Humoral response to SARS-CoV-2 mRNA vaccine on in ABO blood type incompatible kidney transplant recipients treated with low-dose rituximab – Scientific Reports

Background of patients

Figure 1A summarizes the characteristics of the patients incorporated in this study. This study included 154 nontransplant controls, 122 K recipients who had received the mRNA vaccine after KT, and 9 recipients who had received the mRNA vaccine before KT. Of the 122 recipients who had received the mRNA vaccine after KT, 50 had received the third dose of mRNA vaccine after KT. 68 The median time between the second and third vaccination was 7 months. The other 82 recipients were not received the third dose of mRNA vaccine at the end of June 2022. Recipients with a previous SARS-Cov-2 infection were not included. The background characteristics of the study cohort are summarized in Table 1. The number of ABO-incompatible KT recipients and the number of recipients treated with low-dose rituximab were 28 and 50, respectively.

The median dosages of maintenance immunosuppression in tacrolimus, mycophenolate mofetil (MMF), and prednisolone were 3.0 mg (IQR 2.0–4.5 mg), 1000 mg (IQR 750–1000 mg), 5 mg as (IQR 5.0–5.0 mg). Everolimus was administrated in 10 patients with the median dose of 1.5 mg (IQR 1.0–1.5 mg) The median trough level of tacrolimus was 3.9 mg (IQR 3.1–4.9 ng/mL).

Of the 50 recipients who had received the third dose of mRNA vaccine after KT, rituximab was administrated in 21 (42%) KT recipients, including 7 (14%) ABO-incompatible KT recipients. All recipients received combined immunosuppressive therapy with a median of three agents. The median period after KT was 5.8 (IQR 2.9, 10.3) years. No recipient had biopsy-proven rejection or viral events during the current study period.

Trends in anti-SARS-CoV-2 S IgG antibody

The third dose of mRNA vaccine caused a marked increase in antibody titers in both nontransplant controls (Fig. 1B) and KT recipients (Fig. 1C). The median IgG antibody titers in the nontransplant controls before and after the third dose of mRNA vaccine were 593 and 9110 U/mL, respectively (P < 0.001). All nontransplant controls were seropositive (100%).

Antibody titer and seropositivity

In KT recipients, the anti-SARS-CoV-2 S IgG antibody titer was significantly increased after the third dose of mRNA vaccine, as compared to that during the post-second dose (436 vs. 0.43 U/mL, P < 0.001; Fig. 2A). The rates of anti-SARS-CoV-2 S IgG antibody titer level ≥ 0.8 and ≥ 15 U/mL were 70% (n = 35/50) and 64% (n = 32/50), respectively in the KT recipients. The seropositivity rates were significantly higher after the third dose than after the second dose (P = 0.001 and P < 0.001, respectively; Fig. 2B). Of the 50 recipients, 18 (36%) and 32 (64%) were seropositive and seronegative, respectively, before the third dose of the mRNA vaccine. However, 17 recipients (34%) who were seronegative after the second dose became seropositive after the third dose of the mRNA vaccine (Fig. 2C). There were no significant differences in the background characteristics between the KT recipients with seronegativity (n = 15) and seropositivity (n = 35) after the third of the mRNA vaccine, except for any responses in the anti-SARS-CoV-2 S IgG antibody titer to the second dose of the mRNA vaccine, which was significantly associated with seropositivity after the third dose of the mRNA vaccine (Table 2).

Comparison of anti-SARS-CoV-2 IgG S antibody titers and seropositivity rates after the second and third doses of the mRNA vaccine in kidney transplant recipients. (A) A comparison of antibody titers after the second and third doses of the mRNA vaccine in kidney transplant (KT) recipients. (B) A comparison of the seropositivity rate after the second and third doses of the mRNA vaccine in KT recipients (n = 50). Seropositivity was defined as anti-SARS-CoV-2 S IgG antibody titers of ≥ 0.80 or ≥ 15 U/mL. (C) Changes in seropositivity from the second to third dose of the mRNA vaccine in KT recipients (n = 50). (D) A comparison of the seropositivity rate after the second (n = 122) and third (n = 50) doses of the mRNA vaccine between the ABO-compatible and ABO-incompatible KT recipients. (E) A comparison of the seropositivity rate after the second (n = 122) and third (n = 50) doses of the mRNA vaccine between the KT recipients with and without rituximab. SARS-CoV-2 severe acute respiratory syndrome coronavirus 2, S spike, IGG immunoglobulin G.

