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Humoral response to SARS-CoV-2 infection among liver transplant recipients
  1. Chiara Becchetti1,
  2. Annelotte G C Broekhoven2,
  3. Géraldine Dahlqvist3,
  4. Montserrat Fraga4,
  5. Marco Fabrizio Zambelli5,
  6. Olga Ciccarelli6,
  7. Anne-Catherine Saouli4,7,
  8. Arianna Trizzino5,
  9. Vanessa Banz1,
  10. Jean-François Dufour1,8,
  11. Anna H E Roukens9,
  12. Shessy P Torres Morales10,
  13. Sebenzile K Myeni10,
  14. Marjolein Kikkert10,
  15. Mariet C W Feltkamp11,
  16. Minneke J Coenraad2
  1. 1 Department of Visceral Surgery and Medicine, Bern University Hospital, University of Bern, Bern, Switzerland
  2. 2 Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
  3. 3 Hepatogastroenterology Unit, Cliniques universitaires Saint-Luc, Bruxelles, Belgium
  4. 4 Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
  5. 5 Department of Surgery, General Surgery and Abdominal Transplant Unit, Papa Giovanni XXIII Hospital, Bergamo, Lombardia, Italy
  6. 6 Department of Abdominal Surgery and Transplantation, Cliniques Universitaires Saint-Luc, Brussels, Belgium
  7. 7 Transplantation Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
  8. 8 Department of Biomedical Research, University of Bern, Bern, Switzerland
  9. 9 Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands
  10. 10 Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
  11. 11 Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands
  1. Correspondence to Dr Minneke J Coenraad, Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden 2300 RC, The Netherlands; M.J.Coenraad{at}lumc.nl

Abstract

Objective Immunosuppressive agents are known to interfere with T and/or B lymphocytes, which are required to mount an adequate serologic response. Therefore, we aim to investigate the antibody response to SARS-CoV-2 in liver transplant (LT) recipients after COVID-19.

Design Prospective multicentre case–control study, analysing antibodies against the nucleocapsid protein, spike (S) protein of SARS-CoV-2 and their neutralising activity in LT recipients with confirmed SARS-CoV-2 infection (COVID-19-LT) compared with immunocompetent patients (COVID-19-immunocompetent) and LT recipients without COVID-19 symptoms (non-COVID-19-LT).

Results Overall, 35 LT recipients were included in the COVID-19-LT cohort. 35 and 70 subjects fulfilling the matching criteria were assigned to the COVID-19-immunocompetent and non-COVID-19-LT cohorts, respectively. We showed that LT recipients, despite immunosuppression and less symptoms, mounted a detectable antinucleocapsid antibody titre in 80% of the cases, although significantly lower compared with the COVID-19-immunocompetent cohort (3.73 vs 7.36 index level, p<0.001). When analysing anti-S antibody response, no difference in positivity rate was found between the COVID-19-LT and COVID-19-immunocompetent cohorts (97.1% vs 100%, p=0.314). Functional antibody testing showed neutralising activity in 82.9% of LT recipients (vs 100% in COVID-19-immunocompetent cohort, p=0.024).

Conclusions Our findings suggest that the humoral response of LT recipients is only slightly lower than expected, compared with COVID-19 immunocompetent controls. Testing for anti-S antibodies alone can lead to an overestimation of the neutralising ability in LT recipients. Altogether, routine antibody testing against separate SARS-CoV-2 antigens and functional testing show that the far majority of LT patients are capable of mounting an adequate antibody response with neutralising ability.

  • COVID-19
  • liver transplantation
  • immune response

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Data availability statement

Data are available upon reasonable request.

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Footnotes

  • CB and AGCB contributed equally.

  • Contributors CB and AGCB contributed to this paper with conception, collection of the data, data analysis, literature review and writing the manuscript. GD, MF, AT and MFZ participated in collecting data, critical revision and editing. OC, A-CS and VB contributed in critical revision. AHER contributed in gathering the control samples for serological measurement and critical revision. SPTM, SKM, MK and MCWF contributed with microbiological analysis and critical revision. J-FD and MJC contributed to this paper with conception, methodology development, drafting, critical revision and editing the manuscript. All the authors approved the final version of the manuscript. MJC is the author responsible for the overall content and act as the guarantor of the study.

  • Funding CB received financial support from the Stiftung für Leberkrankheiten Bern.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; internally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.