Vaccination In Transplant Recipients Research Articles

Safety and immunogenicity of the live-attenuated varicella vaccine in pediatric solid organ transplant recipients: A systematic review and meta-analysis

This study aimed to synthesize the available evidence on the immunogenicity, safety, and effectiveness of live-attenuated varicella vaccine in solid organ transplant recipients. Medline and EMBASE were searched using predefined search terms to identify relevant studies. The included articles reported varicella vaccine administration in the posttransplant period in children and adults. A pooled proportion of transplant recipients who seroconverted and who developed vaccine-strain varicella and varicella disease was generated. Eighteen articles (14 observational studies and 4 case reports) were included, reporting on 711 transplant recipients who received the varicella vaccine. The pooled proportion was 88.2% (95% confidence interval 78.0%-96.0%, 13 studies) for vaccinees who seroconverted, 0% (0%-1.2%, 13 studies) for vaccine-strain varicella, and 0.8% (0%-4.9%, 9 studies) for varicella disease. Most studies followed clinical guidelines for administering live-attenuated vaccines, with criteria that could include being at least 1 year posttransplant, 2 months postrejection episode, and on low-dose immunosuppressive medications. Varicella vaccination in transplant recipients was overall safe in the included studies, with few cases of vaccine-strain-induced varicella or vaccine failure, and although it was immunogenic, the proportion of recipients who seroconverted was lower than that seen in the general population. Our data support varicella vaccination in select pediatric solid organ transplant recipients.

Analysis of Acquisition of COVID-2019 Neutralizing Antibodies in Organ Transplant Recipients

This study confirmed the kinetics of antibodies acquired by SARS-CoV-2 vaccination in solid-organ transplant recipients and examined their association with the development of COVID-19 and immunosuppressive status in organ transplant recipients. We measured COVID-19 neutralizing antibody titer in 21 organ transplant recipients vaccinated with the COVID-19 vaccine and 14 nontransplant recipients (control group) 3 times before and at 1 and 6 months after the third dose of vaccine. By confirming the kinetics of the acquired antibodies, we examined the relevance of the background characteristics of organ transplant recipients, such as the development of infectious diseases and immunosuppressive status. The proportion of patients with neutralizing antibodies was significantly higher in the nontransplant group than in the transplant group. Neutralizing antibody titers were significantly lower in transplant recipients when they were compared before the third dose and 1 month later. In the transplant recipient group, 11 patients were positive, and 10 were negative for neutralizing antibodies. When the causal relationship between the neutralizing antibody titer and background was examined, a positive correlation was found between the antibody titer and the number of years since transplantation, and a negative correlation was found between the tacrolimus trough values, amount of mycophenolate mofetil or steroids taken internally, and antibody titer. This study suggests that the effectiveness of vaccination in transplant recipients is associated with the post-transplant period before vaccination and the dose of immunosuppressive agents.

Humoral and Cellular Response of Transplant Recipients to a Third Dose of mRNA SARS-CoV-2 Vaccine: A Systematic Review and Meta-analysis.

High rates of nonresponse to 2 doses of mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine have been reported in transplant recipients. Several studies have investigated the efficacy of a third dose in this population. However, efficacy remains unclear, as response rates vary across studies. Therefore, we conducted a systematic review and meta-analysis to determine the efficacy of a third dose of any mRNA SARS-CoV-2 vaccine in transplant recipients. Preferred Reporting Items for Systematic Review and Meta-Analysis reporting guidelines (PROSPERO:CRD42021281498) were followed. Medline, Embase, and CENTRAL were searched from inception to December 2, 2021, without restrictions. All full-text studies reporting on the efficacy of a third dose of any mRNA SARS-CoV-2 vaccine in pediatric and adult transplant recipients were included. The National Institutes of Health quality assessment tool for case series and the Cochrane risk of bias tool determined study quality. Meta-analysis was performed via the DerSimonian-Laird random-effect model. Of 84 records, 12 studies totaling 1257 patients met inclusion criteria. One study was a randomized controlled trial, whereas all other studies were observational. Across 7 studies (801 patients), humoral response after 3 doses was observed in 66.1% (95% confidence interval, 62.8%-69.4%; I2 = 0%) of transplant recipients. Triple immunosuppression, mycophenolate, antiproliferatives, and belatacept use were associated with reduced odds of humoral response in studies reporting multivariate analyses. Transplant recipients receiving a third dose displayed higher levels of neutralizing antibodies to SARS-CoV-2 variants (Alpha, Beta, and Delta) compared with placebo. A third dose SARS-CoV-2 mRNA vaccine should be strongly considered in transplant recipients. Limitations included lack of controlled studies and clinically relevant thresholds to determine response to vaccination.

