High prevalence of asymptomatic SARS-CoV-2 infection in a cohort of liver transplant recipients in central Italy

Asymptomatic subjects account for 25 to 45% of SARS-CoV-2 infections, and in particular, subjects on mild immunosuppressive therapy may have symptoms masked and could spread virus for an extended period of time. To determine the cumulative incidence of symptomatic and asymptomatic SARS-CoV-2 infections and associated risk factors, we conducted a prospective clinical and serological survey in a cohort of 278 liver transplant recipients (LTRs) from Central Italy. Three different serology tests were performed every 4 months in 259 LTRs between April 2020 and April 2021: one based on raw extract of whole SARS-CoV-2 virus and two on specific viral antigens (nucleoprotein and receptor binding domain) to detect specific IgG, IgM and IgA. Hundred fifteen LTRs who reported symptoms or close contact with a SARS-CoV-2-positive subject, or had a positive serological result underwent molecular testing by standard screening procedures (RT-PCR on naso-pharyngeal swab). Thirty-one past or active SARS-CoV-2 infections were identified: 14 had positive molecular test (64% symptomatic), and 17 had positive serology only (18% symptomatic). SARS-CoV-2 infection was not statistically related to gender, age, obesity, diabetes, renal impairment, type of anti-rejection therapy or time from transplant. Asymptomatic SARS-CoV-2 cases (61.3%) were more frequent in males and in those with glomerular filtrate rate >50 ml/min. Overall, the addition of repeated serology to standard diagnostic molecular protocols increased detection of SARS-CoV-2 infection from 5.1% to 10.9%. Anti-SARS-CoV-2 seroprevalence among our LTRs (11.2%) is comparable to the general population of Central Italy, considered a medium-impact area. Only one asymptomatic subject (6%) was found to carry SARS-CoV-2 in respiratory tract at the time of serological diagnosis.Copyright © 2021 The Authors

Inferior Liver Transplant Outcomes during early COVID-19 pandemic in United States

Background:: Since its declaration as a global pandemic on March11th 2020, COVID-19 has had a significant effect on solid-organ transplantation. The aim of this study was to analyze the impact of COVID-19 on Liver transplantation (LT) in United States. Method(s):: We retrospectively analyzed the United Network for Organ Sharing database regarding characteristics of donors, adult-LT recipients, and transplant outcomes during early-COVID period (March 11- September 11, 2020) and compared them to pre-COVID period (March 11 - September 11, 2019). Result(s):: Overall, 4% fewer LTs were performed during early-COVID period (4107 vs 4277). Compared to pre-COVID period, transplants performed in early-COVID period were associated with: increase in alcoholic liver disease as most common primary diagnosis (1315 vs 1187, P< 0.01), higher MELD score in the recipients (25 vs 23, P<0.01), lower time on wait-list (52 vs 84 days, P<0.01), higher need for hemodialysis at transplant (9.4 vs 11.1%, P=0.012), longer distance from recipient hospital (131 vs 64 miles, P<0.01) and higher donor risk index (1.65 vs 1.55, P<0.01). Early-COVID period saw increase in rejection episodes before discharge (4.6 vs 3.4%, P=0.023) and lower 90-day graft/patient survival (90.2 vs 95.1 %, P<0.01;92.2 vs 96.5 %, P<0.01). In multivariable cox-regression analysis, early-COVID period was the independent risk factor for graft failure at 90-days post-transplant (Hazard Ratio 1.77, P<0.01). Conclusion(s):: During early-COVID period in United States, overall LT decreased, alcoholic liver disease was primary diagnosis for LT, rate of rejection episodes before discharge was higher and 90-days post-transplant graft survival was lower.Copyright © 2022 The Author(s)

Durability of Immune Response after Application of a Third Dose of SARS-CoV-2 Vaccination in Liver Transplant Recipients.

