key: cord-0696615-bbqzlkfg authors: Lieberman, Joshua A; Mays, James A; Wells, Candy; Cent, Anne; Bell, Deborah; Bankson, Daniel D; Greninger, Alex L; Jerome, Keith R; Limaye, Ajit P title: Expedited SARS‐CoV‐2 Screening of Donors and Recipients Supports Continued Solid Organ Transplant date: 2020-06-01 journal: Am J Transplant DOI: 10.1111/ajt.16081 sha: d9ab728829686b4140d89a2df364243ae2942d85 doc_id: 696615 cord_uid: bbqzlkfg Universal screening of potential organ donors and recipients for SARS‐CoV‐2 is now recommended prior to transplantation in the United States during the COVID‐19 pandemic. Challenges have included limited testing capacity, short windows of organ viability, brief lead time for notification of potential organ recipients, and the need to test lower respiratory donor specimens to optimize sensitivity. In an early US epicenter of the outbreak, we designed and implemented a system to expedite this testing and here report results from the first three weeks. The process included a Laboratory Medicine designee for communication with organ recovery and transplant clinical staff, specialized sample labeling and handoff, and priority processing. Thirty‐two organs recovered from 14 of 17 screened donors were transplanted versus 70 recovered from 23 donors during the same period in 2019. No pre‐transplant or organ donors tested positive for SARS‐CoV‐2. Median turnaround time from specimen receipt was 6.8h (donors), 6.5h (recipients): 4.5h faster than daily inpatient median. No organ recoveries or transplants were disrupted by a lack of SARS‐CoV‐2 testing. Waitlist inactivations for COVID‐19 precautions were reduced in our region. Systems that include specialized ordering pathways and adequate testing capacity can support continued organ transplantation even in a SARS‐CoV‐2 hyperendemic area. The SARS-CoV-2 epidemic in the United States has led to the intentional reduction or suspension of many non-urgent medical procedures in order to reserve hospital capacity for surge capacity to meet the COVID-19 threat, conserve personal protective equipment (PPE), and prevent nosocomial SARS-CoV-2 transmission. 1, 2 The COVID-19 pandemic has also threatened solid organ transplant (SOT) due to multiple factors, including increased demand for intensive care resources, PPE shortages, and concerns for donor transmitted SARS-CoV-2 and/or increased morbidity and mortality in SOT recipients. [3] [4] [5] [6] While the Center for Medicare and Medicaid Services has designated organ transplantation within its highest priority (Tier 3b) "do not delay" category, 7 early reports from Italy suggested a 25% reduction in organ procurement during the first 4 weeks of the COVID-19 outbreak there. 8 Starting March 2020, patients awaiting transplant in the United States could temporarily be assigned to inactive status out of concern for COVID-19; such patients would not receive organ offers until reactivated. During March thousands of patients were deferred nationwide (https://UNOS.org/COVID, accessed 16 April 2020). Global guidelines consider proven or suspected SARS-CoV-2 infection as a contraindication to donation and require negative donor testing prior to transplant. 9, 10 In the region of the US first hit by the pandemic, the Pacific Northwest, similar guidelines were adopted by local transplant programs and donations from living donors temporarily suspended. The University of Washington hospital system expanded this requirement to include testing of transplant candidates. In order for SOT to continue, laboratory capacity for SARS-CoV-2 testing must be sufficient to return results within the window of organ viability. Some of the challenges have included limited in vitro testing capacity for SARS-CoV-2 in the US, shortages in key supply chains, and, until recently, absence of rapid testing platforms approved by the Food and Drug Administration (FDA) Emergency Use Authorization (EUA). 11 The University of Washington Medical Center (UWMC) is a large academic multiorgan transplant center in Washington State. The clinical laboratory went live with SARS-CoV-2 testing on 2 March 2020 12 . The laboratory sought to support organ donation by rapidly developing and implementing a system to expedite SARS-CoV-2 testing for organ donors and potential transplant recipients identified by the Transplant Surgery clinical services. The local organ procurement This article is protected by copyright. All rights reserved organization (OPO), LifeCenter Northwest serves the largest geographic region of all 58 OPOs in the US, including most of Washington, Alaska, Montana, and northern Idaho, exacerbating the challenge of pre-donation testing due to significant pre-laboratory specimen transport times. In addition, UWMC's location in Seattle/King County was at the center of the rapidly expanding outbreak in Washington, complicating transplant screening due to high demand for SARS-CoV-2 testing for hospital system patients and from other local and regional systems seeking reference laboratory testing services. Here we describe key components of the system designed to expedite screening for donors and potential recipients while maintaining and without disrupting the flow of the large volume of non-transplant related specimens handled by our laboratory. We describe the first three weeks of universal COVID-19 screening in the organ donor and recipient populations and highlight important pitfalls that could result in missed transplant opportunities. This article is protected by copyright. All rights reserved This article is protected by copyright. All rights reserved regions defined by the Department of Health and Human