A Comparative Study on the Variation in Seropositivity Rates After 2-Dose COVID-19 Vaccination Before or After Transplant: A Single-Center Analysis

Many researchers have demonstrated that the seropositivity rate after SARS-CoV-2 coronavirus vaccination is lower in patients receiving oral immunosuppressants. In this article, we report on a comparative study on the seropositivity rate after 2 doses of coronavirus vaccine before or after kidney transplant. We studied 111 recipients vaccinated after transplant, 19 patients vaccinated before transplant, and 10 healthy patients. We retrospectively measured antibody titers using preserved serum samples. The antibody testing was performed 1 month and 3 months after vaccination. The measurement was via LABScreen COVID Plus, which enables simultaneous determination of 5 coronavirus protein antigens. Seropositivity to coronavirus antibodies was observed in all 19 patients vaccinated before transplant (100%) and in all the 10 healthy patients (100%). Forty- six of the 111 recipients (42%) vaccinated after transplant developed seropositivity. Analyzed at each time point after vaccination, the mean fluorescence intensity of antibodies was unchanged between 1 month and 3 months after vaccination in transplant recipients who were vaccinated after transplant and developed seropositivity. On the other hand, the antibody mean fluorescence intensity in patients vaccinated before transplant was markedly lower at 3 months (posttransplant). All patients with renal failure who were vaccinated before transplant showed a high seropositivity rate, similar to that in healthy patients. The seropositivity rate for each of the viral fragment antibodies in patients vaccinated before transplant was maintained, as seen in healthy patients. However, in patients vaccinated before transplant who tested positive for antibody production at 1 month after vaccination,the antibody mean fluorescence intensity at 3 months after vaccination (posttransplant) was remarkedly lower than the mean fluorescence intensity at 1 month, which was probably caused by the types of immunosuppressive regimens used atthe time of transplant.

Development of donor specific antibodies after SARS-CoV-2 vaccination in kidney and heart transplant recipients

This study examined the development of new or changes in donor specific antibodies (DSA) mean-fluorescence intensity (MFI) after SARS-CoV-2 vaccination in 100 kidney and 50 heart transplant recipients. The study was performed when the Center for Disease Control and Prevention (CDC) recommended two doses of Pfizer/BioNTech [BNT162b2] and Moderna [mRNA-1273 SARS-CoV-2] vaccine or 1 dose Johnson & Johnson/Janssen [Ad26.COV2·S] vaccines for full vaccination in transplant recipients. A novel assay bead-based platform for detecting antibodies against 4 domains of the SARS-CoV-2 spike protein to determine vaccine response (SA) and one nucleocapsid protein (NC) to determine prior SARS-CoV-2 infection was utilized. These assays were performed on the multiplex, bead-based platform utilized to assay DSA levels. 61/150 patients (40.7%) had successful vaccination. 18 patients had confirmed SARS-CoV-2 infection based on positive NC assay or previous Covid-19 oropharyngeal swab. 138 patients had no DSA prior to vaccination but 3 heart recipients developed new DSA's. Among 12 patients with known DSA prior to vaccination, 4 developed new DSA's or increased MFI. All 7 patients with new or increased DSA had stable graft function without rejection and had no changes in immunosuppression. All 8 patients with stable post vaccine DSA had stable graft function and immunosuppression was not changed. The presence of DSA before vaccination was associated with subsequent development of increased MFI or new DSA's (p = 0.001). There was no association between pre-vaccine DSA and positive vaccine response (NS). There was no association with successful vaccination or prior SARS-CoV-2 infection and DSA changes (NS).

