SARS-CoV-2 Infection Enhances Humoral Immune Response in Vaccinated Liver Transplant Recipients

Abstract

In the spring of 2020, the SARS-CoV-2 pandemic presented a formidable challenge to national and global healthcare systems. Immunocompromised individuals or those with relevant pre-existing conditions were particularly at risk of severe coronavirus disease 2019 (COVID-19). Thus, understanding the immunological processes in these patient groups is crucial for current research. This study aimed to investigate humoral immunity following vaccination and infection in liver transplant recipients. Humoral immunity analysis involved measuring IgG against the SARS-CoV-2 spike protein (anti-S IgG) and employing a surrogate virus neutralization test (sVNT) for assessing the hACE2 receptor-binding inhibitory capacity of antibodies. The study revealed that humoral immunity post-vaccination is well established, with positive results for anti-S IgG in 92.9% of the total study cohort. Vaccinated and SARS-CoV-2-infected patients exhibited significantly higher anti-S IgG levels compared to vaccinated, non-infected patients (18,590 AU/mL vs. 2320 AU/mL, p < 0.001). Additionally, a significantly elevated receptor-binding inhibitory capacity was observed in the cPass^TMTM sVNT (96.4% vs. 91.8%, p = 0.004). Furthermore, a substantial enhancement of anti-S IgG levels (p = 0.034) and receptor-binding inhibition capacity (p < 0.001) was observed with an increasing interval post-transplantation (up to 30 years), calculated by generalized linear model analysis. In summary, fully vaccinated liver transplant recipients exhibit robust humoral immunity against SARS-CoV-2, which significantly intensifies following infection and with increasing time after transplantation. These findings should be considered for booster vaccination schemes for liver transplant recipients.

Keywords: SARS-CoV-2 infection; humoral immunity; liver transplantation; surrogate virus neutralization test; vaccination.

Figure 1

Humoral immunity in patients after liver transplantation. (A) Qualitative results of the cPass^TM sVNT; cutoff: 30% inhibition. (B) Comparison of the cPass^TM sVNT results between patients with or without a history of SARS-CoV-2 infection. (C) Detection of anti-S IgG levels in patients in with and without a history of SARS-CoV-2 infection by the Abbott CMIA. (D) Inhibition of RBD-hACE2 binding by sera of patients with and without a history of SARS-CoV-2 infection as measured by cPass^TM sVNT; cutoff: 30% inhibition. Mann–Whitney U test was used to evaluate differences between groups. ** p < 0.01; *** p < 0.001.

Figure 2

Linear model (LM) plots illustrating the humoral immune response over time, since liver transplantation. (A) Increase in anti-S IgG levels (AU/mL) with increasing time post-transplantation. (B) Increase in relative hACE2 binding inhibition percentage, indicative of enhanced viral neutralization capacity over time following transplantation. Inhibition over time in patients without (C) and with (D) a history of SARS-CoV-2 infection as determined by cPass^TM sVNT. Anti-S IgG levels over time in patients without (E) and with (F) a history of SARS-CoV-2 infection as measured by CMIA. Cutoff value cPass^TM sVNT: 30% inhibition; the linear range of the anti-S CMIA ends at 40,000 AU/mL.