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

Abstract

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.1Grupper A, Rabinowich L, Schwartz D, et al. Reduced humoral response to mRNA SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients without prior exposure to the virus [published online ahead of print April 18, 2021]. Am J Transplant. 2021. https://doi.org/10.1111/ajt.16615Google Scholar 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 1Characteristics of the cohortParametersControls n = 20Kidney transplant recipients n = 20p valueCOVID–19 (–) n = 10COVID–19 (+) n = 10COVID–19 (–) n = 10COVID–19 (+) n = 10Age, years51.5 (10.5)45.1 (10.4)49.7 (13.8)52.7 (13.8)0.53Female gender, n (%)3 (30)4 (40)5 (50)6 (60)0.57BMI, kg/m224.58 (3.28)25.68 (2.95)26.45 (3.84)26.45 (4.67)0.71Time from KTx, months121.7 (106.0)77.8 (41.8)0.57Deceased donor, n (%)8 (80)9 (90)0.53CNIs, n (%)10 (100)10 (100)1.00Antimetabolite, n (%)10 (100)7 (70)0.37mTOR inhibitors, n (%)0 (0)1 (10)1.00Methylprednisolone, n (%)4 (40)5 (50)1.00Serum creatinine, mg/dl1.08 (0.29)1.55 (0.61)0.13Delay between COVID-19 and vaccination, days154.2 (107.1)158.2 (77.0)0.44Evolution of anti-S1/S2 IgG titerT1, median (min–max), AU/ml = first BNT162b2 injection0 (0)35 (0–98)0 (0)107 (0–205)<0.001aKTR COVID-19(+) vs. KTR COVID-19(–).<0.001bControl COVID-19(+) vs. control COVID-19(–).0.031cKTR COVID-19(+) vs. control COVID-10(+).1.00dKTR COVID-19(–) vs. control COVID-19(–).T2, median (min–max), AU/ml = second BNT162b2 injection35.5 (0–118)1520 (79–7290)0 (0)1131 (94–9040)<0.001aKTR COVID-19(+) vs. KTR COVID-19(–).<0.001bControl COVID-19(+) vs. control COVID-19(–).0.59cKTR COVID-19(+) vs. control COVID-10(+).<0.001dKTR COVID-19(–) vs. control COVID-19(–).T3, median (min–max), AU/ml = ~15 days after T2263 (153–2090)2300 (1470–6250)0 (0–60)2105 (212–18300)<0.001aKTR COVID-19(+) vs. KTR COVID-19(–).<0.001bControl COVID-19(+) vs. control COVID-19(–).0.88cKTR COVID-19(+) vs. control COVID-10(+).<0.001dKTR COVID-19(–) vs. control COVID-19(–).T4, median (min–max), AU/ml = ~50 days after T20 (0–46)Note: 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.a KTR COVID-19(+) vs. KTR COVID-19(–).b Control COVID-19(+) vs. control COVID-19(–).c KTR COVID-19(+) vs. control COVID-10(+).d KTR COVID-19(–) vs. control COVID-19(–). Open table in a new tab Note: 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. 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.2Boyarsky BJ Werbel WA Avery RK et al.Antibody response to 2-dose SARS-CoV-2 mRNA vaccine series in solid organ transplant recipients [published online ahead of print May 5, 2021].JAMA. 2021; 325 (https://doi.org/10.1001/jama.2021.7489.): 2204Crossref PubMed Scopus (589) Google Scholar 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.1Grupper A, Rabinowich L, Schwartz D, et al. Reduced humoral response to mRNA SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients without prior exposure to the virus [published online ahead of print April 18, 2021]. Am J Transplant. 2021. https://doi.org/10.1111/ajt.16615Google Scholar,3Benotmane I Gautier-Vargas G Cognard N et al.Low immunization rates among kidney transplant recipients who received 2 doses of the mRNA-1273 SARS-CoV-2 vaccine [published online ahead of print April 20, 2021].Kidney Int. 2021; 99 (S0085-2538[21]00389-6): 1498-1500Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar,4Cucchiari D, Egri N, Bodro M, et al. Cellular and humoral response after mRNA-1273 SARS-CoV-2 vaccine in kidney transplant recipients [published online ahead of print May 26, 2021]. Am J Transplant. 2021. Am J Transplant. 2021. https://doi.org/10.1111/ajt.16701Google Scholar 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 recommendations5World Health Organization. Coronavirus disease (COVID-19) advice for the public. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public. Updated May 12, 2021. Accessed June 9, 2021.Google Scholar 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.

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