COvid-19 vaccination and Biomarkers in cirrhosis And post-Liver Transplantation

The Covid-19 pandemic is the largest public health challenge in living memory.
The illness due to Covid-19 has a variable presentation, ranging from
asymptomatic to severe pneumonia with multiorgan failure. The efficacy of
vaccinations for Covid-19 in patients with chronic liver disease (CLD) or
post-liver transplantation (LT) is one of the most urgent public health
questions in hepatology. Patients with chronic liver disease (CLD), including
cirrhosis, have dysregulated innate and adaptive immunity, and therefore may be
at higher risk of complications from Covid-19 or Covid-19 vaccination.
Sub-optimal immune responses to vaccines are common in cirrhosis and post-LT,
and thus additional protective strategies may be necessary for our patients.
Determination of the relative efficacy and toxicity of vaccines for Covid-19 in
CLD and post-LT is an urgent, unmet clinical need.

The primary objective of this observational study is:
- to determine if patients with Chronic Liver Disease (CLD) mount comparable
humoral immune responses to healthy controls at 8-months following SARS-CoV-2
vaccination.

Secondary objectives of this observational study are to determine:
- if there are differences in humoral immune response between subgroups with
cirrhosis, autoimmune CLD or post-LT,
- the minimum effective level of humoral immunity in cirrhosis, autoimmune CLD
or post-LT to provide protection against Covid-19,
- if there are adverse effects or toxicity from vaccination in the context of
underlying cirrhosis, autoimmune CLD or post-LT,
- the degree of humoral response to booster doses of Covid-19 vaccination, if
these are administered as part of routine clinical care.

COBALT is a pan-European, large-scale, prospective observational cohort study
in approximately 100 liver centres across Europe, sampling ~5,000
patients with cirrhosis, autoimmune CLD or post-LT for cirrhosis. Additionally,
500 healthy participants will be recruited.

-Biological sampling: The primary endpoint will be determined by sampling at 30
weeks (±6 weeks) following final vaccination dose (for either one-dose or
two-dose regimens). For secondary endpoints, further optional sampling time
points will be at baseline (within 4 weeks prior to initial vaccination dose),
and at 7 weeks (±3 weeks) following final vaccination dose. Additionally, if
patients undergo a booster Covid-19 vaccination dose, a further optional
sampling point will be at 7 weeks (±4 weeks) following this booster dose.
-Data for secondary endpoints will be collected up to 12 months following
inclusion, for all seven subgroups. Specific episodes to be collected are:
diagnosis of Covid-19 (PCR positive), hospitalisation due to Covid-19,
liver-related hospitalisation, liver-related mortality, all-cause
hospitalisation, all-cause mortality and incident liver transplantation for
patients with CLD.

All participants of the study will receive standard of care. The burden and
risks associated with participation is very limited (1 physical examination and
a maximum of 4 vena punctures-30 minutes in total), negligible risks,
resitricted to those associated with a peripheral venapuncture.