P16.11: Decreased Immunogenicity After SARS-CoV-2 Vaccination in Liver and Kidney Transplant Recipients

Background: Recently published studies have found an impaired immune response after SARS-CoV-2 vaccination in solid organ recipients. However, most of these studies have not assessed immune cellular responses in solid organ transplant recipients. And no studies have yet demonstrated the efficacy of a booster (third) dose of SARS-CoV-2 vaccination in these patients. In this study, a prospective double-arm cohort study was performed to evaluate the humoral and the cellular immune response to SARS-CoV-2 vaccination in solid organ transplant recipients compared to healthy staff members with the normal function of the immune system. Methods: A total of 64 transplant patients and an age-matched control group of 103 healthy staff members were included. Blood samples were obtained and analyzed after the second dose and the boosting (third) dose, respectively. For evaluation of the virus-neutralization capacity of each group, serum was analyzed using a surrogate SARS-CoV-2 neutralization test to quantify the functional inhibitory capacity of neutralizing antibodies (Genscript) against SARS-CoV-2 spike protein. Inhibition scores of under 30% was considered negative. Results: Except the vaccination subgroup of the initial two dosages of AstraZeneca followed by Pfizer was significantly higher in the healthy control group, another prime-booster combination subgroup proportions were similar between the group. After the standard two doses of vaccination, only 28.3% of the transplant recipients demonstrated positive functional inhibition of neutralizing antibodies, significantly lower than 70.9% of the healthy control group (p <0.001). Even after the booster (third) dose of vaccination, 43.2% of the transplant recipients showed positive functional inhibition of neutralizing antibodies, significantly lower than 100% of the healthy control group (p <0.001). No other immune-associated complications such as acute rejection has occurred after SARS-CoV-2 vaccination in the transplant recipient group. Conclusion: Our data strongly suggest revised vaccination approaches in immunocompromised patients, including individual immune monitoring for the protection of this vulnerable group at risk of developing severe COVID-19. It urges for a review of future vaccine strategies in these patients.

P16.36: Effectiveness of SARS-Cov 2 Vaccination in Kidney Transplant Patients in Chile

Introduction: The humoral response to COVID-19 vaccines in transplant recipients has been reported to be lower than the obtained in the general population. For the Pfizer vaccine, an antibody response in 5-59% of those vaccinated is described, depending on the immunosuppressive maintenance therapy implemented, with a 56% of cellular response after the 2nd dose of the vaccine. The clinical significance of this poorer immune reaction is unclear. On the other hand, the degree of response to the Sinovac vaccine, the most used early in Chile, is unknown. Taking into account that the lethality of SARS-CoV-2 infection in transplanted patients was 6 times higher than the general population during the first wave of the pandemic (renal FUTAC data), we carried out this study with the aim of knowing the clinical effectiveness of the first two vaccines implemented in Chile in kidney transplant patients. Methods: Prospective, observational, multicenter study. The FUTAC database was available with a periodic report from all transplant centers in the country with 98% coverage and information available from 3/27/2020 to 7/7/2021. The data of transplanted patients who were infected with SARS-COV-2 were recorded comparing between those who had been fully vaccinated or not, with the Sinovac or Pfizer vaccine, evaluating the incidence of hospitalization and lethality. The group with complete vaccination was defined if the infection occurred 15 days after the second dose and the unvaccinated group corresponded to those without vaccination, with incomplete vaccination or in a period < 15 days after the second dose. Results: Of a total of 424 cases, 16 were discarded due to incomplete data, analysing 408 patients, of which 336 (82%) suffered the infection without being effectively vaccinated and 72 (18%) who were fully vaccinated. Of the total patients fully vaccinated, 57% (40/70) received Sinovac vaccine and 43% (30/70) Pfizer. No differences were found between COVID-19 infection rates between 2020 and 2021. Of the fully vaccinated patients, 42/72 (58%) were hospitalized, and 14/72. (19%) died; in this group, there are 7 patients who are alive but seriously ill at the time of closing the registry. In the unvaccinated group, 53% (179/336) were hospitalized and 15% (50/336) died, without significant differences in hospitalization or fatality rates. No differences were found in hospitalization or fatality rates between those vaccinated with Pfizer or Sinovac. Conclusions: The transplanted population, although fully vaccinated, maintains a high fatality rate, which is still 6 times higher than the general population. Although these data could be biased by the patients who did not consult, they were an input to decide a third dose of vaccination just applied to this highly vulnerable population, whose results are waiting to be evaluated. In Chile, the third booster dose was started in September 2021 and a 4th booster dose is currently being delivered starting in January 2022. Marion Alarcon; Loreto Oliva; Silvana Morales.

Predicting a Positive Antibody Response After 2 SARS-CoV-2 mRNA Vaccines in Transplant Recipients: A Machine Learning Approach With External Validation.

