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
Footnotes
B.J.B., I.B., T.P.-Y. C., M.T.O., R.S.G., A.T.T., M.R.K., J.I.L., J.M.G.-W., R.K.A., A.B.M., D.L.S., and W.A.W. participated in the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; drafting the work or revising it critically for important intellectual content; final approval of the version to be published; and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
This research was made possible with generous support of the Ben-Dov family. This work was supported by grant number F32DK124941 (B.J.B.), K01DK101677 (A.B.M.), and K23DK115908 (J.M.G.-W.) from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); K24AI144954 (D.L.S.) from the National Institute of Allergy and Infectious Diseases (NIAID); and gSAN-201C0WW (W.A.W.) from the Transplantation and Immunology Research Network of the American Society of Transplantation. The analyses described here are the responsibility of the authors alone and do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.
D.L.S. has received consulting or speaking honoraria from Sanofi, Novartis, CSL Behring, Jazz Pharmaceuticals, Veloxis, Mallinckrodt, and Thermo Fisher Scientific. R.K.A. has study/grant support from Aicuris, Astellas, Chimerix, Merck, Oxford Immunotec, Qiagen, and Takeda/Shire. The other authors declare no conflicts of interest.
REFERENCES
- 1.Krammer F, Srivastava K, Alshammary H, et al. Antibody responses in seropositive persons after a single dose of SARS-CoV-2 mRNA vaccine. N Engl J Med. 2021;384:1372–1374. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Boyarsky BJ, Werbel WA, Avery RK, et al. Antibody response to 2-dose SARS-CoV-2 mRNA vaccine series in solid organ transplant recipients. JAMA. 2021;325:2204–2206. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Boyarsky BJ, Chiang TP-Y, Ou MT, et al. Antibody response to the Janssen COVID-19 vaccine in solid organ transplant recipients. Transplantation. 2021;105:e82–e83. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Boyarsky BJ, Ruddy JA, Connolly CM, et al. Antibody response to a single dose of SARS-CoV-2 mRNA vaccine in patients with rheumatic and musculoskeletal diseases. Ann Rheum Dis. 2021;80:1098–1099. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Manisty C, Otter AD, Treibel TA, et al. Antibody response to first BNT162b2 dose in previously SARS-CoV-2-infected individuals. Lancet. 2021;397:1057–1058. [DOI] [PMC free article] [PubMed] [Google Scholar]