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

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.

SARS-CoV-2 and the liver: clinical and immunological features in chronic liver disease

“…With respect to the cellular immune response, most LTR are able to develop T cell responses against the spike, nucleocapsid or membrane protein of SARS-CoV-2 99–101. Notably, the magnitude of T cell responses was comparable in LTR and healthy individuals and the cellular immune responses in LTR were longitudinally detectable and remained stable over 12-month postinfection99 100 (figure 2B).…”

“…With respect to the cellular immune response, most LTR are able to develop T cell responses against the spike, nucleocapsid or membrane protein of SARS-CoV-2 99–101. Notably, the magnitude of T cell responses was comparable in LTR and healthy individuals and the cellular immune responses in LTR were longitudinally detectable and remained stable over 12-month postinfection99 100 (figure 2B). In a recent study, Citores et al performed a functional analysis of virus-specific CD4+ and CD8+ T cells 12 months after COVID-19 and observed a non-significant trend towards lower levels of IL2, IL10, TNF-α and IFN-γ in LTR compared with healthy individuals 101.…”

High vaccination coverage and infection rate result in a robust SARS‐CoV‐2‐specific immunity in the majority of liver cirrhosis and transplant patients: A single‐center cross‐sectional study

“…Previously, Kirchner et al reported a stable cellular immune response over 1 year in convalescent LTR despite a decline in the humoral response. 27 The clinical significance of a low cellular SARS-CoV-2 immune response in these patients and ways to overcome this require further investigation. However, there is a general understanding that the T-cell response is essential in preventing severe disease courses.…”

Seroprevalence of Anti-SARS-CoV-2 Antibodies Following the Omicron BA.1 Wave

“…Studies also revealed that immunocompromised patients had a consistently lower prevalence of anti-SARS-CoV-2 antibodies compared to immuno-competent persons [ 12 ]. Liver transplant recipients showed a lower prevalence of anti-nucleocapsid and anti-spike IgG antibodies one year after SARS-CoV-2 infection [ 13 ]. Kidney transplant patients were able to generate normal (but delayed) serum levels of anti-SARS-CoV-2 IgG upon infection, with serum antibody levels decreasing more rapidly compared with immunocompetent subjects [ 14 ].…”