COVID-19 Vaccines in Pancreatic Transplant Recipients: A Single-Center Observative Study

The SARS-CoV-2 pandemic was a real test of doctors’ abilities to adapt and respond to patients’ needs. The course of infection varied from influenza-like symptoms to severe infections with multi-organ failure and death. Therefore, the possibility of vaccination against the COVID-19 virus brought great hope.Since 2004, 240 pancreas and pancreas with kidney (simultaneous pancreas and kidney transplantation, pancreas after kidney, pancreas transplants alone) transplants were performed in our center. Currently, 130 transplant patients are under the care of the transplant clinic. All patients were informed about the possibility of vaccination against SARS-CoV-2 with the mRNA vaccine.The aim of the study was to evaluate the development of antibodies to SARS-CoV-2 in patients who had previously undergone transplantation. Fifty-three patients were vaccinated with the full double dose and 37 patients received an additional third dose.The level of antibodies in the IgM and IgG classes was assessed in patients’ serum. The level of antibodies was assessed before administration of the vaccine and then after administration of the first and second doses.Most patients had no response to vaccination after 1 dose of the vaccine and 21 patients achieved therapeutic antibody levels after the full dose of vaccination. However, the highest titer of immunoglobulins was found in recipients who received the third dose.The use of vaccinations is safe and can protect the group of patients after pancreas transplantation from serious complications of SARS-CoV-2 infection despite the use of immunosuppressive drugs.     

Panel Reactive Antibody Responses Against Influenza Vaccination in Kidney Transplant Recipients

IntroductionSeasonal influenza is an important cause of morbidity and mortality in the post-transplant period; therefore, the influenza vaccination has been recommended for all kidney transplant recipients before the influenza season. However, at least theoretically, the introduction of antigens via vaccines may trigger rejection attacks by causing an antibody response. In this study, we examined the development of de novo panel reactive antibody (PRA) development against the influenza vaccine in kidney transplant recipients.Materials and MethodsOverall, 41 kidney transplant recipients who received the influenza vaccination and 50 kidney transplant recipients (study group) who refused to receive the influenza vaccination (control group) were enrolled in the study. Following basal biochemistry examination, the inactivated trivalent influenza vaccine was administered intramuscularly. Panel reactive antibodies were screened in all patients before and after vaccination on days 30 and 180. The primary outcome variable was development of de novo panel reactive antibodies.ResultsOne patient in the study group developed de novo class I and II PRA at 6 months after vaccination (P > .05), while no antibody development was noted in the control group. Graft dysfunction or biopsy-confirmed rejection was not observed during the follow-up period in both groups.ConclusionThe influenza vaccination is generally effective and safe in solid organ transplant recipients. The vaccination procedure has the potential to trigger antibody development and occurrence of rejection. Therefore, vaccinated kidney transplant recipients should be monitored more carefully with regard to PRA; if the graft deteriorates, a rapid transplant biopsy should be performed.     

Comparison of Humoral Response in Kidney Transplant Recipients and Donors and Healthy Volunteers Following Second Dose of SARS-CoV-2 mRNA Vaccine

PurposeTo investigate the kinetics and durability of anti-spike glycoprotein (S) immunoglobulin G (IgG) after the second dose of mRNA-based SARS-CoV-2 vaccine in kidney transplant recipients (recipients) compared with those in kidney donors (donors) and healthy volunteers (HVs) and identify factors negatively associated with SARS-CoV-2 vaccine effectiveness in recipients.MethodsWe enrolled 378 recipients with no history of COVID-19 and no anti-S-IgG before the first vaccine and who received a second mRNA-based vaccine dose. Antibodies were detected using an immunoassay more than 4 weeks after the second vaccine dose. Anti-S-IgG <0.8, ≥0.8 to 15, and ≥15 U/mL were considered negative, weak positive, and strongly positive, respectively, whereas anti–nucleocapsid protein IgG was negative. Anti-S-IgG titer was determined in 990 HVs and 102 donors.ResultsAnti-S-IgG titers were 154, 2475, and 1181 U/mL in the recipient, HV, and donor groups, respectively, with values significantly lower in recipients. The anti-S-IgG-positivity rate of recipients gradually increased following the second vaccination, suggesting that recipients had a delayed response compared with the HV and donor groups, who had a 100% positivity rate at an earlier time point. Anti-S-IgG titers decreased in donors and HVs, whereas they remained stable in recipients, although at a significantly lower level. Independent negative factors associated with anti-S-IgG titers in recipients were age >60 years and lymphocytopenia (odds ratio: 2.35 and 2.44, respectively).ConclusionsKidney transplant recipients demonstrate delayed and attenuated responses, with lower SARS-CoV-2 antibody titers after the second dose of the mRNA-based COVID-19 vaccine.     

