The Journal of Heart and Lung Transplantation
International Society for Heart and Lung Transplantation.
Original Clinical Science|Articles in Press

Invasive fungal infections after respiratory viral infections in lung transplant recipients are associated with lung allograft failure and chronic lung allograft dysfunction within 1 year

Published:February 19, 2023DOI:


      Respiratory viral infections (RVI) are associated with chronic lung allograft dysfunction (CLAD) and mortality in lung transplant recipients (LTRs). However, the prevalence and impact of secondary invasive fungal infections (IFIs) post RVIs in LTRs have not been investigated.


      We performed a single center retrospective study including LTRs diagnosed with 5 different respiratory viral pathogens between January 2010 to May 2021 and evaluated their clinical outcomes in 1 year. The risk factors of IFIs were evaluated by logistic regression. The impact of IFIs on CLAD stage progression/death was examined by Cox regression.


      A total of 202 RVI episodes (50 influenza, 31 severe acute respiratory syndrome coronavirus-2, 30 metapneumovirus, 44 parainfluenza, and 47 respiratory syncytial virus) in 132 patients was included for analysis. Thirty-one episodes (15%) were associated with secondary IFIs, and 27 occurred in LTRs with lower respiratory tract infection (LRTI; 28% from 96 LRTI episodes). Aspergillosis was the most common IFI (80%). LTRs with IFIs had higher disease severity during RVI episodes. In multivariable analysis, RVI with LTRI was associated with IFI (adjusted odds ratio [95% confidence interval (CI)] of 7.85 (2.48-24.9). Secondary IFIs were associated with CLAD stage progression/death after accounting for LRTI, pre-existing CLAD, intensive care unit admission, secondary bacterial pneumonia and underlying lung diseases pre-transplant with adjusted hazard ratio (95%CI) of 2.45 (1.29-4.64).


      This cohort demonstrated 15% secondary IFI prevalence in LTRs with RVIs. Importantly, secondary IFIs were associated with CLAD stage progression/death, underscoring the importance of screening for fungal infections in this setting.



      ACR (acute cellular rejection), AMR (acute antibody mediated rejection), ANC (absolute neutrophil count), BAL (bronchoalveolar lavage), BMI (body mass index), CAPA (COVID-19 associated pulmonary aspergillosis), CLAD (chronic lung allograft dysfunction), CMV (cytomegalovirus), COVID-19 (coronavirus disease 2019), CT (computed tomography), DSA (donor-specific antibodies), FEV1 (forced expiratory volume in one second percent), FCV (forced vital capacity), HLA (human anti-leukocyte antibody), HMPV (human metapneumovirus), HRs (hazard ratios), IAPA (influenza associated pulmonary aspergillosis), ICU (intensive care unit), IFI (invasive fungal infections), ISHLT (International Society for Heart and Lung Transplantation), LRTI (lower respiratory tract infection), LTRs (lung transplant recipients), OR (odds ratio), PCR (polymerase chain reaction), PIV (parainfluenza virus), RSV (respiratory syncytial virus), RVI (respiratory viral infections), SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), SD (standard deviation), SOT (solid organ transplant recipients), URTI (upper respiratory tract infection)
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