Humoral and cellular immune responses to Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine in adolescents with liver transplantation: Single center experience

Background Immune responses to vaccines against severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 are variable. In the absence of disease, youngsters are expected to better react to vaccines than adults. Nevertheless, chronic immunosuppression in transplant recipients may impair their capability to generate protection. We aim to explore immune responses after BNT162b2 SARS-CoV-2 vaccination in our cohort of young liver-transplanted patients. Methods A prospective study of adolescent liver-transplanted patients (n=33) in the long-term follow-up was performed. Immune responses after receiving Pfizer-BioNTech BNT162b2 vaccine were analyzed at two time-points: baseline and 30 days after the second dose. Humoral responses were measured by fluoroenzyme-immunoassay and T-cell responses by interferon-γ-release assay. Post-vaccine coronavirus disease (COVID-19) events were recorded by a survey. Results Pre-vaccine SARS-CoV-2-specific antibodies were undetectable in 27/32 (84.4%), negative/indeterminate in 3/32 (9.4%) and positive in 2/32 (6.3%) patients. Cellular responses at baseline were negative in 12/18 (66.6%), positive in 3/18 (16.6%) and indeterminate in 3/18 (16.6%) recipients. None of the baseline positives recalled any symptoms. Post-vaccine antibodies were detected in all patients and 92.6% showed levels >816 BAU/mL. Twenty (71.4%) recipients had positive T-cell responses. Regarding post-vaccine SARS-Cov-2 infection, 10 (30.3%) patients reported COVID-19 without hospitalization and 21 (63.6%) did not notify any infection. Negative and positive cell-response groups after vaccination showed statistically significant differences regarding COVID-19 cases (62.5% vs 22.2%, respectively;p=0.046). Conclusions Adolescents and young adults with liver transplantation responded to SARS-Cov-2 vaccine, generating both humoral and cellular responses. Recipients developing cellular responses after vaccination had a lower incidence of COVID-19.

Pediatric transplantation in Europe during the COVID-19 pandemic: Early impact on activity and healthcare.

The current pandemic SARS-CoV-2 has required an unusual allocation of resources that can negatively impact chronically ill patients and high-complexity procedures. Across the European Reference Network on Pediatric Transplantation (ERN TransplantChild), we conducted a survey to investigate the impact of the COVID-19 outbreak on pediatric transplant activity and healthcare practices in both solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT). The replies of 30 professionals from 18 centers in Europe were collected. Twelve of 18 centers (67%) showed a reduction in their usual transplant activity. Additionally, outpatient visits have been modified and restricted to selected ones, and the use of telemedicine tools has increased. Additionally, a total of 14 COVID-19 pediatric transplanted patients were identified at the time of the survey, including eight transplant recipients and six candidates for transplantation. Only two moderate-severe cases were reported, both in HSCT setting. These survey results demonstrate the limitations in healthcare resources for pediatric transplantation patients during early stages of this pandemic. COVID-19 disease is a major worldwide challenge for the field of pediatric transplantation, where there will be a need for systematic data collection, encouraging regular discussions to address the long-term consequences for pediatric transplantation candidates, recipients, and their families.

Epidemiological pattern, incidence, and outcomes of COVID-19 in liver transplant patients.

BACKGROUND & AIMS: The incidence and outcomes of coronavirus disease 2019 (COVID-19) in immunocompromised patients are a matter of debate. METHODS: We performed a prospective nationwide study including a consecutive cohort of liver transplant patients with COVID-19 recruited during the Spanish outbreak from 28 February to 7 April, 2020. The primary outcome was severe COVID-19, defined as the need for mechanical ventilation, intensive care, and/or death. Age- and gender-standardised incidence and mortality ratios (SIR and SMR) were calculated using data from the Ministry of Health and the Spanish liver transplant registry. Independent predictors of severe COVID-19 among hospitalised patients were analysed using multivariate Cox regression. RESULTS: A total of 111 liver transplant patients were diagnosed with COVID-19 (SIR = 191.2 [95% CI 190.3-192.2]). The epidemiological curve and geographic distribution overlapped widely between the liver transplant and general populations. After a median follow-up of 23 days, 96 patients (86.5%) were admitted to hospital and 22 patients (19.8%) required respiratory support. A total of 12 patients were admitted to the ICU (10.8%). The mortality rate was 18%, which was lower than in the matched general population (SMR = 95.5 [95% CI 94.2-96.8]). Overall, 35 patients (31.5%) met criteria of severe COVID-19. Baseline immunosuppression containing mycophenolate was an independent predictor of severe COVID-19 (relative risk = 3.94; 95% CI 1.59-9.74; p = 0.003), particularly at doses higher than 1,000 mg/day (p = 0.003). This deleterious effect was not observed with calcineurin inhibitors or everolimus and complete immunosuppression withdrawal showed no benefit. CONCLUSIONS: Being chronically immunosuppressed, liver transplant patients have an increased risk of acquiring COVID-19 but their mortality rates are lower than the matched general population. Upon hospital admission, mycophenolate dose reduction or withdrawal could help in preventing severe COVID-19. However, complete immunosuppression withdrawal should be discouraged. LAY SUMMARY: In liver transplant patients, chronic immunosuppression increases the risk of acquiring COVID-19 but it could reduce disease severity. Complete immunosuppression withdrawal may not be justified. However, mycophenolate withdrawal or temporary conversion to calcineurin inhibitors or everolimus until disease resolution could be beneficial in hospitalised patients.