Serologic Status According Severe Acute Respiratory Syndrome Coronavirus 2 in Patients After Orthotopic Heart Transplantation

BackgroundThe SARS-CoV-2 pandemic is ongoing. In this context, patients after organ transplantation are especially endangered because of their increased susceptibility to infections. Real effectiveness of vaccinations against SARS-CoV-2 and exposition to the virus in populations after organ transplantation is still being assessed.MethodsWe investigated 371 adult patients (82.7% men, 17.3% women), aged 54 ± 14 years, with a median time from transplantation of 1296 days (interquartile range, 473-400 days) after orthotopic heart transplantation consecutively admitted to the transplant center between February and September 2021. SARS-CoV-2 spike protein antibodies were assessed quantitatively by Elecsys Anti-SARS-CoV-2 S. Data according to past COVID-19 infection and vaccination were compared with the test results.Among the whole group, 59 patients were unvaccinated and had no past COVID-19 infection, 200 patients had a full course of vaccination (2 doses) with an mRNA vaccine, 1 patient had received a viral vector vaccine, 11 patients had had a single dose of an mRNA vaccine, and 99 patients had previously had a COVID-19 infection. Median time from vaccination to antibody assessment was 54 days (interquartile range, 30-76 days).AimThe aim of this study was to determine exposure to the virus among patients after heart transplantation before vaccination and humoral response to the vaccination and assess the role of antispike antibodies in the prevention of infection.ResultsAfter vaccination, 22.3% had no antibodies (45 patients), 47.3% had titers between 0.8 U/mL [0.82 binding antibody units (BAU)/mL] and 250 U/mL (257.25 BAU/mL; 95 patients), and 30.2% had titers above 250 U/mL (257.25 BAU/mL; 61 patients). After a single dose of vaccine, 63% patients had no antibodies. In the group of unvaccinated patients, 3 patients had titers above 250 U/mL (257.25 BAU/mL; 5.1%) and 12 patients had titers up to 250 U/mL (257.25 BAU/mL; 20.3%).In patients after COVID-19 infection, only 2% did not show antispike antibodies, and in 61.4% the titers were above 250 U/mL (257.25 BAU/mL).In the group of patients infected after the full course of vaccination (4 patients after a single dose and 2 after 2 doses), none of the patients developed antibodies after vaccination. Up to the end of September 2021, none of the patients with antibodies against SARS-CoV-2 developed COVID-19.ConclusionsThe presence of spike protein antibodies may be a relevant marker of effective vaccination. In patients after heart transplantation, exposure to SARS-CoV-2 is high.     

SARS-CoV-2 Infection After Vaccination: Kidney Transplant Recipient Profile and Disease Evolution in a Single Center

BackgroundSARS-CoV-2 infection has had a major impact on kidney transplant patients. Recent evidence suggests that solid organ transplant recipients who received mRNA vaccines reach low immunization rates. There are only few reports about the risk factors and severity of COVID-19 in these patients. Our single center experience describes the patient profile and disease evolution observed in this vulnerable group after inoculation.Material and MethodsRetrospective cohort study with kidney transplant patients who received a COVID-19 vaccine before testing positive for SARS-CoV-19 using polymerase chain reaction. Demographic characteristics and clinical information are described and compared with our previous series of patients who were infected before the initiation of the vaccination rollout.ResultsSixteen kidney transplant recipients diagnosed with COVID-19 after being vaccinated were included and compared with our previous series of 76 unvaccinated patients who were positive for COVID-19. No differences were found among risk factors such as age, time after transplant, hypertension, and obesity between groups (P value > .05). After COVID-19 diagnosis among inoculated patients, 10 patients were hospitalized, and 4 of who met the criteria for admission to the intensive care unit. Three patients died of COVID-19 complications. Despite this, the incidence of infections has decreased after vaccination rollout (P value < .05).ConclusionsPatients’ risk profiles remain constant among recipients who were positive for COVID-19 between waves. We did not find significant differences in hospitalization and severity rates in this reduced group of patients. However, the overall incidence in our kidney transplant population has decreased.     

