ABSTRACT
Background. Solid organ transplant (SOT) recipients are at higher risk than general population for complicated COVID-19 course. Moreover COVID-19 vaccination in this setting is associated with a suboptimal immune response. However, the impact of this finding on the risk of breakthrough infection (BI) in SOT recipients has to be yet determined. Methods. Single-center prospective longitudinal cohort of adult SOT recipients who received three doses of mRNA COVID-19 vaccine between February and December 2021 and were followed up to March 30 2022. Patients were tested for antibody response at several timepoints (1 st dose, 2 nd dose, 3+/-1 month after 1 st dose, and 1 month after 3 rd dose). Main endpoints were: i) BI defined as laboratory confirmed SARS-CoV2 infection diagnosed >=14 day after 2 nd dose;ii) positive antibody response (AbR) defined as anti-rapid binding domain titer >=5 U/ml determined by Elecsys Anti-SARS-CoV-2 ECLIA assay (Roche Diagnostics, CH), the last available determination before BI was considered. Results. Study cohort consists of 642 SOT (277 kidney, 191 liver, 144 heart, 37 lung) recipients: 63.9% males, median age 54 +/- 14.5 years. Of them, 111 (17.8%) developed BI, BI rates were 19.9%, 18.1%, 15.2% and 10.8% among liver, heart, kidney and lung transplant recipients, respectively. Positive-AbR was observed in 60% of all patients, but rates varied from 8.7% to 91.3% among patients with BI and without BI, respectively. Predictors of BI infection at multivariable analysis were liver (vs. other grafts) transplant (OR 2.98, 95%CI 1.47-6.03), mycophenolate (1.63, 0.92-2.88) and steroids (1.8, 1.05- 3.33), while positive-AbR (0.61, 0.35-1.04) and age (0.97, 0.95-0.99) were protective. On the other hand, liver transplant (1.94, 1.02-3.69), time from transplant (1.09, 1.05-1.21), and Moderna vaccine (2.32, 1.46-3.70) were associated with positive-AbR, while age (0.97, 0.95-0.98), heart transplant (0.56, 0.33-0.96), mycophenolate (0.65, 0.39-1.06) and steroids (0.39, 0.23-0.65) with lower probability of positive-AbR. Conclusion. Although associated with positive-AbR, liver transplant and younger age were also BI predictors, suggesting the importance of social factors and the controversial role of immune monitoring.
ABSTRACT
Background and aims: Solid organ transplant recipients (SOTRs) have been considered as an extremely vulnerable population in respect to SARS-CoV-2 infection. We aimed to assess the incidence and lethality rate of SARS-CoV-2 infection in different organ transplant settings using the liver as a comparator. Methods: In this nationwide population-based study we compared the crude incidence and lethality rates of SARS-CoV-2 infection [95% Bonferroni adjusted CI (Ba-CI)] among Italian LTRs as compared to non-liver SOTRs and to general population. The following independent groups had been compared: Italian general population, all SOTRs, liver transplant recipients (LTRs) and non-Liver SOTRs in area with different incidence of infection. Incidence rate ratio (IRR) and lethality rate ratio (LRR) was assessed. Community risk exposures in transplant settings were assessed. Results: From February 21 to June 22, 2020, there were 450 cases of SARS-CoV-2 infections over 14168 LTRs (n=89) and 29815 non-liver SOTRs (n= 361). A significantly lower risk of infection [IRR 0.56 (Ba-CI 0.34-0.92), 0.45 (Ba-CI 0.26-0.79), 0.52 (Ba-CI 0.36-0.75)] and a lower lethality rate ratio [(LRR 0.61 (Ba-CI 0.23-1.57), 0.37 (0.08-1.76), 0.52 (0.23-1.18] was found among LTRs as compared to non-liver SOTRs in the three areas. Excluding Lombardy, the risk of infection and lethality in LTRs was lower compared to general population. Non-Liver SOTRs showed an increased risk of infection and lethality at all geographic levels compared to general population. No significant difference in the adherence to mitigation policies was found. Conclusions: Liver transplantation was associated with a significantly lower risk of SARS-CoV-2 infection and lethality in respect to non-liver solid organ transplants. A separate evaluation of organ-specific risk stratification analysis and vaccination responses in transplant population is needed.
ABSTRACT
Background: Despite the dominance of respiratory disease, acute-on-chronic liver failure (ACLF) and acute decompensation (AD) have been reported in patients with COVID-19 and preexisting liver disease, in particular cirrhosis. Moreover, COVID-19 has been associated with increased mortality in patients with end-stage liver disease (ESLD). Aim our study is to evaluate the impact of SARS-CoV-2 infection in patients with ESLD listed for liver transplant (LT). Methods: Data from adults listed for LT with laboratory-confirmed SARS-CoV-2 infection were collected from 7 LT centers across Italy. Results: From March 1st to October 31st 2020, 29 patients listed for LT were tested positive for SARS-CoV-2 infection. Twenty-one patients (72%) were male, median age was 59 years (20-71). The most common indication (70%) for LT was ESLD. The mean MELD score was 18 (8-32). At diagnosis, twenty patients (69%) presented at least one symptom: 38% fever, 28% dry cough, and 31% respiratory distress. Notably, 25% of patients presented hepatic encephalopathy as first presenting symptom. The remaining 9 patients (31%) were completely asymptomatic: nasopharyngeal swab was performed according to surveillance protocols. Twenty-one patients (70%) required hospitalization for the management of COVID-19. Respiratory support was necessary in 13 patients (45%): 5 (17%) required O2-supply, 4 (14%) non-invasive ventilation and 4 (14%) mechanical ventilation. Only five patients (17%) received at least one drug for infection treatment (see table). Heparin was administrated in 7 patients (28%). No bleeding episodes were reported. Eight (%) patients died after a median time of 6 days (2-29) from Covid-19 diagnosis, with a 30-day-mortality rate of 30%. Three patients died of liver failure, while the remaining of multiple organ failures. In the univariate analysis, factors associated with 30-days mortality were respectively presence of comorbidities (0.07), severity of liver disease according to MELD score (0.05) and severity of respiratory failure (0.011). In the cox-regression analysis, only the severity of respiratory failure was significantly associated with the mortality (HR 3.13, IC 1.53-6.3). Conclusions: COVID-19 is associated with elevated mortality in LT candidates, listed for ESLD.