Successful lung transplantation using an allograft from a COVID-19–recovered donor: a potential role for subgenomic RNA to guide organ utilization

Saharia, Kapil; Ramelli, Sabrina; Stein, Sydney; Roder, Allison; Kreitman, Allie; Banakis, Stephanie; Chung, Joon‐Yong; Burbelo, Peter D.; Singh, Manmeet; Reed, Robert M.; Patel, Vipul; Rabin, Joseph; Krupnick, Alexander S.; Cohen, Jeffrey I.; Wit, Emmie de; Ghedin, Elodie; Hewitt, Stephen M.; Vannella, Kevin M.; Chertow, Daniel S.; Grazioli, Alison

doi:10.1016/j.ajt.2022.09.001

Cited by 7 publications

(3 citation statements)

References 24 publications

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“…The use of thoracic organs from COVID-19 positive donors is being explored. Potential use of tests that can predict viral infectivity, such as sub-genomic RNA testing, has been observed to be successful for lung transplantation using an allograft from a COVID-19–recovered donor [ 12 ▪▪ ]. Recent small series have shown that lungs from donors with a positive SARS-CoV-2 PCR may be successfully utilized for lung transplantation with careful donor selection, including asymptomatic status, positive nasopharyngeal (NPS) swab, negative bronchoalveolar lavage, cycle threshold values more than 34, first positive NPS COVID-19 test older than 20 days [ 11 , 13 , 14 ].…”

Section: Sars-cov-2mentioning

confidence: 99%

Donor-derived infections in solid organ transplant recipients

Peghin

Grossi

2023

Current Opinion in Organ Transplantation

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Purpose of review The potential for transmission of donor-derived infections (DDIs) is impossible to eliminate, but a thoughtful and systematic approach to donor evaluation can mitigate the risk. Prevention is a key issue and clinicians must maintain a high index of suspicion and remain vigilant in staying up to date on emerging infections. COVID-19 and Monkeypox have represented a new challenge for infectious disease screening and recommendations have been evolving, as knowledge in the field has grown. Additional considerations for pretransplant deceased donor screening include testing for neglected and endemic infectious diseases such as strongyloidiasis and HTLV 1/2. Molecular diagnostic tests have improved awareness on pathogenicity of mollicutes and fungi in the setting of DDIs. The aim of this review is to provide an update on the most recent literature on DDI with a special focus on these emerging hot topics. Recent findings Donor screening for uncommon pathogens must be guided by knowledge of changing epidemiology of infectious disease and availability of new diagnostic methods. Summary Appropriate screening, early recognition, timely reporting, close monitoring, and appropriate management are essential to help reducing the risk of emerging DDIs.

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Section: Sars-cov-2mentioning

confidence: 99%

Donor-derived infections in solid organ transplant recipients

Peghin

Grossi

2023

Current Opinion in Organ Transplantation

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“…Furthermore, as the number of individuals recovered from COVID-19 is increasing, it is mandatory to define whether and when organs from these potential donors can be safely used. Few available reports among donors with prior COVID-19 infection indicate low rates of transmission to the recipient and transplanted organ dysfunction, depending on the infection status ( Kute et al, 2021 ; Saharia et al, 2023 ). However, few studies have been conducted until now, indicating that viral transmission by organ donation could not be completely ruled out.…”

Section: Discussionmentioning

confidence: 99%

Viable SARS-CoV-2 Omicron sub-variants isolated from autopsy tissues

Maffia-Bizzozero,

Cevallos,

Lenicov

et al. 2023

Front. Microbiol.