Retrospective Evaluation of COVID-19 Infection and COVID-19 Vaccines in Heart Transplant Patients

BackgroundPatients who have performed solid organ transplantation in terms of COVID-19 infection are included in the high-risk group. In this study, it was aimed to evaluate the relationship between vaccination and retrospective evaluation of 32 patients who underwent a heart transplant in the clinic and tested positive for SARS-CoV-2 polymerase chain reaction.MethodsIn this study, demographic characteristics of the cases, comorbidities, timing of heart transplantation, immunosuppressive treatments, symptoms of COVID-19 infection, lung imaging findings, follow-up (outpatient/inpatient), treatments, 1-month mortality, and vaccination histories against COVID-19 infection were evaluated. The data obtained from the study were analyzed with SPSS version 25.0.ResultsThe 3 most common symptoms are cough (37.5%), myalgia (28.1%), and fever (21.8%). COVID-19 infection was severe in 6.2% of the patients, moderate in 37.5%, and mild in 56.2%. Hospitalization was required in 5 patients (15.6%, 1 in the intensive care unit), and the other patients were followed up as an outpatient. Severe COVID-19 infection was seen more in 33% of unvaccinated patients; 93.5% were vaccinated. Nineteen patients (68%) were vaccinated before COVID-19 infection. Our patients received the CoronoVac (Sinovac, China) vaccine.ConclusionCOVID-19 infection is more likely to be severe and mortal in patients with heart transplant recipients. It is also crucial to comply with preventive measures other than immunization in this group of patients. This study is the largest series investigating COVID-19 infection in heart transplant recipient patients in our country.     

Serologic response to a third dose of an mRNA-based SARS-CoV-2 vaccine in lung transplant recipients

Lung transplant recipients have an increased risk for severe coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A third dose of a SARS-CoV-2 vaccine has been recommended for all solid organ transplant recipients, but data from lung transplant recipients specifically are scarce. In this study, the serologic response to a third dose of an mRNA-based SARS-CoV-2 vaccine was measured in 78 lung transplant recipients. Sixty-two percent (n = 48) had a serological response to vaccination, which was significantly higher than after the second vaccine dose (27 patients (35%); p = 0.0013). A positive serologic response was associated with having had COVID-19 (p = 0.01), and higher serum IgG level and complement mannose binding lectin pathway activity prior to vaccination (p = 0.04 and p = 0.03, respectively). Serologic response was not associated with the dose of mycophenolate mofetil or prednisone or other immune status parameters. Eleven patients (14%) developed COVID-19 after the second or third vaccine dose, but this did not associate with serologic response after the second vaccine dose (9% in patients who developed COVID-19 versus 39% in patients who did not develop COVID-19 (p = 0.09)), or with serologic response above cut-off values associated with clinical protection in previous studies. In conclusion, the response to mRNA-based SARS-CoV-2 vaccines in lung transplant recipients improves significantly after a third vaccine dose. Factors associated with a positive serologic response are having had COVID-19 prior to vaccination, and serum IgG and complement mannose binding lectin pathway activity prior to vaccination. Serologic response did not associate with clinical protection against COVID-19 in this study.     

