Community-Acquired Respiratory Virus Infections: A Threat to Long-Term survivors after Allogeneic Stem Cell Transplant?

Background: Studies on late community-acquired respiratory virus (CARV) infections in long-term allogeneic hematopoietic stem cell transplantation (allo-HCT) survivors are scarce, creating knowledge gaps on the epidemiology, risk of progression to lower respiratory tract disease (LRTD), and conditions linked to poor outcomes.

Patients And Methods: We included consecutive CARV infection episodes occurring up to six months after allo-HCT registered in our database from December 2013 to June 2023 at two Spanish transplant centers.

Results: Among 426 allo-HCT recipients, 1070 CARV episodes were recorded, 791 (74%) with only upper respiratory tract disease (URTD) and 279 (15%) progressing to LRTD, at a median of 18.6 months post-transplant. The most common CARVs were rhinovirus, respiratory syncytial virus (RSV), and influenza. The LRTD progression rate was 26%, with a 4.9% all-cause mortality rate at 100 days post-CARV detection. Risk factors for LRTD progression included graft-versus-host disease prophylaxis [odds ratio (OR) 3.08], corticosteroid use (0.1 to <30 mg/day: OR 2.44; ≥30 mg/day: OR 5.19), absolute lymphocyte count (ALC) <1 × 10^9/L (OR 1.60), fever at CARV screening (OR 4.27), RSV (OR 2.46), and human metapneumovirus (HMPV) [OR 2.76]. Risk factors for 100-day all-cause mortality included HLA mismatch [hazard ratio (HR) 2.49]; corticosteroid use (0.1 to <30 mg/day: HR 3.87; ≥30 mg/day: HR 5.77); ALC <1 × 10^9/L (HR 2.44); neutropenia <0.5 × 10^9/L (HR 6.74), and age ≥ 40 years (HR 4.85).

Conclusion: Recipients with profound and prolonged immunosuppression remain at risk for severe CARV infection outcomes late after allo-HCT, necessitating intensive clinical monitoring for respiratory symptoms.