TTS Masterclasses continue: Immunosuppression series begins June 30

Delivered by the world’s best known and regional experts, each Masterclass includes presentations by an international and a regional expert to bring perspective to the topic, highlight differences and opportunities, and bolster active discussions.

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Selected Publications by TTS Education Committee. This week's selection made by Dr. Enver Akalin.

Prospective Clinical, Virologic, and Immunologic Assessment of COVID-19 in Transplant Recipients.

Marinelli T et al.
Transplantation. 2021 Jun 18. doi: 10.1097/TP.0000000000003860. PMID: 34149003
In the 161 solid organ transplant recipients diagnosed with COVID-19, the spectrum of disease ranged from asymptomatic infection (4.3%) to hospitalization (60.6%), supplemental oxygen requirement (43.1%), mechanical ventilation (22.7%) and death (15.6%). Increasing age (OR:1.031 95%CI 1.001-1.062, p=0.046) and >=2 comorbid conditions (OR:3.690 95%CI 1.418-9.615, p=0.007) were associated with need for supplemental oxygen. Allograft rejection was uncommon (3.7%) despite immunosuppression modification. Antibody response at >=14 days post-symptoms onset was present in 90% (anti-RBD) and 76.7% (anti-NP) with waning of anti-NP titers and stability of anti-RBD over time. Median duration of nasopharyngeal positivity was 10.0 days (IQR: 5.5-18.0) and shedding beyond 30 days was observed in 6.7% of patients.

Impaired Humoral and Cellular Immunity after SARS-CoV2 BNT162b2 (Tozinameran) Prime-Boost Vaccination in Kidney Transplant Recipients

Arne Sattler et al.
J Clin Invest. 2021 Jun 8:150175. doi: 10.1172/JCI150175. PMID: 34101623
The study cohort consisted of 39 healthy controls, 39 age-matched kidney transplant (KTx) recipients treated with standard immunosuppressive medication, and 26 individuals with kidney failure on hemodialysis (HD). Spike S1 domain specific IgG reactivity was noted in all 39 healthy controls, 22/26 (84.62 %) dialysis patients, but only in 1/39 (2.6 %) KTx patients at day 8±1 after booster immunization with minor changes until day 23±5. Neutralizing antibodies were detected in all 39 healthy individuals, 20/26 (76.92 %) dialysis patients, but in none of the 6 KTx patients examined. Although most transplanted patients mounted spike-specific T helper cell responses, frequencies were significantly reduced compared to controls and dialysis patients, accompanied by a broad impairment in effector cytokine production, memory differentiation and activation-related signatures. Spike-specific CD8+ T cell responses were less abundant than their CD4+ counterparts in healthy controls and hemodialysis patients and almost undetectable in transplant patients.

Safety and Immunogenicity of a Third Dose of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: A Case Series

William Werbel et al.
Ann Intern Med 2021 Jun 15. doi: 10.7326/L21-0282 PMID: 34125572
Thirty patients reported receiving a third dose of vaccine. During the initial vaccination, 57% of the 30 patients received 2 doses of the 162b2 vaccine (Pfizer/BioNTech), and 43% received 2 doses of the mRNA1273 vaccine (Moderna). 24 patients had no and 6 had low antibodies against the spike protein at a median of 9 days (IQR, 2 to 33 days) before they received their third dose of vaccine. Patients received the third dose of vaccine a median of 67 days (IQR, 54 to 81 days) after the second dose of their initial vaccine series; 15 patients received the Ad26.COV2.S vaccine (Johnson & Johnson/Janssen), 9 received the mRNA-1273 vaccine (Moderna), and 6 received the 162b2 vaccine (Pfizer/BioNTech). Of the 6 patients with low-positive antibody titers before the third dose, all had high-positive antibody titers after the third dose. In contrast, of the 24 patients with negative antibody titers before the third dose, only 6 (25%) had high-positive antibody titers after the third dose. Two (8%) had low-positive antibody titers, and 16 (67%) remained negative.

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