Immunogenicity after SARS-CoV-2 vaccination is known to be impaired in liver transplant (LT) recipients, but the results after the application of a third dose show significant improvement in seroconversion rates. In the general population, the antibody response wanes over the course of time after two doses of the vaccination, but seems to be more robust after the application of three doses. Still, the durability of the antibody response in LT recipients who receive a third dose of SARS-CoV-2 vaccination has not been analyzed yet. We therefore assessed antibody responses in a total of 300 LT recipients and observed antibody titers for six months each after patients had received the second and the third doses of the vaccination, explicitly excluding all patients who had suffered from SARS-CoV-2 infection. The initial antibody response was compared to a control group of 122 healthcare workers. After the application of two doses of the vaccination, 74% of LT recipients (158 out of 213) developed antibodies against SARS-CoV-2; this result depended significantly on whether the patients were taking the medication mycophenolate mofetil, and on the age of the patients. Antibody titers declined significantly within six months from 407 BAU/mL (IQR: 0-1865) to 105 BAU/mL (IQR: 0-145) (p ≤ 0.001), but increased after the application of the third vaccine dose in 92% of patients (105 out of 114), showing an antibody response (p ≤ 0.001). After a further six-month period, despite showing a decline from 2055 BAU/mL (IQR: 500 to >2080) to 1805 BAU/mL (IQR: 517 to >2080), the waning of antibody titers was not significant (p = 0.706), and antibody durability appeared to be more robust than that after the second dose. In conclusion, our study confirms the high efficacy of the application of a third dose of SARS-CoV-2 vaccination in LT recipients, and a reasonably sustained humoral response with superior durability in comparison to antibody kinetics after the application of the second dose of the vaccination.

Reduced Neutralization Efficacy against Omicron Variant after Third Boost of BNT162b2 Vaccine among Liver Transplant Recipients.

The immune responses of liver transplant (LT) recipients after the third boost of the BNT162b2mRNA vaccine improved. This study evaluates the durability of the immune response of LT recipients after the third boost, its predictors, and the impact of emerging variants. The receptor-binding domain IgG was determined at median times of 22 (first test) and 133 days (second test) after the administration of the third boost. IgG antibody titers > 21.4 BAU/mL were defined as a positive response. The neutralization efficacies of the vaccine against the wild-type, Omicron, and Delta variants were compared in the first test. The 59 LT recipients were of a median age of 61 years (range 25−82); 53.5% were male. Following administration of the third dose, the positive immune response decreased from 81.4% to 76.3% between the first and second tests, respectively, (p < 0.0001). The multivariate analysis identified CNI monotherapy (p = 0.02) and hemoglobin > 12 g/dL (p = 0.02) as independent predictors of a maintained positive immune response 133 days after the third dose. The geometric mean titers of Omicron neutralization were significantly lower than the wild-type and Delta virus (21, 137, 128, respectively; p < 0.0001). The immune response after the third BNT162b2mRNA vaccine dose decreased significantly in LT recipients. Further studies are required to evaluate the efficacy of the fourth vaccine dose and the durability of the immune response.

Clinical Outcomes of SARS-CoV-2 Breakthrough Infections in Liver Transplant Recipients during the Omicron Wave.

At the start of the pandemic, liver transplant recipients (LTR) were at high risk of developing severe COVID-19. Here, the outcomes of breakthrough infections in fully vaccinated LTR (n = 98) during the Omicron wave were assessed. In most patients, a mild disease course was observed, but 11 LTR (11.2%) required hospitalization for COVID-19-related complications. All patients survived. The LTR requiring hospitalization were older (67 years vs. 54 years; p < 0.001), had a higher Charlson comorbidity index (9 vs. 5; p < 0.001), and a lower anti-S RBD titer (Roche Elecsys) prior to infection (508.3 AU/mL vs. 2044 AU/mL; p = 0.03). Long-lasting symptoms for ≥4 weeks were reported by 37.5% of LTR (30/80). Risk factors in LTR included female sex (p = 0.01; Odds Ratio (OR) = 4.92 (95% confidence interval (CI) (1.5-16.5)) and dyspnea (p = 0.009; OR = 7.2 (95% CI (1.6-31.6)) during infection. Post-infection high anti-S RBD antibody levels were observed in LTR, and healthy controls (HC), while the cellular immune response, assessed by interferon-gamma release assay (EUROIMMUN), was significantly lower in LTR compared with HC (p < 0.001). In summary, in fully vaccinated LTR, SARS-CoV-2 breakthrough infections during the Omicron wave led to mild disease courses in the majority of patients and further boosted the humoral and cellular hybrid anti-SARS-CoV-2-directed immune response. While all patients survived, older and multimorbid LTR with low baseline antibody titers after vaccination still had a substantial risk for a disease course requiring hospitalization due to COVID-19-related complications.