Services. Statistical analysis was performed by two-tailed Fisher's Exact test in GraphPad Prism v7.0d. based on data from the Organ Procurement and Transplantation Network. Wilcoxon signed rank test performed in R version 3.5.0 was used to compare patient/donor TATs paired with the median TAT for inpatient samples on that day. screening of potential SOT donors and recipients in collaboration with the SOT Infectious Diseases service and LifeCenter Northwest ( Figure 1A ). Key goals were to make specimens highly visible, quickly traceable, and processed immediately. Prior to specimen submission, the Laboratory Medicine physician on call for SOT was paged and provided with identifying patient information, including the UNOS number and estimated time of arrival at the specimen receiving area of the laboratory. To clearly distinguish SOT-related specimens requiring expedited testing from the large volume of other specimens, a printed "flag" ( Figure 1B ) was attached to each specimen to identify SOT specimens, and were hand delivered to the laboratory with a verbal handoff to a Lead Technologist in Specimen Processing. Specimens were immediately logged for rapid transport to the Clinical Virology laboratory for SARS-CoV-2 testing. Donor specimens were transported by an OPOdesignated courier service. Potential recipients' specimens were placed in individual specimen batches, transported by hospital couriers who transported specimens to the Clinical Virology laboratory every 2 hours. Testing staff recognized specimens by virtue of the "flag" and ensured SOT-related specimens were unbatched and processed immediately upon receipt. Job aids were created for Specimen Processing and Virology staff and couriers. SOT specimens were thus processed first even within the highest priority testing tier, previously established by hospital policy, that included specimens from inpatients and health care workers. During the study period (starting on 31 March 2020), rapid assays (75 -90min runtime) were verified at each of the three hospital study sites for on-site testing of pre-operative patients. Five of 17 specimens from transplant patients had NP swabs tested on this platform, including 3 of 4 post- This article is protected by copyright. All rights reserved transplant patients who required additional surgical procedures. Since only NP swabs could be run on the DiaSorin assays at the time, 14 donor specimens were not included as BAL and sputum specimens were an important component of pre-organ recovery screening, particularly for potential lung donation. Figure S1 ). Other tissues (e.g., heart for valves, bone, skin), were collected from 7 donors ( Table 2) . As a comparison, during the same time frame in 2019, 70 organs were recovered and transplanted from 23 donors ( Figure S2 ). Although specimens from OPO clinical staff were eligible for expedited testing, the pathway was not automatically deployed and did not need to be activated for them during the study period. (Table S1 ). One patient did not receive a transplant for other reasons not related to COVID-19 infection and was not screened. A second case was not delayed, but the result was reported within an hour of scheduled start time. No procedures for posttransplant patients were delayed while awaiting SARS-CoV-2 results. specimen receipt were similar for both donors (median 6.8h, IQR 6.2 -8.0h) and candidates/recipients (median 6.5h, IQR 3.8 -7.9) and slightly longer for donors when calculated from time of collection (Table 1) , reflecting the broad geographic range served by the OPO. Donor This article is protected by copyright. All rights reserved and recipient TATs were faster than median inpatient TAT (median -4.5h, IQR -3.3 --6.2, p = 6.6 x 10 -9 ) which varied over the course of the study period with a trend toward faster result time (Figure 2 ). Weekly median TAT for donors and recipients also decreased during the study period, with a marked decrease in recipient TAT in Week 3 following the implementation of the rapid assay (Table S2) Table S4 ). Throughout the remainder of the study period and in the week after (Week 4), the percentage of waitlisted patients inactivated due to COVID-19 precautions was less than 25%, including 0 patients during Week 2 ( Figure 3 ; Table S3 ). The proportion of COVID-19 related inactivations in the NW was significantly less than all other regions throughout Weeks 2, 3, and 4 except during Week 4 the SW region was not different (p = 0.4050) and the S Midwest had fewer COVID-19 related inactivations (p = 0.002, Figure 3 , Table S3 ). This occurred despite high to very high COVID-19 activity tracked by the Centers for Disease Control and Prevention in the Pacific NW throughout the study period. 15 3.6 Near Misses and Unanticipated Challenges. Although no opportunities for transplant or organ recovery were missed due to a delay or lack of access to COVID-19 screening during the study period, several near misses occurred: two donor and four transplant patient specimen submissions. The second donor specimen submitted was transported from Alaska and arrived during a specimen backlog. The samples were not identified by the laboratory as potential donor specimens but were retrieved by the on-call Laboratory Medicine provider after being re-contacted by the responsible OPO clinical staff member. The donor tested negative and organ recovery proceeded as planned. This event prompted the use of SOT flags ( Figure 1B) . In a second case, a donor ETT sputum trap was separated from the SOT flag and UNOS identifier; brief phone conversations between the on-call This article is protected by copyright. All rights reserved