Background.Solid organ transplant recipients (SOTRs) are less likely to mount an antibody response to SARS-CoV-2 mRNA vaccines. Understanding risk factors for impaired vaccine response can guide strategies for antibody testing and additional vaccine dose recommendations.Methods.Using a nationwide observational cohort of 1031 SOTRs, we created a machine learning model to explore, identify, rank, and quantify the association of 19 clinical factors with antibody responses to 2 doses of SARS-CoV-2 mRNA vaccines. External validation of the model was performed using a cohort of 512 SOTRs at Houston Methodist Hospital.Results.Mycophenolate mofetil use, a shorter time since transplant, and older age were the strongest predictors of a negative antibody response, collectively contributing to 76% of the model’s prediction performance. Other clinical factors, including transplanted organ, vaccine type (mRNA-1273 versus BNT162b2), sex, race, and other immunosuppressants, showed comparatively weaker associations with an antibody response. This model showed moderate prediction performance, with an area under the receiver operating characteristic curve of 0.79 in our cohort and 0.67 in the external validation cohort. An online calculator based on our prediction model is available at http://transplantmodels.com/covidvaccine/.Conclusions.Our machine learning model helps understand which transplant patients need closer follow-up and additional doses of vaccine to achieve protective immunity. The online calculator based on this model can be incorporated into transplant providers’ practice to facilitate patient-centric, precision risk stratification and inform vaccination strategies among SOTRs.

The efficacy of SARS-CoV-2 antibody response after two dose mRNA vaccination in kidney and heart transplant recipients using a multiplex bead-based assay: Evaluating the factors affecting vaccine response

Background: The extent that which immunosuppressive factors contribute to the antibody response to SARS-Cov-2 vaccination in solid organ transplant patients is being better understood. This study examined antibody formation against the spike SARS-CoV-2 protein (SA) when full vaccinations were up to 2 doses and boosters were not recommended. Immunosuppressive factors that affected the vaccine responsiveness in a cohort of 100 kidney and 50 heart transplant patients were evaluated. This study utilized a novel assay to detect antibodies against 4 different domains of the spike protein and the nucleocapsid protein (NC) of the SARS-CoV-2 virus on a multiplex, bead-based platform. Positive SARS-COV-2 antibodies (SA) response required identification of the receptor-binding domain and one of the three other spike protein domains. Prior SARS-CoV-2 infection could be determined by the presence of positive NC. Results: 150 patients were enrolled in the study (100 kidneys; 50 heart recipients). This study was performed when the Center for Disease Control and Prevention (CDC) recommended only two doses of Pfizer/BioNTech [BNT162b2] and Moderna [mRNA-1273 SARS-CoV-2] vaccine or 1 dose of Johnson &amp; Johnson/Janssen [Ad26.COV2.S] vaccines for full SARS-CoV-2 vaccination in transplant recipients. Patients that reported a positive COVID-19 swab or had positive NC were excluded from the review because the prior infection may impact vaccine response (n = 134). Conclusions: SA were identified in 48/134 patients (36%); 25/46 heart (54%) and 23/88 kidney transplant patients (26%) (P = 0.0012). For the patients on prednisone therapy 25/93 responded with SA (27%) while for patients not on prednisone therapy, 23/41 responded with SA (56%) (P = 0.0012). The dose of steroids (5mg a day or greater) at the time of vaccination did not adversely affect vaccine efficacy (p = 0.054). Of the patients using antimetabolite therapy, 36/113 responded with SA (32%) while 12/21 patients not on antimetabolites responded with SA (57%) (P = .027). Time since transplant was not found to affect the rate of SA production when populations were separated by type of organ transplanted. T-cell depletion induction method, calcineurin inhibitor use, and type of SARS-CoV-2 vaccine were not found to be statistically significant.

Variances in Humoral Responses to Different Spike Protein Domains After SARS-CoV-2 Vaccination in Lung and Heart Transplant Recipients

