Predictors of Humoral Response to mRNA COVID19 Vaccines in Kidney Transplant Recipients: A Longitudinal Study—The COViNEPH Project

Dębska-Ślizień, Alicja; Ślizień, Zuzanna; Muchlado, Marta; Kubanek, Alicja; Piotrowska, Magdalena; Dąbrowska, Małgorzata; Tarasewicz, Agnieszka; Chamienia, Andrzej; Biedunkiewicz, Bogdan; Renke, Marcin; Tylicki, Leszek

doi:10.3390/vaccines9101165

Cited by 41 publications

(46 citation statements)

References 30 publications

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“…In line with the available literature, our data favours the usage of mRNA-1273 over BNT162b2 in KTR [ 16 , 17 ] as well as HD [ 14 , 15 ] to ensure optimal response. As of to date, no such recommendation has found entry in international, national or scientific guidelines on vaccination strategies.…”

Section: Discussionsupporting

confidence: 89%

“…Factors/conditions discussed to predispose non-response and a severe COVID-19 course in these patients are advanced age, comorbidities, the uremic environment in HD, and immunosuppressive medication in KTR. Factors that are associated with non-response in the existing literature include age [ 9 , 10 ], diabetes [ 11 ], lower hemoglobin [ 9 ], lower eGFR (per mL/min/1.73 m 2 ) [ 12 ], longer HD vintage [ 13 ], BNT162b2 instead of mRNA-1273 [ 14 , 15 , 16 , 17 ], treatment with antimetabolites [ 18 ] or belatacept [ 19 , 20 ], treatment with rituximab [ 21 ] or high dose cortisone in the last year [ 9 ], and triple immunosuppression (calcineurin inhibitor plus antimetabolite plus steroid) [ 9 ]. The extent and impact of the abovementioned factors are poorly understood, and possible mitigation strategies are lacking.…”

Section: Introductionmentioning

confidence: 99%

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Antibody Response to mRNA Vaccines against SARS-CoV-2 with Chronic Kidney Disease, Hemodialysis, and after Kidney Transplantation

Buchwinkler

Solagna

Messner

et al. 2021

JCM

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Most trials on mRNA vaccines against SARS-CoV-2 did not include patients with chronic kidney disease (CKD), hemodialysis (HD) patients, or kidney transplant recipients (KTR). However, those patients have a higher risk for a severe course of COVID-19 disease and mortality. Available literature has demonstrated a reduced efficacy of mRNA vaccines in HD patients and KTR, while data on CKD patients is scarce. Additionally, factors associated with non-response are poorly understood and not well characterized. We assessed antibody (AB) response (n = 582, 160 CKD patients, 206 patients on HD, 216 KTR) after the administration of two doses of a mRNA-vaccine with either BNT162b2 or mRNA-1273. AB measurements were carried out after a median of 91 days after first vaccinations, demonstrating non-response in 12.5% of CKD patients, 12.1% of HD patients, and 50% of KTR. AB titers were significantly higher in CKD patients than in HD patients or KTR. Factors associated with non-response were treated with rituximab in CKD patients, the use of calcineurin inhibitors in HD patients and older age, and the use of BNT162b2, mycophenolic acid, or glucocorticoids and lower hemoglobin levels in KTR. This study contributes to the understanding of the extent and conditions that predispose for non-response in patients with impaired kidney function.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Antibody Response to mRNA Vaccines against SARS-CoV-2 with Chronic Kidney Disease, Hemodialysis, and after Kidney Transplantation

Buchwinkler

Solagna

Messner

et al. 2021

JCM

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“…Overall, 82 studies were included for meta-analysis ( table 1 , supplementary table 2). 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 …”

Section: Resultsmentioning

confidence: 99%

Efficacy of covid-19 vaccines in immunocompromised patients: systematic review and meta-analysis

