key: cord-0702675-7g25vwe3 authors: Toapanta, Nestor; Bestard, Oriol; Soler, María José title: SARS CoV-2 vaccination in patients receiving kidney replacement therapies: where are we now with the protective immune response? date: 2021-07-21 journal: Nephrol Dial Transplant DOI: 10.1093/ndt/gfab227 sha: 16e0bb0a5e79943fa046030ec946643274589908 doc_id: 702675 cord_uid: 7g25vwe3 nan In the new pandemic COVID-19 era that started in 2020, early studies demonstrated that patients with advanced chronic kidney disease (CKD) such as hemodialysis and kidney transplant patients are at high risk of mortality from SARS CoV-2 [1] [2] [3] [4] [5] . For this reason several scientific societies taking care of these patients have recommended to prioritize their vaccination 6,7,8 . The higher mortality rate in this group of patients may be in part ascribed to a dysregulation in their immune system 9 . However, studies in COVID-19 convalescent immunosuppressed solid organ transplant (SOT) recipients have showed the capacity of these patients to achieve a robust adaptive immune response, similar to immunocompetent convalescent individuals, despite a concerning initial delay, thus suggesting that an optimal immune response may be also achieved among these high-risk patient population after vaccination 10 . Vaccination against SARS CoV-2 infection has raised hopes for ending the pandemic protecting high risk population such as haemodialysis or kidney transplant patients. Notably, studies reported by Dagan et al. demonstrated that the BNT162b2 (Pfizer-BioNTech) vaccine against SARS CoV-2 is effective for preventing symptomatic COVID-19 and reducing the rates of severe COVID19 infections in the general population, being the antibody response of up to 94% after a second dose 11 . However little is known about the immune response in patients receiving kidney replacement because few of these patients have been included in the initial clinical trials on vaccines against SARS CoV-2 and most importantly, because the actual follow-up of these patients after vaccination is short. Patients undergoing haemodialysis are known to have frequent infections, as well as a suboptimal response to vaccines, in part due to alterations in both innate and adaptive immunity 12 Transplantation 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 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 against a control group composed of 95 health care worked after receiving two doses of the Transplantation 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 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 4 who received mRNA-1273 were more likely to develop an antibody response than those receiving BNT162b2 (69% vs 31%, respectively; adjusted IRR, 2.15 [95% CI, 1.29-3.57]; P = 0.003) 23 . Nevertheless, the serological immune response to a second dose of mRNA SARS-CoV-2 vaccine was detectable in the majority of transplant recipients, although patients without a response after the first dose had generally low antibody levels. Likewise, after dose, a poorer humoral response was persistently associated with use of antimetabolite immunosuppression 23 Transplantation 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 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 5 patients(30.4%) showed detectable T-cell frequencies on day 28, and 1 month after the second injection, respectively 29 (Table1). Recently, Boyarsky et al evaluated 12 transplant recipients who received the Janssen vaccine, observing in only 2 of 12 patients a detectable anti-RBD (receptor-binding domain) antibody response, being significantly lower than that observed among recipients of the mRNA vaccine series, with significantly lower titers than those of the mRNA group, suggesting that the Janssen vaccine may result in an even lower humoral immunity than the mRNA vaccines in these patients 30 In conclusion, the evidence to date suggests that the majority of renal replacement patients remain at high risk for COVID-19 despite vaccination. Among haemodialysis patients the seroconversion after the administration of the two doses of the vaccine ranges from 80 to 96%, being the eldest patients at especial higher risk of developing a suboptimal antibody response. Of especial concern seem to be the kidney transplant patient population, in whom seroconversion rates after the administration of the two doses varies between 22 -37.5%. Maintenance immunosuppression therapy with antimetabolites, the co-stimulation blocker belatacept, as well as older age and worse renal function seem to be risk factors for a low None declared. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 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 Transplantation 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 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 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 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 BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data. Lancet (London, England). Transplantation 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 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 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 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 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 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 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 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 Chronic kidney disease is a key risk factor for severe COVID-19: a call to action by the ERA-EDTA CKD is a key risk factor for COVID-19 mortality BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting Uremia impairs monocyte and monocyte-derived dendritic cell function in hemodialysis patients Infections in hemodialysis: A concise review. Part II: Blood transmitted viral infections Humoral Response to the Pfizer BNT162b2 Vaccine in Patients Undergoing Maintenance Hemodialysis Hemodialysis Patients Show a Highly Diminished Antibody Response after COVID-19 mRNA Vaccination Compared to Healthy Controls Neutralizing SARS-CoV-2 antibody response in dialysis patients after the first dose of the BNT162b2 mRNA Covid-19 vaccine. The war is far from being won Experience with SARS-COV-2 BNT162b2 mRNA vaccine in dialysis patients Efficacy of the BNT162b2 mRNA Covid-19 Vaccine in a hemodialysis cohort. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association -European Renal Association Seroprevalence of antibody to S1 spike protein following vaccination against COVID-19 in patients receiving hemodialysis: a call to arms Immunogenicity of a Single Dose of SARS-CoV-2 Messenger RNA Vaccine in Solid Organ Transplant Recipients Antibody Response to 2-Dose SARS-CoV-2 mRNA Vaccine Series in Solid Organ Transplant Recipients Reduced humoral response to mRNA SARS-Cov-2 BNT162b2 vaccine in kidney transplant recipients without prior exposure to the virus. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Antibody response to mRNA SARS-CoV-2 vaccine among kidney transplant recipients -Prospective cohort study. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases Weak anti-SARS-CoV-2 antibody response after the first injection of an mRNA COVID-19 vaccine in kidney transplant recipients Impaired Humoral Response in Renal Transplant Recipients to SARS-CoV-2 Vaccination with BNT162b2 (Pfizer-BioNTech) Poor Anti-SARS-CoV-2 Humoral and T-cell Responses After 2 Injections of mRNA Vaccine in Kidney Transplant Recipients Treated with Belatacept Antibody Response to the Janssen COVID-19 Vaccine in Solid Organ Transplant Recipients Impact and effectiveness of mRNA Page 9 of 14 Nephrology Dialysis Transplantation