PurposeSolid organ transplant recipients are lacking an adequate immune response to SARS-CoV-2 vaccination. Therefore, these patients are still at risk and potentially in need of booster vaccinations. Furthermore, it is important to differentiate between the recipients of distinct organs. The efficacy of SARS-CoV-2 vaccination is usually examined via antibodies specific for the spike protein with assays containing the S1 and receptor-binding-domains (RBD) and rather rarely the S2 domain. To gain information about the humoral response in Tx recipients, it is feasible to compare the immunogenicity of these three domains. To address this, we compared the IgG antibody levels specific for the three spike protein domains in heart (HTx) vs lung (LTx) transplant recipients.MethodsBlood plasma 4-6 weeks after the second dose of SARS-CoV-2 vaccination (85% mRNA) of n=100 LTx and n=40 HTx patients was analysed for S1, S2 and RBD-specific IgG antibodies by Luminex-based multiplex assays. The threshold for positive antibody responses was set separately for each spike domain based on the median MFI + 2σ in an unexposed pre-pandemic control group.ResultsFor all three spike protein domains, HTx patients showed a significantly higher rate of positive IgG responses than the LTx patients (73% vs 43%). The comparison of MFI values for S1-, S2- and RBD-specific IgG further underlines the superior antibody response by HTx patients with higher MFI values for S1 (p = 0.0001, S2 p = 0.008, RBD p < 0.0001). In the LTx cohort, MFI values for S2- (p < 0.0001) as well as for RBD-specific IgG (p < 0.0001) were higher than for S1. The same applies for S2 vs S1 (p < 0.0001) and RBD vs S1 (p = 0.0018) in the HTx cohort. Comparing the MFI of S2 vs RBD, the levels of domain-specific IgG were higher for S2 than RBD in both LTx (p < 0.0001) and HTx patients (p = 0.0914).ConclusionHTx patients exhibit a moderately good IgG response to vaccination while LTx recipients show lower antibody responses. Based on the more efficient antibody production against S2 as opposed to the RBD and especially S1-domain, the S2-specific IgG response should be taken into consideration when evaluating the general immune response and the resulting protection after SARS-CoV-2 vaccination in transplant recipients. Both groups of patients might benefit from booster vaccinations.

POS-912 EFFECTIVENESS OF SARS-COV 2 VACCINATION IN KIDNEY TRANSPLANT PATIENTS IN CHILE

The humoral response to COVID-19 vaccines in transplant recipients has been reported to be lower than the obtained in the general population. For the Pfizer vaccine, an antibody response in 5-59% of those vaccinated is described, depending on the immunosuppressive maintenance therapy implemented, with a 56% of cellular response after the 2nd dose of the vaccine. The clinical significance of this poorer immune reaction is unclear. On the other hand, the degree of response to the Sinovac vaccine, the most used in Chile, is unknown.

An Open-label Randomized Controlled Parallel-group Pilot Study Comparing the Immunogenicity of a Standard-, Double-, and Booster-dose Regimens of the 2014 Seasonal Trivalent Inactivated Influenza Vaccine in Kidney Transplant Recipients.

Immunogenicity of influenza vaccine in transplant recipients is suboptimal and alternative vaccination regimens are necessary. We compared the immunogenicity of a standard-dose trivalent inactivated influenza vaccination (SDTIIV), double-dose trivalent inactivated influenza vaccination (DDTIIV), and booster-dose trivalent inactivated influenza vaccination (BDTIIV) of the 2014 seasonal trivalent inactivated influenza vaccine in kidney transplant recipients. We randomized 176 participants to SDTIIV (59), DDTIIV (59), and BDTIIV regimens (58). Antibody titers were determined by hemagglutination inhibition at enrollment and 21 d postvaccination. Seroprotection rates (SPRs), seroconversion rates (SCRs), and geometric mean ratios (GMRs) were analyzed separately for participants with low (<1:40) and high (≥1:40) prevaccination antibody titers. Vaccination was confirmed for 172 participants. Immunogenicity analysis was done for 149 participants who provided postvaccination blood samples. In the subgroup with high prevaccination antibody titers, all vaccination regimens induced SPR > 70% to all antigens, but SCR and GMR were below the recommendations. In the subgroup with low prevaccination antibody titers, DDTIIV and BDTIIV regimens induced adequate SCR > 40% and GMR > 2.5 for all antigens, whereas SDTIIV achieved the same outcomes only for influenza B. SPRs were >70% only after DDTIIV (A/H1N1-77.8%) and BDTIIV (A/H3N2-77.8%). BDTIIV regimen independently increased seroprotection to A/H1N1 (PR = 2.58; P = 0.021) and A/H3N2 (PR = 2.21; P = 0.004), whereas DDTIIV independently increased seroprotection to A/H1N1 (PR = 2.59; P = 0.021). Our results suggest that DDTIIV and BDTIIV regimens are more immunogenic than SDTIIV, indicating the need for head-to-head multicenter clinical trials to further evaluate their efficacy.

Safety and Reactogenicity of 2 Doses of SARS-CoV-2 Vaccination in Solid Organ Transplant Recipients.

