The understanding of how the host immune response differs in T-cell phenotype and memory formation during SARS-CoV-2 infection in liver transplant recipients (LTRs) remains limited. LTRs who recovered from COVID-19 infection without prior vaccination represent a unique population for studying immune responses to SARS-CoV-2. Six LTRs with positive neutralizing antibodies (nAb+) and six LTRs with negative nAb (nAb-) were included at 6 months following COVID-19 infection. It was found that nAb+ LTRs had higher anti-RBD IgG titers and greater neutralizing percent inhibition compared to nAb- LTRs. Fifteen T-cell subsets were identified in COVID-19 convalescent LTRs, and it was shown that only terminal effector CD8+ - 3 decreased in the nAb+ group, while elevated IL-10 expression levels were found in the nAb- group. After stimulation with the SARS-CoV-2 XBB spike peptide pool in vitro, it was observed that the nAb+ group exhibited an increase in effector memory CD4+ cells with lower PD-1 expression, a reduction in effector memory CD4+ - 2 cells, and terminal effector CD8+ - 3 cells, while the nAb- group showed high expression of CTLA-4 and IL-10 in terminal effector CD8+ - 3 cells. Four SARS-CoV-2-specific T-cell subsets were identified, with high expression of TNF-α and IFN-γ in terminal effector CD8+ - 1 and terminal effector CD8+ - 2 cells in both groups. Perforin was mainly detected in terminal effector CD8+ - 2 cells in nAb+ LTRs. In addition to these proportional differences, stem cell memory CD4+ cells with higher IL-17A expression and stem cell memory CD8+ cells with higher CTLA-4 expression were also found in nAb- LTRs. These findings suggest that LTRs who developed nAb+ following SARS-CoV-2 infection exhibit stronger T-cell responses, with more robust immune activation and memory recall, compared to nAb- LTRs. This study underscores the importance of understanding T-cell responses during SARS-CoV-2 recovery for guiding vaccination strategies and managing immunity in LTRs.

The COVID-19 pandemic highlighted the vulnerability of immunocompromised individuals, including liver transplant recipients (LTRs), who often exhibit reduced vaccine immunogenicity. While initial vaccine doses and subsequent boosters improved immune response, LTRs were prioritized for vaccination. Studies have shown increased antibody response after each booster dose. Vaccine hesitancy, defined as delayed or refused vaccination despite availability, poses a public health challenge, often fueled by misinformation. This study aimed to evaluate anti-spike antibody responses in vaccinated LTRs after two initial doses and at least one booster, also assessing adherence to subsequent doses.

We conducted a retrospective observational study at a transplant center in Milan, Italy, between January 2021 and December 2023. LTRs who had received four or more doses of mRNA vaccines (Pfizer or Moderna) were included. Anti-spike antibody levels were measured 60-80 days after each dose. Data on vaccination status were collected in January 2024. Statistical analysis was performed to compare antibody responses and identify predictive factors.

LTRs showed a significant increase in anti-spike antibody responses after the first booster compared to the second dose with a trend versus a further increase following the fourth dose in a subgroup of the patients receiving two booster doses. However, adherence to booster doses decreased over time. In LTRs, predictors of a weaker response after the second dose were chronic kidney disease and metabolic etiology at transplant.

The study highlighted that in LTRs, multiple doses of the COVID-19 vaccine led to a continuous increase in anti-spike antibody responses. The progressive decline in adherence of LTRs "to further booster doses" should be related to the fact that after the spread of vaccination programs worldwide, COVID-19 is still a current infection, but it is much less severe than before.

Patients with cirrhosis and liver transplant recipients are at increased risk of infections. Malnutrition, multiple hospital admissions, immune dysfunction related to cirrhosis, and immunosuppressive agents used for liver transplantation predispose the recipient to various life-threatening infections. Some of these infections are preventable with vaccines. With the COVID-19 pandemic, there has been an accelerated research in vaccination technology and platforms, which in turn may also improve awareness of physicians regarding this healthy and often ignored aspect of management of patients with cirrhosis and transplant recipients. The organ transplant candidates should complete the recommended vaccination schedule as early as possible (especially patients with compensated cirrhosis) or at least during their pretransplant work-up so as to prevent or reduce the severity of various infections.

