Insufficient response to mRNA SARS-CoV-2 vaccine and high incidence of severe COVID-19 in kidney transplant recipients during pandemic

et al. 2022

Transpl Int

This article gives a personal, historical, account of the impact of the COVID-19 pandemic on transplantation services. The content is based on discussions held at two webinars in November 2020, at which kidney transplantation experts from prestigious institutions in Europe and the United States reflected on how the pandemic affected working practices. The group discussed adaptations to clinical care (i.e., ceasing, maintaining and re-starting kidney transplantations, and cytomegalovirus infection management) across the early course of the pandemic. Discussants were re-contacted in October 2021 and asked to comment on how transplantation services had evolved, given the widespread access to COVID-19 testing and the roll-out of vaccination and booster programs. By October 2021, near-normal life and service delivery was resuming, despite substantial ongoing cases of COVID-19 infection. However, transplant recipients remained at heightened risk of COVID-19 infection despite vaccination, given their limited response to mRNA vaccines and booster dosing: further risk-reduction strategies required exploration. This article provides a contemporaneous account of these different phases of the pandemic from the transplant clinician’s perspective, and provides constructive suggestions for clinical practice and research.

Section: Post Script: October 2021 Reflections From the Groupmentioning

confidence: 99%

Impact of COVID-19 on Global Kidney Transplantation Service Delivery: Interim Report

Papalois¹,

Kotton

et al. 2022

Transpl Int

“…2 At the same time the mortality of SOT recipients acquiring COVID-19 is unacceptably high, with rates up to 20% reported in registries. 3,4 Recent data from the United Kingdom collected between September 2020 and August 2021 show an unadjusted COVID-19 case fatality rate of 9.8% in SOT. The vaccination with two doses did not prevent infections in SOT recipients and increased 28-day survival in COVID-19 infected SOTs only marginally from 88.8% to 91.8%.…”

Section: Introductionmentioning

confidence: 99%

Serological Response to Three, Four and Five Doses of SARS-CoV-2 Vaccine in Kidney Transplant Recipients

Osmanodja

Ronicke

et al. 2022

Preprint

Background Mortality from COVID-19 among kidney transplant recipients (KTR) is high, and their response to three vaccinations against SARS-CoV-2 is strongly impaired. Methods We retrospectively analyzed serological response of up to five doses of SARS-CoV-2 vaccine in KTR from December 27, 2020, until December 31, 2021. Particularly, the influence of different dose adjustment regimens for mycophenolic acid (MPA) on serological response to fourth vaccination was analyzed. Results In total, 4.277 vaccinations against SARS-CoV-2 in 1.478 patients were analyzed. Serological response was 19.5% after 1.203 basic immunizations, and increased to 29.4%, 55.6%, and 57.5% in response to 603 third, 250 fourth and 40 fifth vaccinations, resulting in a cumulative response rate of 88.7%. In patients with calcineurin inhibitor and MPA maintenance immunosuppression, pausing MPA and adding 5 mg prednisolone equivalent before the fourth vaccination increased serological response rate to 75% in comparison to no dose adjustment (52%) or dose reduction (46%). Belatacept-treated patients had a response rate of 8.7% (4/46) after three vaccinations and 12.5% (3/25) after four vaccinations. Conclusion Except for belatacept-treated patients, repeated SARS-CoV-2 vaccination of up to five times effectively induces serological response in kidney transplant recipients. It can be enhanced by pausing MPA at the time of vaccination.

“…Specifically, reduced immunogenicity of SARS-CoV-2 vaccines leads to a low rate of sufficient serological response -below 50% after the third dose of vaccine -and lower levels of antibodies in KTR (8)(9)(10). The result is a lack of protection against COVID-19 in KTR as compared with healthy individuals (11,12). A third vaccination was recommended early on for KTR in order to increase immune response (13).…”

Section: Introductionmentioning

confidence: 99%

Declining Course of Humoral Immune Response in Initially Responding Kidney Transplant Recipients after Repeated SARS-CoV-2 Vaccination

Ronicke

Osmanodja

et al. 2022

Preprint

Immunogenicity of SARS-CoV-2 vaccines in kidney transplant recipients is limited, resulting in inadequately low serological response rates and low immunoglobulin (Ig) levels, correlating with reduced protection against death and hospitalization from COVID-19. We retrospectively examined the time course of anti-SARS-CoV-2 Ig antibody levels after up to five repeated vac-cinations in 644 previously nonresponding kidney transplant recipients. Using anti SARS-CoV-2 IgG/IgA ELISA and the total Ig ECLIA assays, we compare antibody levels at 1 month with levels at 2 and 4 months, respectively. Additionally, we correlate the measurements of the used assays. Between 1 and 2 months, and between 1 and 4 months, mean anti-SARS-CoV-2 Ig levels in re-sponders decreased by 14% and 25%, respectively, depending on the assay. Absolute Ig values and time course of antibody levels and showed high interindividual variability. Ig levels de-creased by at least 20% in 77 of 148 paired samples with loss of sufficient serological protection over time occurring in 18 out of 148 (12.2%). IgG ELISA and total Ig ECLIA assays showed a strong positive correlation (Kendall's tau=0.78), yet the two assays determined divergent results in 99 of 751 (13.2%) measurements. IgG and IgA assays showed overall strong correlation but divergent results in 270 of 1.173 (23.0%) cases and only weak correlation of antibody levels in positive samples. Large interindividual variability and significant loss of serological protection after 4 months supports repeated serological sampling and consideration of shorter vaccination intervals in kidney transplant recipients.