Insufficient response to mRNA SARS-CoV-2 vaccine and high incidence of severe COVID-19 in kidney transplant recipients during pandemic

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination may fail to sufficiently protect transplant recipients against coronavirus disease 2019 (COVID-19). We retrospectively evaluated COVID-19 in kidney transplant recipients (n = 226) after BNT162b2 mRNA vaccine administration. The control group consisted of unvaccinated patients (n = 194) during the previous pandemic wave. We measured anti-spike protein immunoglobulin G (IgG) levels and cellular responses, using enzyme-linked immunosorbent spot assay, in a prospective cohort after vaccination (n = 31) and recovery from COVID-19 (n = 19). COVID-19 was diagnosed in 37 (16%) vaccinated and 43 (22%) unvaccinated patients. COVID-19 severity was similar in both groups, with patients exhibiting a comparable need for hospitalization (41% vs. 40%, p = 1.000) and mortality (14% vs. 9%, p = .726). Short posttransplant periods were associated with COVID-19 after vaccination (p < .001). Only 5 (16%) patients achieved positive SARS-CoV-2 IgG after vaccination, and 17 (89%, p < .001) recovered from COVID-19 (median IgG levels, 0.6 vs. 52.5 AU/ml, p < .001). A cellular response following vaccination was present in the majority (n = 22, 71%), with an increase in interleukin 2 secreting T cells (p < .001). Despite detectable T cell immunity after mRNA vaccination, kidney transplant recipients remained at a high risk of severe COVID-19. Humoral responses induced by vaccination were significantly lower than that after COVID-19.

Keywords: SARS-CoV-2/COVID-19; clinical research / practice; infection and infectious agents - viral; infectious disease; kidney transplantation / nephrology; vaccine.

FIGURE 1

Flow of patients through the study. COVID-19, coronavirus disease 2019. ^aIncluded 5 patients with COVID-19 after 1^st dose and 11 patients <14 days after 2^nd dose. ^bMore than 14 days after 2^nd dose

FIGURE 2

Humoral response after mRNA vaccination and after COVID-19. IgG levels against S1 subunit of SARS-CoV-2 spike protein are shown (A) and the percentage of patients with positive response are defined by a value of ≥10 AU/ml (B). Minimum and maximum values excluding outliers represented by whiskers, median and interquartile range inside boxes. A Wilcoxon signed-rank test was used for comparison of IgG levels before and after vaccination, a Mann-Whitney U-test and χ² test used for comparison of IgG levels and positive response after vaccination and after COVID-19. COVID-19, coronavirus disease 2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2

FIGURE 3

Cellular response after mRNA vaccination by IFN-γ (A, B) or IL-2 (C, D) secreting T cells. Assessed by ELISpot after stimulation by SARS-CoV-2 SMNO or S1 antigen pools and expressed as SFC per 2 × 10⁵ PBMC. Minimum and maximum values excluding outliers represented by whiskers, median and interquartile range inside boxes. Wilcoxon signed-rank test used for comparison. M, membrane protein; N, nucleoprotein; O, open reading frame proteins; S, spike protein; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SFC, spot forming cells; PBMC, peripheral blood mononuclear cells

FIGURE 4

Local and systemic reactions reported after the BNT162b2 mRNA vaccination. Assessed in patients without COVID-19 after vaccination (n = 31). There were no grade 3 or 4 adverse reactions nor any hospitalizations related to vaccination. Serum creatinine remained stable 4 weeks after the second dose of vaccine (157 ± 97 μmol/L) compared to pre-vaccination level (162 ± 94 μmol/L)