key: cord-0836854-6f0sj1hm
authors: Meyer, Keith C
title: Risks of lung transplantation in the SARS-CoV-2 era
date: 2020-12-01
journal: Lancet Respir Med
DOI: 10.1016/s2213-2600(20)30561-0
sha: c934802796cb0412cd4f29a46ad5b0f9ff30fe89
doc_id: 836854
cord_uid: 6f0sj1hm

nan

As the COVID-19 pandemic has swept the world, the provision of health care for conditions that are unrelated to COVID-19 has been extensively disrupted. This is especially the case for patients in need of solid organ transplantation, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have complicated the approach that transplant centres must take to ensure that recipients are not placed at risk of potentially fatal outcomes or severe allograft dysfunction should they become infected with SARS-CoV-2.

Many DNA and RNA viruses pose both immediate and delayed-onset, potentially serious risks for lung transplant recipients, 1 and disruption of host-virus relationships after solid organ transplantation can lead to both reactivation of latent viruses residing in donor tissues and new infections. Additionally, lung transplant recipients who have had successful transplantations are at risk of developing community-acquired respiratory virus infections, which have been linked to both acute and chronic lung allograft dysfunction. 2 Infection with the novel SARS-CoV-2 is associated with substantial morbidity and mortality, and many survivors of COVID-19 have long-term or permanent detrimental health effects. 3 Airborne transmission is the predominant route of disease spread 4 and it has become clear that virus-containing aerosols can linger in ambient air for hours before settling out via gravity. Asymptomatic infected individuals can be important vectors of virus spread, and should solid organ transplant recipients become infected with SARS-CoV-2, they might be at increased risk of severe disease and a fatal outcome compared with the general population. 5 However, community-acquired SARS-CoV-2 infections in lung transplant recipients can have a benign clinical course. 6 SARS-CoV-2 rapidly replicates once it gains access to respiratory epithelium. 3, 4 It can then spread via the circulation as it infects endothelial cells, not only causing respiratory dysfunction-organising pneumonia, diffuse alveolar damage, intravascular clotting, and acute respiratory distress syndrome (ARDS)-but potentially causing severe dysfunction of other organs, including heart, brain, gastrointestinal tract, and kidneys. 7 Viral loads can be very large and virus shedding can persist for many weeks. 8 Transplanting lungs from a SARS-CoV-2-positive donor into a SARS-CoV-2-naive recipient or transplanting donor lungs into a patient whose irreversible respiratory failure has occurred as a consequence of severe ARDS with pulmonary fibrosis associated with COVID-19 are two potential scenarios in which a SARS-CoV-2 primary infection or SARS-CoV-2 reactivation could cause lifethreatening complications and a poor outcome for lung transplant recipients.

In The Lancet Respiratory Medicine, Laurens Ceulemans and colleagues 9 report a successful double-lung transplantation using lungs from a SARS-CoV-2 IgG antibody-positive donor who had recovered from a presumed case of symptomatic COVID-19 3 months before transplantation. The SARS-CoV-2-naive recipient had a typical post-transplantation course, and although a lung biopsy done at the time of implantation showed the presence of SARS-CoV-2 RNA by PCR testing, posttransplantation nasopharyngeal swab testing, repeated PCR tests of bronchoalveolar lavage specimens, viral culture of bronchoalveolar lavage and donor lung tissue to detect viral replication, and serum anti-SARS-CoV-2 antibodies were negative. The good transplantation outcome and absence of virus activation despite the intense immunosuppression regimen given to the recipient suggest that transplanting organs harvested from a donor whose SARS-CoV-2 infection has resolved can be safely performed.

Although many patients succumb to respiratory failure with acute COVID-19 pneumonia, a substantial number of survivors with refractory ARDS develop severe, non-resolving pulmonary fibrosis that leaves them persistently ventilator-dependent and unlikely to survive without a lung transplant. Lang and colleagues 10 reported using lung transplantation as a salvage therapy for a patient with severe, treatmentrefractory COVID-19-induced ARDS requiring prolonged extracorporeal membrane oxygenation support. Repeated nasopharyngeal swabs and bronchoalveolar lavage specimens before transplantation were PCR positive, but Vero cell cultures did not show viable virus. Although post-transplant PCR on multiple sequential nasopharyngeal swab and bronchoalveolar lavage specimens remained positive before turning negative after day 10, Vero cell cultures were negative,

ktsdesign/Science Photo Library suggesting that infective virus was no longer present, and the recipient had a good transplantation outcome.

What lessons do these case reports provide? As new cases of COVID-19 are exponentially on the rise in the general population in many countries, it is increasingly likely that donors might have a history of previous infection, either resolved or still active, when assessed for transplantation suitability. Potential donors must be thoroughly screened for active SARS-CoV-2 infection, but transplanting lungs from a donor whose infection has resolved and whose respiratory function is not compromised can be safe, possibly even if SARS-CoV-2 RNA persists in lung tissue. Additionally, when lung transplantation is considered in patients with end-stage ARDS or fibrosis caused by COVID-19, although PCR from respiratory tract specimens might be persistently positive up to and shortly after transplantation, active infection with shedding of viable virus is not necessarily observed, as shown by Lang and colleagues, 10 and lung transplantation can be safely performed. Experienced transplant teams need to adequately screen donor lungs for active SARS-CoV-2 infection, and transplant candidates whose transplant indication is refractory COVID-19 ARDS must be carefully selected. Because there is still much to learn concerning the effect of the SARS-CoV-2 virus on lung transplantation outcomes, a careful approach with attention to short-term and longterm follow-up after transplantation is essential.

Although effective vaccines might soon be available and vaccination combined with other strategies will hopefully curb and eventually stop the COVID-19 pandemic, infections will probably continue to affect world populations for months to years. Evolving experience in the era of SARS-CoV-2 at lung transplantation centres around the world will provide guidance for developing best practices to deal with the threat that this novel virus poses to successful solid organ transplantation.

Viral infections in lung transplantation

Infection prophylaxis and management of viral infection

Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review

Natural history of COVID-19 and current knowledge on treatment therapeutic options

COVID-19 in solid organ transplant recipients: initial report from the US epicenter

SARS-CoV-2 infection in two patients following recent lung transplantation

Organ-specific manifestations of COVID-19 infection

Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study

Successful double-lung transplantation from a donor previously infected with SARS-CoV-2

Lung transplantation for COVID-19-associated acute respiratory distress syndrome in a PCR-positive patient