High Immune Response Rate to the Fourth Boost of the BNT162b2 Vaccine against the Omicron Variants of Concern among Liver Transplant Recipients.

The immune response of liver transplant (LT) recipients to a third dose of the BNT162b2 mRNA vaccine significantly waned after four months. We aimed to evaluate the immune response and breakthrough infection rates of a fourth dose against the Omicron variants among LT recipients. LT recipients who had no past or active SARS-CoV-2 infection and received three doses of the BNT162b2mRNA vaccine were included. Of the 73 LT recipients, 50 (68.5%) received a fourth dose. The fourth dose was associated with a significantly higher positive immune response than the third dose. Receptor-binding domain (RBD) IgG and Omicron BA.1 and BA.2 neutralizing antibodies were determined at a median of 132 and 29 days after the third and fourth vaccines. They were 345 binding antibody units per milliliter (BAU/mL) vs. 2118 BAU/mL (p < 0.0001), 10 vs. 87 (p < 0.0001), and 15 vs. 149 (p = 0.001), respectively. Breakthrough infections were documented among nine (18%) LT recipients after the fourth dose and among seven (30.4%) patients following the third dose (p = 0.2); 93.5% of breakthrough infections were mild. The infection rate after the fourth dose was higher among diabetic vs. nondiabetic recipients (33.3% vs. 6.9%, respectively; p = 0.02). Further studies are needed to evaluate additional factors influencing the breakthrough infection rate among LT recipients.

Study of Adherence to Medication in Pediatric Liver Diseases ("SAMPLD" Study) in Indian Children.

Background/objectives: Adherence to medication(s) is an essential component of holistic management in any chronic disease including in post liver transplant (LT) patients. Thus, this study aimed to assess adherence to medications in Indian pediatric liver disease patients (including post LT recipients) and to identify variables affecting its occurrence. Methods: A cross-sectional study was conducted among pediatric (<18 years of age) subjects with Wilson disease (WD) and autoimmune liver disease (AILD) along with post LT recipients from May 2021 to October 2021. Structured tools using prevalidated questionnaires (Medication adherence measure and the Child & Adolescent Adherence to Medication Questionnaire) were used to collect data related to nonadherence prevalence (based on missed and late doses) and factors influencing the adherence. Results: A total of 152 children were included in the study (WD 39.5%, AILD 32.9%, and post LT 27.6%). Prevalence of missed and late dose nonadherence (at a cut-off of ≥20%) was 12.5% and 16.4%, respectively. Older age (odd's ratio/O.R 1.185), stay in a rural area (O.R 5.08), and barriers like bad taste of medication (O.R 4.728) and hard to remember the medication (O.R 7.180) were independently associated with nonadherence (P < 0.05). Conclusions: Overall, nonadherence was seen in 12-16%, i.e., around one-sixth of the patients, with least nonadherence seen in post LT recipients (0-2.4%). Older age of the patient, rural place of stay and personal barriers like hard to remember/forgetfulness and bad medication taste were identified as factors independently leading to nonadherence.

COMPARISON OF BLOOD PARAMETERS IN LIVER TRANSPLANT PATIENTS WITH AND WITHOUT COVID-19 INFECTION

The available data on COVID-19 infection in liver transplant (LT) recipients are not conclusive and are limited to several case series. Transplant recipients are considered as “clinically extremely vulnerable” sub-population for COVID-19 because of lifelong immunosuppressive therapy and their higher rate of underlying comorbidities. We collected data from a Bulgarian liver transplant program at a single center for adult recipients of LT who were followed up from May, 2020, through May, 2022 despite the pandemic environment. The current study aims analyzing the statistically significant differences in over 50 biochemical blood parameters between cohorts of liver transplant patients with SARS-CoV-2 infection and LT patients without symptoms of infection © 2022. Academic Publications

Clinical outcomes of coronavirus disease 2019 in liver transplant recipients.