Laboratory Medicine provider for SOT and the laboratory personnel involved quickly resolved this issue. Challenges arose when testing recipients due to evolving hospital procedures for outpatient COVID-19 screening and transition to the rapid DiaSorin Simplexa FDA-EUA cleared assay. In one case early in the study period a SOT flag was missed, although the result was reported in time to proceed with transplant. In another case, two patient specimens were collected at a drive-through clinic without first contacting Laboratory Medicine personnel on-call for SOT patients/specimens. These were identified and expedited, but one caused a brief delay (<2h) to the surgical start time. This occurred prior to rapid assay implementation. A fourth patient's result was delayed due to unexpected instrument downtime (failed positive control, followed by successful trouble shooting), but was still reported in time for patient care needs. During an escalating phase of the SARS-CoV-2 outbreak in one of the early US COVID-19 epicenters, we developed, implemented, and refined a system that facilitated rapid testing to support our center's SOT program and organ recovery from donors across a wide geographic area. The system was designed to expedite SARS-CoV-2 testing to screen donors, potential recipients, and posttransplant patients needing follow-up procedures or surgeries. The key components of the system included: 1) consolidated specimen transport by OPO designated couriers from collection to delivery at the Clinical Virology laboratory ( Figure 1A) ; 2) verbal handoffs and expedited logging by a specimen processing lead; 3) unique, highly visible identifier attached to the patient specimen ( Figure 1B) ; 4) priority processing of these specimens; and 5) an on-call Laboratory Medicine provider to track specimens. During the first three weeks of this process, no transplant or organ recovery opportunities were missed due to delays or lack of access to SARS-CoV-2 test results. This resulted in 14 organ recovery procedures, permitting transplant of 32 organs ( Figure S1 ). Our hospital was able to provide transplants for 8 of 13 candidates during the study period ( This article is protected by copyright. All rights reserved and recipients (6.5h) was faster than other specimens, including other inpatients (Figure 2 ). Recipient specimen TAT was accelerated in Week 3 by implementation of an FDA-EUA cleared rapid assay. The first week of the study period coincided with UNOS instituting and tracking a new waitlist inactivation status due to precautions for COVID-19. While the proportion of waitlisted patients in our region (NW) inactivated for COVID-19 precautions was significantly higher during Week 1 than either the national average or for most other regions, that proportion dropped significantly and was less than or equal to all other regions for the remainder of the study period (Weeks 2 and 3) and for all but the South Midwest during the week following the study period ( Figure 3 , Table S3 ). It is unclear to what extent our expedited testing pathway contributed to this reduction, although we note that our local OPO recovers organs for much of the Northwest Region. While it is possible the expedited COVID-19 screening pathway described here helped to reduce the number of temporary waitlist inactivations due to COVID-19 precautions, the differences may reflect regional variation in the progression of the outbreak in the United States or the significant testing capacity available through our hospital laboratory. The expedited testing pathway continues to successfully support organ recovery and transplant during the COVID-19 outbreak in our area. However, the system we designed was feasible due to several key factors. First, the UW Clinical Virology laboratory developed an assay, received EUA early (go-live 2 March 2020), rapidly expanded capacity, and is part of a robust reference laboratory. Second, a small group of Laboratory Medicine personnel were able to devote significant attention to managing these specimens and adapt the pathway in real-time to avoid system failures. This article is protected by copyright. All rights reserved Global guidance for surgical care during the COVID-19 pandemic Cancer Surgeries and Organ Transplants Are Being Put Off for Coronavirus. Can They Wait? ProPublica COVID-19 in long-term liver transplant patients: preliminary experience from an Italian transplant centre in Lombardy. The Lancet Gastroenterology & Hepatology Successful Treatment of Severe COVID-19 Pneumonia in a Liver Transplant Recipient SARS Cov2 infection in a renal transplanted patients. A case report Early Impact of COVID-19 on Transplant Center Practices and Policies in the United States Non-Emergent, Elective Medical Services, and Treatment Recommendations The COVID-19 outbreak in Italy: initial implications for organ transplantation programs Recommendations regarding the use of organs and tissues with regard to the risk of infection with the SARS-CoV-2 virus All rights reserved 10. Agence de la Biomédicine. Recommendations regarding the use of organs and tissues with regard to the risk of infection with the SARS-CoV-2 virus. Third stage: epidemia SARS-CoV-2 Testing Comparative Performance of SARS-CoV-2 Detection Assays using Seven Different Primer/Probe Sets and One Assay Kit Comparison of Commercially Available and Laboratory Developed Assays for in vitro Detection of SARS-CoV-2 in Clinical Laboratories Food and Drug Administration O of IVD and RH. EUA200026/A002 Trade/Device Name: Simplexa COVID-19 Direct assay Approval Letter COVIDView: A Weekly Surveillance Summary of U.S. COVID-19 Activity