Liver transplant recipients (LTRs) have been considered a population group that is vulnerable to COVID-19 as they are chronically immunosuppressed patients with frequent comorbidities. This study describes the course of the SARS-CoV-2 disease from February 2020 to December 2023 along seven pandemic "waves". We carried out an observational study on 307 COVID-19 cases in a cohort of LTRs with the aim of evaluating the changes in the disease characteristics over time and determining the risk factors for severe COVID-19. An older age and serum creatinine level ≥ 2 mg/dL were found to be risk factors for hospital admission and respiratory failure. The use of calcineurin inhibitors was a protective factor for death, hospitalization, and respiratory failure from COVID-19. One hundred percent of patients who died (N = 12) were on mycophenolate mofetil, which was a determinant for respiratory failure. Azathioprine was associated with admission to the intensive care unit (ICU) and with invasive mechanical ventilation (IMV). Vaccination was a protective factor for hospitalization, respiratory failure, and mortality. The severe COVID-19 rate was higher during the first five waves, with a peak of 57.14%, and the highest mortality rate (21.43%) occurred in the fourth wave. The IMV and ICU admission rates did not show significant differences across the periods studied.

Despite the lower virulence of current SARS-CoV-2 variants and high rates of vaccinated and previously infected subjects, COVID-19 remains a persistent threat in kidney transplant recipients (KTRs). This study evaluated the parameters of anti-SARS-CoV-2 antibody production in 120 KTRs. The production of neutralizing antibodies in KTRs, following booster vaccination with the mRNA vaccine BNT162b2, was significantly decreased and their decline was faster than in healthy subjects. Factors predisposing to the downregulation of anti-SARS-CoV-2 neutralizing antibodies included age, lower estimated glomerular filtration rate, and a full dose of mycophenolate mofetil. Neutralizing antibodies correlated with those targeting the SARS-CoV-2 receptor binding domain (RBD), SARS-CoV-2 Spike trimmer, total SARS-CoV-2 S1 protein, as well as with antibodies to the deadly SARS-CoV-1 virus. No cross-reactivity was found with antibodies against seasonal coronaviruses. KTRs exhibited lower postvaccination production of neutralizing antibodies against SARS-CoV-2; however, the specificity of their humoral response did not differ compared to healthy subjects.

Here, we report that four functional fragments of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) spike protein including receptor binding motif (RBM), fusion peptide (FP), heptad repeat 1 (HR1) and heptad repeat 2 (HR2) were chosen to develop a recombinant S subunit protein vaccine. This recombinant protein consisting of S230 amino acids (aa) (S230) bound specifically to the antibody from COVID-19-patients serum, which showed very strong antigenicity. The S230 was then engineered to present on the surface of Hepatitis B core (HBc) virus-like particles (VLPs) to develop HBc-S230 chimeric VLPs vaccine. Both vaccines induced strong humoral and cellular immune responses in mice, however, HBc-S230 chimeric VLPs elicited significantly higher immunogenicity than the S230. HBc-S230 chimeric VLPs promoted to generate not only dramatically higher levels of S230-specific serum antibodies, but also marked higher CD4+/CD8 + T cells ratio and substantially higher yields of IFN-γ and IL-6. Furthermore, HBc-S230 chimeric VLPs induced serum antibodies that could effectively neutralize the infection with three SARS-CoV-2 pseudoviruses (Wild type, Delta and Omicron). Our results demonstrated that HBc-S230 chimeric VLPs immunization conveyed the humoral immunity, which lasted longer than six months. Clearly, HBc-S230 chimeric VLPs enhanced immunogenicity of the S230, which could provide potent and durable protection against SARS-CoV-2 infection, indicating that HBc-S230 chimeric VLPs possessed great potential for developing highly immunogenic vaccines against SARS-CoV-2.

The efficacy of monovalent BNT162b2 Omicron XBB.1.5 booster vaccination in liver transplant recipients (LTRs) has yet to be described, particularly regarding the immune response to emerging variants like JN.1.

This study evaluated humoral and cellular immune responses in 34 liver transplant recipients (LTRs) with varying SARS-CoV-2 immune histories before and after receiving a BNT162b2 Omicron XBB.1.5 booster vaccination. The assessment involved variant-specific serology, pseudovirus neutralization tests, and Interferon-γ release assays.

Participants had a median of four prior vaccinations, with 91.2% having a history of infection. Post-vaccination, significant increases in both Wuhan anti-S and Omicron-specific IgG antibodies and improved neutralization of B.1, XBB.1.5, and JN.1 pseudovirus particles were observed. Also, T-cell responses significantly increased post-vaccination. However, 17.6% of LTRs had no neutralizing antibodies against XBB.1.5 and JN.1, while 100% of healthy controls did. Shortly after vaccination, 18% of patients developed mild COVID-19. These LTRs had particularly low immune responses at baseline.