BACKGROUND: Liver transplant patients are at higher risk of infection due to immunosuppression. Whether liver transplant recipients are also more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and will have worse outcomes than the general population if they develop coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 is a topic of ongoing studies, including ours. AIM: To assess the clinical outcomes of COVID-19 in liver transplant recipients. METHODS: This was a case-control study, with a database search performed (at the study site) from March 1, 2020 through February 28, 2021. Patients 18 years or older who tested positive for SARS-CoV-2 via polymerase chain reaction (PCR) were included in the study. Patients with infection other than pneumonia at the time of admission were excluded. After selection, patients who had been the recipient of liver transplant were considered cases and those without as controls. After being matched by age, sex, and obesity, two controls were randomly selected for each case. Death and hospitalization due to COVID-19 infection were the primary outcomes. Secondary outcomes were pertinent only to patients who were hospitalized, and they included duration of hospital stay, need for supplemental oxygen, presence of at least one type of end-organ damage, effects on liver enzymes, incidence of acute liver failure, effect on d-dimer levels, and incidence of venous thromboembolism (VTE). Chi-square or Fisher's exact test was used to compare all primary and secondary outcomes with the exception of duration of hospital stay and d-dimer levels, which were compared using the Wilcoxon signed-rank test. Alpha criterion was set at 0.05. Logistic regression was performed for each primary outcome (as the dependent variable). Statistical analyses were performed using R software. RESULTS: Of the 470 Liver transplant recipients who were tested for COVID-19 via the PCR test, 39 patients tested positive (8.3%). There was no significant difference between cases and controls regarding death [odds ratio (OR): 2.04, 95% confidence interval (CI): 0.14-29.17; P = 0.60] and hospitalization rates (OR: 1.38, 95%CI: 0.59-3.24; P = 0.46). There also was no significant difference between cases and controls with respect to all secondary outcomes. Among all patients who had elevated liver enzymes, their levels were either normalized, improving, or remained stable at the time of discharge. No patient developed acute liver failure. Of the 31 hospitalized patients, 27 received a prophylactic anticoagulation dose and no patient developed VTE in either group. Among cases who were hospitalized, immunosuppression was decreased in 5 patients and there was no change in immunosuppression among the remaining 7 patients. One patient died in each of these two subgroups. Logistic regression analysis was done, but all of the models had poor model predictions as well as insignificant predictors (independent variables). Therefore, they could not be used for either prediction or inference. CONCLUSION: Clinical outcomes of COVID-19 in liver transplant recipients are not different than those without transplantation. COVID-19 should not impact timely health care access and immunosuppression continuation among these patients.

Humoral and Cellular Immune Response After Third and Fourth SARS-CoV-2 mRNA Vaccination in Liver Transplant Recipients.

BACKGROUND & AIMS: Liver transplant recipients (LTRs) show a decreased immune response after 2 severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccinations compared with healthy controls (HCs). Here, we investigated the immunogenicity of additional vaccinations. METHODS: In this prospective study, humoral (anti-SARS-CoV-2 receptor-binding domain [anti-S RBD]) and cellular (interferon-gamma release assay) immune responses were determined after mRNA-based SARS-CoV-2 vaccination in 106 LTRs after a third vaccination and in 36 LTRs after a fourth vaccination. Patients with anti-S RBD antibody levels >0.8 arbitrary unit (AU)/mL after vaccination were defined as responders. RESULTS: After 3 vaccinations, 92% (97/106) of LTRs compared with 100% (28/28) of HCs were responders. However, the antibody titer of LTRs was lower compared with HCs (1891.0 vs 21,857.0 AU/mL; P < .001). Between a second and third vaccination (n = 75), the median antibody level increased 67-fold in LTRs. In patients seronegative after 2 vaccinations, a third dose induced seroconversion in 76% (19/25), whereas all HCs were already seropositive after 2 vaccinations. A spike-specific T-cell response was detected in 72% (28/39) after a third vaccination compared with 32% (11/34) after a second vaccination. Independent risk factors for a low antibody response (anti-S RBD <100 AU/mL) were first vaccination within the first year after liver transplant (odds ratio [OR], 8.00; P = .023), estimated glomular filtration rate <45 mL/min (OR, 4.72; P = .006), and low lymphocyte counts (OR, 5.02; P = .008). A fourth vaccination induced a 9-fold increase in the median antibody level and seroconversion in 60% (3/5) of previous non-responders. CONCLUSIONS: A third and fourth SARS-CoV-2 vaccination effectively increases the humoral and cellular immune response of LTRs, but to a lesser extent than in HCs. A fourth vaccination should be generally considered in LTRs.

