Discussion:
This study compares the cellular and humoral response in cirrhotic and
immunocompetent HCW after one year of receiving ChAdOx1nCoV-19 Vaccine
(Covishield). All individuals received two doses of vaccine. The study
found that both groups showed had similar seroconversion as denoted by
titers of anti RBD and neutralizing antibodies (P=0.312, P=0.277).
Though the T-cells were significantly reduced in cirrhotic patients,
CD4:CD8 T-cell ratio was normal in cirrhotic patients. Both CD4+ and
CD8+T-cell subsets developed comparable CM and SCM in cirrhotic and HCW,
which is suggestive of similar cellular immune response.
Due to the ongoing fear of developing fatal complication of SARS-CoV-2
infection, immunocompromised patients like HIV, cancer, and patients
with solid organ transplant, needs special care and
precaution.21 Lee A et al in a meta-analysis of 83
studies using mRNA, VVV & inactivated whole virus vaccine in
immunocompromised patients (solid cancer, inflammatory diseases, HIV &
transplant recipients) found that after first dose of vaccination
seroconversion rate was half in immunocompromised patients compared to
the immunocompetent one. Second dose of vaccine was associated with
consistently improved seroconversion in all groups with lesser magnitude
in transplant individuals. Based on the above data authors advocated for
the targeted intervention (third or booster dose) in immunocompromised
patients.22 Costiniuk et al in their study on HIV
patients, found that anti-RBD and anti S antibody levels were maintained
in 92 % patients after 6 months and in 100% patients after one month
of third dose and suggested timely booster administration in HIV
patients for improved immune response.23 Studies have
shown reduced seroconversion in immunocompromised
patients.24 Therefore, many European countries
recommend booster (third) dose for immunocompromised individuals; even
some countries advocate extended (forth dose) or yearly dose in
susceptible and vulnerable population with different cut-off for age,
citing the waning effect of vaccination over time.25
Effective vaccination develops both humoral and cellular response that
can elicit adequate immune response on reinfection. Effector memory (EM)
T-cells serves as immediate effector function at frontline barriers and
recall responses are mediated by CM and SCM even in the absence of neutralizing antibodies.26 Crucial role of T-cell
immune response in SARS-CoV-1 infection has been clearly studied in
animal models. On long term follow-up, only 8.69% (2/23) patients of
SARS-CoV-1 patients have shown detectable levels of IgG at six years
indicating reduce humoral immunity over time whereas durable memory
T-cells were detected against SARS-CoV-1 at even >10 years
after infection. These findings may help us to understand the potential
cross-reactivity with existing SARS-CoV-2 and effectiveness of T-cell
memory cells.7
Cirrhosis is associated with dysfunction of both innate and adaptive
immune system and is a state of acquired
immunodeficiency.18 Cirrhotic patients developing
COVID-19 infection seem to have a worse outcome than those
otherwise.27 Data on the duration of vaccine efficacy
towards COVID-19 in patients with cirrhosis is sparse. Literature
suggests that the underlying immune dysfunction in cirrhosis may lead to
suboptimal response to vaccination as seen with hepatitis B and
pneumococcal vaccines.28,29 However, recent studies
have shown an improved outcome, reduced hospital stay and mortality in
patients with cirrhosis undergoing COVID-19 vaccination.
Our study shows concordance in equal seroconversion in cirrhotic &
immunocompetent HCW in developing comparable titers of anti-RBD and
neutralizing antibodies after one year of initial dose of vaccination,
however, differ in concept of booster dose requirement as persistent
cellular immune response in form of induced stem cell memory & central
memory were intact and similar in both cirrhotic and HCW which upon
antigenic exposure have ability to mediate adequate immune response.
Several studies have revealed the disparity between B cell and T-cell
mediated immune response in recipients of kidney transplant . It has
been observed that prevalence of S-protein specific CD4+T in transplant
recipient is comparable to healthy control despite a lower humoral
response after two dose of vaccination.30Additionally, research has demonstrated that cytokines are produced by
S-protein-reactive T-cells on ex-vivo antigenic stimulation indicating
that they can mediate antiviral response activity and safeguard patients
against severe COVID-19, despite the lack of antibodies. Consequently,
relying solely on antibody detection to assess vaccination response may
underestimate existing antiviral protection.31
Feng et al in their randomized control trial of vaccine efficacy study
determined a binding antibody unit of 264 or a pseudo-virus
neutralization assay titer of 26 IU/ml corresponded to 80% efficacy
against symptomatic COVID-19 though they could not determine threshold
for asymptomatic infections in their study.32Therefore, more studies with a long-term follow-up on larger population
(including vulnerable and different spectrum of immunocompromised
individuals) are required to define the reliable vaccine specific
correlates of protection as in Hepatitis B.
In summary, the study found that both healthy individuals and cirrhosis
patients generate similar levels of memory T-cells after being
vaccinated, which is an indication of effective and durable immunity.
Therefore, cirrhosis patients may not need additional vaccine doses
compared to healthy individuals.
One of the strengths of the study is that it examined the detailed
cellular and humoral immune responses of cirrhotic patients with varying
degrees of liver disease severity and causes, over a one-year period
after receiving the ChAdOx1nCoV-19 vaccine. However, a limitation of the
study is the small sample size, with fewer patients in the CTP class C
category.