The monovalent XBB.1.5 booster improved overall SARS-CoV-2-specific immunity. However, some LTRs still showed low or undetectable immune responses, indicating that ongoing monitoring and further booster doses are necessary in this high-risk group.

The global pandemic caused by the highly contagious SARS-CoV-2 virus led to the emergency approval of COVID-19 vaccines to reduce rising morbidity and mortality. However, limited research exists on evaluating the impact of these vaccines on immunocompromised individuals, such as recipients of living donor liver transplantation, highlighting the need for further studies to better understand their effectiveness in this specific population.

From June 2021, we followed up on the effectiveness of the vaccine for patients taking immunosuppressive drugs after living-donor liver transplantation (LDLT). A total of 105 immunocompromised individuals participated, of which 50 patients with hepatitis B were taking antiviral drugs. Patients were assessed to analyze how the combination of immunosuppressive and antiviral drugs affected the efficacy of the BNT162b2, mRNA-1273, and ChAdOx1 nCoV-19 COVID-19 vaccines.

Before and after the vaccinations, patients were monitored to establish differences between immunosuppressed patients and those additionally taking antiviral drugs. In immunocompromised patients taking antiviral drugs for hepatitis B, we confirmed that the effect of the COVID-19 vaccine was reduced when compared to immunocompromised patients. Interestingly, 23 patients (11 without and 12 additionally with hepatitis B drug administration) encountered breakthrough infections, and although there was a minor discrepancy in vaccine efficacy among the patients taking antiviral drugs for hepatitis B, it did not reach statistical significance.

Additional COVID-19 vaccination is recommended for patients taking immunosuppressive drugs and hepatitis B antiviral drugs after LDLT.

The capacity of different anti-SARS-CoV-2 vaccines to elicit immune response is not equivalent in the healthy population compared to chronically immunosuppressed patients. Most of the reports available to assess the effects of anti-SARS-CoV-2 vaccines on solid organ transplant recipients (SOTR) were performed using mRNA-based vaccines.

This study aims to assess the seroconversion rate in a cohort of liver and liver- intestinal transplant patients after vaccination with the non-replicative vector-based vaccines after transplantation used in our country, Argentina (rAd26-rAd5 (Sputnik V) and ChAdOx11 nCoV-19 (AZD1222) (Astra Zeneca-Oxford).

One hundred and three (103) liver and liver-intestinal transplant recipients were enrolled. Patients with previous PCR-confirmed COVID19 were excluded, therefore 77 were finally included for analysis; 75 were liver transplant recipients, 1 was a combined liver-intestine and 1 a multivisceral transplant. All received their first vaccine dose between March and June 2021; 66,2% males, and the mean age was 56,3 years. All patients have a post-transplant follow up longer than 1 year (mean 6.6 years, median 5 years, range 1-23 years). Immune response after first, second and third doses were determined using three different spike (S)-S commercial ELISA kits and an in-house made anti nucleocapsid-protein (N) ELISA.

Following the three doses, 57.1 % (44/77) of the patients seroconverted, while 33/77 (42.9 %) did not present anti-SARS-CoV-2 antibodies. The seroconversion rate was different for each dose. We found that 5/27 (18.5 %) of transplant patients seroconverted after a single dose; 18/29 pts (62.0 %) had anti-SARS-Cov-2 antibodies after the second doses; and 18/21 pts (85.7 %) reached the seroconversion after the third doses. The proportion of seroconversion was significantly increased in the second doses regardless the response observed after the first doses (p = 0.012, Fisher's exact test), particularly when two doses of ChAdOx11 vaccine was administrated (p = 0.040, Chi-square). However, the comparisons of seroconversion rate between Sputnik V and ChAdOx11 vaccines showed no differences after the different vaccination doses. No significant statistical difference in patient́s gender, age, comorbidities, type of vaccine, post-transplant, or maintenance immunosuppressive therapy was found between responders and non-responders.

Despite having a lower seroconversion rate compared to the general population, viral-vector vaccines benefit SOTR patients increasing the seroconversion rate using at least two doses of vaccine. These results support the concept of developing tailor-made vaccination guidelines for this specific population. This analysis provides further support to safety and efficacy of viral-vector vaccines in liver and liver-intestine transplant patients.