Inferior Liver Transplant Outcomes during early COVID-19 pandemic in United States

Background : Since its declaration as a global pandemic on March11th 2020, COVID-19 has had a significant effect on solid-organ transplantation. Aim of this study was to analyze the impact of COVID-19 on Liver transplantation (LT) in United States. Methods : We retrospectively analyzed the United Network for Organ Sharing database regarding characteristics of donors, adult-LT recipients, and transplant outcomes during early-COVID period (March 11- September 11, 2020) and compared them to pre-COVID period (March 11 - September 11, 2019). Results : Overall, 4% fewer LTs were performed during early-COVID period (4107 vs 4277). Compared to pre-COVID period, transplants performed in early-COVID period were associated with: increase in alcoholic liver disease as most common primary diagnosis (1315 vs 1187, P< 0.01), higher MELD score in the recipients (25 vs 23, P<0.01), lower time on wait-list (52 vs 84 days, P<0.01), higher need for hemodialysis at transplant (9.4 vs 11.1%, P=0.012), longer distance from recipient hospital (131 vs 64 miles, P<0.01) and higher donor risk index (1.65 vs 1.55, P<0.01). Early-COVID period saw increase in rejection episodes before discharge (4.6 vs 3.4%, P=0.023) and lower 90-day graft/patient survival (92.2 vs 96.5 %, P<0.01;90.2 vs 95.1 %, P<0.01). In multivariable cox-regression analysis, early-COVID period was the independent risk factor for graft failure at 90-days post-transplant (HR 1.77, P<0.01). Conclusions : During early-COVID period in United States, overall LT decreased, alcoholic liver disease was primary diagnosis for LT, rate of rejection episodes before discharge was higher and 90-days post-transplant graft survival was lower.

Antibody response after a booster dose of SARS-CoV-2 vaccine in liver transplant recipients and those with chronic liver diseases.

INTRODUCTION AND OBJECTIVES: Lower antibody (Ab) responses after SARS-CoV-2 vaccination have been reported in liver transplant (LT) recipients and those with chronic liver diseases (CLD). The role of a booster dose in those with poor responses to initial vaccination is not well defined. METHODS: In this prospective study, we determined antibody (Ab) response to spike protein after a booster dose in LT recipients and those with chronic liver diseases (CLD) with and without cirrhosis after they had a poor response to an initial standard regimen. RESULTS: Of the 80 patients enrolled, 45 had LT, and 35 had CLD (18 with cirrhosis). A booster dose was given at a median of 138.5 days after the completion of the standard regimen. After the booster dose, 58 (73%, 31 LT, 27 CLD) had good response (≥250 U/mL), and 22 (28%, 14 LT, and 8 CLD) had poor response (7 undetectable and 15 with low Ab levels). No patient had any serious adverse events. The antibody responses were lower in those who had undetectable Ab (80 U/mL) than those who had low levels of Ab (0.80-249 U/mL) after the standard vaccination regimen (42% vs. 87%, p=0.0001). The antibody responses after homologous and heterologous booster doses were similar. CONCLUSIONS: We have shown that a booster dose will enhance Ab responses in LT recipients and those with CLD who had poor responses after an initial vaccine regimen.

A third dose of the BNT162b2 mRNA vaccine significantly improves immune responses among liver transplant recipients.

