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

Abstract

International recommendations on coronavirus disease 2019 (COVID-19) vaccine distribution have given priority to immunocompromised patients, including kidney transplant recipients (KTRs).1Centers for Disease Control and Prevention. COVID-19 vaccination program operational guidance. Available at:.https://www.cdc.gov/vaccines/covid-19/covid19-vaccination-guidance.htmlDate accessed: March 1, 2021Google Scholar,2ECD. COVID-19 vaccination and prioritisation strategies in the EU/EEA. Available at:.https://www.ecdc.europa.eu/sites/default/files/documents/COVID-19-vaccination-and-prioritisation-strategies.pdfDate accessed: March 1, 2021Google Scholar 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).Table 1Characteristics of kidney transplant recipients, according to serologic response after the first dose of the Moderna mRNA-1273 vaccineCharacteristicsEntire cohort (n=241)aThe patient who developed coronavirus disease 2019 after the first injection was excluded from the analysis.SARS-CoV-2 seronegative patients (n=215)SARS-CoV-2 seropositive patients (n=26)P valueMissing dataAge, yr57.7 (49.3–67.6)57.7 (49.6–67.7)58.4 (43.3–66.9)0.510Male sex156 (64.7)142 (66.1)14 (53.9)0.280BMI, kg/m225.7 (22.6–29.5)25.7 (22.8–29.4)26.4 (21.9–29.9)0.732Time from kidney transplantation, yr6.4 (2.9–13)5.8 (2.8–11.9)15.4 (8.6–25.9)<0.0012First transplantation202 (83.8)176 (81.8)26 (100)0.010Deceased donor192 (79.6)172 (80)20 (76.9)0.80ABO group0.022 O94 (39.3)82 (38.5)12 (46.2) A101 (42.3)93 (43.7)8 (30.8) B30 (12.6)29 (13.6)1 (3.9) AB14 (5.9)9 (4.2)5 (19.2)Induction treatment0.0017 Anti-thymocyte globulin138 (59.5)127 (60.8)11 (47.8)9 Anti-CD2588 (37.9)80 (38.3)8 (34.8) No induction6 (2.6)2 (1)4 (17.4)CNI0.060 Tacrolimus133 (55.2)124 (57.7)9 (34.6) Ciclosporin82 (34)69 (32.1)14 (50) No CNI26 (10.8)22 (10.2)4 (15.4)MMF/MPA191 (79.3)177 (82.3)14 (53.9)0.0020Azathioprine7 (2.9)4 (1.86)3 (11.5)0.030mTOR inhibitors35 (14.5)32 (14.9)3 (11.6)10Steroids142 (58.9)133 (61.9)9 (34.6)0.010Belatacept9 (3.8)9 (4.2)00.260eGFR, ml/min per 1.73 m251.6 (38.1–68)51 (37.9–66.5)64.9 (39.9–72.2)0.080Serum creatinine, μmol/L118 (99–158)120 (101–159)104 (85–134)0.050BMI, 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 (%).a The patient who developed coronavirus disease 2019 after the first injection was excluded from the analysis. Open table in a new tab 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 (%). 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.3Jackson L.A. Anderson E.J. Rouphael N.G. et al.An mRNA vaccine against SARS-CoV-2 — preliminary report.N Engl J Med. 2020; 383: 1920-1931Crossref PubMed Scopus (1796) Google Scholar,4Prendecki M. Clarke C. Brown J. et al.Effect of previous SARS-CoV-2 infection on humoral and T-cell responses to single-dose BNT162b2 vaccine.Lancet. 2021; 397: 1178-1181Abstract Full Text Full Text PDF PubMed Scopus (186) Google Scholar 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. Immune response to SARS-CoV-2 infection and vaccination in patients receiving kidney replacement therapyKidney InternationalVol. 99Issue 6PreviewIn this issue of Kidney International, the initial experience regarding the immunogenicity of prior coronavirus disease 2019 (COVID-19) infection and the response to the COVID-19 vaccines among patients on maintenance dialysis and kidney transplant recipients is summarized. Preliminary data suggest that there is durability of immune response after COVID-19 infection. Although immune response to the first dose of vaccine is less in infection-naïve patients than healthy individuals in both groups, after the second vaccine dose a significant portion of patients receiving maintenance dialysis develop robust antibody titers, whereas kidney transplant recipients show a less-strong immune response. Full-Text PDF Risk factors associated with poor response to COVID-19 vaccination in kidney transplant recipientsKidney InternationalVol. 100Issue 5PreviewThe 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). Full-Text PDF Low immunization rates among kidney transplant recipients who received 2 doses of the mRNA-1273 SARS-CoV-2 vaccineKidney InternationalVol. 99Issue 6PreviewThe efficacy rates of vaccines to prevent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been specifically investigated in kidney transplant recipient (KTRs). Preliminary results suggest that among KTRs who received the first injection of an mRNA-based vaccine, the antibody response is weak.1,2 This study reports on the immunization rates of KTRs who received 2 doses of the mRNA-1273 SARS-CoV-2 vaccine (Moderna).3 Full-Text PDF