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IntroductionPulmonary and extrapulmonary manifestations have been described after infection with SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). The virus is known to persist in multiple organs due to its tropism for several tissues. However, previous reports were unable to provide definitive information about whether the virus is viable and transmissible. It has been hypothesized that the persisting reservoirs of SARS-CoV-2 in tissues could be one of the multiple potentially overlapping causes of long COVID.MethodsIn the present study, we investigated autopsy materials obtained from 21 cadaveric donors with documented first infection or reinfection at the time of death. The cases studied included recipients of different formulations of COVID-19 vaccines. The aim was to find the presence of SARS-CoV-2 in the lungs, heart, liver, kidneys, and intestines. We used two technical approaches: the detection and quantification of viral genomic RNA using RT-qPCR, and virus infectivity using permissive in vitro Vero E6 culture.ResultsAll tissues analyzed showed the presence of SARS-CoV-2 genomic RNA but at dissimilar levels ranging from 1.01 × 102 copies/mL to 1.14 × 108 copies/mL, even among those cases who had been COVID-19 vaccinated. Importantly, different amounts of replication-competent virus were detected in the culture media from the studied tissues. The highest viral load were measured in the lung (≈1.4 × 106 copies/mL) and heart (≈1.9 × 106 copies/mL) samples. Additionally, based on partial Spike gene sequences, SARS-CoV-2 characterization revealed the presence of multiple Omicron sub-variants exhibiting a high level of nucleotide and amino acid identity among them.DiscussionThese findings highlight that SARS-CoV-2 can spread to multiple tissue locations such as the lungs, heart, liver, kidneys, and intestines, both after primary infection and after reinfections with the Omicron variant, contributing to extending knowledge about the pathogenesis of acute infection and understanding the sequelae of clinical manifestations that are observed during post-acute COVID-19.

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“…Since sgRNA is transcribed only in infected cells and is not packaged into virions, sgRNA levels reflect virus replication [ 13 ]. Recently, sgRNA was described as a useful tool for assessing viral infectivity for organ transplant [ 14 ] and monitoring the virological response in patients who receive remdesivir [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Analytical validation of quantitative SARS-CoV-2 subgenomic and viral load laboratory developed tests conducted on the Panther Fusion® (Hologic) with preliminary application to clinical samples

Lakhal-Naouar,

Hack,

Moradel

et al. 2023

PLoS ONE

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Objective Validate the performance characteristics of two analyte specific, laboratory developed tests (LDTs) for the quantification of SARS-CoV-2 subgenomic RNA (sgRNA) and viral load on the Hologic Panther Fusion® using the Open Access functionality. Methods Custom-designed primers/probe sets targeting the SARS-CoV-2 Envelope gene (E) and subgenomic E were optimized. A 20-day performance validation following laboratory developed test requirements was conducted to assess assay precision, accuracy, analytical sensitivity/specificity, lower limit of detection and reportable range. Results Quantitative SARS-CoV-2 sgRNA (LDT-Quant sgRNA) assay, which measures intermediates of replication, and viral load (LDT-Quant VLCoV) assay demonstrated acceptable performance. Both assays were linear with an R2 and slope equal to 0.99 and 1.00, respectively. Assay precision was evaluated between 4–6 Log10 with a maximum CV of 2.6% and 2.5% for LDT-Quant sgRNA and LDT-Quant VLCoV respectively. Using negative or positive SARS-CoV-2 human nasopharyngeal swab samples, both assays were accurate (kappa coefficient of 1.00 and 0.92). Common respiratory flora and other viral pathogens were not detected and did not interfere with the detection or quantification by either assay. Based on 95% detection, the assay LLODs were 729 and 1206 Copies/mL for the sgRNA and VL load LDTs, respectively. Conclusion The LDT-Quant sgRNA and LDT-Quant VLCoV demonstrated good analytical performance. These assays could be further investigated as alternative monitoring assays for viral replication; and thus, medical management in clinical settings which could inform isolation/quarantine requirements.

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Successful lung transplantation using an allograft from a COVID-19–recovered donor: a potential role for subgenomic RNA to guide organ utilization

Cited by 7 publications

References 24 publications

Donor-derived infections in solid organ transplant recipients

Donor-derived infections in solid organ transplant recipients

Viable SARS-CoV-2 Omicron sub-variants isolated from autopsy tissues

Analytical validation of quantitative SARS-CoV-2 subgenomic and viral load laboratory developed tests conducted on the Panther Fusion® (Hologic) with preliminary application to clinical samples

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