BACKGROUND & AIMS: Immune responses of solid organ transplant recipients to 2 doses of the BNT162b2 mRNA anti-SARS-CoV-2 vaccine are impaired. The immunogenicity and safety of a third dose among liver transplant (LT) recipients are unknown. This work aimed to evaluate the immune response of LT recipients to a third dose of the BNT162b2 mRNA vaccine. METHODS: Consecutive LT recipients (n = 61) in follow-up at Sheba Medical Center were included. Receptor binding domain (RBD) IgG, neutralizing antibody (NA) titers, and T-cell levels before and 21-28 days after a third vaccine dose were determined. Adverse effects after the third dose were monitored. RESULTS: The median age of LT recipients was 65 years and 57.4% were male. The humoral immune response rate improved significantly, with 56% of patients showing a response before the third vaccine dose compared to 98% after the third dose. The cellular response in 12 evaluated patients improved significantly (p = 0.008). The geometric mean of anti-RBD IgG levels, NA levels, and T-cell count also increased significantly after the third dose. NA titers after the third dose negatively correlated with age (p = 0.03), mycophenolate mofetil treatment (p = 0.005), and combined immunosuppression as opposed to calcineurin inhibitor monotherapy (p = 0.001). After the third dose, adverse effects were reported by 37% of recipients and were mostly mild (local pain and fatigue). CONCLUSION: After a third BNT162b2 mRNA vaccine, the immune response improved significantly among LT recipients, without serious adverse effects. Further studies are needed to evaluate immune response durability and to determine the optimal number and schedule of booster vaccine doses. LAY SUMMARY: The Pfizer-Biotech BNT162b2SARS-CoV-2 vaccine induced significant immunity among liver transplant recipients after a third dose. The majority of the patients developed sufficient levels of both humoral and cellular immune responses. Factors that predict non-response were older age and immunosuppressive medications.

Impact of covid-19 pandemic on quality of life and psychosocial difficulties among liver transplant recipients.

Background: The first wave of the COVID-19 pandemic affected health in all domains i.e., physical, mental, and social aspects. Liver transplant (LT) recipients faced a multitude of challenges during the first wave of lockdown. The aim was to identify the psychosocial difficulties and quality of life during the first year of the pandemic. Methods: A cross-sectional survey was conducted on LT recipients with a predefined structured questionnaire that included clinical, COVID-19 anxiety scale, and Post-Transplant Quality of life questionnaire (pLTQ). Results: A total of 109 patients were studied; with a mean age of 50.5 ± 11.1 years, with a median post-transplant follow-up of 52.4 months and a live donor transplant in the majority (79.8%). Almost all (99.1%) could come to the hospital for regular follow-up, prior to the pandemic. But during the first wave only 57% could maintain planned hospital visits and about 88% could not pursue their regular activities, and 39% missed their routine exercise because of imposed restrictions. Similarly, financial implications were responsible for 4% defaulting from treatment; while 7.3% managed by curtailing supportive drugs (on their own) leading to deranged liver tests in 4.6%; requiring immediate attention. The psychosocial difficulties raised the stress of pandemic (median score 18), and impacted quality of life (mean total pLTQ score 4.7 ± 0.9). Conclusions: For LT recipients, the first wave of COVID-19 pandemic affected their physical, mental, financial, and social wellbeing; in addition to the disease itself. Awareness, psychosocial support, and comprehensive care are some unmet needs for this special group; especially when it is expected that subsequent waves may continue to occur.

High prevalence of asymptomatic SARS-CoV-2 infection in a cohort of Liver Transplant Recipients in Central Italy

Asymptomatic subjects account for 25% to 45% of SARS-CoV-2 infections, and in particular, subjects on mild immunosuppressive therapy may have symptoms masked and could spread virus for an extended period of time. To determine the cumulative incidence of symptomatic and asymptomatic SARS-CoV-2 infections and associated risk factors, we conducted a prospective clinical and serological survey in a cohort of 278 liver transplant recipients (LTRs) from Central Italy. Three different serology tests were performed every 4 months in 259 LTRs between April 2020 and April 2021: one based on raw extract of whole SARS-CoV-2 virus and two on specific viral antigens (nucleoprotein and receptor binding domain) to detect specific IgG, IgM and IgA. Hundred fifteen LTRs who reported symptoms or close contact with a SARS-CoV-2-positive subject, or had a positive serological result underwent molecular testing by standard screening procedures (RT-PCR on naso-pharyngeal swab). Thirty-one past or active SARS-CoV-2 infections were identified: 14 had positive molecular test (64% symptomatic), and 17 had positive serology only (18% symptomatic). SARS-CoV-2 infection was not statistically related to gender, age, obesity, diabetes, renal impairment, type of anti-rejection therapy or time from transplant. Asymptomatic SARS-CoV-2 cases (61.3%) were more frequent in males and in those with glomerular filtrate rate >50 ml/min. Overall, the addition of repeated serology to standard diagnostic molecular protocols increased detection of SARS-CoV-2 infection from 5.1% to 10.9%. Anti-SARS-CoV-2 seroprevalence among our LTRs (11.2%) is comparable to the general population of Central Italy, considered a medium-impact area. Only one asymptomatic subject (6%) was found to carry SARS-CoV-2 in respiratory tract at the time of serological diagnosis.