The reduced susceptibility of mRNA vaccines and diminished neutralizing activity of therapeutic monoclonal antibodies against Omicron variants, including BQ.1.1, XBB, and their descendants, highlight the importance of antiviral therapies. Here, we assessed the efficacy of two antivirals, molnupiravir, targeting a viral RNA-dependent RNA polymerase, and nirmatrelvir, targeting a main protease, against BQ.1.1 in hamsters. We found that prophylactic or therapeutic treatment with either drug significantly reduced the viral load in the lungs of infected hamsters. We also evaluated the risk of emergence of drug-resistant viruses in immunocompromised hamsters. Although 13 days of drug treatment reduced viral titers, the immunocompromised hosts could not completely clear the virus. Viruses isolated from drug-treated immunocompromised hamsters did not show reduced susceptibility to the drugs. Molnupiravir and nirmatrelvir remain effective in vivo against variants with reduced susceptibility to monoclonal antibodies and mRNA vaccine-induced antibodies, with limited emergence of drug-resistant variants under the conditions tested.

Novel mRNA-based vaccines have been proven to be powerful tools in combating the global pandemic caused by SARS-CoV-2 protecting individuals, especially the immunocompromised, from COVID-19. Still, it remains largely unknown how solid organ transplant and different immunosuppressive medications affect development of vaccine-induced immunity.

In this work, we monitored humoral and cellular memory responses after mRNA SARS-CoV-2 two-doses and booster doses vaccination in cystic fibrosis lung transplanted patients (CFT) and compared them with both cystic fibrosis patients without lung transplant (CF) and with kidney transplant recipients (KT). In particular, we investigated the effects of immunosuppressive regimens on immune memory to SARS-CoV-2 after mRNA SARS-CoV-2 vaccine in transplanted patients.

Our results showed that immunocompromised transplanted patients displayed a weak cellular and humoral memory to SARS-CoV-2 mRNA vaccination. In addition, obtained data clearly demonstrate that immunosuppressive therapy regimen including antimetabolites, further reduces patients' ability to respond to vaccination at both humoral and cell-mediated level. Notably, patient treated with antimetabolites showed a lower humoral and cellular response also after a booster dose vaccination.

These results, even if obtained on a small patient's cohort, question whether immunocompromised patients need interventions to improve vaccine SARS-CoV-2 mRNA vaccine response such as additional jab or modulation of immunosuppressive therapy.

Solid organ transplant (SOT) activities, such as liver transplant, have been greatly influenced by the pandemic of coronavirus disease 2019 (COVID-19), a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Immunosuppressed individuals of liver transplant recipients (LTRs) tend to have a high risk of COVID-19 infection and related complications. Therefore, COVID-19 vaccination has been recommended to be administered as early as possible in LTRs.

The keywords "liver transplant", "SARS-CoV-2", and "vaccine" were used to retrieve articles published in PubMed.

The antibody response following the 1st and 2nd doses of vaccination was disappointingly low, and the immune responses among LTRs remarkably improved after the 3rd or 4th dose of vaccination. Although the 3rd or 4th dose of COVID-19 vaccine increased the antibody titer, a proportion of patients remained unresponsive. Furthermore, recent studies showed that SARS-CoV-2 vaccine could trigger adverse events in LTRs, including allograft rejection and liver injury.

This review provides the recently reported data on the antibody response of LTRs following various doses of vaccine, risk factors for poor serological response and adverse events after vaccination.

This study assessed humoral and T cell-mediated immune responses to the BNT162b2 vaccine in orthotopic liver transplant (OLT) and lung transplant (LUT) recipients who received three doses of the vaccine from March 2021 at our institution. Serum samples were collected 60 days post-second and third dose to quantify antibodies against the spike region of SARS-CoV-2 while whole blood samples were collected to analyze the SARS-CoV-2-specific T-cell response using an IFN-γ ELISpot assay. We enrolled 244 OLT and 120 LUT recipients. The third dose increased antibody titres in OLT recipients (from a median value of 131 after the second dose to 5523 IU/mL, p < 0.001) and LUT recipients (from 14.8 to 1729 IU/mL, p < 0.001). T-cell response also increased in OLT recipients (from 8.5 to 23 IFN-γ SFU per 250,000 PBMC, p < 0.001) and LUT recipients (from 8 to 15 IFN-γ SFU per 250,000 PBMC, p < 0.001). A total of 128 breakthrough infections were observed: two (0.8%) OLT recipients were hospitalized due to COVID-19 and one died (0.4%); among LUT recipients, seven were hospitalized (5.8%) and two patients died (1.7%). In conclusion, the three-dose schedule of the BNT162b2 vaccine elicited both humoral and T cell-mediated responses in solid organ transplant recipients. The risk of severe COVID-19 post-vaccination was low in this population.

This study aimed to evaluate the efficacy and safety of solid organ transplantation recipients inoculated with an inactivated COVID-19 vaccine.

