Immunogenicity and safety of a third dose of anti-SARS-CoV-2 BNT16b2 vaccine in liver transplant recipients.

BACKGROUND & AIMS: A strategy to improve the low rate of anti-SARS-CoV-2 mRNA vaccine-induced immunogenicity in liver transplant recipients (LTs) is urgently needed. METHODS: We analyzed the rate of positive (≥0.8 U/ml) anti-SARS-CoV-2 receptor domain binding protein (RBD) antibody response two months after a third dose of the BNT16b2 vaccine in 107 LTs who completed the second vaccine dose seven months earlier. RESULTS: A positive anti-SARS-CoV-2-s-RBD antibody response after the third vaccine dose was detected in 98 (91.6%) LTs compared to 82 (76.6%) after the second vaccine dose (p=0.003). The median of anti-SARS-CoV-2 RBD antibody titers increased from 22.9 U/ml six months after the second to 3500 U/ml two months after the third vaccine dose (p<0.001). Fourteen (14.3%) responder patients presented antibody titers <100 U/ml, 57 (58.2%) between 100 and 9999 U/ml and 27 (27.6%) ≥10000 U/ml. Seropositivity after the second dose was maintained after the third dose. Independent predictors of antibody response failure after the third vaccine dose were taking a higher daily dose of mycophenolate mofetil (MMF, p<0.001) and had a lower (<60 ml/min/1.73m2 ) estimated glomerular filtration rate (p=0.007). Nine (9.1%) LTs experienced symptomatic SARS-CoV-2 infection after the third vaccine dose. Median antibody titers were not statistically different between infected and not infected LTs (1325 vs 3515 U/ml, p=0.678). CONCLUSIONS: The third dose of the BNT16b2 vaccine increased the number of LTs who developed a positive anti-SARS-CoV-2 s-RBD antibody response. A proportion of patients remained unresponsive, mainly for modifiable factors, such the use of MMF or multiple immunosuppressants.

Low risk of nosocomial severe acute respiratory syndrome-coronavirus-2 infection in patients with liver disease admitted to a hepatology unit at an academic hospital: A single-center experience.

BACKGROUND: Patients with liver disease may be at increased risk of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection due to immune dysfunction. However, the risk of nosocomial SARS-CoV-2 infection in these patients remains unknown. This study aimed to determine whether patients with liver disease are at an increased risk of nosocomial transmission of SARS-CoV-2 infection upon admission to the hospital for diagnostic or therapeutic procedures. METHODS: The study prospectively enrolled 143 patients who were admitted at least once to the hepatology unit at our hospital; 95 patients (66%) were admitted at least twice during the study period. History of past symptomatic SARS-CoV-2 exposure was assessed on the day before hospital admission via an interview. Patients were evaluated for active SARS-CoV-2 infection via real-time reverse transcription-polymerase chain reaction (RT-PCR) performed on nasopharyngeal swabs and tests for serum anti-SARS-CoV-2 immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies. RESULTS: None of the patients enrolled tested positive for SARS-CoV-2 infection by RT-PCR at the first or the second clinical evaluation. One patient who had previously received a liver transplant and who had a history of symptomatic SARS-CoV-2 infection that occurred 4 months before hospital admission tested positive for anti-SARS-CoV-2 IgG but not IgM antibodies at each of the two hospital admissions. CONCLUSIONS: The results of our study suggest that patients with liver disease are at no increased risk of nosocomial SARS-CoV-2 infection. These data support the policy of maintaining clinical hospital checks that will be necessary until or possibly even after the completion of the current SARS-CoV-2 vaccination campaign.

Past COVID-19 and immunosuppressive regimens affect the long-term response to anti-SARS-CoV-2 vaccination in liver transplant recipients.

BACKGROUND & AIMS: The long-term immunogenicity of anti-SARS-CoV-2 vaccines in liver transplant (LT) recipients is unknown. We aimed to assess the long-term antibody response of the Pfizer-BioNTech® BNT162b2 vaccine in LT recipients compared to controls. METHODS: LT recipients underwent anti-SARS-CoV-2 anti-receptor-binding domain protein IgG (anti-RBD) and anti-nucleocapsid protein IgG antibody (anti-N) measurements at the first and 1, 4 and 6 months after the second vaccination dose. RESULTS: One hundred forty-three LT recipients and 58 controls were enrolled. At baseline, 131/143 (91.6%) LT recipients tested anti-N negative (COVID-19 naïve), and 12/143 (8.4%) tested positive (COVID-19 recovered) compared to negative controls. Among COVID-19 naïve, 22.1% were anti-RBD positives 1 month after the first vaccine dose, while 66.4%, 77%, and 78.8% were 1, 4 and 6 months following the second vaccine dose. In contrast, 100% of controls were positive at 4 months (p <0.001). The median anti-RBD titer 4 months after the second vaccine dose was significantly lower (32 U/ml) in COVID-19 naïve than in controls (852 U/ml, p <0.0001). A higher daily dose of mycophenolate mofetil (MMF) (p <0.001), higher frequency of ascites (p = 0.012), and lower serum leukocyte count (p = 0.016) were independent predictors of anti-RBD negativity at 6 months. All COVID-19 recovered patients tested positive for anti-RBD at each time point. The median antibody titer was similar in those taking MMF (9,400 U/ml, 11,925 U/ml, 13,305 U/ml, and 10,095 U/ml) or not taking MMF (13,950 U/ml, 9,575 U/ml, 3,500 U/ml, 2,835 U/ml, p = NS) 3 weeks after the first and 1, 4 and 6 months after the second vaccine dose, respectively. CONCLUSIONS: In COVID-19-naïve LT recipients, the immunogenicity of anti-SARS-CoV-2 vaccination was significantly lower than that in controls. MMF was the main determinant of vaccination failure in SARS-CoV-2-naïve patients. LAY SUMMARY: The immunogenicity of anti-SARS-CoV-2 vaccination in liver transplant recipients is currently unknown. Herein, we show that liver transplant recipients who have not previously had COVID-19 are less likely to mount effective antibody responses to vaccination than a control population. The main determinant of vaccination failure was the use of the immunosuppressive drug mycophenolate mofetil.

A Streamlined Approach to Rapidly Detect SARS-CoV-2 Infection Avoiding RNA Extraction: Workflow Validation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has rapidly spread worldwide from the beginning of 2020. The presence of viral RNA in samples by nucleic acid (NA) molecular analysis is the only method available to diagnose COVID-19 disease and to assess patients' viral load. Since the demand for laboratory reagents has increased, there has been a worldwide shortage of RNA extraction kits. We, therefore, developed a fast and cost-effective viral genome isolation method that, combined with quantitative RT-PCR assay, detects SARS-CoV-2 RNA in patient samples. The method relies on the addition of Proteinase K followed by a controlled heat-shock incubation and, then, E gene evaluation by RT-qPCR. It was validated for sensitivity, specificity, linearity, reproducibility, and precision. It detects as low as 10 viral copies/sample, is rapid, and has been characterized in 60 COVID-19-infected patients. Compared to automated extraction methods, our pretreatment guarantees the same positivity rate with the advantage of shortening the time of the analysis and reducing its cost. This is a rapid workflow meant to aid the healthcare system in the rapid identification of infected patients, such as during a pathogen-related outbreak. For its intrinsic characteristics, this workflow is suitable for large-scale screenings.