Incidence, characteristics, and outcome of COVID-19 in patients on liver transplant program: a retrospective study in the north of Iran.

The risk of severe coronavirus disease-2019 (COVID-19) disease seems to be higher in individuals with solid organ transplantation. Therefore, the purpose of the present research is to investigate the incidence of COVID-19 and laboratory data and epidemiologic factors in liver transplant recipients and the patients on the waiting list for liver transplantation. In this study, we evaluated the records of patients on the waiting list for liver transplantation and of recipients of a liver transplant. Demographic data, underlying disease, history of drug use and participants' outcomes were collected. The diagnosis of SARS-CoV-2 infection for all patients was confirmed using a nasopharyngeal swab specimen with real-time RT-PCR. During the study period, 172 patients were enrolled, among whom 85 patients (49.4%) were on the waiting list for liver transplantation, and 87 patients (50.6%) were recipients of a liver transplant. Out of them, 10 (5.8%) had a positive result for SARS-CoV-2. Of these patients, 7.05% (6/85) and 4.6% (4/87) of patients on the waiting list and recipients of liver transplants were positive for SARS-CoV-2, respectively. Patients on the waiting list with COVID-19 infection had a higher median of albumin, ALT, AST, TBIL, DBIL, HDL and LDL value. In summary, the incidence of COVID-19 in liver transplant patients was slightly higher. The existence of underlying liver diseases should be well known as one of the poor predictive factors for worse outcomes in patients with COVID-19. So, comparative studies are recommended to identify risk factors for COVID-19 in patients with liver injury.

SARS-CoV2-specific Humoral and T-cell Immune Response After Second Vaccination in Liver Cirrhosis and Transplant Patients.

BACKGROUND & AIMS: Detailed information on the immune response after second vaccination of cirrhotic patients and liver transplant (LT) recipients against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is largely missing. We aimed at comparing the vaccine-induced humoral and T-cell responses of these vulnerable patient groups. METHODS: In this prospective cohort study, anti-SARS-CoV-2 spike-protein titers were determined using the DiaSorin LIAISON (anti-S trimer) and Roche Elecsys (anti-S RBD) immunoassays in 194 patients (141 LT, 53 cirrhosis Child-Pugh A-C) and 56 healthy controls before and 10 to 84 days after second vaccination. The spike-specific T-cell response was assessed using an interferon-gamma release assay (EUROIMMUN). A logistic regression analysis was performed to identify predictors of low response. RESULTS: After the second vaccination, seroconversion was achieved in 63% of LT recipients and 100% of cirrhotic patients and controls using the anti-S trimer assay. Median anti-SARS-CoV-2 titers of responding LT recipients were lower compared with cirrhotic patients and controls (P < .001). Spike-specific T-cell response rates were 36.6%, 65.4%, and 100% in LT, cirrhosis, and controls, respectively. Altogether, 28% of LT recipients did neither develop a humoral nor a T-cell response after second vaccination. In LT recipients, significant predictors of absent or low humoral response were age >65 years (odds ratio [OR], 4.57; 95% confidence interval [CI], 1.48-14.05) and arterial hypertension (OR, 2.50; 95% CI, 1.10-5.68), whereas vaccination failure was less likely with calcineurin inhibitor monotherapy than with other immunosuppressive regimens (OR, 0.36; 95% CI, 0.13-0.99). CONCLUSION: Routine serological testing of the vaccination response and a third vaccination in patients with low or absent response seem advisable. These vulnerable cohorts need further research on the effects of heterologous vaccination and intermittent reduction of immunosuppression before booster vaccinations.

Impact of COVID-19 on liver transplant recipients-A systematic review and meta-analysis.