Evaluation of the Correlation Between Responders and Non-Responders to the Second Coronavirus Disease Vaccination In Kidney Transplant Recipients: A Retrospective Single-Center Cohort Study

BackgroundThe immune response to COVID-19 vaccination in kidney transplant (KTx) recipients is significantly lower than that in healthy controls. We evaluated immune responses after the COVID-19 vaccine and their possible relationship with other cofactors in KTx recipients.MethodsThis retrospective single-center cohort study included 29 KTx recipients 2-8 weeks after receiving 2 doses of the Pfizer-BioNTech SARS-CoV-2 messenger RNA vaccine. Anti-SARS-CoV-2 spike (S) immunoglobulin (Ig)-G levels were evaluated to define cofactors influencing the immune response between the responder (anti-SARS-CoV-2 IgG level ≥0.8 U/mL) (n = 16) and nonresponder groups (anti-SARS-CoV-2 IgG level <0.8 U/mL) (n = 13). The kinetics of antibodies between 2 and 6 months after the second vaccination was also compared between the groups.ResultsKTx recipients with IgG levels ≥0.8 U/mL were younger (54 [interquartile range {IQR}, 46.5-61] years vs 65 [IQR, 55-71.5] years; P = .01), had been transplanted for a longer median time (1588 [IQR, 1382-4751] days vs 1034 [IQR, 548.5-1833] days; P = .02), and were more often treated with a lower mycophenolate mofetil dosage (765.6 ± 119.6 vs 1077 ± 76.9 mg; P = .04) than KTx recipients with IgG levels <0.8 U/mL. There was no significant difference in antibody titers between time periods after the second dose in the responder group. At the 6-month follow-up, a serologic response against the SARS-CoV-2 S was observed in 44.4% of KTx recipients in the nonresponder group.ConclusionsMore than 50% of KTx recipients developed a higher antibody response after the second dose of COVID-19 vaccination.     

Humoral and cellular immune response and safety of two-dose SARS-CoV-2 mRNA-1273 vaccine in solid organ transplant recipients

Solid organ transplant recipients are at high risk of severe disease from COVID-19. We assessed the immunogenicity of mRNA-1273 vaccine using a combination of antibody testing, surrogate neutralization assays, and T cell assays. Patients were immunized with two doses of vaccine and immunogenicity assessed after each dose using the above tests. CD4+ and CD8+ T cell responses were assessed in a subset using flow-cytometry. A total of 127 patients were enrolled of which 110 provided serum at all time points. A positive anti-RBD antibody was seen in 5.0% after one dose and 34.5% after two doses. Neutralizing antibody was present in 26.9%. Of note, 28.5% of patients with anti-RBD did not have neutralizing antibody. T cell responses in a sub-cohort of 48 patients showed a positive CD4+ T cell response in 47.9%. Of note, in this sub-cohort, 46.2% of patients with a negative anti-RBD, still had a positive CD4+ T cell response. The vaccine was safe and well-tolerated. In summary, immunogenicity of mRNA-1273 COVID-19 vaccine was modest, but a subset of patients still develop neutralizing antibody and CD4+T- cell responses. Importantly polyfunctional CD4+T cell responses were observed in a significant portion who were antibody negative, further highlighting the importance of vaccination in this patient population. IRB Statement: This study was approved by the University Health Network Research Ethics Board (CAPCR ID 20–6069).     

COVID-19 and solid organ transplantation: Finding the right balance

BackgroundThe COVID-19 pandemic has a great impact on solid organ transplant (SOT) recipients due to their comorbidities and their maintenance immunosuppression. So far, studies about the different aspects of the impact of the pandemic on SOT recipients are limited.ObjectivesThis systematic review summarizes the risk factors that make SOT patients more vulnerable for severe COVID-19 disease or mortality and the impact of immunosuppressive therapy. Furthermore, their clinical outcomes, mortality risk, immunosuppression, immunity and COVID-19 vaccination efficacy are discussed.MethodsA systematic search on PubMed was performed to select original articles on SOT recipients concerning the following four topics: (1) mortality and clinical course; (2) risk factors for mortality and composite outcomes; (3) maintenance immunosuppression; (4) immunity to COVID-19 infection and (5) vaccine immunogenicity. Relevant data were extracted, analyzed and summarized in tables.ResultsThis systematic review includes 77 articles. Mortality was associated with advanced age. Post-transplantation time or comorbidities were variably identified as independent risk factors for mortality or severe disease. However, generally, no comorbidity was reported as a major risk factor. SOT recipients have a higher risk of acute kidney injury, but no higher rate of mortality compared to non-transplanted patients was found. Immunosuppression was individually adjusted, without leading to high rates of graft dysfunction. Generally, no association between type of immunosuppression and mortality was found. SOT patients established humoral and cellular immune responses after COVID-19 disease comparable to immunocompetent people. At last, SOT patients experience a diminished immune response after two-dose vaccination with SARS-COV-2-mRNA-vaccines.ConclusionMore research is needed to address the direct effect of COVID-19 disease on the graft in lung transplant recipients, as well as the factors ameliorating the immune response in SOT recipients.     

