SEROLOGICAL RESPONSE TO SARS-COV-2 VACCINES IN LIVER TRANSPLANT PATIENTS

Introduction. Solid organ transplant recipients were excluded from the pivotal clinical trials of COVID-19 vaccines. Therefore, the safety and efficacy data of the different types of available vaccines in this susceptible population is scarce. The goal of the present analysis was to evaluate the humoral response to the COVID-19 vaccines in orthotopic liver transplant (OLT) recipients. Methods. Participants were included from February to September 2021. No prioritized vaccination was performed for OLT patients, and they were included in the regular schedule according to age and place of residency. Controls were otherwise healthy people, mainly family members of patients. All subjects completed the full vaccination schemes, and blood samples were taken after at least 15 days of the complete vaccine doses. The samples were analyzed according to the manufacturer instructions using Liaison XL platform from DiaSorin, LIAISON® SARS-CoV-2 S1/S2 IgG (DiaSorin S.p.A., Italy), and SARS-COV-2 IgG II Quant (COV-2 IgG II) (Abbott Diagnostics, IL, USA). Results. In all, 187 participants (133 OLT, 54 controls, median age: 60 years, 58.8% women) were included for the analysis;74.3% had at least one comorbidity (31.6% had hypertension, 32.6% diabetes, 7% neoplasia, and 23% obesity). By vaccine brands, 50.3% received Pfizer-BioNTech, 13.9% received Oxford-AstraZeneca, 10.7% received Sinovac, 7.0% Cansino;16% Sputnik-V and 2.1% received Moderna. The serologic response in OLT patients was lower than in controls (median 549 AU/mL vs. 3450 AU/mL, respectively;p 0.001). A positive humoral response was found in 133 OLT individuals: 89.2% with Pfizer-BioNTech, 60% Oxford-AstraZeneca, 76.9% Sinovac, 55.6% Cansino, 68.2% Sputnik-V, and 100% with Moderna. In controls, only Cansino had a 75% humoral response;all other vaccines had a 100% response. In a multivariable model adjusted for relevant confounders, the antecedent of COVID-19 and Pfizer-BioNTech inoculation were associated positively with the serologic response, while the use of prednisone (compared with other immunosuppressants) interfere with this response. Conclusion. The serologic response to COVID-19 vaccines in OLT patients is lower than otherwise healthy controls. In these patients, the Pfizer-BioNTech vaccine was associated with a higher serologic response. Other variables significantly associated with the humoral response were the COVID-19 antecedent (positively) and prednisone exposure (negatively). At the moment, further analysis is necessary to determine whether this serological response is associated with SARS-COV2 infection or reinfection. (Figure Presented)

IN-HOSPITAL CASE FATALITY RATE DUE TO MODERATE-TO-SEVERE COVID-19 IN PATIENTS WITH CIRRHOSIS: A MULTICENTER COHORT STUDY

Background: The presence of comorbidities has been associated with worse outcomes in patients with SARS-CoV2 virus infection. It has been reported that patients with cirrhosis and COVID-19 showed higher mortality rates than patients without cirrhosis. This study aims to analyze the case fatality rate (CFR) in patients with cirrhosis and COVID-19, as well as the implications that this infection has on the incidence of acute decompensations. Methods: A multicenter prospective cohort study was conducted in 13 COVID-19 centers in Mexico. Patients with cirrhosis and COVID-19 were compared with randomly selected age- and sex-matched controls with COVID-19 without cirrhosis. The characteristics and development of decompensation in patients with cirrhosis were analyzed. Results: A total of 96 patients with cirrhosis and COVID-19 and 193 controls with COVID-19 were studied. Age (56.80 vs. 56.45 years, respectively;P=0.80) and male sex proportion (65.6% vs. 65.6%, respectively;P=0.98) was comparable between the two groups. Patients with cirrhosis and COVID-19 had a higher CFR than patients without cirrhosis (29.2% versus 19.2%, respectively, P=0.05) (Figure 1). There were no differences in the use of invasive mechanical ventilation, vasopressors, or the hospitalization length. The most common decompensations were worsening ascites (43%), encephalopathy (42%), and variceal bleeding (13%). Acute kidney injury occurred in 60% of patients with cirrhosis and 30% fulfill criteria of hepatorenal syndrome. Conclusion: Cirrhosis may impose a significant death risk factor in moderateto- severe COVID-19. Moreover, COVID-19 might be an important trigger of acute decompensation of cirrhosis, which could influence short-term CFR. (Figure Presented)

