The coronavirus disease 2019 (COVID-19) pandemic has had a major global impact on solid organ transplantation (SOT). An estimated 16% global reduction in transplant activity occurred over the course of 2020, most markedly impacting kidney transplant and living donor programs, resulting in substantial knock-on effects for waitlisted patients. The increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection risk and excess deaths in transplant candidates has resulted in substantial effort to prioritize the safe restart and continuation of transplant programs over the second year of the pandemic, with transplant rates returning towards prepandemic levels. Over the past 2 y, COVID-19 mortality in SOT recipients has fallen from 20%–25% to 8%–10%, attributed to the increased and early availability of SARS-CoV-2 testing, adherence to nonpharmaceutical interventions, development of novel treatments, and vaccination. Despite these positive steps, transplant programs and SOT recipients continue to face challenges. Vaccine efficacy in SOT recipients is substantially lower than the general population and SOT recipients remain at an increased risk of adverse outcomes if they develop COVID-19. SOT recipients and transplant teams need to remain vigilant and ongoing adherence to nonpharmaceutical interventions appears essential. In this review, we summarize the global impact of COVID-19 on transplant activity, donor evaluation, and patient outcomes over the past 2 y, discuss the current strategies aimed at preventing and treating SARS-CoV-2 infection in SOT recipients, and based on lessons learnt from this pandemic, propose steps the transplant community could consider as preparation for future pandemics.

https://journals.lww.com/transplantjournal/Fulltext/9900/The_Global_Impact_of_COVID_19_on_Solid_Organ.26.aspx

The Global Impact of COVID-19 on Solid Organ Transplantation: Two Years Into a Pandemic

http://www.thelancet.com/article/S1473309922006508/pdf

Alternative strategies to increase the immunogenicity of COVID-19 vaccines in kidney transplant recipients not responding to two or three doses of an mRNA vaccine (RECOVAC): a randomised clinical trial

https://doi.org/10.1016/j.vaccine.2022.08.065

SARS-CoV-2 anti-spike antibodies after a fourth dose of COVID-19 vaccine in adult solid-organ transplant recipients

An urgent need exists to improve the suboptimal COVID-19 vaccine response in kidney transplant recipients (KTRs). We aimed to compare three alternative strategies with a control single dose mRNA-1273 vaccination: a double vaccine dose, heterologous vaccination, and temporary discontinuation of mycophenolate mofetil or mycophenolic acid.This open-label randomised trial, done in four university medical centres in the Netherlands, enrolled KTRs without seroconversion after two or three doses of an mRNA vaccine. Between Oct 20, 2021, and Feb 2, 2022, 230 KTRs were randomly assigned block-wise per centre by a web-based system in a 1:1:1 manner to receive 100 μg mRNA-1273, 2 × 100 μg mRNA-1273, or Ad26.COV2-S vaccination. In addition, 103 KTRs receiving 100 μg mRNA-1273, were randomly assigned 1:1 to continue (mycophenolate mofetil+) or discontinue (mycophenolate mofetil-) mycophenolate mofetil or mycophenolic acid treatment for 2 weeks. The primary outcome was the percentage of participants with a spike protein (S1)-specific IgG concentration of at least 10 binding antibody units per mL at 28 days after vaccination, assessed in all participants who had a baseline measurement and who completed day 28 after vaccination without SARS-CoV-2 infection. Safety was assessed as a secondary outcome in all vaccinated patients by incidence of solicited adverse events, acute rejection or other serious adverse events. This trial is registered with ClinicalTrials.gov, NCT05030974 and is closed.Between April 23, 2021, and July 2, 2021, of 12 158 invited Dutch KTRs, 3828 with a functioning kidney transplant participated in a national survey for antibody measurement after COVID-19 vaccination. Of these patients, 1311 did not seroconvert after their second vaccination and another 761 not even after a third. From these seronegative patients, 345 agreed to participate in our repeated vaccination study. Vaccination with 2 × mRNA-1273 or Ad26.COV2-S was not superior to single mRNA-1273, with seroresponse rates of 49 (68%) of 72 (95% CI 56-79), 46 (63%) of 73 (51-74), and 50 (68%) of 73 (57-79), respectively. The difference with single mRNA-1273 was -0·4% (-16 to 15; p=0·96) for 2 × mRNA-1273 and -6% (-21 to 10; p=0·49) for Ad26.COV2-S. Mycophenolate mofetil- was also not superior to mycophenolate mofetil+, with seroresponse rates of 37 (80%) of 46 (66-91) and 31 (67%) of 46 (52-80), and a difference of 13% (-5 to 31; p=0·15). Local adverse events were more frequent after a single and double dose of mRNA-1273 than after Ad26.COV2-S (65 [92%] of 71, 67 [92%] of 73, and 38 [50%] of 76, respectively; p<0·0001). No acute rejection occurred. There were no serious adverse events related to vaccination.Repeated vaccination increases SARS-CoV-2-specific antibodies in KTRs, without further enhancement by use of a higher dose, a heterologous vaccine, or 2 weeks discontinuation of mycophenolate mofetil or mycophenolic acid. To achieve a stronger response, possibly required to neutralise new virus variants, repeated booster vaccination is needed.The Netherlands Organization for Health Research and Development and the Dutch Kidney Foundation. 

