT) and cellular therapy recipients. According to the U.S. CDC, SARS-CoV-2 was the predominant pathogen driving hospitalizations throughout the 2023-2024 respiratory viral season (RVS). However, at our comprehensive cancer center, we observed fewer hospitalizations attributed to SARS-CoV-2 during the 2023-2024 RVS compared to prior years during the pandemic (Figure 1). Here, we aimed to compare RVI severity and outcomes of respiratory syncytial virus (RSV), influenza (IFV), and SARS-CoV-2 in HCT and cellular therapy recipients during this past season. We performed a retrospective analysis of adult HCT and cellular therapy recipients diagnosed with RSV, IFV, or SARS CoV-2 RVIs from October 2023 to April 2024. Outcomes were assessed through day 30 following their RVI diagnosis. Primary outcomes were hospitalization, lower respiratory tract infection (LRI) and all-cause 30-day mortality. We analyzed 275 patients with 297 consecutive viral episodes, 157 (53%) allo-HCT, 114 (38%) autologous HCT, and 67 (23%) post-cellular therapy recipients (may overlap). RVIs were secondary to SARS-CoV-2 in 124 (42%) cases, RSV in 100 (34%) cases, and IFV in 66 (22%) cases. In seven cases, co-infection was noted. Among RSV-infected individuals, 41% of cases had LRI at diagnosis, and 12% of upper respiratory tract infection (URI) cases progressed to LRI within 30 days, compared to only 29% and 6% of SARS-CoV-2 cases, respectively (Table 1). The 30-day mortality rate was 5.5% (7% in RSV, 6% in IFV, and 4% in COVID-19, p=0.611). On multivariable analysis, RSV and IFV infections were associated with increased LRI risk compared to SARS-CoV-2 (aOR 2.37, 95% CI 1.33-4.22, p=0.003, and aOR 1.91, 95% CI 1.01-3.63, p=0.048, respectively), as well as older age and lymphopenia (an absolute lymphocyte count of ≤200 cells/ml), whereas remission status was associated with lower LRI risk (aOR 0.50, 95% CI 0.29-0.86, p=0.013). Among HCT and cellular therapy recipients infected with SARS-CoV-2, RSV, or IFV during the 2023-2024 RVS, SARS-CoV-2 was associated with the lowest risk for LRI and 30-day mortality. In contrast, RSV had the highest rates of progression to LRI and 30-day mortality. Hospitalization across all RVIs was comparable. These findings underscore a critical need for heightened vigilance and prevention of all RVI in the post-pandemic era, as poor outcomes associated with non-SARS-CoV-2 RVIs still remain.