Respiratory Virus Infections and Pulmonary Impairment after Allogeneic Hematopoietic Cell Transplantation.

Abstract

BACKGROUND Respiratory virus infections (RVI) are common after hematopoietic cell transplantation (HCT), but their effect on pulmonary outcomes, including bronchiolitis obliterans syndrome (BOS), and mortality is poorly defined. METHODS Prospective cohort study of 471 allogeneic HCT recipients transplanted in the pre-COVID-19 pandemic era in an academic cancer center. Participants were prospectively followed for one year with serial handheld spirometry, symptom questionnaires, and multiplex 11-virus PCR. Pulmonary function testing occurred at recommended intervals. Cox proportional hazard and generalized estimating equation models were used to estimate associations between RVI and weekly spirometry with late airflow obstruction (AFO), BOS, and overall mortality. RESULTS The one-year cumulative incidence of at least one RVI was 62%; lower respiratory tract disease (LRTD) occurred in 7.6% of patients. Late AFO developed in 15.6% of patients and BOS in 3.9% of patients. Any symptomatic viral upper respiratory tract infections (URTI) were associated with AFO (adjusted HR [aHR] 1.87, 95% CI 1.11-3.16) and BOS (aHR 2.65, 95% CI 1.02-6.91). Individually, PIV-3 URTI were associated with AFO (aHR 2.83, 95% CI 1.01-7.97) and RSV URTI were associated with BOS (aHR 6.32, 95% CI 2.04-19.6). Short-term airflow decline was associated with AFO. Any LRTD (aHR 3.49, 95% CI 2.18-5.57), as well as symptomatic influenza URTI (aHR 2.68, 95% CI 1.52-4.72), were associated with mortality. CONCLUSIONS RVI after HCT, particularly those caused by RSV, PIV-3 and influenza, increase the risk of pulmonary impairment and mortality. These infections should be targeted for specific anti-viral approaches and intensified monitoring for late onset pulmonary disease.