Lung donation following SARS-CoV-2 infection

Abstract

There have been over 177 million cases of COVID-19 worldwide, many of whom could be organ donors. Concomitantly, there is an anticipated increase in the need for donor lungs due to expanding indications. Given that the respiratory tract is most commonly affected by COVID-19, there is an urgent need to develop donor assessment criteria while demonstrating safety and "efficacy" of lung donation following COVID-19 infection. Accordingly, we report an intentional transplant using lungs from a donor with recent, microbiologically confirmed, COVID-19 infection into a recipient suffering from COVID-19 induced ARDS and pulmonary fibrosis. In addition to the standard clinical assays, both donor and recipient lungs were analyzed using RNAscope, which confirmed that tissues were negative for SARS-CoV-2. Immunohistochemistry demonstrated colocalized KRT17+ basaloid-like epithelium and COL1A1+ fibroblasts, a marker suggestive of lung fibrosis in COVID-19 associated lung disease, in the explanted recipient lungs but absent in the donor lungs. We demonstrate that following a thorough assessment, lung donation following resolved COVID-19 infection is safe and feasible.

Keywords: clinical research/practice; donors and donation; lung transplantation/pulmonology; lung transplantation: living donor.

FIGURE 1

Assessment of recipient and donor lungs. (A–D) Pre-transplant chest radiograph and computed tomography of the recipient demonstrating honeycombing and pulmonary fibrosis. (E, F) Donor lung images showing normal radiograph and mild bibasilar atelectasis with signs of aspiration in left lung. (G) Intraoperative donor lung assessment demonstrating normal compliance and no gross fibrosis. (H) Normal lung compliance and gross appearance of donor allograft following implantation. (I) Chest radiograph of the donor allografts a week following implantation

FIGURE 2

Pathological examination of native and donor lungs. (A–C) Gross appearance of the explanted native lungs showing fibrosis and honeycombing. (D) Normal appearance donor lung allografts prior to cold storage. Histological assessment of the explanted lungs showed (E) interstitial fibrosis (200x), (F) microcysts with histiocytic reaction (100x), (G) microscopic honey comb changes (100x), (H) diffuse interstitial fibrosis (20x), (I) acute and chronic inflammation (100x), while the donor lung was normal (J)

FIGURE 3

RNAScope and IHC of native and donor lung tissue. (A–C) RNAScope of the explanted native lung (A) and implanted donor lung (B) in comparison to autopsy lung tissue from a patient who died of COVID-19 as a positive control (C). Nuclear staining (blue), positive strand SARS-CoV-2 RNA (red), negative strand SARS-CoV-2 RNA (yellow). Positive strand SARS-CoV-2 RNA was detected in the positive control denoted by a red arrow with rare negative strand SARS-CoV-2 RNA denoted by a yellow arrow in epithelial cells. Neither positive or negative RNA was found in the implanted or explanted lung tissues. (D–G) Immunofluorescence microscopy of KRT17 (magenta) and COL1A1 (green) of the explanted lung (D and E) and implanted donor lung (F and G). Immunofluorescence microscopy revealed Krt17+ cells colocalized with Col1a1+ fibroblasts in the distal parenchyma of the explanted lung tissue without normal airway architecture (red box). KRT17 staining was absent in the donor lung tissue

FIGURE 4

Institutional practice for assessment of lungs from donor with historic COVID-19