Risk factors associated with poor response to COVID-19 vaccination in kidney transplant recipients.

To the editor:

The case fatality ratio of coronavirus disease 2019 (COVID-19) in kidney transplant recipients is between 10% and 30%, , underscoring the importance of vaccination to prevent COVID-19. However, kidney transplant recipients have a reduced response to COVID-19 vaccines (18%–54%). , 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.