key: cord-0733559-pd4gtehi
authors: Wadowski, Benjamin J.; Bacchetta, Matthew; Kon, Zachary N.
title: Beware the Deus Ex Machina of Covid-19
date: 2020-08-29
journal: Ann Thorac Surg
DOI: 10.1016/j.athoracsur.2020.08.001
sha: 2bf2cacf4a3489871120c07bdb36c3e37b8bd29c
doc_id: 733559
cord_uid: pd4gtehi

nan

As our society marks four months since the World Health Organization declared the Covid-19 outbreak a pandemic, we note the development of encouraging strategies to slow the spread of disease, streamline resource allocation, and adapt the cutting edge of critical care medicine to answer the challenges brought to bear by SARS-CoV-2. Despite these efforts and accomplishments, clinicians on the front lines continue to encounter patients with severe acute respiratory distress syndrome (ARDS) who fail to improve despite aggressive therapy such as extracorporeal membrane oxygenation (ECMO). Therefore, we were interested to read three non-peer-reviewed reports of patients undergoing double lung transplant for Covid-19 associated respiratory failure.

In the field of transplantation, we are accustomed to providing a treatment of last resort.

Medications may be costly, operations may be risky, but few other modern medical interventions represent true zero-sum choices in which the opportunity to treat one patient comes at the expense of treating another. Even before the Covid-19 pandemic, the United States was experiencing a shortage in donor lungs relative to the number of patients awaiting transplant; it is too early to assess the full impact of this crisis on organ availability, but it is difficult to envision a scenario in which a widespread transmissible respiratory illness increases the number of suitable donor lungs relative to need.

Nonetheless, it is unsurprising that lung transplant is being explored for Covid-19 patients. This operation has proven life-changing for tens of thousands of patients with chronic pulmonary diseases, and while transplantation for ARDS is uncommon, it is not without precedent. 1 In addition to its potential clinical advantages, this reapplication of lung transplantation would continue to foster hope for the most devastated Covid-19 patients and for society at large as we work toward a vaccine and improved medical therapies. However, we identify several reasons to remain circumspect in the consideration of lung transplantation for Covid-19-induced ARDS.

Organ allocation is predicated in part on achieving long-term benefit for the recipient. At present, the natural history of Covid-19 in general and for transplant recipients remains uncertain in several key respects. While there are many tests for active SARS-CoV-2 infection and antibody development, whether they can reflect true resolution of disease or prove absence of extrapulmonary viral reservoirs is J o u r n a l P r e -p r o o f unknown. There is also uncertainty surrounding the efficacy of humoral immunity in preventing reactivation of or recurrent infection. Even if these risks are low for the general population, transplant recipients (especially the newly immunosuppressed) represent a distinct and vulnerable risk pool. This is supported by emerging data from the New York State transplant consortia demonstrating that recipients suffer mortality due to Covid-19 disproportionate to the general public. Technical success notwithstanding, it is simply too soon to quantify the mid-or long-term effects of Covid-19 infection on transplant recipients, including lung recipients in the handful of cases which have occurred.

We recognize that in the face of critical illness, immediate solutions can sometimes take precedence over these longer-term considerations. ECMO, once itself seen as a bold new rescue measure, is now applied as an intermediary between respiratory failure and transplant as cure. However, the manner in which this is carried out has a significant impact on transplant outcomes. Historically, patients who were sick enough to require ECMO bridge to transplantation have fared poorer than the standard transplant population (Figure 1 ; Appendix). Our groups and other highly specialized centers have since developed bridging practices to ameliorate this gap, offering safer transplants to previously high-risk patients. 2 Notably, these protocols emphasize gradual physiologic optimization and rely on a careful perioperative rehabilitation program: these are luxuries that may not be tolerated by many critically ill Covid-19 patients. There may still be distinct clinical circumstances under which salvage transplantation, i.e. transplant for worsening status despite maximal therapy, is warranted. On balance, however, years of experience and data have shown that patients in this difficult scenario face outcomes more similar to early efforts to transplant from ECMO rather than those achieved with modern bridging practice. As stewards of donor organs, it is the responsibility of transplant physicians to ensure that they are offered to patients who are likely to derive the greatest benefit.

Consideration of transplant in refractory Covid-19-associated ARDS may also be driven, in part, by the risks and perceived futility of prolonged veno-venous (VV) ECMO support. Afflicted lungs have been shown to suffer severe alveolar damage with microangiopathy, 3 leading to concern for irreversible loss of function. However, our experience has shown that VV-ECMO can be safely and effectively J o u r n a l P r e -p r o o f deployed for weeks to months, facilitating recovery even in severe cases of ARDS. We previously studied patients with ARDS treated with ECMO for more than 3 weeks (median 36 days, IQR 24-68 days), finding noninferior survival to hospital discharge compared to patients receiving less than 3 weeks of ECMO support (73% vs. 57%, p=0·5). 4 Recovery of native lung function from ARDS after more than 100 days of VV-ECMO has also been described. 5 More recently, as of the writing of this report, at our institution in New York City we have brought COVID-19 patients from critical pulmonary failure to recovery after >21 (N=11), >42 (N=6), >56 (N=4), >63 (N=3), and >112 (N=1) days of ECMO therapy (unpublished data). We suggest that, based on these and similar data in ARDS, 6 many of these patients will improve and the pursuit of transplantation should not be a forgone conclusion.

The COVID-19 pandemic has tested many of our resources, but perhaps none is more important than hope. We applaud the heroic efforts put forth to serve the patients hit hardest during these uncertain times. For previously healthy patients with isolated respiratory illness, transplant may appear to be the natural solution to an otherwise intractable disease -we certainly identify with good-faith efforts to offer our best treatments to patients even in exceptional circumstances. For this reason, we look forward to the valuable insights to be gained from these unique experiences. Until those are available, for the uncertainties and limitations described, we urge caution and temperance in considering the inclusion of lung transplant in the broader armamentarium against COVID-19 at this juncture. 

Lung transplantation as a therapeutic option in acute respiratory distress syndrome

Outcomes of extracorporeal membrane oxygenation as a bridge to lung transplantation

Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19

Long-term venovenous extracorporeal membrane oxygenation support for acute respiratory distress syndrome

Prolonged maintenance of VV ECMO for 104 days with native lung recovery in acute respiratory failure

Support time-dependent outcome analysis for venovenous extracorporeal membrane oxygenation