BACKGROUND: Immunosuppression and comorbidities increase the risk of severe coronavirus disease-2019 (COVID-19) in solid organ transplant (SOT) recipients. The outcomes of COVID-19 in liver transplant (LT) recipients remain unclear. We aimed to analyse the outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in LT recipients. METHODS: The electronic databases were searched for articles published from 1 December 2019 to 20 May 2021 with MeSH terms COVID-19, SARS-CoV-2, and liver transplantation. Studies reporting outcomes in more than 10 LT recipients were included for analysis. LT vs non-LT patients with COVID-19 infection were compared for all-cause mortality, which was the primary outcome studied. We also evaluated the relation between the timing of COVID-19 infection post-LT (< one year vs > one year) and mortality. FINDINGS: Eighteen articles reporting 1,522 COVID-19 infected LT recipients were included for the systematic review. The mean age (standard deviation [SD]) was 60·38 (5·24) years, and 68·5% were men. The mean time (SD) to COVID-19 infection was 5·72 (1·75) years. Based on 17 studies (I2 = 7·34) among 1,481 LT recipients, the cumulative incidence of mortality was 17·4% (95% confidence interval [CI], 15·4-19·6). Mortality was comparable between LT (n = 610) and non-LT (n = 239,704) patients, based on four studies (odds ratio [OR], 0·8 [0·6-1·08]; P = 0·14). Additionally, there was no significant difference in mortality between those infected within one year vs after one year of LT (OR, 1·5 [0·63-3·56]; P = 0·35). The cumulative incidence of graft dysfunction was 2·3% (1·3-4·1). Nearly 23% (20·71-25) of the LT patients developed severe COVID-19 infection. Before infection, 71% and 49% of patients were on tacrolimus and mycophenolate mofetil, respectively. Immunosuppression was modified in 55·9% (38·1-72·2) patients after COVID-19 infection. INTERPRETATION: LT and non-LT patients with COVID-19 have a similar risk of adverse outcomes.

Humoral Response to SARS-Cov-2 Vaccination in Liver Transplant Recipients-A Single-Center Experience.

Vaccination against SARS-CoV-2 infection is currently approved and shows favorable outcomes, but little known about antibody responses in solid organ transplant recipients, since these patients are known to have an impaired immune response upon vaccination and have not been included in admission studies. We therefore analyzed immunogenicity in 43 liver transplant (LT) recipients in a median of 15 days (IQR, 12-24) after receiving two doses of the mRNA-based SARS-CoV-2 vaccine BNT162b2 following the standard protocol, and compared these results to a control group consisting of 20 healthcare workers (HCWs). Thirty-four of the 43 (79%) LT recipients developed antibodies, compared to 20 out of 20 (100%) in the control group (p = 0.047). The median SARS-CoV-2 IgG titer was significantly lower in the LT recipients compared to the control group (216 vs. >2080 BAU/mL, p = 0.0001). Age and sex distribution was similar in the LT patients that developed antibodies after vaccination compared to those who did not. Interestingly, the patients who received mycophenolate mofetil exhibited a reduced vaccination response compared to the other LT patients (5 of 11 (45.5%) vs. 29 of 32 (90.6%), p = 0.004). In conclusion, our data reveal lower immunogenicity of SARS-CoV-2 vaccine BNT162b2 in LT patients compared to the control group, but still show superior results compared to other solid organ transplant recipients reported so far.

The Impact of COVID-19 Global Pandemic on Morbidity and Mortality of Liver Transplant Recipients Children and Adults: A Systematic Review of Case Series.

The pandemic of coronavirus disease 2019 (COVID-19) changed the surgical everyday practice overnight. Currently, the first articles reporting outcomes of liver transplant recipients infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are published. The aim of the present study was to summarise the existing evidence of impact of COVID-19 global pandemic on liver transplant recipients. Electronic databases were searched in accordance with Preferred Reporting Items in Systematic Reviews and Meta-Analyses (PRISMA). Five studies were selected from a pool of 12 studies with a total of 854 liver transplant recipients of whom 700 were children and the rest 154 were adults. The present evidence, based on case reports and series demonstrated lower mortality in liver transplant recipients compared to general population.