key: cord-0781940-85eajngf
authors: Delman, Aaron M.; Turner, Kevin M.; Jones, Courtney R.; Vaysburg, Dennis M.; Silski, Latifa S.; King, Corey; Luckett, Keith; Safdar, Kamran; Quillin, Ralph C.; Shah, Shimul A.
title: Keeping the Lights On: Telehealth, Testing, and 6-Month Outcomes for Orthotopic Liver Transplantation During the COVID-19 Pandemic
date: 2021-01-13
journal: Surgery
DOI: 10.1016/j.surg.2020.12.044
sha: d46f28014642c6128ae7d13f3d5faceee3f833fc
doc_id: 781940
cord_uid: 85eajngf

INTRODUCTION: The COVID-19 pandemic has seen transplant volume decrease nationwide, resulting in a 2.2-fold increase in waitlist mortality. In particular, solid organ transplant patients are subjected to increased morbidity and mortality from infection. In the face of these challenges, transplant centers need to develop innovative protocols to ensure high-quality care. METHODS: A multidisciplinary protocol was developed that included: virtual selection meetings, COVID-19 negative donors, pre-transplant symptom screening, rapid testing on presentation, telehealth follow-up, and weekly community outreach town-halls. All OLTs completed between January 2018 and August 2020 were included in the study (n=344). The cohort was stratified from January 2018 – February 2020 as “pre-COVID-19,” and March 2020-August 2020 as “COVID-19.” Patient demographics and post-operative outcomes were compared. RESULTS: From March 2020 - August 2020 there was a significant decrease in average monthly referrals for liver transplantation (OLT) (29.8 vs. 37.1, p = 0.01). However, listings (11.0 vs. 14.3, p = 0.09) and transplant volume remained unchanged (12.2 vs. 10.6, p = 0.26). Rapid testing was utilized on arrival for transplant, zero patients tested positively preoperatively and median time from test result until abdominal incision was 4.5 hours [1.2, 9.2]. Simultaneously, telehealth visits increased rapidly, peaking at 85% of all visits. Importantly, there was no difference in outcomes between cohorts. CONCLUSION: OLT can be accomplished safely and effectively in the COVID-19 era without compromising outcomes through increasing utilization of telehealth, rapid COVID-19 testing, and multidisciplinary protocols for managing immunosuppressed patients.

Warp Speed," currently finishing accrual with multiple candidates in phase III trials, mass 77 vaccination in the United States is predicted to take until at least mid-late 2021. Therefore, we 78 will need to define a new normal for continuing to care for our patients in the year(s) ahead. 16) The aim of this study is to report our center's protocolized 87 response to the COVID-19 pandemic. Our mission was, and remains to continue to offer safe 88 OLT for patients with ESLD throughout the pandemic. Through leveraging multidisciplinary 89 expertise, we report our COVID-19 testing protocols and results, telehealth utilization, and 90 perioperative outcomes. 91

Protocolized Response to COVID-19 93 94

A uniform, multidisciplinary protocol was efficiently established at the onset of the 95 global pandemic to safely serve patients from waitlist through their transplant and into their post-96 operative follow-up. Paramount to this effort was the principle of safely maintaining a high 97 volume of life-saving transplants during this trying time without putting providers and patients at 98 undue risk. With this in mind, we adopted a series of additional methods to care for liver 99 transplant patients, in addition to appropriate standard precautions. All multi-disciplinary 100 meetings were held virtually. This included selection meetings, quality meetings, education 101 conferences, and multi-team rounds. Due to the unknown effects of COVID-19 infection on 102 potential organs, all organ procurements were only conducted on COVID-19 negative donors. In 103 addition, transplant coordinators conducted weekly pre-transplant symptom screening on all 104 J o u r n a l P r e -p r o o f listed patients. Any patient who complained of fevers, chills, cough, or shortness of breath, was 105 asked to take a COVID-19 test. Similarly, testing of the transplant team was conducted for 106 symptomatic individuals, or after experiencing a COVID-19 positive exposure. 107

Rapid COVID-19 testing played a significant role in minimizing organ cold ischemia 108 time during OLTs. The rapid test utilized was the "Xpert Xpress SARS-CoV-2 test" made by 109

Cepheid Innovation, which is an amplified nucleic acid assay authorized by the U.S. Food and 110

Drug Administration under an Emergency Use Authorization. The limit of detection of this test 111 was set at 95% accuracy, and the test was validated by the FDA with a 97.8% positive percent 112 agreement and a 95.6% negative percent agreement.(17) All potential transplant recipients were 113 required to take a rapid COVID-19 test on presentation for transplant; then, they were placed in 114 contact, droplet, and airborne precautions, and had a non-contrast chest computed-tomography 115 scan to rule out infection (Supplemental Figure 1 ). If the rapid COVID-19 test had not resulted 116 prior to incision, N-95 masks were worn throughout the operation. Moreover, repeat COVID-19 117 testing was done prior to any additional invasive procedures. Given the unprecedented demand for intensive-care unit (ICU) beds and ventilators, 129 patient selection for transplantation included consideration for patients who were likely to have a 130 rapid recovery. Patient selection was not just the sickest patients, but also patients that were 131 anticipated to have shorter ICU stays and avoid tying up resources during the pandemic. 132

Specifically, patients without significant cardiac and respiratory comorbidities were 133 preferentially selected. The need to ensure continued care for patients with ESLD and organ 134 utilization, was coupled with the need to minimize hospital resource utilization. 135