We studied the safety and reactogenicity SARS-CoV-2 mRNA vaccines in transplant recipients because immunosuppressed patients were excluded from vaccine trials. US transplant recipients were recruited into this prospective cohort study through social media; those who completed the full vaccine series between December 9, 2020 and March 1, 2021 were included. We collected demographics, medical history, and safety information within 7 d after doses 1 and 2 (D1, D2). Associations between characteristics and reactions were evaluated using modified Poisson regression. We studied 741 transplant recipients who underwent BNT162b2 (54%) or mRNA-1273 (46%) vaccination. Median (interquartile range) age was 60 (44-69) y, 57% were female, and 10% were non-White. Although local site reactions decreased after D2 (85% D1 versus 78% D2, P < 0.001), systemic reactions increased (49% D1 versus 69% D2, P < 0.001). Younger participants were more likely to develop systemic symptoms after D1 (adjusted incidence rate ratio [aIRR] per 10 y = 0.850.900.94, P < 0.001) and D2 (aIRR per 10 y = 0.910.930.96, P < 0.001). Participants who experienced pain (aIRR = 1.111.662.47, P = 0.01) or redness (aIRR = 1.833.928.41, P < 0.01) were more likely to develop an antibody response to D1 of mRNA vaccines. No anaphylaxis, neurologic diagnoses, or SARS-CoV-2 diagnoses were reported. Infections were minimal (3% after D1, <0.01% after D2). One patient reported incident acute rejection post-D2. In solid organ transplant recipients undergoing mRNA vaccination, reactogenicity was similar to that reported in the original trials. Severe reactions were rare. These early safety data may help address vaccine hesitancy in transplant recipients.

Immunogenicity and Reactogenicity After SARS-CoV-2 mRNA Vaccination in Kidney Transplant Recipients Taking Belatacept.

Belatacept may impair humoral immunity, impacting the effectiveness of SARS-CoV-2 mRNA vaccines in transplant recipients. We investigated immunogenicity after SARS-CoV-2 mRNA vaccines in kidney transplant recipients who are and are not taking belatacept. Participants were recruited between December 9, 2020, and April 1, 2021. Blood samples were collected after dose 1 and dose 2 (D1, D2) and analyzed using either an anti-SARS-CoV-2 enzyme immunoassay against the S1 domain of the SARS-CoV-2 spike protein or immunoassay against the receptor-binding domain of the SARS-CoV-2 spike protein. Stabilized inverse probability of treatment weights was used to compare immunogenicity, and a weighted logistics regression was used to calculate fold change of positive response. Among the 609 participants studied, 24 (4%) were taking belatacept. After dose 1, 0/24 (0%) belatacept patients had detectable antibodies, compared with 77 of 568 (14%) among the equivalent nonbelatacept population (P = 0.06). After dose 2, 1/19 (5%) belatacept patients had detectable antibodies, compared with 190/381 (50%) among the equivalent nonbelatacept population (P < 0.001). Belatacept use was associated with 16.7-fold lower odds of having a positive post-D2 titer result (P < 0.01). Additional measures need to be explored to protect kidney transplant recipients taking belatacept. Best safety practices should be continued despite vaccination among this population.

COVID-19 Reinfection by the Gamma Variant in Kidney Transplant Recipients.

