Human metapneumovirus and parainfluenza virus infections in lung transplant recipients: The effects on lung allograft and clinical outcomes

Background. Human metapneumovirus (HMPVi) and parainfluenza virus (PIVi) infections are common community-acquired infections in lung transplant recipients (LTRs), but data are extremely limited. Methods. A retrospective study including all LTRs at the Johns Hopkins Hospital during July 2010–June 2019 with positive HMPV and PIV polymerase chain reaction respiratory specimens was performed. Results. Thirty-one HMPV- and 53 PIV-infected LTRs were identified. LTRs with HMPVi and PIVi had similar baseline characteristics, infection parameters, treatment allocation, and allograft function outcomes. Among entire cohort, 31.6% had chronic allograft dysfunction (CLAD) stage progression within 1 y postinfections (29.2% versus 35.5% for PIVi versus HMPVi, respectively, P=0.56). In forced expiratory volume in 1 s percent (FEV₁%) trajectory analysis showed steadily decline of FEV₁ across time among CLAD stage progressors from both viruses. FEV₁% decline ≥10% at 90 d had adjusted hazard ratio for CLAD stage progression of 18.4 (4.98-67.76) and 4.6 (1.36-15.34) for PIVi and HMPVi, respectively. PIVi caused higher donor-specific antigen development (11.8% versus 3.2%, P=0.18) and 1-y mortality (9.4% versus 0%, P=0.11), compared with HMPVi, even though the results were not statistically significant. Ribavirin did not show protective effect, and mycophenolate discontinuation during infection did not increase risk of CLAD stage progression. Conclusions. One-third of HMPV- and PIV-infected LTRs developed CLAD stage progression within 1 y. The lack of early lung function recovery may predict long-term CLAD progression.