Characterizing Respiratory Virus Infections during the Peri‐engraftment Period of Allogeneic Hematopoietic Cell Transplant

Background Community‐acquired respiratory virus (CARV) infections are frequent and potentially severe in allogeneic hematopoietic stem cell transplant (allo‐HCT) recipients. However, their impact during the peri‐engraftment period remains underexplored. Methods In this retrospective multicenter study, we assessed the characteristics, effects on neutrophil engraftment, and risk factors for lower respiratory tract disease (LRTD) progression and 100‐day mortality of symptomatic peri‐engraftment CARV infections [from Day −8 until Day +36 after stem cell infusion]. A total of 112 allo‐HCT recipients and 114 CARV episodes were included. Univariable and multivariable Cox regression analyses and cumulative incidence estimates were used. Results The median patient age was 51 years. Rhinovirus (47%) and respiratory syncytial virus (23%) were the most common pathogens. Half of the infections occurred before neutrophil engraftment (median day +18), and 50% progressed to LRTD. The 100‐day mortality rate was 17%, increasing to 27% in those with LRTD. CARV infection prior to engraftment was associated with delayed neutrophil recovery (Day +18 vs. +16; p = 0.04) in multivariable cause‐specific Cox regression analysis (HR 0.42, p < 0.001). Multivariable analysis identified lymphocyte count <0.2×10⁹/L (HR 3.1, p = 0.004) and active graft‐versus‐host disease (HR 2.36, p = 0.004) as independent predictors of LRTD. Risk factors for 100‐day mortality included LRTD (HR 3.34, p = 0.04), use of anti‐thymocyte globulin (HR 3.48, p = 0.019), and bacterial coinfection (HR 4.48, p = 0.006). Conclusion CARV infections during the peri‐engraftment allo‐HCT phase carry a high risk for delayed engraftment and LRTD in case of profound lymphopenia and GvHD. LRTD, ATG use, and bacterial coinfections contributed significantly to mortality.