Ten Years of Ribavirin Treatment for Pneumovirus and Paramyxovirus Infections in Lung Transplant Recipients

PURPOSE: Respiratory tract infection with respiratory syncytial virus (RSV), human metapneumo virus (hMPV) or parainfluenza virus (PIV) are increasingly associated with chronic lung allograft dysfunction in the form of bronchiolitis obliterans syndrome (BOS) in lung transplant recipients (LTR). Ribavirin as treatment option is under debate since its effectiveness is unclear, especially in light of infection severity. METHODS: We retrospectively analyzed 10 years of RSV, hMPV and PIV infections in LTR in our center. Main endpoints were FEV1 at 3 and 6 months post-infection, expressed as a percentage of pre-infection FEV1 (by hierarchical linear mixed model) and incidence of new or progressed BOS 6 months post infection (by logistic regression). Patients with acute rejection < 3 mo. or transplantation <6 mo. prior to infection or with concomitant fungal infection were excluded. Time since transplantation, virus type (RSV, hMPV or PIV), viral co-infection, bacterial co-infection, presence of BOS prior to infection, severe or mild infection, follow-up time point (three vs. six months), tacrolimus use, mycophenolate mofetil (MMF) use, and ribavirin treatment (any form) were used as covariates in the multivariable models. RESULTS: A total of 139 infections were included, 88 (63%) with a severe infection (defined as a >10% FEV1 decline at infection), and 51 (37%) with a mild infection (≤10% FEV decline). Median [IQR] FEV1 decline during infection was notable and similar across the viruses (RSV 14% [22], hMPV 15% [14], PIV 16% [20]. Overall post-infection BOS incidence was 20% (27% for severe, 10% for mild). There were no virus related deaths. The linear mixed model found estimated associations on post-infection FEV1 for ribavirin treatment vs. no ribavirin (+13.2% [7.79;18.67]) and severe infection vs. mild infection (-11.1% [-14.76; -7.37). Ribavirin treatment (aOR 0.24 [0.10-0.59]), severe infection (aOR 4.63 [1.66;12.88]) and surprisingly also MMF use (aOR 0.38 [0.14;0.97]) were factors associated with new or progressed BOS at 6 months. LTR with a mild infection tended to recover well, regardless of antiviral therapy. CONCLUSION: We conclude that ribavirin should be considered as treatment option to possibly prevent allograft dysfunction in LTR with severe RSV, hMPV or PIV infection. We found no reason to discontinue MMF during these infections.