Lee

Wong

Chai

et al. 2022

BMJ

302

234

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Objective To compare the efficacy of covid-19 vaccines between immunocompromised and immunocompetent people. Design Systematic review and meta-analysis. Data sources PubMed, Embase, Central Register of Controlled Trials, COVID-19 Open Research Dataset Challenge (CORD-19), and WHO covid-19 databases for studies published between 1 December 2020 and 5 November 2021. ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched in November 2021 to identify registered but as yet unpublished or ongoing studies. Study selection Prospective observational studies comparing the efficacy of covid-19 vaccination in immunocompromised and immunocompetent participants. Methods A frequentist random effects meta-analysis was used to separately pool relative and absolute risks of seroconversion after the first and second doses of a covid-19 vaccine. Systematic review without meta-analysis of SARS-CoV-2 antibody titre levels was performed after first, second, and third vaccine doses and the seroconversion rate after a third dose. Risk of bias and certainty of evidence were assessed. Results 82 studies were included in the meta-analysis. Of these studies, 77 (94%) used mRNA vaccines, 16 (20%) viral vector vaccines, and 4 (5%) inactivated whole virus vaccines. 63 studies were assessed to be at low risk of bias and 19 at moderate risk of bias. After one vaccine dose, seroconversion was about half as likely in patients with haematological cancers (risk ratio 0.40, 95% confidence interval 0.32 to 0.50, I 2 =80%; absolute risk 0.29, 95% confidence interval 0.20 to 0.40, I 2 =89%), immune mediated inflammatory disorders (0.53, 0.39 to 0.71, I 2 =89%; 0.29, 0.11 to 0.58, I 2 =97%), and solid cancers (0.55, 0.46 to 0.65, I 2 =78%; 0.44, 0.36 to 0.53, I 2 =84%) compared with immunocompetent controls, whereas organ transplant recipients were 16 times less likely to seroconvert (0.06, 0.04 to 0.09, I 2 =0%; 0.06, 0.04 to 0.08, I 2 =0%). After a second dose, seroconversion remained least likely in transplant recipients (0.39, 0.32 to 0.46, I 2 =92%; 0.35, 0.26 to 0.46), with only a third achieving seroconversion. Seroconversion was increasingly likely in patients with haematological cancers (0.63, 0.57 to 0.69, I 2 =88%; 0.62, 0.54 to 0.70, I 2 =90%), immune mediated inflammatory disorders (0.75, 0.69 to 0.82, I 2 =92%; 0.77, 0.66 to 0.85, I 2 =93%), and solid cancers (0.90, 0.88 to 0.93, I 2 =51%; 0.89, 0.86 to 0.91, I 2 =49%). Seroconversion was similar between people with HIV and immunocompetent controls (1.00, 0.98 to 1.01, I 2 =0%; 0.97, 0.83 to 1.00, I 2 =89%). Systematic review of 11 studies showed that a third dose of a covid-19 mRNA vaccine was associated with seroconversion among vaccine non-responders with solid cancers, haematological cancers, and immune mediated inflammatory disorders, although response was variable in transplant recipients and inadequately studied in people with HIV and those receiving non-mRNA vaccines. Conclusion Seroconversion rates after covid-19 vaccination were significantly lower in immunocompromised patients, especially organ transplant recipients. A second dose was associated with consistently improved seroconversion across all patient groups, albeit at a lower magnitude for organ transplant recipients. Targeted interventions for immunocompromised patients, including a third (booster) dose, should be performed. Systematic review registration PROSPERO CRD42021272088.

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“…Other factors have been independently correlated with rate of response elicited by vaccination, including corticosteroid treatment and type of mRNA vaccination [32,33].…”

Section: Discussionmentioning

confidence: 99%

Immune Response to BNT162b2 in Solid Organ Transplant Recipients: Negative Impact of Mycophenolate and High Responsiveness of SARS-CoV-2 Recovered Subjects against Delta Variant

et al. 2021

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The immunogenicity of severe acute respiratory syndrome 2 virus (SARS-CoV-2) vaccines in immunocompromised patients remains to be further explored. Here, we evaluated the immunogenicity elicited by complete vaccination with BNT162b2 vaccine in solid organ transplant recipients (SOTRs). A cohort of 110 SOTRs from Northern Italy were vaccinated with two doses of BNT162b2 mRNA vaccine and prospectively monitored at baseline and after 42 days. Both SARS-CoV-2 naïve and recovered subjects were included. Humoral response elicited by vaccination, including SARS-CoV-2 neutralizing antibodies (SARS-CoV-2 NT Abs), was evaluated; additionally, ex-vivo ELISpot assay was performed for the quantification of Spike-specific T-cell response. Results were compared with those obtained in a cohort of healthy subjects. In a subset of patients, humoral and T-cell responses against delta variant were also evaluated. Less than 20% of transplanted subjects developed a positive humoral and cell-mediated response after complete vaccination schedule. Overall, median levels of immune response elicited by vaccination were significantly lower with respect to controls in SARS-CoV-2 naïve transplant, but not in SARS-CoV-2 recovered transplanted patients. Additionally, a significant impairment of both humoral and cell-mediated response was observed in mycophenolate-treated patients. Positive delta-SARS-CoV-2 NT Abs levels were detected in almost all the SARS-CoV-2 recovered subjects but not in previously uninfected patients. Our study supports previous observations of a low level of seroconversion after vaccination in transplanted patients.

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Predictors of Humoral Response to mRNA COVID19 Vaccines in Kidney Transplant Recipients: A Longitudinal Study—The COViNEPH Project

Cited by 41 publications

References 30 publications

Antibody Response to mRNA Vaccines against SARS-CoV-2 with Chronic Kidney Disease, Hemodialysis, and after Kidney Transplantation

Antibody Response to mRNA Vaccines against SARS-CoV-2 with Chronic Kidney Disease, Hemodialysis, and after Kidney Transplantation

Efficacy of covid-19 vaccines in immunocompromised patients: systematic review and meta-analysis

Immune Response to BNT162b2 in Solid Organ Transplant Recipients: Negative Impact of Mycophenolate and High Responsiveness of SARS-CoV-2 Recovered Subjects against Delta Variant

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