All OLTs completed between January 1, 2018 and August 30, 2020 were included in the 138 study. Baseline demographic information and patient characteristics were collected. As well as 139 COVID-19 screening test results, referrals for transplant, transplant listings, transplants 140 completed, and short-term outcomes including length of stay, early allograft dysfunction, 141 primary non-function, reoperations, bile leak, hepatic artery thrombosis, and readmission rates 142 were collected. Outpatient pre-operative and post-operative clinic visits were collected and 143 stratified by "type" of visit: in-person, telephone, or video. Subsequently, we divided our patient 144 population into two cohorts: "pre-COVID-19" and "COVID-19." The "pre-COVID-19" cohort 145 was all patients who underwent OLT from January 1 st , 2018 -February 28 th , 2020. The 146 "COVID-19" cohort was defined as any patient who underwent OLT from March 1 st 2020 -147

August 30 th 2020. pandemic. Patient demographics and baseline clinical characteristics are described in Table 1 . 158 There was no difference in age, sex, or race between the pre-COVID-19 and COVID-19 cohorts. 159

However, the average match MELD score of transplanted patients during COVID-19 was 160 significantly decreased from the average match MELD score pre-COVID-19 (18.9 ± 7.5 vs. 22.6 161 ± 7.6, p < 0.01). There was no difference in the percentage of patients called in from home 162 versus those hospitalized at the time of transplant or difference in patients admitted to the ICU at 163 time of transplant (Table 1) . Of note, there was a decrease in patients with malignancy 164 undergoing transplant during COVID-19 (1.1% vs. 9.9%, p < 0.01). 165

The COVID-19 pandemic, coupled with the recent change in organ allocation policy, 166

were correlated with a shift in donor organ procurement location from predominantly local-167 regional to national (Table 2 ). In addition, the percent of organ donation offers that were 168 accepted under expedited placement was increased during COVID-19 (29.6% vs. 16.8%, < 0.05). 169

Expedited placement organ offers are organs that are offered while procurement is ongoing and 170 the primary center has declined the offer. This increase may illustrate the strain on transplant 171 centers during these times, and the uncertainty regarding outcomes of higher risk donor organs 172 and recipients. Even with a higher percentage of organs being accepted through the expedited 173 J o u r n a l P r e -p r o o f process, there was no significant difference in cold ischemia time between cohorts (5.0 ± 2.8 174 hours vs. 5.1 ± 3.5 hours, p = 0.87). 175

The COVID-19 pandemic resulted in a significant decrease in patients referred for OLT. 177

The average referral rate per month was 37.1 in the pre-COVID-19 era and this decreased to 29.8 178 during the COVID-19 pandemic (p = 0.01) (Figure 1 ). The average number of listings for OLT 179 per month in the pre-COVID-19 era was 14.3 and this decreased to 11.0 per month (p=0.09). Patients who underwent OLT during the COVID-19 pandemic (n=70) did not experience 212 a significant change in short term outcomes compared to the pre-COVID-19 era (Table 3) . There 213 was no difference in 30-day or 90-day patient survival. Similarly, there was no significant 214 difference in 30-day or 90-day graft survival. As Table 3 shows, the rates of primary non-215 function, relisting, unplanned reoperations, hepatic artery thrombosis, early allograft dysfunction, 216 and bile leak were unchanged between cohorts. In addition, there was a significant decrease in 217 the number of patients who remained ventilated at 24 hours post-operatively from OLT during 218 COVID-19 (8.6% vs. 18.6%, p = 0.04). As well as a decrease in the hospital length of stay for 219 patients undergoing OLT (8.5 days ± 5.1 vs. 13.1 days ± 15.2, p = 0.02). Although COVID-19 220 posed unprecedented challenges to OLT, with multidisciplinary protocols and added safety 221 measures, we did not see a change in patient outcomes. 222

This analysis of the policies, procedures, and short-term outcomes of a busy OLT center 224 provides preliminary evidence that it is safe to continue to care for these high-risk patients in the The ability to safely perform OLTs requires in-hospital multi-disciplinary teams, surgical 261 ICU beds, mechanical ventilators, and blood products which were accessible throughout the 262 pandemic. However, due to a scarcity of designated COVID-19 positive ICU beds in the medical 263 ICU and cardiovascular ICU, the surgical intensive care unit was forced to accept COVID-19 264 positive and COVID-19 negative patients in the same unit; fortunately, this did not increase 265 COVID-19 infections in our cohort. Cross-infection was best prevented with personal protective 266 equipment, standard infection control guidelines, and minimizing the number of providers 267 physically seeing patients. Importantly, patients who were more likely to have a rapid recovery 268 and decreased ICU length of stay were preferentially selected for transplant, and this is reflected 269 in the decreased number of patients ventilated > 24 hours (8.6% vs. 18.6%, p=0.04) and 270 decreased hospital length of stay (8.5 days vs. 13.1 days, p = 0.02) ( Table 2) transplant centers to continue to provide care for patients with ESLD will increasingly become 305 reliant on center flexibility, rapid testing, telehealth, and virtual platforms for the delivery of 306 high-quality care to this high-risk population. As the expected winter surge of COVID-19 cases 307 comes closer,(34) it becomes even more necessary to share multi-disciplinary protocols and 308 experiences between liver transplant centers to ensure optimal preparedness and the best possible 309 outcomes for patients with End-Stage Liver Disease. 530  531  532  533  534  535  536  537  538  539  540  541  542  543  544  545  546  547  548  549  550  551  552  553  554  555  556  557  558  559  560  561 In this manuscript we detail the protocolized utilization of telehealth, rapid COVID-19 testing, and virtual town-halls in Liver Transplantation to continue transplanting through the COVID-19 pandemic. The importance of this manuscript is to provide solid organ transplant centers with proven protocols for safe transplantation in the COVID-19 pandemic.

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