Serological response to mRNA SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients depends on prior exposure to SARS-CoV-2.

To the Editor:

Grupper et al. have reported on a positive humoral response post full vaccination with mRNA SARS‐CoV2 BNT162b2 in only 51/136 (37.5%) kidney transplant recipients (KTRs) without prior exposure to the virus. We have conducted an IRB‐approved (B707201215598–2021/80) prospective small sample‐size study comparing the humoral response to BNT162b2 in 40 consecutive individuals early exposed to the Belgian vaccination program, including 20 KTRs with (n = 10, COVID‐19(+)) vs. without (n = 10, COVID‐19(−)) history of exposure to SARS‐CoV‐2 and 20 controls including 10 COVID‐19(+) vs. 10 COVID‐19(−). The quantification of S1/S2 IgGs by DiaSorin LIAISON® chemiluminescence immunoassay was performed at three time‐points: first BNT162b2 injection (T1); second BNT162b2 injection (T2, i.e., ~21 days post T1); and ~15 days after T2 (T3). The generalized linear mixed model tested the effects of time, group, and interactions. No epidemiological difference was observed between KTRs vs. controls, nor between COVID‐19(+) vs. COVID‐19(−) (Table 1). The median delay between PCR‐proven COVID‐19 and T1 was 129 [64; 352] days. None of the 20 KTRs received IV corticosteroids or rituximab within 12 months prior to vaccination.

TABLE 1

Characteristics of the cohort

Parameters	Controls n = 20		Kidney transplant recipients n = 20		p value
	COVID−19 (−) n = 10	COVID−19 (+) n = 10	COVID−19 (−) n = 10	COVID−19 (+) n = 10
Age, years	51.5 (10.5)	45.1 (10.4)	49.7 (13.8)	52.7 (13.8)	0.53
Female gender, n (%)	3 (30)	4 (40)	5 (50)	6 (60)	0.57
BMI, kg/m2	24.58 (3.28)	25.68 (2.95)	26.45 (3.84)	26.45 (4.67)	0.71
Time from KTx, months			121.7 (106.0)	77.8 (41.8)	0.57
Deceased donor, n (%)			8 (80)	9 (90)	0.53
CNIs, n (%)			10 (100)	10 (100)	1.00
Antimetabolite, n (%)			10 (100)	7 (70)	0.37
mTOR inhibitors, n (%)			0 (0)	1 (10)	1.00
Methylprednisolone, n (%)			4 (40)	5 (50)	1.00
Serum creatinine, mg/dl			1.08 (0.29)	1.55 (0.61)	0.13
Delay between COVID‐19 and vaccination, days		154.2 (107.1)		158.2 (77.0)	0.44
Evolution of anti‐S1/S2 IgG titer
T1, median (min–max), AU/ml = first BNT162b2 injection	0 (0)	35 (0–98)	0 (0)	107 (0–205)	<0.001 a
					<0.001 b
					0.031 c
					1.00 d
T2, median (min–max), AU/ml = second BNT162b2 injection	35.5 (0–118)	1520 (79–7290)	0 (0)	1131 (94–9040)	<0.001 a
					<0.001 b
					0.59 c
					<0.001 d
T3, median (min–max), AU/ml = ~15 days after T2	263 (153–2090)	2300 (1470–6250)	0 (0–60)	2105 (212–18300)	<0.001 a
					<0.001 b
					0.88 c
					<0.001 d
T4, median (min–max), AU/ml = ~50 days after T2			0 (0–46)

Data presented as mean (SD) unless otherwise stated.

Abbreviations: AZA, azathioprine; BMI, body mass index; CNIs, calcineurin inhibitors; KTx, kidney transplantation; MMF, mycophenolate mofetil; MPA, mycophenolate sodium; mTORs, mammalian target of rapamycin inhibitors.

KTR COVID‐19(+) vs. KTR COVID‐19(−).

Control COVID‐19(+) vs. control COVID‐19(−).

KTR COVID‐19(+) vs. control COVID‐10(+).

KTR COVID‐19(−) vs. control COVID‐19(−).

At T1, the median concentration of S1/S2 IgGs in the 20 COVID‐19(+) was 56 [0; 205] AU/ml. No IgG was detectable in COVID‐19(−) individuals (Table 1). At T2, a response was observed in 19/20 controls, with significantly higher IgG titers in COVID‐19(+) compared to COVID‐19(−). In KTRs, no humoral response was observed in COVID‐19(−) whereas all COVID‐19(+) showed detectable IgG levels. The magnitude of serological response was not different between COVID‐19(+) KTRs and COVID‐19(+) controls (Table 1). At T3, all controls had measurable IgGs, with significantly higher titers in COVID‐19(+) vs. COVID‐19(−). In KTRs, IgGs were detectable in only 1/10 COVID‐19(−) (60 AU/ml), whereas IgG levels in COVID‐19(+) KTRs were similar to COVID‐19(+) controls (Table 1). An additional serological testing of the 10 COVID‐19(−) KTRs after 50 days [39; 121] post T2 was positive in 3/10, with median IgG titers of 30 AU/ml [15; 46]. From a longitudinal point of view, serum S1/S2 IgG levels in the 20 COVID‐19(+) KTR and non‐KTR individuals increased significantly from T1 to T2, with no further increase from T2 to T3. The kinetics was different in the 10 COVID‐19(−) controls, with significant increases from T1 to T2 and from T2 to T3.

As a whole, a history of COVID‐19 impacts the kinetics and the magnitude of S1/S2 IgG development post BNT162b2 vaccination in KTRs, as recently demonstrated by Cucchiari et al. We have no information about the cellular response post BNT162b2 vaccination in our cohort. Consistently with recent publications, SARS‐CoV‐2‐naïve KTRs have a poor serological response to BNT162b2 vaccine. , , One may not exclude that additional vaccine injections and/or a longer follow‐up may eventually elicit a full humoral response in KTRs. Still, given the current knowledge, KTRs with no history of PCR‐proven COVID‐19 should be advised to maintain the WHO sanitary recommendations against SARS‐CoV‐2 after BNT162b2‐based vaccination. By contrast, one single BNT162b2 injection might be sufficient in KTRs with detectable S1/S2 IgGs before vaccination.