Seropositivity in ABO-incompatible KT recipients

The seropositivity rate after the second dose of mRNA vaccine was not significantly different between the ABO-compatible (n = 44/94, 46.8%) and ABO-incompatible (n = 13/28, 46.4%) KT recipients (P = 1.00). The seropositivity rate after the third dose of mRNA vaccine was not significantly different between the ABO-compatible (n = 28/43, 65.1%) and ABO-incompatible (n = 7/7, 100%) KT recipients (P = 0.087) (Fig. 2D).

Seropositivity in KT recipients with or without rituximab

The seropositivity rate after the second dose of mRNA vaccine was not significantly different between the KT recipients without rituximab (n = 36/72, 50.0%) and with rituximab (n = 21/50, 42.0%) (P = 0.461). The seropositivity rate after the third dose of mRNA vaccine was not significantly different between the KT recipients without rituximab (n = 20/29, 69.0%) and with rituximab (n = 15/21, 71.4%) (P = 1.00) (Fig. 2E).

Impact of vaccinations prior to transplantation

The trends in anti-SARS-CoV-2 S IgG antibody titer in the recipients who had received the mRNA vaccine before KT (n = 9) showed that eight recipients who had received the second or third dose of the mRNA vaccine were seropositive, whereas one recipient who had received only a single dose before KT showed seronegativity after KT even if the recipient was vaccinated later (Fig. 3). No serious adverse event was observed in patients receiving a third vaccination.

Trends in anti-SARS-CoV-2 IgG S antibody titers in each kidney transplant recipient who had received the mRNA vaccine before kidney transplantation. *, case 1: a single dose of the MRNA vaccine before KT, followed by second and third doses after KT. SARS-CoV-2 severe acute respiratory syndrome coronavirus 2, S spike, IGG immunoglobulin G, KT kidney transplantation.

COVID-19 infection event

We evaluated COVID-19 infection events between June 21, 2021 and December 31, 2022. We observed no significant difference in the rate of symptomatic COVID-19 infection events between patients on 3 doses (n = 11/72, 15.3%) and those on 2 doses alone (n = 7/50, 14%) (P = 1.00). The rate of hospitalization was 0% in patients on 3 doses and 2 doses alone (n = 1, 2%) (Fig. 4A). There were no deaths related to COVID-19 during this period. The rate of symptomatic COVID-19 infection events was not significantly different between patients with ABO-compatible KT (n = 13/94, 13.8%) and those with ABO-incompatible KT (n = 5/28, 17.9%) (P = 0.558) (Fig. 4B) and between patients with rituximab (n = 9/50, 18%) and those without rituximab (n = 9/72, 12.5%) (P = 0.443) (Fig. 4C). Among all KT recipients (n = 183), the rates of symptomatic COVID-19 infection with and without mRNA vaccines were 13.7% (n = 18/131) and 9.6% (n = 5/52), respectively (P = 0.622). The rates of hospitalization with and without mRNA vaccine were 0.8% (n = 1/131) and 1.9% (n = 1/52), respectively (P = 0.489) (Fig. 4D).

Comparison of COVID-19 infection event in kidney transplant recipients. (A) A comparison of COVID-19 infection event between the kidney transplant (KT) recipients who received two doses alone and those who received three doses of mRNA vaccine. (B) A comparison of COVID-19 infection event between the ABO-compatible and ABO-incompatible KT recipients. (C) A comparison of COVID-19 infection event between the KT recipients with rituximab and those without rituximab. (D) A comparison of COVID-19 infection event between the KT recipients with mRNA vaccine and those without mRNA vaccine.