key: cord-0706324-izqvn6nr authors: Kaul, Daniel R.; Valesano, Andrew L.; Petrie, Joshua G.; Sagana, Rommel; Lyu, Dennis; Lin, Jules; Stoneman, Emily; Smith, Lane M.; Lephart, Paul; Lauring, Adam S. title: Donor to recipient transmission of SARS‐CoV‐2 by lung transplantation despite negative donor upper respiratory tract testing date: 2021-03-15 journal: Am J Transplant DOI: 10.1111/ajt.16532 sha: c48831dce19259de7330f45f5e2b66c2559351d8 doc_id: 706324 cord_uid: izqvn6nr We describe a case of proven transmission of SARS‐CoV‐2 from lung donor to recipient. The donor had no clinical history or findings suggestive of infection with SARS‐CoV‐2 and tested negative by reverse transcriptase polymerase chain reaction (RT‐PCR) on a nasopharyngeal (NP) swab obtained within 48 h of procurement. Lower respiratory tract testing was not performed. The recipient developed fever, hypotension, and pulmonary infiltrates on posttransplant day (PTD) 3, and RT‐PCR testing for SARS‐CoV‐2 on an NP swab specimen was non‐reactive, but positive on bronchoalveolar lavage (BAL) fluid. One thoracic surgeon present during the transplantation procedure developed COVID‐19. Sequence analysis of isolates from donor BAL fluid (obtained at procurement), the recipient, and the infected thoracic surgeon proved donor origin of recipient and health‐care worker (HCW) infection. No other organs were procured from this donor. Transplant centers and organ procurement organizations should perform SARS‐CoV‐2 testing of lower respiratory tract specimens from potential lung donors, and consider enhanced personal protective equipment for HCWs involved in lung procurement and transplantation. agents of concern have included H1N1 pandemic influenza (2009), West Nile virus, Ebola virus, and Zika virus. [2] [3] [4] The disruption in solid organ transplantation (SOT) resulting from the COVID-19 epidemic has, however, been unprecedented. Particularly in hard-hit areas early in the pandemic, resource limitations led to a drastic decline in SOTs. 5 Transplant centers and organ procurement organizations (OPOs) have been forced to grapple with many unknowns regarding the most effective donor clinical assessment and testing processes to reduce the risk of donor to recipient disease transmission. Further, OPOs and transplant centers have to consider how to protect their staff from exposure to potential donors infected with SARS-CoV-2. To our knowledge, in the United States, no proven case of donor to recipient transmission of SARS-CoV-2 has been reported. We report a case of proven donor to recipient transmission of SARS-CoV-2 despite negative pre-procurement donor nasopharyngeal (NP) SARS-CoV-2 testing. Lower respiratory tract testing was not performed. In addition, we describe transmission to a health-care worker (HCW) associated with the transplant procedure. Laboratory studies and recipient medical records were reviewed. Donor medical records from DonorNet were also reviewed. At the transplant center (and for transplant center employees participating in procurement), per institutional policy, HCWs were considered to have a high-risk exposure if prolonged contact occurred while not wearing appropriate personal protective equipment (PPE) (mask and eyewear protection for routine exposures, and N95/PAPR for aerosol generating procedures). Exposed employees were notified and those with high-risk exposures were instructed to undergo SARS-CoV-2 testing 5 days from the last exposure. All employees with low risk exposures were provided with a list of symptoms consistent with COVID-19 and instructed to contact occupational health for testing should symptoms develop. The organ donor was a woman from the upper Midwest who suffered severe brain injury in an automobile accident and quickly progressed to brain death during a 2-day hospital admission. Computed tomography (CT) of the chest performed on the day of admission showed areas of consolidation within the posterior right lower lobe. The radiologist interpretation was that these areas represented atelectasis and pulmonary contusion. The left lung was clear aside from mild atelectasis at the base. A bronchoscopy performed 1 day after admission showed inflammation in the trachea and minimal thick white secretions, which were not persistent, and submucosal erythema and punctate hemorrhage in the distal trachea and mainstem bronchi felt to be secondary to contusion. SARS-CoV-2 RT-PCR testing was performed within 48 h of procurement on a nasopharyngeal swab and was resulted as not detected (Roche Cobas SARS-CoV-2, Roche Molecular Systems). History obtained from family revealed no history of travel or any recent fever, cough, headache, or diarrhea. It is unknown if the donor had any recent exposures to persons known or suspected to be infected with SARS-CoV-2. The bilateral lung recipient had chronic