Emergency Lung Transplantation after COVID-19: Immunopathological Insights on Two Affected Patients

G.A. Croci, V. Vaira, D. Trabattoni, M. Biasin, L. Valenti, G. Baselli, M. Barberis, E. Guerini Rocco, G. Gregato, M. Scandroglio, E. Fominskiy, A. Palleschi, L. Rosso, M. Nosotti, M. Clerici, S. Ferrero

Research output: Contribution to journalArticlepeer-review


We herein characterize the immunopathological features of two Italian COVID-19 patients who underwent bilateral lung transplantation (bLTx). Removed lungs underwent histopathological evaluation. Gene expression profiling (GEP) for immune-related signatures was performed on lung specimens and SARS-CoV-2-stimulated peripheral blood mononuclear cells (PBMCs). Cytokine levels were measured on lungs, bronchoalveolar lavage fluids and in culture supernatants. Pathologi-cal assessment showed extensive lung damage with the pattern of proliferative to fibrotic phases, with diffuse alveolar damage mimicking usual interstitial pneumonia (UIP). Lungs’ GEP revealed overexpression of pathogen recognition receptors, effector cytokines and chemokines, immune activation receptors and of the inflammasome components. Multiplex cytokine analysis confirmed a proinflammatory state, with high levels of monocyte/macrophage chemotactic and activating factors and of IL-6 and TNF-α. A similar profile was observed in SARS-CoV-2-stimulated PBMCs collected 7 days after transplant. The pattern of tissue damage observed in the lungs suggests that this may represent the output of protracted disease, resembling a diffuse UIP-like picture. The molecular immune profiling supports the paradigm of a persistent proinflammatory state and sustained humoral immunity, conditions that are maintained despite the iatrogenic immunosuppression.

Original languageEnglish
Article number611
Issue number3
Publication statusPublished - 2021


  • ARDS
  • COVID-19
  • immunology
  • lung transplantation
  • SARS-CoV-2
  • usual interstitial pneumonia
  • chemokine
  • cytokine
  • inflammasome
  • interleukin 6
  • tumor necrosis factor
  • adolescent
  • blood
  • bronchoalveolar lavage fluid
  • case report
  • cytology
  • gene expression profiling
  • gene expression regulation
  • genotype
  • human
  • lung
  • lymph node
  • male
  • metabolism
  • middle aged
  • mononuclear cell
  • pathology
  • plasma
  • respiratory distress syndrome
  • single nucleotide polymorphism
  • virology
  • Adolescent
  • Bronchoalveolar Lavage Fluid
  • Chemokines
  • Cytokines
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genotype
  • Humans
  • Inflammasomes
  • Interleukin-6
  • Leukocytes, Mononuclear
  • Lung
  • Lung Transplantation
  • Lymph Nodes
  • Male
  • Middle Aged
  • Plasma
  • Polymorphism, Single Nucleotide
  • Respiratory Distress Syndrome
  • Tumor Necrosis Factor-alpha


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