Background. The clinical effectiveness of coronavirus disease 2019 (COVID-19) vaccination in kidney transplant (KT) recipients is lower than in the general population. Methods. From April to October 2021, 481 KT recipients with COVID-19, included in the Spanish Society of Nephrology COVID-19 Registry, were analyzed. Data regarding vaccination status and vaccine type were collected, and outcomes of unvaccinated or partially vaccinated patients (n = 130) were compared with fully vaccinated patients (n = 351). Results. Clinical picture was similar and survival analysis showed no differences between groups: 21.7% of fully vaccinated patients and 20.8% of unvaccinated or partially vaccinated died (P = 0.776). In multivariable analysis, age and pneumonia were independent risk factors for death, whereas vaccination status was not related to mortality. These results remained similar when we excluded patients with partial vaccination, as well as when we analyzed exclusively hospitalized patients. Patients vaccinated with mRNA-1273 (n = 213) showed a significantly lower mortality than those who received the BNT162b2 vaccine (n = 121) (hazard ratio: 0.52; 95% confidence interval, 0.31-0.85; P = 0.010). Conclusions. COVID-19 severity in KT patients has remained high and has not improved despite receiving 2 doses of the mRNA vaccine. The mRNA-1273 vaccine shows higher clinical effectiveness than BNT162b2 in KT recipients with breakthrough infections. Confirmation of these data will require further research taking into account the new variants and the administration of successive vaccine doses.

https://journals.lww.com/transplantjournal/Fulltext/9900/Breakthrough_Infections_Following_mRNA_SARS_CoV_2.3.aspx

Breakthrough Infections Following mRNA SARS-CoV-2 Vaccination in Kidney Transplant Recipients

http://www.amjtransplant.org/article/S1600613522299195/pdf

Heterologous Ad.26.COV2.S versus homologous BNT162b2/mRNA-1273 as a third dose in solid organ transplant recipients seronegative after two-dose mRNA vaccination

S olid organ transplant recipients (SOTRs) have sub-optimal antibody responses to 2-dose severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, with some improvement after receiving a third dose. 1,2 Further boosting with a fourth dose (D4) has been suggested in small cohorts of SOTRs, but the evidence remains limited and restricted to kidney recipients with poor preceding seroresponse. 3-5 To expand on these early observations, we updated our original case series of 18 participants to a more granular evaluation of 128 participants, diverse in organ type and pre-D4 vaccine response. One-hundred twenty-eight SOTRs without prior reported SARS-CoV-2 infection who reported 4 doses of SARS-CoV-2 vaccine were identified from a previously described national, prospective observational cohort. 1 Semiquantitative anti-spike (anti-S) serologic testing was performed using the Roche Elecsys anti-SARS-CoV-2 S enzyme immunoassay, which tests for the receptor-binding domain (RBD), or the EUROIMMUN Anti-SARS-CoV-2 enzyme immunoassay, which tests for the S1 domain of the SARS-CoV-2 spike pro-tein,

https://journals.lww.com/transplantjournal/Fulltext/9900/Antibody_Response_to_a_Fourth_Dose_of_SARS_CoV_2.29.aspx

Jake D Kim

Papers

Heterologous Ad.26.COV2.S versus homologous BNT162b2/mRNA-1273 as a third dose in solid organ transplant recipients seronegative after two-dose mRNA vaccination

Antibody Response to a Fourth Dose of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: An Update

Improved Antibody Response After a Fifth Dose of a SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: A Case Series.

6-mo Antibody Kinetics and Durability After 3 Doses of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: A Case Series.

Humoral and Cellular Immune Response to a Third Dose of SARS-CoV-2 Vaccine in Kidney Transplant Recipients Taking Belatacept.