We retrospectively analyzed the antibody levels and related adverse events of non-transplantation subjects and solid organ transplant recipients, both pre-transplantation (individuals awaiting organ transplantation) and post-transplantation (individuals who have undergone organ transplantation), who received inactivated COVID-19 vaccines from February 2021 to July 2022.

The study included 38 pre-transplantation vaccination group, 129 post-transplantation vaccination group, and 246 non-transplantation group. The antibody titer was assessed monthly within the period of 1-12 months after the last injection. The antibody-positive rate among the three groups were 36.84, 20.30, 61.17% (P < 0.05). The antibody-positive rates among three groups with one, two doses vaccine were not significantly different (P > 0.05), but were significantly different after three doses (P < 0.05). The antibody titers among three groups were significantly different after two doses (P < 0.05). Adverse reactions occurred in six transplant recipients, which were relieved after treatment, and not in the non-transplantation subjects.

Inactivated COVID-19 vaccine is safe and effective for solid organ transplantation recipients, at least two doses of which should be completed before organ transplant surgery.

Immunosuppressed individuals, such as people living with HIV (PLWH), remain vulnerable to severe COVID-19. We analyzed the persistence of specific SARS-CoV-2 humoral and cellular immune responses in a retrospective, cross-sectional study in PLWH on antiretroviral therapy. Among 104 participants, 70.2% had anti-S IgG antibodies, and 55.8% had significant neutralizing activity against the Omicron variant in a surrogate virus neutralization test. Only 38.5% were vaccinated (8.76 ± 4.1 months prior), all displaying anti-S IgG, 75% with neutralizing antibodies and anti-S IgA. Overall, 29.8% of PLWH had no SARS-CoV-2 serologic markers; they displayed significantly lower CD4 counts and higher HIV viral load. Severe immunosuppression (present in 12.5% of participants) was linked to lower levels of detectable anti-S IgG (p = 0.0003), anti-S IgA (p < 0.0001) and lack of neutralizing activity against the Omicron variant (p < 0.0001). T-cell responses were present in 86.7% of tested participants, even in those lacking serological markers. In PLWH without severe immunosuppression, neutralizing antibodies and T-cell responses persisted for up to 9 months post-infection or vaccination. Advanced immunosuppression led to diminished humoral immune responses but retained specific cellular immunity.

Children with very early onset inflammatory bowel disease (VEO-IBD) may respond differently to coronavirus disease 2019 (COVID-19) immunization compared to healthy children or other patients with IBD. We recruited children with VEO-IBD <6 years of age and younger following receipt of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Demographics, IBD characteristics, medication use, adverse events (AEs) and IBD exacerbations were collected. Blood draws (optional) were obtained for measurement of antireceptor binding domain (RBD) IgG antibodies following vaccination. Of 41 participants, none required emergency department visit or hospitalization due to AE, and only one experienced IBD exacerbation. Detectable antibody was present in 19/19 participants who provided blood sample; 6/7 participants (86%) had durable humoral response 12 months postvaccination. Children with VEO-IBD experience robust humoral immune response to COVID-19 immunization. Severe AEs were rare. These findings provide reassurance that children with VEO-IBD respond well and safely to SARS-CoV-2 vaccination.

In the third year of the SARS-CoV-2 pandemic, little is known about the vaccine- and infection-induced immune response in liver transplant recipients (LTR) and liver cirrhosis patients (LCP).

This cross-sectional study assessed the vaccination coverage, infection rate, and the resulting humoral and cellular SARS-CoV-2-specific immune responses in a cohort of LTR and LCP at the University Medical Center Hamburg-Eppendorf, Germany between March and May 2023.

Clinical and laboratory data from 244 consecutive patients (160 LTR and 84 LCP) were collected via chart review and a patient survey. Immune responses were determined via standard spike(S)- and nucleocapsid-protein serology and a spike-specific Interferon-gamma release assay (IGRA).

On average, LTR and LCP were vaccinated 3.7 and 3.3 times, respectively and 59.4% of patients received ≥4 vaccinations. Altogether, 68.1% (109/160) of LTR and 70.2% (59/84) of LCP experienced a SARS-CoV-2 infection. Most infections occurred during the Omicron wave in 2022 after an average of 3.0 vaccinations. Overall, the hospitalization rate was low (<6%) in both groups. An average of 4.3 antigen contacts by vaccination and/or infection resulted in a seroconversion rate of 98.4%. However, 17.5% (28/160) of LTR and 8.3% (7/84) of LCP demonstrated only low anti-S titers (<1000 AU/ml), and 24.6% (16/65) of LTR and 20.4% (10/59) of LCP had negative or low IGRA responses. Patients with hybrid immunity (vaccination plus infection) elicited significantly higher anti-S titers compared with uninfected patients with the same number of spike antigen contacts. A total of 22.2% of patients refused additional booster vaccinations.