Cellular immunity predominates over humoral immunity after homologous and heterologous mRNA and vector-based COVID-19 vaccine regimens in solid organ transplant recipients

Knowledge on the immunogenicity of vector-based and mRNA-vaccines in solid organ transplant recipients is limited. Therefore, SARS-CoV-2–specific T cells and antibodies were analyzed in 40 transplant recipients and 70 controls after homologous or heterologous vaccine-regimens. Plasmablasts and SARS-CoV-2–specific CD4 and CD8 T cells were quantified using flow cytometry. Specific antibodies were analyzed by ELISA and neutralization assay. The two vaccine types differed after the first vaccination, as IgG and neutralizing activity were more pronounced after mRNA priming (p = .0001 each), whereas CD4 and CD8 T cell levels were higher after vector priming (p = .009; p = .0001). All regimens were well tolerated, and SARS-CoV-2–specific antibodies and/or T cells after second vaccination were induced in 100% of controls and 70.6% of transplant recipients. Although antibody and T cell levels were lower in patients, heterologous vaccination led to the most pronounced induction of antibodies and CD4 T cells. Plasmablast numbers were significantly higher in controls and correlated with SARS-CoV-2–specific IgG- and T cell levels. While antibodies were only detected in 35.3% of patients, cellular immunity was more frequently found (64.7%) indicating that assessment of antibodies is insufficient to identify COVID-19-vaccine responders. In conclusion, heterologous vaccination seems promising in transplant recipients, and combined analysis of humoral and cellular immunity improves the identification of responders among immunocompromised individuals.     

Low Performance of Sinovac Vaccine Particularly With Belatacept Therapy in a Study With Different Types of COVID-19 Vaccines in Transplanted Patients

The huge impact of SARS-CoV-2 infections on organ transplant recipients makes it necessary to optimize vaccine efficacy in this population. To effectively implement multiple strategies, it is crucial to understand the performance of each type of available vaccine. In our study, the antibody titer was measured, and the presence of antibodies against SARS-CoV-2 was evaluated after 90 days of immunization; furthermore, the differences between hybrid immunity, immunity by vaccination, and immunosuppressant type were identified. As a result, of the patients included in this study (n = 160), 53% showed antibodies against SARS-CoV-2 90 days after the first dose in patients who had completed the vaccination schedule. Antibody titers were higher in patients with hybrid immunity, and the proportion of nonresponsive patients was higher among those who received the immunosuppressant belatacept in their post-transplant regimen (P = .01). Only 15% of patients treated with this medicine seroconverted and patients vaccinated with CoronaVac and treated with belatacept showed no response. In conclusion, a reduced response to vaccines against SARS-CoV-2 was identified in the transplant population, and this response varied with the type of vaccine administered and the immunosuppressive treatment.     

Evaluation of SARS-CoV-2 Serum Level in Patients Vaccinated With Sinopharm/BBIBP-CorV With Kidney Transplantation