obstructive lung disease. Due to the atypical presentation of septic shock with cardiomyopathy, the BAL fluid was sent for SARS-CoV-2 PCR testing along with a second NP swab. The NP swab was not detected but the BAL sample was positive for SARS-CoV-2 with a low cycle threshold (Ct) value. Repeat testing the following day revealed positive testing of both tracheal aspirate and NP swab. Due to concern for donor origin of the SARS-CoV-2, BAL fluid obtained from the donor at the time of procurement was tested at the transplant center and was positive with a low Ct value ( Table 1 ). The patient's ongoing posttransplant course in the ICU was complicated by multisystem organ failure requiring prolonged mechanical ventilation and circulatory support. Specific treatment for COVID-19 has included remdesivir (two 5-day courses) and convalescent plasma on two occasions. Tacrolimus was continued and mycophenolate mofetil was held; her corticosteroid dosing was maintained at methylprednisolone 30 mg daily then tapered. She developed worsening respiratory distress and required veno-venous extracorporeal membrane oxygenation. Her overall clinical status continued to decline and she was not considered a candidate for re-transplantation. Support was withdrawn and she died on PTD 61. Her SARS-CoV-2 PCR remained positive on PTD 60 with a Ct value of 29.3. Testing for SARS-CoV-2 was performed 5 or more days postexposure for high-risk exposed HCWs. In addition, some HCW with low-risk exposures chose to be tested. While one thoracic surgeon tested positive for SARS-CoV-2 on PTD 4 (Table 1) , a surgical trainee, two anesthesia faculty, two anesthesia and one surgery critical care trainee, two nurses, the procuring surgeon, and one perfusionist tested negative. No member of the procurement team was infected. The surgeon was not present at the time of procurement, but did prepare the lungs for implantation and performed the transplant procedure. He did describe potential exposure to mucous and sputum when cutting off the bronchial staple line resulting in deflation. No other exposed HCW was diagnosed with SARS-CoV-2 linked to this event. All experiments using SARS-CoV-2 were performed at the University of Michigan in compliance with containment procedures in labora- Whole genome consensus sequences were aligned to the Wuhan-Hu-1 reference with MAFFT (version 7.467) 6 as implemented in the augur pipeline. 7 We constructed the phylogenetic tree with IQ-TREE using a GTR model and 1000 ultrafast bootstrap replicates and performed ancestral reconstruction for node sequences with TreeTime (version 0.7.6). 8 All analysis code, patient sequences, and metadata are available https://github.com/lauri nglab/ Donor Deriv edInf ection. Original sequence reads are available at www.ncbi.nlm.nih.gov/sra under BioProject. performed. Donor-derived infection with SARS-CoV-2 has significant implications for the health of the recipient, but also for HCWs who may be exposed prior to recipient diagnosis. Donor-derived infection with SARS-CoV-2 in a lung recipient is not surprising as donor-derived infection with viruses that infect the respiratory tract has been well described. 1 While SARS-CoV-2 infection has been detected in kidneys, liver, heart, and blood, 9, 10 The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation. Data sharing not applicable to this article as no datasets were generated or analyzed during the current study. Daniel R. Kaul https://orcid.org/0000-0003-0990-4148 Ten years of donor-derived disease: a report of the disease transmission advisory committee Identifying Risk Factors for West Nile Virus (WNV) Organ Procurement and Transplantation Network Ebola virus disease: implications for solid organ transplantation Organ procurement and transplantation during the COVID-19 pandemic MAFFT multiple sequence alignment software version 7: improvements in performance and usability Nextstrain: real-time tracking of pathogen evolution TreeTime: maximum-likelihood phylodynamic analysis SARS-CoV-2 renal tropism associates with acute kidney injury Multiorgan and renal tropism of SARS-CoV-2 SARS-CoV-2 infections among recent organ recipients American Society of Transplantation. SARS-CoV-2 (Coronavirus, 2019-nCoV): recommendations and guidance for organ donor testing Regarding the SARS CoV-2 pandemic. https:// ishlt.org/ishlt/ media/ docum ents/SARS-CoV-2_Guida nce-for-Cardi othor acic-Trans plant -and-VAD-center Usefulness of bronchoalveolar lavage in the management of patients presenting with lung infiltrates and suspect COVID-19-associated pneumonia: a case report Clinical samples for SARS-CoV-2 detection: review of the early literature Detection of SARS-CoV-2 in different types of clinical specimens Donor to recipient transmission of SARS-CoV-2 by lung transplantation despite negative donor upper respiratory tract testing