An Analysis of Serological Response and Infection Outcomes Following Oxford-AstraZeneca (AZD1222) and Pfizer-BioNTech (mRNA BNT162b2) SARS-CoV-2 Vaccines in Kidney and Kidney-pancreas Transplants.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 is associated with high mortality among transplant recipients. Comparative data that define humoral responses to the Oxford-AstraZeneca (AZ) and BNT162b2 (Pfizer-BioNTech) vaccines are limited. METHODS: We recruited 920 kidney transplant patients receiving at least 1 dose of severe acute respiratory syndrome coronavirus 2 vaccine, excluding patients with virus pre-exposure. Serological status was determined with the COVID-SeroKlir ELISA (Kantaro-EKF Diagnostics). Patients with a corrected antibody level of <0.7 AU/mL were considered seronegative. RESULTS: Four hundred ninety-five AZ and 141 Pfizer patients had a sample analyzed after first dose and 593 after second dose (346 AZ versus 247 Pfizer). After first dose, 25.7% of patients seroconverted (26.6% AZ, 22.8% Pfizer). After second dose, 148 (42.8%) of AZ seroconverted compared with 130 (52.6%) of Pfizer (P = 0.02; hazard ratio, 1.48; 95% confidence interval, 1.07-2.06). When negative responders were excluded, Pfizer patients were shown to have significantly higher response than AZ patients (median 2.6 versus 1.78 AU/mL, P = 0.005).Patients on mycophenolate had a reduced seroconversion rate (42.2% versus 61.4%; P < 0.001; hazard ratio, 2.17) and reduced antibody levels (0.47 versus 1.22 AU/mL, P = 0.001), and this effect was dose dependent (P = 0.05). Prednisolone reduced the seroconversion from 58.2% to 43.6% (P = 0.03) among Pfizer but not AZ recipients. Regression analysis showed that antibody levels were reduced by older age (P = 0.002), mycophenolate (P < 0.001), AZ vaccine (versus Pfizer, P = 0.001), and male gender (P = 0.02). Sixteen of 17 serious postvaccine infections occurred to patients who did not seroconvert. CONCLUSIONS: Both seroconversion and antibody levels are lower in AZ compared with Pfizer vaccinated recipients following 2 vaccine doses. Mycophenolate was associated with lower antibody responses in a dose-dependent manner. Serious postvaccine infections occurred among seronegative recipients.

SARS-CoV-2 Infection Can Lead to an Increase in Tacrolimus Levels in Renal Transplant Patients: A Cohort Study.

The aim of this study is to evaluate the effect of SARS-CoV-2 infection on serum tacrolimus levels. Tacrolimus levels of 34 transplant patients diagnosed with SARS-CoV-2 in 2020 were compared with their pre-infection values and those of a control group with alternative infections. 20 out of 34 (59%) had high levels. At diagnosis, median tacrolimus level in the SARS-CoV-2 cohort was 9.6 µg/L (2.7-23) compared to 7.9 µg/L in the control group (p = 0.07, 95% CI for difference -0.3-5.8). The ratio of post-infection to pre-infection tacrolimus values was higher in the SARS-CoV-2 group (1.7) compared to the control group (1.25, p = 0.018, 95% CI for difference 0.08-0.89). The acute kidney injury rate was 65% (13 of 20) in SARS-CoV-2 patients with a level >8 µg/dl, compared to 29% (4 of 14) in those with lower levels (p = 0.037). Median length of stay was 10 days among SARS-CoV-2 infected patients with high tacrolimus levels compared to 0 days in the rest (p = 0.04). Four patients with high levels died compared to 2 in the control group. Clinicians should be aware of this potential effect on tacrolimus levels and take appropriate measures.

SARS-CoV-2 in Kidney Transplant and Waitlisted Patients During the First Peak: The Welsh Experience.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) global pandemic has led to many health care services, including transplantation, being temporarily suspended. For transplantation to safely recommence, there is a need to understand the effects of SARS-CoV-2 in transplant and waitlist patients. We identified 21 patients with proven SARS-CoV-2 infection (13 transplant; 8 waitlist) during the first peak of coronavirus disease 2019 in Wales. Median patient age was 57 years (range, 24-69), 62% were male, and all were white. Median body mass index was 29 kg/m2 (range, 22-42), and 81% had 1 or more significant comorbidities. Median time from transplant to SARS-CoV-2 infection was 135 months (range, 9-356) and median time since being listed was 17.5 months (range, 5-69) for waitlisted patients. Seventeen patients were admitted to the hospital (81%), 18% (n = 3) in intensive care unit, and 5 patients died (4 transplant recipients and 1 waitlist patient; 24%). Two of the 4 transplant patients who died had recent malignancy. Although the mortality of hospitalized transplant patients was high, their infection rate of 0.87% meant that the overall mortality of transplant patients due to SARS-CoV-2 was low and comparable to that of patients on the waitlist. These data provide confidence in restarting the transplant program, provided that a series of measures aiming to avoid infections in newly transplanted patients are taken.