Coronavirus disease 2019 (COVID-19) reinfections were recently reported in the general population,1 and a few case reports described reinfection in organ transplant recipients.2,3 We hereby describe 2 cases of COVID-19 reinfections by the gamma (formerly P.1) variant of concern (VOC) in kidney transplant recipients. This variant emerged in the Brazilian Amazon region in November 2020 and rapidly became the dominant strain in Brazil and several other Latin American countries. It is estimated that the gamma variant is 1.7- to 2.4-fold more transmissible than non-P1 lineage and that previous (non-P1 lineage) infections provide 54% to 79% of the protection against the gamma VOC infection. This study was approved by the institutional review board. Patient 1. A 39-y-old female living in Manaus (Amazon region) received a deceased donor kidney graft 12 y earlier and was immunosuppressed with prednisone, mycophenolic acid (MPA), and tacrolimus. In May 2020, she was admitted to a hospital in Manaus with fever and cough, and the COVID-19 infection was confirmed by real-time polymerase chain reaction (RT-PCR) from a nasopharyngeal swab sample. The clinical course of the disease was mild, MPA was withheld, and she was discharged a week later, asymptomatic with an increment in the serum creatinine from 2.5 to 3.3 mg/dL. In January 2021, she presented with a headache, myalgia, fever, and cough. The chest computed tomography scan showed ground-glass lesions with 30% to 40% lung involvement, and COVID-19 infection was confirmed by RT-PCR. At this time, COVID-19 genotyping revealed the gamma VOC. She recovered within 9 d without complications other than an increment of serum creatinine to 4.0 mg/dL (Figure 1). In April 2021, she received 2 doses of the CoronaVac COVID-19 vaccine.FIGURE 1.: Patients 1 and 2. Summary of clinical presentation, radiologic findings, diagnosis, treatment, and outcome in the first and second episodes of coronavirus disease 2019 (COVID-19) infection. CT, computed tomography; HCQ, hydroxychloroquine; MPA, mycophenolic acid; RT-PCR, real-time reverse-transcription polymerase chain reaction; VOC, variant of concern.Patient 2. A 49-y-old male, from the Southern region of Brazil, received a deceased donor kidney graft 6 y earlier and was immunosuppressed with prednisone, MPA, and tacrolimus. In August 2020, he sought emergency treatment complaining of a cough with sputum. The chest x-ray revealed no significant findings, and COVID-19 was diagnosed by an RT-PCR. MPA was withheld, and he was discharged after 2 d. At the end of the quarantine, MPA was reintroduced. In March 2021, he returned to the emergency with a fever and cough and, COVID-19 reinfection was again diagnosed by RT-PCR. At that time genotyping revealed the gamma VOC. A chest computed tomography scan showed lower ground-glass opacities and consolidations in 50% of the lungs, and immunosuppressive drugs were withheld due to clinical deterioration (Figure 1). He recovered after 19 d, and immunosuppression was reintroduced. Graft function remained stable (creatinine 1.4 mg/dL), and he was discharged, receiving the first dose of the AstraZeneca COVID-19 vaccine, in May 2021. By the end of June 2021, 230 kidney transplant recipient patients in our program were infected with severe acute respiratory syndrome coronavirus 2 and, these 2 patients (0.9%) had reinfections diagnosed. In both cases, the first infection occurred before the emergence of the gamma variant and the second in a period when gamma VOC was highly dominant in Brazil. Our cases add to the concerns regarding the effectiveness and duration of immunity after COVID-19 infection, higher transmissibility, and immune evasion by VOC.4 Also concerning is the low antibody response rate observed after SARS-CoV-2 vaccination in transplant recipients reinforced by disease development in fully vaccinated solid organ transplant recipients.5 Therefore, preventive measures remain crucial to reduce the high mortality rate observed in such patients. Nonetheless, it remains to be clarified if timely successful vaccination may prevent infections or reduce the severity of the disease in this vulnerable population.

Perspectives on COVID-19 vaccination among kidney and pancreas transplant recipients living in New York City.

PurposeSolid organ transplant recipients are at increased risk of morbidity and mortality from coronavirus disease 2019 (COVID-19), but limited vaccine access and vaccine hesitancy can complicate efforts for expanded vaccination. We report patient perspectives and outcomes from a vaccine outreach initiative for a vulnerable population of transplant recipients living in New York City.MethodsThis was a retrospective review of qualitative perspectives from a COVID-19 vaccine outreach initiative. In the outreach effort, kidney and pancreas transplant recipients under care at the transplant center at NewYork-Presbyterian Hospital were initially contacted electronically with educational material about vaccination followed by telephone outreach to eligible unvaccinated patients. Calls were used to schedule vaccine appointments for patients who agreed, answer questions, and assess attitudes and concerns for patients not yet ready to be vaccinated, with conversational themes recorded.ResultsOf the 1,078 patients living in the 5 New York City boroughs who had not reported receiving COVID-19 vaccination, 320 eligible patients were contacted by telephone. Of these, 210 patients were scheduled for vaccination at our vaccine site (including 13 who agreed to vaccination after initially declining), while 110 patients were either not ready or not interested in being vaccinated. The total number of patients willing to be vaccinated was 554 when also including those already vaccinated. Unwillingness to be vaccinated was associated with younger age (median age of 47 vs 60 years, P < 0.001), Black race (P = 0.004), and residence in Bronx or Brooklyn counties (P = 0.018) or a zip code with a medium level of poverty (P = 0.044). The most common issues raised by patients who were ambivalent or not interested in vaccination were regarding unknown safety of the vaccines in general, a belief that there was a lack of data about the vaccines in transplant recipients, and a lack of trust in the scientific process underlying vaccine development, with 34% of the patients contacted expressing vaccine hesitancy overall.ConclusionOur qualitative summary identifies determinants of COVID-19 vaccine hesitancy in a diverse transplant patient population, supporting the need for transplant centers to implement tailored interventions to increase vaccine acceptance in this vulnerable population.

