Weak anti-SARS-CoV-2 antibody response after the first injection of an mRNA COVID-19 vaccine in kidney transplant recipients.

To the editor:

International recommendations on coronavirus disease 2019 (COVID-19) vaccine distribution have given priority to immunocompromised patients, including kidney transplant recipients (KTRs). , Unfortunately, this guidance has been released without inclusion of this clinical population in vaccine clinical trials. In an effort to shed light on the efficacy and safety of an mRNA COVID-19 vaccine in KTRs, this preliminary study was undertaken to investigate the anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody response after the first injection.

We examined 242 KTRs who received the first injection of the Moderna mRNA-1273 vaccine (100 μg) at the Strasbourg University Hospital (Strasbourg, France) between January 21 and 28, 2021. All had a negative history for COVID-19 and tested negative for anti–SARS-CoV-2 antibodies on the day of the first injection. The anti–SARS-CoV-2 antibody response against the spike protein was assessed at 28 days after injection using the ARCHITECT IgG II Quant test (Abbott, Abbott Park, IL), with titers >50 arbitrary units (AUs)/ml being considered as positive (detection range, 6.8–40,000 AUs/ml; positive agreement, 99.4%; negative agreement, 99.6%).

One patient developed mild symptomatic COVID-19 7 days after injection, and only 26 (10.8%) KTRs had a positive serology at 28 days after injection. The median IgG titer was 224 AUs/ml (interquartile range, 76−496 AUs/ml), whereas the median IgG titer in the seronegative group was <6.8 AUs/ml (Figure 1 ). Patients who seroconverted had longer time from transplantation, received less immunosuppression, and had a better kidney function (Table 1 ).

Figure 1

Anti-spike IgG antibody titers measured at 28 days after vaccination in 215 seronegative kidney transplant recipients (median titer, <6.8 arbitrary units [AUs]/ml [interquartile range, <6.8−<6.8 AUs/ml]) and 26 seropositive kidney transplant recipients (median titer, 224 AUs/ml [interquartile range, 76−496 AUs/ml]). The dotted line indicates the cutoff for positivity (50 AUs/ml).

Table 1

Characteristics of kidney transplant recipients, according to serologic response after the first dose of the Moderna mRNA-1273 vaccine

Characteristics	Entire cohort (n=241)a	SARS-CoV-2 seronegative patients (n=215)	SARS-CoV-2 seropositive patients (n=26)	P value	Missing data
Age, yr	57.7 (49.3–67.6)	57.7 (49.6–67.7)	58.4 (43.3–66.9)	0.51	0
Male sex	156 (64.7)	142 (66.1)	14 (53.9)	0.28	0
BMI, kg/m2	25.7 (22.6–29.5)	25.7 (22.8–29.4)	26.4 (21.9–29.9)	0.73	2
Time from kidney transplantation, yr	6.4 (2.9–13)	5.8 (2.8–11.9)	15.4 (8.6–25.9)	<0.001	2
First transplantation	202 (83.8)	176 (81.8)	26 (100)	0.01	0
Deceased donor	192 (79.6)	172 (80)	20 (76.9)	0.8	0
ABO group				0.02	2
O	94 (39.3)	82 (38.5)	12 (46.2)
A	101 (42.3)	93 (43.7)	8 (30.8)
B	30 (12.6)	29 (13.6)	1 (3.9)
AB	14 (5.9)	9 (4.2)	5 (19.2)
Induction treatment				0.001	7
Anti-thymocyte globulin	138 (59.5)	127 (60.8)	11 (47.8)		9
Anti-CD25	88 (37.9)	80 (38.3)	8 (34.8)
No induction	6 (2.6)	2 (1)	4 (17.4)
CNI				0.06	0
Tacrolimus	133 (55.2)	124 (57.7)	9 (34.6)
Ciclosporin	82 (34)	69 (32.1)	14 (50)
No CNI	26 (10.8)	22 (10.2)	4 (15.4)
MMF/MPA	191 (79.3)	177 (82.3)	14 (53.9)	0.002	0
Azathioprine	7 (2.9)	4 (1.86)	3 (11.5)	0.03	0
mTOR inhibitors	35 (14.5)	32 (14.9)	3 (11.6)	1	0
Steroids	142 (58.9)	133 (61.9)	9 (34.6)	0.01	0
Belatacept	9 (3.8)	9 (4.2)	0	0.26	0
eGFR, ml/min per 1.73 m2	51.6 (38.1–68)	51 (37.9–66.5)	64.9 (39.9–72.2)	0.08	0
Serum creatinine, μmol/L	118 (99–158)	120 (101–159)	104 (85–134)	0.05	0

BMI, body mass index; CD, cluster of differentiation; CNI, calcineurin inhibitor; eGFR, estimated glomerular filtration rate; MMF, mycophenolate mofetil; MPA, mycophenolic acid; mTOR, mechanistic target of rapamycin; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Continuous variables are presented as medians (interquartile ranges), whereas categorical variables are given as n (%).

The patient who developed coronavirus disease 2019 after the first injection was excluded from the analysis.

In summary, the burden of immunosuppression may induce a weak anti–SARS-CoV-2 antibody response in KTRs after the first injection of an mRNA COVID-19 vaccine. This finding is strikingly different compared with immunocompetent subjects, who invariably seroconverted after the first injection. , We highlight the need not to delay the second vaccine injection in immunocompromised patients. Close surveillance is also recommended to discuss the opportunity of a third dose in less responsive patients.