Human Metapneumovirus and Parainfluenza Virus Infections in Lung Transplant Recipients: The Effects on Lung Allograft and Clinical Outcomes

Abstract

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.

Impact of COVID-19 on Lung Allograft and Clinical Outcomes in Lung Transplant Recipients: A Case-control Study

“…Lung transplant recipients (LTRs) are at risk of unique complications post-respiratory viral infections (RVIs) including allograft rejection and chronic lung allograft dysfunction (CLAD) stage progression. [10][11][12][13] The data regarding COVID-19 outcomes in LTRs are very limited, as most large SOT cohorts contained only small numbers of LTRs and did not provide clinical outcomes specific to this patient population. 4,8,9 Early in the pandemic, case series from France and New York reported mortality in LTRs at 15% and 34%, respectively; however, more contemporary follow-up incorporating current COVID treatment and an examination of outpatient outcomes are Original Clinical Science-General Background.…”

CARVs, CLAD, and CMV: A Call for Heightened Awareness in Lung Transplant Recipients

“…Indeed, forced expiratory volume in 1s percentage decline of ≥10% from baseline at 90 d after CARV infection was a potential predictor for CLAD progression in this study. 4 In our earlier prospective study, 1 the functional evaluation at 3 mo was indeed predictive of CLAD after CARV infections and readily adoptable in clinical practice. 1 Given the lack of therapeutic options, such studies 1,2,4 also provide a rationale to develop novel treatments and prevention measures, including risk-adapted preemptive therapies for CARVs and for local cytomegalovirus replication in LuTRs, to mitigate CLAD progression.…”

“…1 Given the lack of therapeutic options, such studies 1,2,4 also provide a rationale to develop novel treatments and prevention measures, including risk-adapted preemptive therapies for CARVs and for local cytomegalovirus replication in LuTRs, to mitigate CLAD progression. 4 The current severe acute respiratory syndrome coronavirus 2 pandemic has resulted in a paradigmatic reevaluation of CARV infections, the modalities of transmission, pathophysiology, prevention, and treatment in all patient groups, including in transplant patients as described. 5…”

“…[1][2][3] Notably, the variety of different CARVs seems to have a different propensity in this regard. We congratulate Permpalung et al 4 for their focus on human metapneumovirus (HMPV) and human parainfluenza virus (HPIV) infections in LuTRs. In their single-center retrospective study (2010-2019), the authors identified 31 HMPV-infected and 53 HPIV-infected LuTRs, of whom one-third developed CLAD within 1 y postinfection irrespective of ribavirin use and mycophenolate discontinuation.…”

“…1 Given the lack of therapeutic options, such studies 1,2,4 also provide a rationale to develop novel treatments and prevention measures, including risk-adapted preemptive therapies for CARVs and for local cytomegalovirus replication in LuTRs, to mitigate CLAD progression. 4 The current severe acute respiratory syndrome coronavirus 2 pandemic has resulted in a paradigmatic reevaluation of CARV infections, the modalities of transmission, pathophysiology, prevention, and treatment in all patient groups, including in transplant patients as described. 5 Therefore, the contribution by Permpalung et al is most important for not scotomizing CARVs, such as HMPV, HPIV, HRSV, and influenza viruses, for which a tsunami wave must be feared as they return after low seasonal circulation and waning specific immunity during the past 2 seasons of the severe acute respiratory syndrome coronavirus 2 pandemic and for which we need to prepare.…”