By spring 2023, high vaccination coverage and infection rate have resulted in a robust, mostly hybrid, humoral and cellular immune response in most LTR and LCP. However, booster vaccinations with vaccines covering new variants seem advisable, especially in patients with low immune responses and risk factors for severe disease.

COVID-19 vaccination has proved to be effective to prevent symptomatic infection and severe disease even in immunocompromised patients including liver transplant patients. We aim to assess the impact of COVID-19 vaccination on the mortality and development of severe and critical disease in our center.

A retrospective cohort study of LT patients in a reference center between March 2020 and February 2022. Demographic data, cirrhosis etiology, time on liver transplantation, immunosuppressive therapies, and vaccination status were recorded at the time of diagnosis. Primary outcome was death due to COVID-19, and secondary outcomes included the development of severe COVID-19 and intensive care unit (ICU) requirement.

153 of 324 LT recipients developed COVID-19, in whom the main causes of cirrhosis were HCV infection and metabolic-associated fatty liver disease. The vaccines used were BNT162b2 (48.6%), ChAdOx1 nCoV-19 (21.6%), mRNA-1273 vaccine (1.4%), Sputnik V (14.9%), Ad5-nCoV-S (4.1%) and CoronaVac (9.5%). Case fatality and ICU requirement risk were similar among vaccinated and unvaccinated LT patients (adjusted relative case fatality for vaccinated versus unvaccinated of 0.68, 95% CI 0.14-3.24, p = 0.62; adjusted relative risk [aRR] for ICU requirement of 0.45, 95% CI 0.11-1.88, p = 0.27). Nonetheless, vaccination was associated with a lower risk of severe disease (aRR for severe disease of 0.32, 95% CI 0.14-0.71, p = 0.005).

Vaccination reduces the risk of severe COVID-19 in LT patients, regardless of the scheme used. Vaccination should be encouraged for all.

Liver transplant recipients (LTRs) are at a high risk of severe COVID-19 owing to immunosuppression and comorbidities. LTRs are less responsive to mRNA vaccines than healthy donors (HDs) or other immunosuppressed patients. However, the disruption mechanism in humoral and cellular immune memory responses is unclear.

We longitudinally collected peripheral blood mononuclear cells and plasma samples from HDs (n = 44) and LTRs (n = 54) who received BNT162b2 or mRNA-1273 vaccines. We measured the levels of anti-receptor-binding domain (RBD) antibodies and spike-specific CD4+ and CD8+ T-cell responses.

Here, we show that the induction of anti-RBD IgG was weaker in LTRs than in HDs. The use of multiple immunosuppressive drugs is associated with lower antibody titers than only calcineurin inhibitor, and limits the induction of CD4+ T-cell responses. However, spike-specific CD4+ T-cell and antibody responses improved with a third vaccination. Furthermore, mRNA vaccine-induced spike-specific CD8+ T cells are quantitatively, but not qualitatively, limited to LTRs. Both CD4+ and CD8+ T cells react to omicron sublineages, regardless of the presence in HDs or LTRs. However, there is no boosting effect of spike-specific memory CD8+ T-cell responses after a third vaccination in HDs or LTRs.

The third mRNA vaccination improves both humoral responses and spike-specific CD4+ T-cell responses in LTRs but provides no booster effect for spike-specific memory CD8+ T-cell responses. A third mRNA vaccination could be helpful in LTRs to prevent severe COVID-19, although further investigation is required to elicit CD8+ T-cell responses in LTRs and HDs.

Numerous United States transplant centers require solid organ transplantation candidates to be vaccinated against the coronavirus disease of 2019 to be active on the United Network for Organ Sharing waiting list. This study examined characteristics of adult patients on one center's kidney transplantation waiting list whose status was inactivated due to a lack of coronavirus disease 2019 vaccination by July 1, 2022, and who did not subsequently provide proof of vaccination by August 31, 2022 (cases). Patients in the control group were retrospectively matched to patients in the case group in a 4-to-1 fashion according to age, sex, and "active" status on the waiting list. Multivariable logistic regression was performed, with race/ethnicity, primary language, health insurance, education, and Vaccine Equity Metric (VEM, a measure of health equity at the zip code level) quartile as covariates. Results revealed that patients from zip codes in the lowest VEM quartile (odds ratio [OR] 1.89; P = .02) and those insured by governmental payors (Medicare: OR, 2.00; P < .01 and Medicaid: OR, 2.89; P < .01) had higher odds of being inactivated than those from zip codes that make up the highest VEM quartile and those insured by commercial payors, respectively. These findings serve as a cautionary tale regarding universal pretransplantation vaccination requirements, which may raise equity concerns that should be considered upon policy implementation.

