Reduced humoral but stable cellular SARS-CoV-2-specific immunity in liver transplant recipients in the first year after COVID-19

PLoS One. 2022 Nov 2;17(11):e0276929. doi: 10.1371/journal.pone.0276929. eCollection 2022.

Abstract

Mortality due to COVID-19 is not increased in immunosuppressed individuals after liver transplantation (OLT) compared to individuals without immunosuppression. Data on long-term protective immunity against SARS-CoV-2 in immunosuppressed convalescents, is limited. We prospectively measured immune responses against SARS-CoV-2 by quantifying antibodies against 4 different antigens (spike protein 1 and 2, receptor binding domain, nucleocapsid) and T cell responses by IFN-γ ELISPOT against 4 antigens (membrane, nucleocapsid, spike protein 1 and 2) in 24 OLT convalescents with immunosuppressive therapy longitudinally in the first year after COVID-19 including a booster vaccination in comparison to a matched cohort of non-immunosuppressed convalescents (non-IS-Con). Pre-pandemic OLT samples were retrieved from our prospective OLT biorepository (n = 16). No relevant T cell reactivity or immunoglobulin G (IgG) against SARS-CoV-2 were detectable in pre-pandemic samples of OLT recipients despite reactivity against endemic corona-viruses. OLT convalescents had a lower prevalence of IgG against nucleocapsid (54% vs. 90%) but not against spike protein domains (98-100% vs. 100%) after vaccination in the second half-year after COVID-19 compared to non-IS-Con. Also, concentrations of anti-nucleocapsid IgG were lower in OLT convalescents than in non-IS-Con. Concentration of IgG against spike protein domains was significantly increased by a booster vaccination in OLT convalescents. But concentration of IgG against two of three spike protein domains remains slightly lower compared to non-IS-Con finally. However, none of these differences was mirrored by the cellular immunity against SARS-CoV-2 that remained stable during the first year after COVID-19 and was not further stimulated by a corona vaccination in OLT convalescents. In conclusion, despite lower concentrations of anti-SARS-CoV-2 IgG in OLT convalescents anti-SARS-CoV-2 cellular immunity was as robust as in non-IS-Con.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Viral
  • COVID-19*
  • Humans
  • Immunity, Cellular
  • Immunity, Humoral
  • Immunoglobulin G
  • Liver Transplantation*
  • Prospective Studies
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus
  • Transplant Recipients
  • Vaccination

Substances

  • Spike Glycoprotein, Coronavirus
  • Antibodies, Viral
  • Immunoglobulin G
  • spike protein, SARS-CoV-2

Grants and funding

The work was supported by grants from the COVID-19 Research Network of the State of Lower Saxony (COFONI, projects 1FT21 (R.T.), 8FT21(C.F.), 4FF22 (C.F.) and 14-76103-184 CORONA-12/20 (R.B., Y.L.), www.umg.eu/forschung/corona/cofoni/) with funding from the Ministry of Science and Culture of Lower Saxony, Germany (www.mwk.niedersachsen.de/startseite/), the German Research Foundation (SFB738 project Z2 (E.J.) and Research Unit 2830 (B.E.-V.); www.dfg.de/en/), the Federal Ministry of Health (ZMVI1-2520COR804 (R.B.), www.bundesgesundheitsministerium.de/index.html) and the Transplantation Center Project (project 19_02 (R.T.), www.mhh.de/transplantationszentrum) from Hannover Medical School. R.T. was supported by the Core 100 advanced clinician scientist program from the Hannover Medical School (www.mhh.de/forschung/nachwuchsfoerderung). B.E. was supported by the Program of Hannover Medical School for Clinician Scientists (PRACTIS, www.clinician-scientist.de/practis/). Collection and analysis of samples of non-immunosuppressed patients were funded by Förderstiftung MHHPlus (I.P., www.mhh.de/plus) Hannover. C.F. was supported by Deutsches Zentrum für Infektionsforschung (DZIF, project TTU-IICH 07_913, www.dzif.de/de). R.B. and B.E-V. were supported by STIFTUNG Sparda-Bank Hannover (sparda-h.de/stiftung/Stiftung.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.