To the editor:
The case fatality ratio of coronavirus disease 2019 (COVID-19) in kidney transplant recipients is between 10% and 30%,1 , 2 underscoring the importance of vaccination to prevent COVID-19. However, kidney transplant recipients have a reduced response to COVID-19 vaccines (18%–54%).3 , 4 We determined severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike IgG (anti–spike IgG) responses to COVID-19 vaccination in 65 kidney transplant recipients who received BNT162b2 (Pfizer–BioNTech), 29 who received mRNA-1273 (Moderna), and 4 who received Janssen Ad26.CoV2.S (Johnson & Johnson) vaccines at a median of 4 years (range, 3 mo–22 yr) after transplantation (Supplementary Table S1). Twenty-one patients had prior COVID-19 infection, and 11 (52%) had SARS-CoV-2 nucleocapsid IgG (anti–nucleocapsid IgG) before vaccination, of whom 20 (95%) generated anti–spike IgG. However, only 24 (32%) of 76 patients without a previous history of COVID-19 and a negative anti–nucleocapsid IgG before vaccination generated an anti–spike IgG response. The median anti–spike IgG level was significantly higher in those with prior COVID-19 (median signal-to-cutoff ratio, 13.3 [95% CI, 7.59–16.20] vs. 6.3 [95% CI, 1.22–15.6]; P < 0.01). African Americans, those on full-dose anti-metabolite therapy, and those with lower median CD3 and CD4 T-cell and serum IgM levels had reduced responses (Table 1 ). A total of 65% of those with CD4 counts >400 and 57% of those with CD3 counts >1000 responded, but only 17% and 13%, respectively, of those with CD4 counts <400 and CD3 counts <500 responded (Supplementary Figure S1A and S1B). In summary, a lack of response to COVID-19 vaccines was associated with African American race; being on high-dose anti-metabolite therapy; and having lower prevaccination CD3, CD4 T-cell, and serum IgM levels.
Table 1.
Baseline demographics of kidney transplant recipients without previous history of COVID-19 and completed COVID-19 vaccination
| Variable | Anti-spike IgG negative (N = 52) | Anti-spike IgG positive (N = 24) | P value |
|---|---|---|---|
| Age, yr | 63 (54–69) | 58 (41–70) | 0.22 |
| <65 | 65 | 67 | 1 |
| ≥65 | 35 | 33 | |
| Male sex | 63 | 50 | 0.39 |
| Race | |||
| White | 12 | 33 | |
| African American | 52 | 25 | 0.04 |
| Hispanic | 29 | 25 | |
| Other | 8 | 17 | |
| Transplant type | |||
| Deceased donor | 83 | 67 | 0.21 |
| Living donor | 17 | 34 | |
| Cause of ESRD | |||
| Diabetes mellitus | 35 | 25 | |
| Hypertension | 31 | 25 | 0.67 |
| Glomerular disease | 29 | 46 | |
| Others | 6 | 4 | |
| Comorbidities | |||
| Diabetes mellitus | 52 | 46 | 0.8 |
| Hypertension | 100 | 100 | 1 |
| Heart disease | 39 | 17 | 0.1 |
| Lung disease | 12 | 17 | 0.8 |
| Cancer | 15 | 25 | 0.49 |
| BMI, kg/m2 | 29.5 (23.7–32.4) | 30.3 (25.5–34.3) | 0.31 |
| Vaccine type | |||
| BNT162B2 (Pfizer–BioNTech) | 64 | 63 | 0.94 |
| mRNA-1273 (Moderna) | 31 | 33 | |
| Adenovirus (Johnson & Johnson) | 5 | 4 | |
| Time to vaccination from transplant, mo | 54 (24–98) | 39 (12–100) | 0.47 |
| Induction with anti-thymocyte globulin | 69 | 48 | 0.13 |
| Immunosuppressive regimen | |||
| CNI | 98 | 100 | 1 |
| MPA/MMF | 87 | 67 | 0.043 |
| Prednisone | 100 | 100 | 1 |
| No MPA/MMF | 14 | 33 | P value for 3 groups = 0.093 |
| MPA/MMF ≤720/1000 mg/d | 33 | 33 | |
| MPA/MMF >720/1000 mg/d | 54 | 33 | P value for no MPA/MMF vs. MPA/MMF >720/1000 mg/d = 0.045 |
| eGFR , ml/min | 55 (36–77) | 62 (44–84) | 0.23 |
| PRA before vaccination, mean (SD) | |||
| Class I | 21 (35) | 16 (29) | 0.35 |
| Class II | 17 (31) | 11 (26) | 0.29 |
| CD3 count, cells/μl | 652 (427–1204) | 1176 (653–1422) | 0.032 |
| CD4 count, cells/μl | 303 (185–503) | 632 (249–858) | 0.046 |
| CD8 count, cells/μl | 314 (184–507) | 454 (223–562) | 0.2 |
| IgM, mg/dl | 67.5 (39–92) | 100 (60–141) | 0.009 |
| IgA, mg/dl | 156.5 (133.8–246.3) | 194 (147.5–277.5) | 0.31 |
| IgG, mg/dl | 1114.5 (801.5–1340) | 954 (885–1183) | 0.5 |
BMI, body mass index; CNI, calcineurin inhibitor; COVID-19, coronavirus disease 2019; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease; IQR, interquartile range; MMF, mycophenolate mofetil; MPA, mycophenolic acid; PRA, panel reactive antibody.
Values are presented as percentage or median (interquartile range), unless otherwise indicated.
Footnotes
Figure S1A. Antibody response rate to vaccination per CD3 cell counts.
Figure S1B. Antibody response rate to vaccination per CD4 cell counts.
Table S1. Baseline demographics of kidney transplant recipients with and without previous history of coronavirus disease 2019 (COVID-19).
Supplementary Methods.
Supplementary Material
References
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