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

Mortality from COVID-19 among kidney transplant recipients (KTR) is high, and their response to three vaccinations against SARS-CoV-2 is strongly impaired. We retrospectively analyzed the serological response of up to five doses of the SARS-CoV-2 vaccine in KTR from 27 December 2020 until 31 December 2021. Particularly, the influence of the different dose adjustment regimens for mycophenolic acid (MPA) on serological response to fourth vaccination was analyzed. In total, 4277 vaccinations against SARS-CoV-2 in 1478 patients were analyzed. Serological response was 19.5% after 1203 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 the serological response rate to 75% in comparison to the 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. 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.

Predictors of Serological Response to SARS-CoV-2 Vaccination in Kidney Transplant Patients: Baseline Characteristics, Immunosuppression, and the Role of IMPDH Monitoring.

Immunosuppression increases the risk of severe coronavirus disease 2019 (COVID-19). Morbidity and mortality of this disease in kidney transplant patients are higher than in the general population. As the vaccination response of transplant patients is weak, serological monitoring was performed. In this cohort study, we analyzed the determinants of vaccination response. All patients had no history of COVID-19. With anti-spike IgG monitoring, 148 responders and 415 non-responders were identified. We compared both groups using multivariate analyses of the cohort and a sub-cohort of mycophenolic-acid-treated patients. We investigated the influence of patient characteristics, immunosuppression, and erythrocyte inosine monophosphate dehydrogenase (IMPDH) activity. In responders, the time after transplantation was longer (13.5 vs. 8.5 years), the glomerular filtration rate was higher (56.9 vs. 47.8 mL/min/1.73 m2), and responders were younger (53.0 vs. 57.4 years). Heterologous vaccination was more effective than homologous vaccination. Calcineurin inhibitors plus mycophenolate reduced the seroconversion rate. No seroconversion was observed in belatacept patients. In mycophenolate-treated patients, IMPDH activity was a significantly better predictor of response than mycophenolate dose (AUC 0.84 vs. 0.62, p < 0.001). Immunosuppression strongly affects vaccine response. Modifications to immunosuppression should be considered in order to facilitate this response. Erythrocyte IMPDH activity can be used to guide mycophenolate treatment.

First diagnosis of thrombotic thrombocytopenic purpura after SARS-CoV-2 vaccine - case report.

BACKGROUND: We report a case of a 25-year-old male patient, who developed acquired thrombotic thrombocytopenic purpura (aTTP) after receiving a first dose of mRNA-based SARS-CoV-2 vaccine Spikevax (mRNA-1273, Moderna Biotech, USA). While this is the first case in literature describing a case of aTTP after receiving the Spikevax vaccine, there are two other cases after mRNA-based Covid-19 vaccine and two after adenoviral SARS-CoV-2 vaccine. CASE PRESENTATION: The patient presented with persisting malaise, fever, headache, word-finding difficulties, nausea, vomiting, petechial bleeding, and hematuria 13 days after receiving a first dose of vaccination. Laboratory testing showed low platelet count, Coombs-negative hemolytic anemia, and mild acute kidney injury. We excluded vaccine induced immune thrombotic thrombocytopenia (VITT) as another important differential diagnosis and the final diagnosis was established after ADAMTS-13 (A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif, member 13) activity was found to be < 1% (reference range > 40%) and ADAMTS-13 antibodies being 72.2 IU/L (reference range < 12 IU/L). We initiated empiric therapy of plasmapheresis and corticosteroids on admission and started caplacizumab the day after. The patient's thrombocyte count normalized 3 days after admission, hemolysis and acute kidney injury resolved after 2 weeks. The patient received 2 doses of rituximab (1 g each) after the diagnosis of immune TTP was established. One month after the initial presentation, the patient is in good overall condition, but still receives daily caplacizumab due to ADAMTS-13 activity of < 1%. CONCLUSIONS: Low platelet count after vaccination against SARS-CoV-2 has gained attraction after vaccine-induced immune thrombotic thrombocytopenia (VITT) has been described as a rare but severe complication of adenoviral-based vaccines. Thrombotic thrombocytopenic purpura (TTP) is an important differential diagnosis, but there are only few reports of TTP following SARS-CoV-2 vaccination. Despite pathophysiological and clinical differences of both entities, diagnostic uncertainty can result in the acute setting, since they share main symptoms such as headache and neurological alterations in addition to thrombocytopenia. In difference to other cases reported, this patient developed first symptoms of TTP as early as 4 days after vaccination, which suggests that vaccination merely acted as trigger for occult TTP, instead of truly inducing an autoimmunological process.