BackgroundEvery year, a large number of people undergo kidney transplants because of various reasons leading to renal failure. These patients usually have low immunoglobulin levels due to the use of immunosuppressive drugs. In recent years, the COVID-19 pandemic has been a major global health risk. Patients who are immunocompromised or who have diabetes are especially at risk.MethodsIn this study, we enrolled 156 patients who had undergone kidney transplant and had received 2 doses of Sinopharm/BIBP-CorV. The serum antibody levels against COVID-19 spike glycoprotein (immunoglobulin [Ig] G and IgM) were measured using a sandwich enzyme-linked immunosorbent assay kit to evaluate whether different immunosuppressive drugs could affect the body's response to the said vaccine.ResultsWe found that only patients receiving Rapamune had increased IgM secondary to COVID-19 vaccine. None of the immunosuppressive drugs in this study have shown a positive correlation with increased IgG levels. The only factor that showed a significant effect on both IgM and IgG was a positive history of COVID-19, which was correlated with increased levels of serum IgG/M.ConclusionsOnly patients treated with Rapamune showed an acute immune reaction to the vaccine in the form of positive serum IgM levels, and no rise of serum IgM antibody was observed in COVID-19-naive patients. Patients who had a previous history of COVID-19 infection showed an elevated serum IgM and IgG level, suggesting that vaccines in general and Sinopharm/BIBP-CorV in particular are not enough to ensure immunity against COVID-19 in transplant recipients. We recommend further studies using different types of vaccines and immunosuppressive drugs.     

Immunologic response and seroconversion following third-dose COVID-19 vaccination in solid organ transplant recipients: A meta-analysis

IntroductionThe immunogenicity and efficacy of COVID-19 vaccination varied by demographic, including solid organ transplant recipients on immunosuppressive therapy.AimThis purpose of this study is to assess seropositivity and seroconversion in solid-organ transplant recipients before and after third-dose COVID-19 vaccination.MethodsThis study is a systematic review and meta-analysis performed using PRISMA guidelines. To analyze clinical and cohort studies reporting immunologic response and seroconversion third-dose vaccination, a systematic search was performed using electronic databases (PubMed, Scopus, Cochrane, Directory of Open Access Journal (DOAJ), and Clinicaltrials.gov).ResultThere were 18 full-text papers that could be analyzed qualitatively and quantitatively. After the third vaccination, the pooled rate seropositivity was 67.00% (95% CI 59.511; 74.047, I2 = 93.82%), and the pooled rate seroconversion was 52.51% (95% CI 44.03; 60.91, I2 = 92.15%). The pooled rate of seroconversion after the mRNA-based booster was 52.380% (95% CI 40.988; 63.649, I2 = 94.35%), and after the viral-vector-based booster was 42.478% (95% CI 35.222; 49.900, I2 = 0.00%).ConclusionBased on the analysis of immunologic responses and seroconversion findings, the third-dose vaccination of solid organ transplant recipients is an effective method in establishing better immunity against COVID-19.     

Serologic response to COVID-19 infection or vaccination in pediatric kidney transplant recipients compared to healthy children

BackgroundDifferences in serologic response to COVID-19 infection or vaccination were reported in adult kidney transplant recipients (KTR) compared to non-immunocompromised patients. This study aims to compare the serologic response of naturally infected or vaccinated pediatric KTR to that of controls.MethodsThirty-eight KTR and 42 healthy children were included; aged ≤18 years, with a previously confirmed COVID-19 infection or post COVID-19 vaccination. Serological response was measured by anti-spike protein IgG antibody titers. Response post third vaccine was additionally assessed in KTR.ResultsFourteen children in each group had previously confirmed infection. KTR were significantly older and developed a 2-fold higher antibody titer post-infection compared to controls [median (interquartile range [IQR]) age: 14.9 (7.8, 17.5) vs. 6.3 (4.5, 11.5) years, p = 0.02; median (IQR) titer: 1695 (982, 3520) vs. 716 (368, 976) AU/mL, p = 0.03]. Twenty-four KTR and 28 controls were vaccinated. Antibody titer was lower in KTR than in controls [median (IQR): 803 (206, 1744) vs. 8023 (3032, 30,052) AU/mL, p < 0.001]. Fourteen KTR received third vaccine. Antibody titer post booster in KTR reached similar levels to those of controls post two doses [median (IQR) 5923 (2295, 12,278) vs. 8023 (3034, 30,052) AU/mL, p = 0.37] and to KTR post natural infection [5282 AU/mL (2583, 13,257) p = 0.8].ConclusionSerologic response to COVID-19 infection was significantly higher in KTR than in controls. Antibody level in KTR was higher in response to infection vs. vaccination, contrary to reports in the general population. Response to vaccination in KTR reached levels comparable to controls only after third vaccine.     