As part of the COVID-19 control strategy, a growing number of vaccine portfolios evolved and got fast-tracked through regulatory agencies, with a limited examination of their efficacy and safety in vulnerable populations, such as patients with chronic conditions and immunocompromised states. Patients with chronic liver disease (CLD), and cohorts post liver transplant (LT) in particular, were underrepresented in the determinant trials of vaccine development, hence the paucity of data on their efficacy and safety in published literature. This systematic review aims to examine the available evidence and ascertain the effectiveness and safety of Covid-19 vaccination in patients with CLD and those with LT.

A systematic review of PubMed (Medline), Google Scholar, Cochrane Library, and ScienceDirect from inception until 1st March 2022 was conducted. We included observational studies and assessed vaccine efficacy regarding seroconversion or immunological rate, whereas serious or significant adverse effects have been considered safety outcomes when reported.

Studies comprised 45275 patients, performed in 11 different countries. Seroconversion or immunological rate after Covid-19 vaccination was mostly the primary endpoint, whereas other endpoints like covid-19 related adverse effects were also reported. Twenty-four of the final analyzed studies are prospective cohort studies, while four are retrospective cohort studies. Twenty-one studies included patients who underwent LT and received the Covid vaccine; nine included patients who had CLD due to various etiologies. The median age range of all included patients varied from 43-69 years. All patients with LT who received at least two doses of Covid vaccine had a seroconversion rate of around 60%. Patients with CLD had a seroconversion rate of about 92% post two doses of Covid vaccination. The average seroconversion rate in post-transplant recipients was around 45% after two doses of the significant Covid vaccines: Pfizer, AstraZeneca, Moderna, and Jansen. Only two studies have reported a higher seroconversion rate of 75% and 73% after the third dose of Covid vaccine. No significant adverse effects were reported in all studies; the most commonly reported negative effect was local injection site pain.

The present systematic review, comprising real-world observational data studies, concludes that Covid-19 vaccination was associated with 92% and 60% seroconversion rates in patients with CLD and LT, respectively. No significant side effects were reported in all studies. This finding helps to resolve the uncertainty associated with Covid-19 vaccination in this cohort of patients.

Background: The role of tailored immunosuppression (IS) in the development of the humoral response (HR) to SARS-CoV-2 mRNA-based vaccination in liver transplant (LT) recipients is unknown. Methods: This is a single-centre prospective study of patients who underwent LT between January 2015 and December 2021 and who have received three doses of mRNA-based SARS-CoV-2 vaccination. Patients undergoing Tacrolimus-based immunosuppression (TAC-IS) were compared with those undergoing Everolimus-based immunosuppression (EVR-IS). Patients receiving the TAC-EVR combination were divided into two groups based on trough TAC concentrations, i.e., above or below 5 ng/mL. HR (analysed with ECLIA) was assessed at 30 to 135 days after vaccination. The primary outcome was the presence of a positive antibody titre (≥0.8 U/mL). Secondary outcomes were the presence of a highly protective antibody titre (≥142 U/mL), median antibody titre, and incidence of COVID-19. Results: Sixty-one participants were included. Twenty-four (40%) were receiving TAC-IS and thirty-seven (60%) were receiving EVR-IS. At the median follow-up of 116 (range: 89-154) days, there were no significant differences in positive antibody titre (95.8% vs. 94.6%; p = 0.8269), highly-protective antibody titre (83.3% vs. 81.1%; p = 0.8231), median antibody titre (2410 [IQ range 350-2500] vs. 1670 [IQ range 380-2500]; p = 0.9450), and COVID-19 incidence (0% vs. 5.4%; p = 0.5148). High serum creatinine and low estimated glomerular filtration rate were risk factors for a weak or absent HR. Conclusions: Three doses of mRNA-based SARS-CoV-2 vaccination yielded a highly protective HR in LT recipients. The use of TAC or EVR-based IS does not appear to influence HR or antibody titre, while renal disease is a risk factor for a weak or null HR.

