Invited Commentary 

August 16, 2023

Lung Transplant for Acute Respiratory Distress Syndrome

Emily Cerier, Ankit Bharat

JAMA Surg. Published online August 16, 2023. doi:10.1001/jamasurg.2023.3474

Accumulating evidence using data from individual centers,¹ as well as national registries,^2,3 substantiating the advantages of lung transplant for patients who experience irreversible lung damage due to COVID-19 infection, finds an essential supplement in the retrospective review by Tasoudis et al.⁴ The study discerned that patients receiving lung transplants for COVID-19–related acute respiratory distress syndrome (ARDS) and pulmonary fibrosis in the US demonstrated comparable overall survival rates with those who exhibited other pretransplant pathologies.

Previously, our team at Northwestern University, the Successful Clinical Response in Pneumonia Therapy (SCRIPT) study investigators, identified that SARS-CoV-2 elicits T-cell chemoattractants when infecting alveolar macrophages.⁵ Recruitment of T cells initiates a positive feedback loop with the infected macrophages, provoking spatially limited alveolitis, which results in persistent alveolar inflammation. Tissue clearing of COVID-19–affected human lungs coupled with matrix imaging revealed that such inflammation can escalate to permanent structural loss marked by the emergence of KRT17-positive aberrant basaloid cells, a potential indicator of irreversible lung damage, underscoring the importance of lung transplant for certain patients who fail to recuperate.⁶

The probability of sufficient lung function recovery appears to decrease over time while receiving extracorporeal support whereas the risk of death increases,⁷ leading many centers, ours included, to contemplate the possibility of transplant after a minimum of 6 weeks of extracorporeal respiratory support. This consideration is particularly pertinent in cases of persistent severe ARDS and the development of medically refractory complications, antimicrobial resistant pneumonia, and sepsis. However, although lung transplant is undeniably a life-saving intervention for selected patients with ARDS, the determination of right timing requires an astute, longitudinal, multidisciplinary assessment to gauge the likelihood of sufficient respiratory function recovery.

Studies highlight the complexity and extensive resource requirements of these transplants in comparison to non–COVID-19 diseases. Therefore, although over 50 centers have reported such transplants in the US, the correlation between transplant volumes, reflective of centers’ resources, and outcomes remains unclear. This aspect is especially relevant for patients with COVID-19 infection and ARDS who experience protracted hospitalizations and numerous iatrogenic complications. Transplant procedures for COVID-19 fibrosis are considerably less complex and can be approached using standard principles for patients with chronic pulmonary fibrosis. The decision between double- vs single-lung transplant largely hinges on medical intuition rather than concrete evidence, with our preference leaning toward double-lung transplant for both ARDS and chronic COVID-19 fibrosis.

Although the current study elucidates the increasing trend in lung transplants for COVID-19 in the US during the defined study period, with the expected recession of the pandemic, we anticipate a decline in double-lung transplant for COVID-19 ARDS. Nevertheless, insights learned from lung transplants for COVID-19 could be extended to patients battling other causes of ARDS—a severe global health care issue with high mortality, affecting over 100 000 patients annually in the US alone. Given the strength of 1-year outcomes as predictors of longer-term success, we anticipate that lung transplants will continue to be a life-saving therapy for selected patients with medically refractory ARDS.