Mortality Due to COVID-19 in Renal Transplant Recipients,Related to Variants of SARS-CoV-2 and Vaccination in Mexico

BackgroundSARS-CoV-2 infection in transplant patients has shown greater lethality and vaccination in this group of patients has shown less information. The objective of this study is to show the statistics in Mexico of lethality in kidney recipients infected with COVID-19 in relation to vaccination and variants of the coronavirus.MethodsThis is a bibliographic search of kidney transplant recipient patients since the start of the pandemic in Mexico to determine lethality after SARS-CoV-2 compared to the general population and in relation to patients, the 4 most important infectious peaks in the country due to identified variants, and also before and after vaccination.ResultsThe global lethality is 26.91% from the beginning of the pandemic to April 9, 2022 in kidney recipients in Mexico (130 deaths of 483 infected kidney transplant recipients) compared to the national lethality of 5.60%. Variant B. 1.1.220 represented the highest lethality with 30.43% and the lowest lethality was Omicron with 16.41%. The lethality prior to vaccination was 30.94% and 23.46% after it.ConclusionBoth some variants and vaccination have influenced a lower lethality due to COVID-19 in Mexico in kidney transplant patients; It is important to consider global recommendations, such as a third or fourth dose, a combination of mRNA vaccines and vectors in order to reduce lethality in this group of patients.     

Immunogenicity and Safety of an Intradermal Boosting Strategy for Vaccination Against Influenza in Lung Transplant Recipients

The immunogenicity of influenza vaccine is suboptimal in lung transplant recipients. Use of a booster dose and vaccine delivery by the intradermal rather than intramuscular route may improve response. We prospectively evaluated the immunogenicity and safety of a 2-dose boosting strategy of influenza vaccine. Sixty lung transplant recipients received a standard intramuscular injection of the 2006-2007 inactivated influenza vaccine, followed 4 weeks later by an intradermal booster of the same vaccine. Immunogenicity was assessed by measurement of geometric mean titer of antibodies after both the intramuscular injection and the intradermal booster. Vaccine response was defined as 4-fold or higher increase of antibody titers to at least one vaccine antigen. Thirty-eight out of 60 patients (63%) had a response after intramuscular vaccination. Geometric mean titers increased for all three vaccine antigens following the first dose (p < 0.001). However, no significant increases in titer were observed after the booster dose for all three antigens. Among nonresponders, 3/22 (13.6%) additional patients responded after the intradermal booster (p = 0.14). The use of basiliximab was associated with a positive response (p = 0.024). After a single standard dose of influenza vaccine, a booster dose given by intradermal injection did not significantly improve vaccine immunogenicity in lung transplant recipients.     

Humoral Response After SARS-CoV-2 Vaccination in Kidney Transplant Recipients: Role of Immunosuppression Therapy

BackgroundMessenger RNA vaccination against COVID-19 has been shown to produce an immune response with sufficient efficacy to prevent natural infection in immunocompetent recipients. However, the response in kidney transplant recipients is low. We aimed to evaluate the specific humoral response to SARS-CoV-2 after vaccination in a population of kidney transplant recipients and assess the main factors associated with a lack of response.MethodsWe undertook a prospective study of 105 kidney transplant recipients and 11 recipients of a combined kidney-pancreas transplant. We analyzed immunoglobulin G and immunoglobulin M antibodies after the patients received their second and third doses of the messenger RNA 1273 (Moderna) or BNT162b1 (BionTECH-Pfizer) vaccinations between February and November 2021.ResultsMean (SD) age of the 116 patients was 50 (16) years, and 65% were men. They had their transplants for 40 months (IQR, 15-123 months), with 14% undergoing retransplant and 11% sensitized. The maintenance immunosuppression regimen was steroids + tacrolimus + mycophenolate (MMF) in 68% of the patients and any combination with mammalian target of rapamycin inhibitor (mTORi) in 28%. A humoral response developed in 40% of the patients 6 weeks (IQR, 4-10 weeks) after receiving the second dose of the vaccine. Of the 67 patients with no response to the second dose, 51 had an analysis of the humoral response after the third dose, which was positive in 16 (31%). A total of 80% received the Moderna vaccine and 20% the BionTECH-Pfizer. No patient experienced major adverse effects after the vaccination.Factors associated with a lack of humoral response to the vaccine were recipient age (odds ratio [OR], 1.02; 95% CI, 1.001-1.05; P = .04), diabetes (OR, 2.8; 95% CI, 1.2-6.9; P = .02), and treatment with MMF (OR, 2.6; 95% CI, 1.08-6.8; P = .03). Treatment with mTORi was associated with a better response to vaccination (OR, 0.3; 95% CI, 0.1-0.9; P = .04).ConclusionsThe humoral response to the COVID-19 vaccine in kidney transplant recipients is poor. Factors related with this lack of immunity are recipient age and diabetes, plus MMF therapy, whereas mTORi therapy was associated with a better response to vaccination.     

