ABSTRACT
Background: Vaccination for SARS-CoV-2 infection has become a mainstay of prevention and mitigation of COVID in the general population. However, there is growing evidence that some subgroups may experience inferior response to currently available vaccine(s). There are few data regarding vaccine responses in subjects with liver disease or subjects immunosuppressed following solid organ transplantation. Methods: Participants were enrolled in a repository cohort study which includes persons with liver disease, as well as nonliver disease subjects classified as either immunocompetent controls or having immunosuppression from solid organ transplant (liver or kidney). Samples were collected following vaccination with any EUA approved SARS-CoV-2 vaccine. Assays performed included a quantitative assay for antibody to spike protein (Euroimmun, NJ), and a neutralization assay that demonstrates the ability of the antibody to block binding to SARS-CoV-2 receptor binding domain (RBD) of the ACE-2 receptor (GenScript, NJ). Results: 40 participants received the full dosing schedule (1 or 2 doses) of an EUA approved vaccine. The majority received 2 doses of the Pfizer/Moderna vaccine (n=35) and 5 the J&J vaccine. These included 13 subjects with chronic liver disease (LD), 18 immunosuppressed (IS) and 9 healthy immunocompetent controls. The majority were white (87.5%), male (50%) with a mean age of 59 years (range: 36-76). Chronic LDs included HCV, HBV, alcoholic hepatitis, and NASH. The IS subjects included 17 liver and 1 kidney recipient on immunosuppressants. Mean days post final dose was 22.6 days (SEM+ 2.76). The mean quantitative antibody to SARS-CoV-2 spike antigen was 522.56 WHO Binding Antibody Units (BAU) in the control group, 391.64 BAU in those with LD and 74.65 BAU with IS. The neutralization assay followed a similar pattern with 89.6% neutralization in the controls compared with 70.4% and 30.2% in the LD and IS groups respectively (p<0.05 for IS vs. other groups). Cirrhosis trended to lower antibody titers and neutralization ability, but this failed to reach statistical significance. Conclusion: Overall SARS-CoV-2 vaccine responses by two assay methodologies suggest lower response rates following a full vaccination series in participants with liver disease and immunosuppressed transplant subjects.
ABSTRACT
Background: A high proportion of patients with COVID-19 demonstrate liver enzyme abnormalities which have been attributed to a variety of etiologies including sepsis, coagulopathy with ischemic injury, and drug effects. We sought to determine the potential for replication and injury due to SARS-CoV-2 infection of hepatocyte cells. Methods: SARS-CoV-2 viral stocks were obtained from ATCC and expanded in Vero E6 cells. The virus was diluted to a multiplicity of infection of 0.1 plaque forming units and placed in medium overlying confluent cells. HepG2 andHuh7.5 hepatocyte cell lines were utilized, with Vero E6 cells (kidney) and WI-38 (lung) cell cultures serving as infection controls. For each cell line, uninfected cells were also maintained for comparison. Infection experiments were run in triplicate. Plaque assays were used to determine supernatant viral titer on days 2 through 8 post infection. Cell culture morphology was monitored by light microscopy. Results: All cell lines demonstrated significant replication potential with multi-log increase in plaque-forming units by day 3 post-infection. Rapid replication was observed through day 5. This was associated with the presence of severe cell injury with loss of attachment of the monolayer, suggesting that hepatocyte cell death limited overall levels of viral replication. Conclusion: Both HepG2 and Huh7.5 cell lines support active replication of SARS-CoV-2, leading to multi-log increases in viral titer. Replication in these cell lines is accompanied by severe injury leading to loss of attachment and cell death. These findings support the concept that SARS-CoV-2 infection may be associated with liver enzyme abnormalities due to acute viral-induced liver injury. (Table Presented).