SARS-CoV-2 anti-spike antibodies after a fourth dose of COVID-19 vaccine in adult solid-organ transplant recipients

Abstract

Background: A fourth dose of SARS-CoV-2 vaccine is recommended in solid-organ transplant (SOT) recipients, but the immunogenicity is poorly known.

Methods: We conducted a retrospective, observational, monocentric study between the 1st January 2021 and 31st March 2022 of the anti-Spike antibody titers after one to four doses of vaccine in SOT.

Results: 825 SOT were included. Median age at first vaccine injection was 61.2 (IQR 50.9-69.3) years; 66.7 % were male; 63.4 % had received four vaccine doses. The proportion of participants with a strong humoral response (>260 BAU/mL) increased with the number of vaccine doses: 10.6 % after the 1st dose (D1), 35.1 % after the 2nd (D2), 48.5 % after the 3rd (D3), and 65.1 % after the 4th (D4) (p < 0.001). Among the tested patients, the proportion with a detectable humoral response was significantly higher after D4 than after D3 (47 % vs 22 %, p = 0.01). Liver transplant recipients had more frequently a strong humoral response after D2, D3 and D4 (OR = 5.3, 3.7 and 6.6 respectively when compared with other organ transplant recipients, p < 0.001). In kidney transplant recipients, belatacept-containing regimen was associated with a lower rate of detectable humoral (9 % vs 40 %, p = 0.025) after D3, but there was no statistical difference after D4.

Conclusion: A fourth dose should be proposed to SOT recipients who did not developed an immune response after 3 doses. Kidney transplant recipients receiving belatacept have a poorer, although frequently detectable response.

Keywords: Antibodies; Booster; COVID-19; Fourth dose; SARS-CoV-2; Solid-organ transplantation; Third dose; Vaccination.

Fig. 1

Level of anti-SARS-CoV-2 antibody response in transplant recipients according to the number of vaccine doses. Post D1 (n = 66) corresponds to the distribution of patients’ serology profiles after a first dose of COVID-19 vaccine. Post D2 (n = 244) corresponds to the repartition of patients’ serology profiles after a second dose of COVID-19 vaccine. Post D3 (n = 538) corresponds to the repartition of patients’ serology profiles after a third dose of COVID-19 vaccine. Post D4 (n = 235) corresponds to the repartition of patients’ serology profiles after a fourth dose of COVID-19 vaccine. Seronegative profile corresponds to patients with no detectable antibodies. Weak humoral-response profile corresponds to patients with a detectable anti-spike antibody level below 260 BAU/mL. Strong humoral-response profile corresponds to patients with an anti-spike antibody level >260 BAU/mL. Serology profiles differed regarding the number of doses of vaccine (p < 0.001, chi-squared test).

Fig. 2

Anti-spike antibody level after two, three, or four vaccine doses given to SOT recipients. All results for antibody levels were capped at 260 BAU/mL. The square represented the mean value of anti-spike antibody level. Evolution of serology between D2 and D3 was evaluated for 44 patients, and for 175 patients between D3 and D4. P-value was determined by the chi-square test.

Fig. 3

All anti-spike antibody levels after two, three, or four vaccine doses given to kidney recipients according to immunosuppressive regimen. All results for antibody levels were capped at 260 BAU/mL. Evolution of serology between D2 and D3 was evaluated for 44 patients, and for 52 patients between D3 and D4. Stacked line on the graft signified that several patient were no responders (bottom of the graft) or strong responders (top of the graft). P-value was determined by the chi-square test.