SARS-CoV-2 Messenger RNA Vaccine Immunogenicity in Solid Organ Transplant Recipients With Prior COVID-19

Abstract

Immunocompetent people with prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (convalescent individuals) have been shown to have a more robust antibody response to the first SARS-CoV-2 mRNA vaccine dose compared with previously uninfected people (naive individuals).1 Given limited immunogenicity of SARS-CoV-2 vaccines in solid organ transplant recipients,2,3 we sought to quantify the antibody response to vaccination among convalescent versus naive transplant recipients. Leveraging our ongoing prospective cohort of transplant recipients who underwent SARS-CoV-2 mRNA vaccination December 18, 2020–April 1, 2021,4 we compared antispike antibody titers after dose 1 in convalescent transplant recipients with prior polymerase chain reaction-confirmed SARS-CoV-2 infection at a median (interquartile range [IQR]) of 3.5 mo (2.6–5.3 mo) before vaccination (n = 28) versus naive recipients (n = 1012) using weighted-by-the-odds Poisson regression. As previously reported, serologic testing was conducted on the Roche Elecsys anti-SARS-CoV-2 S enzyme immunoassay (range, <0.4 to >250 U/mL [positive ≥0.8 U/mL]), which tests for antibodies against the receptor-binding domain of the spike protein, or the EUROIMMUN enzyme immunoassay (positive ≥1.1 AU), which tests for immunoglobulin G to the S1 domain of the spike protein. This study was approved by the Johns Hopkins Institutional Review Board. Convalescent vaccinees were more likely to have a positive antibody response to dose 1 compared with naive vaccinees (89% versus 18%, P < 0.001) (Table 1). After weighting to adjust for age, antimetabolite therapy, and organ transplant type, prior SARS-CoV-2 infection was associated with a 6.28-fold higher chance of a positive antibody response (weighted incidence rate ratio = 5.236.287.54, P < 0.001). Convalescent vaccinees also had a higher post–dose 1 antispike antibody titer than naive vaccinees (median [IQR], 250 [250–250] versus 7.63 [2.02–28.97], P < 0.001 [Roche] and 7.62 [7.44–9.14] versus 3.42 [2.3–5.16], P = 0.02 [EUROIMMUN]). In a sensitivity analysis restricting to only those with a confirmed prevaccine negative antibody result, convalescent recipients were still more likely to have a positive antibody response to dose 1 (75% versus 19%, P < 0.001). TABLE 1. - Demographics of study population stratified by prior SARS-CoV-2 infection status Previously uninfected Previously infected P n 1012 28 Kidney recipient 476 (48.0%) 14 (50.0%) 0.83 Age, median (IQR) 60.0 (45.7–68.1) (n = 1002) 56.6 (50.6–66.3) (n = 28) 0.45 Transplant type 0.88 Kidney 476 (47.0%) 14 (50.0%) Liver 215 (21.2%) 5 (17.9%) Pancreas 12 (1.2%) 0 (0.0%) Heart 145 (14.3%) 4 (14.3%) Lung 107 (10.6%) 3 (10.7%) Other 8 (0.8%) 0 (0.0%) Kidney/pancreas 29 (2.9%) 2 (7.1%) Not available 20 (2.0%) 0 (0.0%) Years since transplant, median (IQR) 6.2 (2.7–13.6) (n = 992) 6.1 (3.8–14.1) (n = 28) 0.56 White 889 (89.4%) 26 (92.9%) 0.56 Antimetabolite 699 (69.1%) 24 (85.7%) 0.059 Tacrolimus 813 (80.3%) 19 (67.9%) 0.15 Prevaccine antibody result <0.001 Positive 3 (0.3%) 8 (28.6%) Negative 495 (48.9%) 4 (14.3%) Not available 514 (50.8%) 16 (57.1%) Post–dose 1 testing platform 0.19 EUROIMMUN 264 (26.1%) 4 (14.3%) Roche 748 (73.9%) 24 (85.7%) Days between dose 1 and post-D1 Ab testing, median (IQR) 21 (19–26) (n = 1003) 21 (19–24.5) (n = 28) 0.93 Ab, antibody; IQR, interquartile range; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. Prevaccine antispike antibody testing was available in 12 of the 28 convalescent recipients and detectable in 8 of 12 (67%). In this population, postvaccine titers were higher than those prevaccine (>250 versus 223.3 U/mL [Roche]; 9.14 versus 5.5 AU [EUROIMMUN]). Limitations include a convenience sample, which may limit generalizability; inclusion of late entries, which limited the availability of prevaccination titers; self-report of SARS-CoV-2, which may have led to information bias; and lack of data on whether antimetabolite immunosuppression was held at the time of SARS-CoV-2 infection. In this study of transplant recipients with prior SARS-CoV-2 infection, antibody response to vaccination was much stronger than in SARS-CoV-2 naive recipients. Furthermore, even in this population with some natural immunity, antibody titers were substantially boosted by 1 dose of a SARS-CoV-2 mRNA vaccine. Prior COVID-19 infection may prime the immune system in a similar way to the intended effect of dose 1 in uninfected patients.5

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