IMPACT OF SARS-COV-2 INFECTION ON RECIPIENTS OF LIVER TRANSPLANT. REPORT OF A MEXICAN COHORT

Introduction: SARS-CoV-2 has caused the first pandemic of the 21st century with a toll of more than 5 million deaths. Although Mexico is one of the most affected countries, no information regarding liver transplant (LT) recipients is available to date. A higher risk of developing COVID-19 has been reported for these subjects in the literature (cumulative incidence 837.41 cases/105 patients vs. 311.93 cases/105 patients). However, a lower mortality has also been reported (18% vs 27.0% among patients older than 60 years, with no deaths recorded in younger LT recipients). This work aims to further examine these trends. Methods: The study was performed in a single center of liver transplantation in Mexico City. The records of all the LT recipients above 18 years old with COVID-19 confirmed by reverse transcription-polymerase chain reaction assay (RT-PCR) between March 2020 and November 2021 were included. Demographic data, comorbidities, cause and date of LT, the immunosuppressive therapy (IT), vaccination status, severity, indication and availability of intensive care unit (ICU) beds, and mortality were extracted. The main outcome was death. Secondary outcomes were severity and need of ICU. Results: Seventy-four LT recipients with SARS-CoV-2 infection were considered. The median age was 54.5 years (45.0-61.3) and 39 patients were men (52.7%). The predominant etiology in our cohort was HCV (27.0%) followed by NASH (21.6%). Mean time from transplantation to infection was 56.2 weeks (33-80). Twenty-one patients had at least 1 vaccine dose at the time of infection (28.4%);15 had a complete scheme (20.2%). Twenty-one (28.4%) patients had severe COVID-19 (Table 1). Overall mortality was 8.10%. No IT treatment was associated with a better or worse prognosis for the whole cohort. Among the vaccinated patients, 4 (19%) had severe COVID-19 with a mean age of 61 years (59-64) and 3 died (mortality 14.3%);All of them had a complete vaccination scheme (1 with BNT162b2, 2 with ChAdOx1 nCoV19) and were taking mycophenolate mofetil (MMF). Among the unvaccinated, 17 patients had a severe illness (32.8%) (Figure 1), mean age of 55 years (50-63) and 3 died (mortality 5.6%). However, none of the latter had an ICU bed available. Conclusions: We present the characteristics of LT recipients with SARS-CoV-2 infection at the largest LT center in Mexico. Overall mortality (8%) was lower than that reported in other cohorts of LT recipients and no patient under 57 years old died. A significant numerical reduction in severe cases and the need for critical care was found among vaccinated patients. An association was found between the use of MMF and mortality among vaccinated patients SARS-CoV-2 vaccination should be encouraged and its access guaranteed among LT recipients. (Figure Presented) (Table Presented)

Unexpected better outcome in a liver transplant recipient with COVID-19: a beneficial effect of tacrolimus? / Evolución clínica en un receptor de trasplante de hígado con la COVID-19: ¿Un efecto benéfico del tacrolimus?

Coronavirus disease 2019 (COVID-19) is a serious respiratory illness caused by SARS-CoV-2. There is controversy about whether their immunosuppressive status is a risk factor or a protective factor for developing severe disease. We report herein the clinical outcome of three family members that had COVID-19 infection, presenting with and without different risk factors that have been described in more severe disease. Paradoxically, the patient with more risks of developing a severe disease, a 64-year-old woman, 2-years liver transplant recipient under treatment with tacrolimus, presented a similar outcome compared to the two other members of the family. She showed shorter hospitalization time, similar clinical outcome with fewer oxygen needs. The present clinical observation raises the question about the possible beneficial effect of tacrolimus in patients with COVID-19. Indeed, tacrolimus (FK-506) have an inhibitory effect on human coronaviruses by: 1) an antiviral effect by binding to the FK-506-binding proteins (FKBP) with a subsequent inhibition of their peptidyl-prolyl cis/trans isomerase (PPIase) activity, which seems to be important for the coronavirus life cycle; and 2) regulating the immune response by the inhibition of the activity of the nuclear factor of activated T-cells (NFAT) required for immunosuppression. The present observation states that liver recipients' patients with COVID-19 may not have worse outcomes when compared with other patients that have COVID-19 risk factors and puts in evidence the two mechanisms related to tacrolimus.

Pharmacologic management of patients with hepatic and pancreatic diseases that involve immunosuppressive therapies. Position statement within the framework of the SARS-CoV-2 (COVID-19) pandemic. / Manejo farmacológico de pacientes con enfermedades hepáticas y pancreáticas que involucran terapias inmunosupresoras. Posicionamiento en el marco de la pandemia de SARS-CoV-2 (COVID-19).

The coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) virus. COVID-19 affected more than 6million persons worldwide in fewer than 4 months, after the report of the first cases in China in December 2019. The relation of the disease caused by SARS-Cov-2 to immunosuppressive treatment used in different gastrointestinal disorders is uncertain, resulting in debate with regard to suspending immunosuppressive therapy to improve infection outcome. Said suspension implies the inherent risk for graft rejection or autoimmune disease exacerbation that can potentially worsen the course of the infection. Based on the presently available evidence, a treatment stance has been established for patients with gastrointestinal diseases that require immunosuppressive therapy.

Pharmacologic management of patients with hepatic and pancreatic diseases that involve immunosuppressive therapies. Position statement within the framework of the SARS-CoV-2 (COVID-19) pandemic

The coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. COVID-19 affected close to 2 million persons worldwide in fewer than 4 months, after the report of the first cases in China in December 2019. The relation of the disease caused by SARS-Cov-2 to immunosuppressive treatment used in different gastrointestinal disorders is uncertain, resulting in debate with regard to suspending immunosuppressive therapy to improve infection outcome. Said suspension implies the inherent risk for graft rejection or autoimmune disease exacerbation that can potentially worsen the course of the infection. Based on the presently available evidence, a treatment stance has been established for patients with gastrointestinal diseases that require immunosuppressive therapy. Resumen La enfermedad por coronavirus 2019 (COVID-19) es causada por el virus de Síndrome Respiratorio Agudo Grave - Coronavirus 2 (SARS-CoV-2). COVID 19 afectó cerca de 2 millones de personas en todo el mundo en menos de 4 meses posterior al reporte de los primeros casos en China en diciembre 2019. La relación que guarda la enfermedad por SARS-Cov-2 con el tratamiento inmunosupresor utilizado en diversos trastornos gastrointestinales es incierta, esto genera el debate sobre suspender el tratamiento inmunosupresor para mejorar el pronóstico de la infección, lo cual incluye el riesgo inherente de rechazo de injerto o agudización de enfermedades autoinmunes que potencialmente pudieran agravar el curso de la infección. En base a la evidencia disponible se logra establecer una postura de tratamiento en pacientes con enfermedades gastrointestinales que requieren terapia inmunosupresora.