A call to routinely test lower respiratory tract samples for SARS-CoV-2 in lung donors

To the Editor: SARS-CoV-2 may be transmissible from organ donor to recipient, although only a single lung transplant case has been reported.1Kaul DR, Valesano AL, Petrie JG, et al. Donor to recipient transmission of SARS-CoV-2 by lung transplantation despite negative donor upper respiratory tract testing. Am J Transplant. 2021. https://doi.org/10.1111/ajt.16532Google Scholar The American Society of Transplantation (AST) has recommended deceased donor screening for SARS-CoV-2 with upper respiratory tract sampling for nucleic acid testing (NAT) within 72 h of procurement.2American Society of Transplantation. Recommendations and guidance for organ donor testing. https://www.myast.org/covid-19-information. Published 2021. Accessed March 11, 2021.Google Scholar,3International Society for Heart and Lung Transplantation. Guidance from the ISHLT regarding the SARS CoV-2 pandemic. https://ishlt.org/covid-19-information. Published 2021. Accessed March 11, 2021.Google Scholar Lower respiratory tract samples are recommended when feasible, although this practice is not consistent across OPOs. This is likely because current NAT assays are not validated for lower respiratory tract samples. In February 2021, we (Toronto, Canada) accepted a lung offer from Pennsylvania. The donor suffered anoxic brain injury secondary to drug overdose. He was screened with two nasopharyngeal swabs (NPS) and had a normal CT chest. Since available information suggested that the likelihood of SARS-CoV-2 was low, a clinical decision was made to proceed. The transplant recipient was a 70-year-old male with pulmonary fibrosis. An admission clinical screen and NPS were negative. During the transplant surgery, the preimplantation bronchial wash (BW) was negative for SARS-CoV-2 NAT. However, a postimplantation BW (performed during the transplant surgery immediately after implantation of the first lung) returned positive for SARS-CoV-2 (Table 1) highly suggesting donor-derived infection. Repeated endotracheal aspirate sampling was also positive. The patient was started on intravenous remdesivir for 5 days. Repeated postoperative testing showed a persistent positive PCR from lower tract samples and a negative NPS. The patient remains on mechanical ventilation on day 25 with evidence of bilateral airspace disease. No transmission occurred to the surgical team who wore N95 masks and face shields during transplant. No transmission occurred to two kidney recipients (one had previous COVID-19 vaccine, and one had previous COVID-19 infection) and one liver recipient. However, one of the kidney recipients died due to a myocardial infarction with no evidence of COVID-19. The remaining two recipients remain well.TABLE 1SARS-CoV-2 NATaNAT testing performed using the Seegene Allplex 2019 nCoV assay. results for lung transplant recipientDayNasopharyngeal swabEndotracheal aspirateBronchial washClinical features–1 (pretransplant)Negative0 (day of transplant)Negative (posttransplant)Recipient native lung NegativePostimplantationPositiveCt values: E gene 26.4 R gene 28.8 N gene 28.3Remdesivir × 5 days startedPulse methylprednisolonePosttransplant day 1PositiveCt values: E gene 10.7R gene 13.1 N gene 13.0Posttransplant day 4PositiveCt values: E gene 20.4 R gene 23.7 N gene 19.4Posttransplant day 7NegativePosttransplant day 14PositiveCt values: E gene 23.9 R gene 27.4 N gene 22.9Second course of Remdesivir × 5 daysPulse methylprednisoloneCycle threshold (Ct) represents the number of PCR cycles needed for detection and is a rough surrogate marker for viral load with an inverse correlation (lower Ct values represent higher viral loads); Ct values in the range reported above represent a relatively strong positive PCR result and a moderate to high viral load, E gene is the envelope gene, R gene is the RNA-dependent RNA polymerase (RdRp) gene, N gene is the nucleocapsid gene. Ct values are provided for overall interpretation but are not required as part of donor screening.a NAT testing performed using the Seegene Allplex 2019 nCoV assay. Open table in a new tab Cycle threshold (Ct) represents the number of PCR cycles needed for detection and is a rough surrogate marker for viral load with an inverse correlation (lower Ct values represent higher viral loads); Ct values in the range reported above represent a relatively strong positive PCR result and a moderate to high viral load, E gene is the envelope gene, R gene is the RNA-dependent RNA polymerase (RdRp) gene, N gene is the nucleocapsid gene. Ct values are provided for overall interpretation but are not required as part of donor screening. One week later, we accepted a lung offer from Oklahoma. The donor was a 40-year-old male with stroke and seizure activity but no symptoms suggestive of COVID-19. He had been screened for SARS-CoV-2 with two negative NP swabs, and CT chest had shown mild multifocal consolidation. A BW sample was transported with the lungs and immediately processed for SARS-CoV-2 PCR, while the lungs were kept in cold storage. The BW testing performed at our hospital returned positive for SARS-CoV-2 (confirmed on repeat testing of sample) and therefore, the lungs were deemed unsuitable for transplant. A kidney transplant was also performed from the same donor but this recipient had no posttransplant COVID. These two cases illustrate the high risk of SARS-CoV-2 transmission from lung donors. Although there are no validated SARS-CoV-2 NAT tests for BW, these cases might have been avoided by sending a lower respiratory tract sample for COVID at the time of donor assessment. In Canada, national guidance states that all deceased donors undergo an upper and lower respiratory NAT for SARS-CoV-2.4Canadian Blood Services. Consensus guidance for organ donation and transplantation services during COVID-19 pandemic. https://profedu.blood.ca/en/organs-and-tissues/covid-19-update-organ-donation-and-transplantation-services. Published 2021. Accessed March 11, 2021.Google Scholar Given our experience with U.S. lung donors, we believe there is a significant possibility that COVID+ donors are missed and potential transmissions are occurring. We recommend that lower respiratory testing for SARS-CoV-2 be performed routinely on all deceased lung donors in order to prevent such transmissions and avoid putting patients and hospital staff at risk. The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.

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