Poor Antibody Response After Two Doses of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine in Transplant Recipients.

A low anti-spike antibody response of 28.6% was observed 28 days after BNT162b2 vaccine second dose among 133 solid organ transplant recipients without previous coronavirus disease 2019 (COVID-19). No serious adverse events were recorded. Four severe COVID-19 cases were reported between or after the 2 doses. Our data suggest to change the vaccine strategy.

Coronavirus disease 2019 vaccination in transplant recipients.

Coronavirus disease 2019 (COVID-19) vaccination is considered one of the most promising and socioeconomically sustainable strategy to help control the pandemic and several vaccines are currently being distributed in nationwide mass immunization campaigns. Very limited data are available on benefits and risks of COVID-19 vaccination in immunocompromised patients and in particular in solid organ or hematopoietic stem cell transplant recipients as they were excluded from phase III trials. This review summarizes current knowledge, international guidelines and controversies regarding COVID-19 vaccination in these vulnerable populations. Various COVID-19 vaccine platforms showed good efficacy in phase III trials in the immunocompetent and there are data arising on the safety and immunogenicity of these vaccines in the immunocompromised population. Transplant recipients could benefit significantly from COVID-19 vaccination, both through active immunization provided they elicit protective vaccine responses, and probably through cocooning by immunization of caregivers and healthcare personnel and thus reducing the risk of SARS-coronavirus-2 exposure. Although awaiting more data on the safety and efficacy of COVID-19 vaccines to inform potential adaptations of vaccine regimens, we strongly recommend prioritizing COVID-19 vaccination of solid and hematopoietic stem cell transplant recipients to decrease COVID-19-related morbidity and mortality.

EASL position paper on the use of COVID-19 vaccines in patients with chronic liver diseases, hepatobiliary cancer and liver transplant recipients

According to a recent World Health Organization estimate, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, which originated in China in 2019, has spread globally, infecting nearly 100 million people worldwide by January 2021. Patients with chronic liver diseases (CLD), particularly cirrhosis, hepatobiliary malignancies, candidates for liver transplantation, and immunosuppressed individuals after liver transplantation appear to be at increased risk of infections in general, which in turn translates into increased mortality. This is also the case for SARS-CoV-2 infection, where patients with cirrhosis, in particular, are at high risk of a severe COVID-19 course. Therefore, vaccination against various pathogens including SARS-CoV-2, administered as early as possible in patients with CLD, is an important protective measure. However, due to impaired immune responses in these patients, the immediate and long-term protective response through immunisation may be incomplete. The current SARS-CoV-2 pandemic has led to the exceptionally fast development of several vaccine candidates. A small number of these SARS-CoV-2 vaccine candidates have already undergone phase III, placebo-controlled, clinical trials in healthy individuals with proof of short-term safety, immunogenicity and efficacy. However, although regulatory agencies in the US and Europe have already approved some of these vaccines for clinical use, information on immunogenicity, duration of protection and long-term safety in patients with CLD, cirrhosis, hepatobiliary cancer and liver transplant recipients has yet to be generated. This review summarises the data on vaccine safety, immunogenicity, and efficacy in this patient population in general and discusses the implications of this knowledge on the introduction of the new SARS-CoV-2 vaccines.

The Role of Systems Vaccinology in Understanding the Immune Defects to Vaccination in Solid Organ Transplant Recipients.

Solid organ transplant recipients (SOTRs) are at increased risk for many infections, whether viral, bacterial, or fungal, due to immunosuppressive therapy to prevent organ rejection. The same immune defects that render transplanted patients susceptible to infection dampen their immune response to vaccination. Therefore, it is vital to identify immune defects to vaccination in transplant recipients and methods to obviate them. These methods can include alternative vaccine composition, dosage, adjuvants, route of administration, timing, and re-vaccination strategies. Systems biology is a relatively new field of study, which utilizes high throughput means to better understand biological systems and predict outcomes. Systems biology approaches have been used to help obtain a global picture of immune responses to infections and vaccination (i.e. systems vaccinology), but little work has been done to use systems biology to improve vaccine efficacy in immunocompromised patients, particularly SOTRs, thus far. Systems vaccinology approaches may hold key insights to vaccination in this vulnerable population.