Despite the fact that COVID is today not a life-threat for the general population, recipients of solid organ transplantation should be viewed as a high risk group for severe COVID. Repetitive doses of SARS-CoV-2 vaccine still fail to protect SOT recipients from infection, disease or even death caused by COVID. A more frequent need for medical care may initially place these patients at greater chances of SARS-CoV-2 infection. Immunosuppression after engrafting and underlying medical conditions that led to the practice of SOT contribute to more risk of severe infection. Immunosuppression also blunts the intensity of humoral and cellular responses after vaccination, even when several booster doses have been administered. Still, vaccination is the best strategy to prevent a fatal outcome in case of SARS-CoV-2 infection, with a particular reduction in mortality. SOT recipients should be considered a high-risk population that need yearly SARS-CoV-2 vaccination.

We report the results of a prospective study on the immunogenicity of a 3rd dose of BNT162b2 in thoracic organ recipients with no or minimal response following a two-dose BNT162b2 vaccination scheme.

A total of 243 transplant recipients received a homologue 3rd dose. Anti-SARS-CoV2-immunoglobulins (IgGs) were monitored immediately before (T1), 4 weeks (T2) as well as 2 and 4 months after the 3rd dose. Neutralizing antibody capacity (NAC) was determined at T2. To reveal predictors for detectable humoral response, patients were divided into a positive response group (n = 129) based on the combined criteria of IgGs and NAC above the defined cut-offs at T2-and a group with negative response (n = 114), with both, IgGs and NAC beyond the cut-offs.

The 3rd dose induced a positive humoral response in 53% of patients at T2, 47% were still non-responsive. Sero-positivity was significantly stronger in patients who presented with weak, but detectable IgGs already prior to the booster (T1), when compared to those with no detectable response at T1. Multivariable analysis identified age > 55 years, a period since transplantation < 2 years, a reduced glomerular filtration rate, a triple immunosuppressive regimen, and the use of tacrolimus and of mycophenolate as independent risk factors for lack of humoral response.

Our data indicate that a lack of immunogenicity is linked to the type and extent of maintenance immunosuppression. The necessity of the cumulative immunosuppressive regimen might individually be questioned and possibly be reduced to enhance the chance of an immune response following an additional booster dose.

Vaccine hesitancy and lack of access remain major issues in disseminating COVID-19 vaccination to liver patients globally. Factors predicting poor response to vaccination and risk of breakthrough infection are important data to target booster vaccine programs. The primary aim of the current study was to measure humoral responses to 2 doses of COVID-19 vaccine. Secondary aims included the determination of factors predicting breakthrough infection.

COVID-19 vaccination and Biomarkers in cirrhosis And post-Liver Transplantation is a prospective, multicenter, observational case-control study. Participants were recruited at 4-10 weeks following first and second vaccine doses in cirrhosis [n = 325; 94% messenger RNA (mRNA) and 6% viral vaccine], autoimmune liver disease (AILD) (n = 120; 77% mRNA and 23% viral vaccine), post-liver transplant (LT) (n = 146; 96% mRNA and 3% viral vaccine), and healthy controls (n = 51; 72% mRNA, 24% viral and 4% heterologous combination). Serological end points were measured, and data regarding breakthrough SARS-CoV-2 infection were collected.

After adjusting by age, sex, and time of sample collection, anti-Spike IgG levels were the lowest in post-LT patients compared to cirrhosis (p < 0.0001), AILD (p < 0.0001), and control (p = 0.002). Factors predicting reduced responses included older age, Child-Turcotte-Pugh B/C, and elevated IL-6 in cirrhosis; non-mRNA vaccine in AILD; and coronary artery disease, use of mycophenolate and dysregulated B-call activating factor, and lymphotoxin-α levels in LT. Incident infection occurred in 6.6%, 10.6%, 7.4%, and 15.6% of cirrhosis, AILD, post-LT, and control, respectively. The only independent factor predicting infection in cirrhosis was low albumin level.

LT patients present the lowest response to the SARS-CoV-2 vaccine. In cirrhosis, the reduced response is associated with older age, stage of liver disease and systemic inflammation, and breakthrough infection with low albumin level.

Prevention of infections is crucial in solid organ transplant (SOT) candidates and recipients. These patients are exposed to an increased infectious risk due to previous organ insufficiency and to pharmacologic immunosuppression. Besides infectious-related morbidity and mortality, this vulnerable group of patients is also exposed to the risk of acute decompensation and organ rejection or failure in the pre- and post-transplant period, respectively, since antimicrobial treatments are less effective than in the immunocompetent patients. Vaccination represents a major preventive measure against specific infectious risks in this population but as responses to vaccines are reduced, especially in the early post-transplant period or after treatment for rejection, an optimal vaccination status should be obtained prior to transplantation whenever possible. This review reports the currently available data on the indications and protocols of vaccination in SOT adult candidates and recipients.