Influenza and pneumococcal vaccination and COVID-19 in kidney transplant patients

BackgroundThis study aims to investigate the effect of recent influenza and pneumococcal vaccines' administration on the development of COVID-19 infection in kidney transplant recipients during the pandemic.MethodsThe effect of influenza and pneumococcal vaccines on the clinical course of the disease in COVID-positive (COVID group, n: 105) and COVID-negative (control group, n: 127) recipients has been examined. The control group included patients with negative rRT-PCR test results. At the time of the study, no patient was vaccinated with COVID-19 vaccine. The patients' influenza and/or pneumococcal vaccination rates in 2019 and 2020 were determined. In 2019 and 2020, 32 and 33 people in the COVID-positive group and 61 and 54 people in the COVID-negative group had received influenza and/or pneumococcal vaccines, respectively. The median study follow-up times of the COVID-negative and COVID-positive groups were 13.04 and 8.31 months, respectively.ResultsCompared with the COVID-negative group, the patients in the COVID-positive group were younger and had a longer post-transplant time. In addition, the rate of transplantation from a living donor and the rate of COVID positivity in family members were also higher. The influenza vaccination rates in the COVID negative group were significantly higher than the COVID-positive group in 2020 (23.8% vs 37%, p = 0.031). Multivariate logistic regression analysis revealed that the presence of COVID-19 in family members and lack of pneumococcal vaccination in 2020 increased the risk of being positive for COVID-19. There was no significant difference in the hospitalization rates, the need for dialysis and intensive care, the hospital stay, and the graft dysfunction in the COVID-positive patients with and without influenza and pneumococcal vaccines.ConclusionThe observations made throughout this study suggest that influenza and pneumococcal vaccination in transplant patients may reduce the risk of COVID-19 disease and provide additional benefits during the pandemic period.     

Positive flow cytometry crossmatch with discrepant antibody testing results following COVID-19 vaccination

The impact of COVID-19 vaccination on the alloimmunity of transplant candidates is unknown. We report a case of positive B cell flow cytometry crossmatch in a patient waiting for second kidney transplantation, 37 days after receiving the COVID-19 vaccine. The preliminary crossmatch, using sample collected before COVID-19 vaccination, was negative. The antibodies to mismatched donor HLA-DR7 were detected only with multi-antigen beads but not with single-antigen beads, excluding possible prozone effects in solid-phase antibody assays. The crossmatches were positive with HLA-DR7–positive surrogates (n = 2) while negative with HLA-DR7–negative surrogates (n = 3), which confirms the HLA-DR7 alloreactivity. The antigen configurations on B lymphocytes are similar to that on the multi-antigen beads while distinct from the single-antigen beads. HLA-DR7 was the repeating mismatched antigen with the failing first kidney allograft. The newly emerged antibody to HLA-DR7 probably is the consequence of bystander activation of memory response by the COVID-19 vaccination. This case highlights the importance of verifying allo-sensitization history and utilizing multiple assays, including cell-based crossmatch and solid-phase assays with multi-antigens. COVID-19 immunization may deserve special attention when assessing the immunological risk before and after organ transplantation.