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.