The RECOVAC Immune-response Study: The Immunogenicity, Tolerability, and Safety of COVID-19 Vaccination in Patients With Chronic Kidney Disease, on Dialysis, or Living With a Kidney Transplant

Abstract

Background. In kidney patients COVID-19 is associated with severely increased morbidity and mortality. A comprehensive comparison of the immunogenicity, tolerability, and safety of COVID-19 vaccination in different cohorts of kidney patients and a control cohort is lacking. Methods. This investigator driven, prospective, controlled multicenter study included 162 participants with chronic kidney disease (CKD) stages G4/5 (eGFR < 30 mL/min/1.73m2), 159 participants on dialysis, 288 kidney transplant recipients, and 191 controls. Participants received 2 doses of the mRNA-1273 COVID-19 vaccine (Moderna). The primary endpoint was seroconversion. Results. Transplant recipients had a significantly lower seroconversion rate when compared with controls (56.9% versus 100%, P < 0.001), with especially mycophenolic acid, but also, higher age, lower lymphocyte concentration, lower eGFR, and shorter time after transplantation being associated with nonresponder state. Transplant recipients also showed significantly lower titers of neutralizing antibodies and T-cell responses when compared with controls. Although a high seroconversion rate was observed for participants with CKD G4/5 (100%) and on dialysis (99.4%), mean antibody concentrations in the CKD G4/5 cohort and dialysis cohort were lower than in controls (2405 [interquartile interval 1287-4524] and 1650 versus 3186 [1896-4911] BAU/ mL, P = 0.06 and P < 0.001, respectively). Dialysis patients and especially kidney transplant recipients experienced less systemic vaccination related adverse events. No specific safety issues were noted. Conclusions. The immune response following vaccination in patients with CKD G4/5 and on dialysis is almost comparable to controls. In contrast, kidney transplant recipients have a poor response. In this latter, patient group development of alternative vaccination strategies are warranted.

Immunogenicity and Risk Factors Associated With Poor Humoral Immune Response of SARS-CoV-2 Vaccines in Recipients of Solid Organ Transplant

“…Among the studies analyzed, the weighted mean (range) seroconversion rate after 1 dose of mRNA vaccine was 10.4% (0%-37.9%) for antispike antibodies (18 studies 12 , 33 , 35 , 37 , 40 , 41 , 42 , 44 , 48 , 51 , 52 , 55 , 57 , 69 , 71 , 76 , 103 , 105 ) and 4.1% (0%-5.9%) for neutralizing antibodies (2 studies 12 , 69 ) ( Figure 2 ). The mean (range) antibody testing time was 25.5 (21-28) days after the first dose.…”

“…The weighted mean (range) total seroconversion rate after 2 doses of mRNA COVID-19 vaccines was 44.9% (0%-79.1%) for antispike antibodies (53 studies 10 , 11 , 12 , 13 , 14 , 32 , 35 , 36 , 38 , 40 , 41 , 42 , 43 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 69 , 70 , 71 , 74 , 79 , 80 , 82 , 84 , 86 , 88 , 91 , 92 , 93 , 94 , 95 , 97 , 102 , 103 , 105 ) and 22.6% (0%-47.5%) for neutralizing antibodies (8 studies 12 , 49 , 62 , <...>…”

“…The BNT162b2 vaccine had a weighted mean (range) seroconversion rate of 44% (range 0%-79.1%) for antispike antibodies (36 studies 11 , 13 , 35 , 40 , 41 , 42 , 43 , 45 , 46 , 47 , 49 , 50 , 51 , 52 , 53 , 54 , 56 , 57 , 60 , 62 , 63 , 64 , 65 , 66 , 67 , 69 , 70 , 80 , 84 , 86 , 88 , 91 , 92 , 93 , 102 , 105 ) and 15.3% (0%-35%) for neutralizing antibodies (5 studies 49 , 62 , 65 , 67 , 69 ). The mRNA-1273 vaccine demonstrated a weighted mean (range) seroconversion rate of 51.4% (29.9%-76.2%) for antispike antibodies (7 studies 10 , 12 , 32 , 48 , 79 , 103 , 105 ) and a mean of 26.9% for neutralizing antibodies (1 study 12 ). The mean (range) antibody testing time after the second dose was 31.9 (8-81) days for all vaccines, 33.8 (8-81) days for the BNT162b2 vaccine, and 25.2 (14-28) days for the mRNA-1273 vaccine.…”

“…Receipt of a deceased donor organ was associated with lower seroconversion rates compared with living donor status (pOR, 0.66 [95% CI, 0.53-0.83]; P < .001; I 2 = 0%) (10 studies 32 , 45 , 47 , 49 , 56 , 59 , 66 , 84 , 94 , 103 ) ( Table , Figure 3 ; eFigure 1 in the Supplement ). Time from transplantation to vaccination was associated with seroconversion rate.…”

“…A total of 25 studies 32 , 45 , 46 , 49 , 50 , 53 , 56 , 57 , 59 , 62 , 63 , 64 , 66 , 70 , 74 , 79 , 80 , 82 , 88 , 91 , 92 , 93 , 94 , 95 , 103 reported on antimetabolite use at the time of vaccine administration, which was associated with lower seroconversion rates (pOR, 0.21 [95% CI, 0.14-0.29]; P < .001; I 2 = 70%) ( Table , Figure 3 ; eFigure 1 in the Supplement ). A total of 21 studies 10 , 32 , 45 , 46 , 49 , 50 , 53 , 56 , 57 , 62 , 63 , 64 , 66 , 70 , 74 , 80 , 82 , 84 , 88 , 93 , 103 reported active use of mammalian (mechanistic) target of rapamycin (mTOR) inhibitors, which was associated with higher seroconversion rates (pOR, 1.46 [95% CI, 1.02-2.08]; P = .04; I 2 = 42%) ( Table , Figure 3 ; eFigure...…”