Benotmane, I., et al. (2021). “Strong antibody response after a first dose of a SARS-CoV-2 mRNA-based vaccine in kidney transplant recipients with a previous history of COVID-19.” American Journal of Transplantation [record in progress].
Boyarsky, B. J., et al. (2021). “SARS-CoV-2 Messenger RNA Vaccine Immunogenicity in Solid Organ Transplant Recipients With Prior COVID-19.” Transplantation [record in progress].
Boyarsky, B. J., et al. (2021). “Antibody Kinetics and Durability in SARS-CoV-2 mRNA Vaccinated Solid Organ Transplant Recipients.” Transplantation [record in progress].
Chenxi Song, C., et al. (2021). “Early experience with SARs-CoV-2 mRNA vaccine breakthrough among kidney transplant recipients.” Transplant Infectious Disease [record in progress]: e13654.
Harhay, M. N., et al. (2021). “Living Organ Donor Perspectives and Sources of Hesitancy about COVID-19 Vaccines.” Kidney360 2(7): 1132-1140.
BACKGROUND: Living organ donation declined substantially in the United States during the COVID-19 pandemic due to concerns about donor and transplant candidate safety. COVID-19 vaccines might increase confidence in the safety of living organ donation during the pandemic. We assessed informational preferences and perspectives about COVID-19 vaccines among US living organ donors and prospective donors. METHODS: We conducted a national survey study of organ donors and prospective donors on social media platforms between 12/28/2020-2/23/2021. Survey items included multiple choice, visual analog scale, and open-ended responses. We examined associations between information preferences, history of COVID-19 infection, influenza vaccination history and COVID-19 vaccine acceptance using multivariable logistic regression and performed a thematic analysis of open-ended responses. RESULTS: Among 342 respondents from 47 US states and the District of Columbia, 35% were between 51-70 years old, 90% were non-Hispanic white, 87% were women; 82% were living donors (94% kidney) and 18% in evaluation to donate (75% kidney).The majority planned to or had received COVID-19 vaccination (76%), whereas 11% did not plan to be receive a vaccine, and 12% were unsure. Adjusting for demographics and donor characteristics, respondents who receive yearly influenza vaccinations had higher COVID-19 vaccine acceptance than those who do not (adjusted Odds Ratio [aOR] 5.06, 95% Confidence Interval [CI] 2.68-9.53). Compared to respondents who prioritized medical information sources (e.g., personal physicians and transplant providers), those who prioritized news and social media had lower COVID-19 vaccine acceptance (aOR 0.34, 95% CI 0.15-0.73). Low perceived personal benefit from vaccination and uncertainty about long-term safety were common themes among those declining COVID-19 vaccines. CONCLUSIONS: Donor informational source preferences were strongly associated with the likelihood of accepting a COVID-19 vaccine. Vaccine guidance for organ donors who are unsure about COVID-19 vaccines could incorporate messaging about safety and benefits of vaccination for healthy people.
Herrera, S., et al. (2021). “Cellular and humoral immune response after mRNA-1273 SARS-CoV-2 vaccine in liver and heart transplant recipients.” American Journal of Transplantation [record in progress].
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 liver and heart transplant recipients. We prospectively studied heart and liver transplant recipients eligible for SARS-CoV-2 vaccination. Patients with past history of SARS-CoV-2 infection or SARS-CoV-2 detectable antibodies (IgM or IgG) were excluded. We assessed IgM/IgG antibodies and ELISpot against the S protein 4 weeks after receiving the second dose of the mRNA-1273 (Moderna) vaccine. Side effects, troponin I, liver tests and anti-HLA donor-specific antibodies (DSA) were also assessed. A total of 58 liver and 46 heart recipients received two doses of mRNA-1273 vaccine. Median time from transplantation to vaccination was 5.4 years (IQR 0.3-27). Sixty-four percent of the patients developed SARS-CoV-2 IgM/IgG antibodies and 79% S-ELISpot positivity. Ninety percent of recipients developed either humoral or cellular response (87% in heart recipients and 93% in liver recipients). Factors associated with vaccine unresponsiveness were hypogammaglobulinemia and vaccination during the first year after transplantation. Local and systemic side effects were mild or moderate, and none presented DSA or graft dysfunction after vaccination. Ninety percent of our patients did develop humoral or cellular responses to mRNA-1273 vaccine. Factors associated with vaccine unresponsiveness were hypogammaglobulinemia and vaccination during the first year after transplantation, highlighting the need to further protect these patients.
Hod, T., et al. (2021). “Humoral Response of Renal Transplant Recipients to the BNT162b2 SARS-CoV-2 mRNA Vaccine Using Both RBD IgG and Neutralizing Antibodies.” Transplantation [record in progress].
BACKGROUND: Data about SARS-CoV-2 vaccines efficacy in renal transplant recipients (RTR) is lacking. METHODS: To reveal predictors for humoral response to BNT162b2 vaccine among RTR, patients were divided to positive (N=42) and negative (N=78) response groups based on receptor-binding domain (RBD) IgG >= 1.1 and neutralizing antibodies (NA) >= 16 dilution versus RBD IgG < 1.1 or NA < 16 respectively. NA were detected using a SARS-CoV-2 pseudo-virus. RESULTS: NA were detected in only 42/120 (35%) of RTR vs. 197/202 (97.5%) immunocompetent controls (p < 0.001). NA geometric mean titers (GMTs) in RTR were significantly lower vs. the control group [83.7 (95% CI 50.5-138.8) vs. 482 (95% CI 411-566), p < 0.001]. In a multivariable analysis, mycophenolic acid (MPA) dose and hemoglobin (Hb) level were found to be independent predictors for antibody response in RTR. A positive response rate of 27% vs. 63% was observed in patients on and off MPA, respectively. An increase in MPA dose by 1 mg/kg weight reduced the odds for a positive response by 17% (OR 0.83, 95% CI 0.75-0.92, p<0.001). GMTs for RBD IgG were significantly reduced as MPA daily dose increased. Hb blood level < 13 g/dL reduced the antibody response by 63% (p=0.04). Pain at the injection site after the second vaccine dose was significantly higher in the responders vs. nonresponders (20.5% vs. 5.5%, p=0.01). CONCLUSIONS: Only 35% of RTR develop NA to the BNT162b2 mRNA vaccine. MPA is a major suppressor of antibody response in RTR.
Holden, I. K., et al. (2021). “Immunogenicity of SARS-CoV-2 mRNA vaccine in solid organ transplant recipients.” Journal of Internal Medicine [record in progress].
BACKGROUND: It is currently not well described if a two-dose regimen of a Covid-19 vaccine is sufficient to elicit an immune response in SOT recipients.
RESULTS: A total of 80 solid organ transplant (SOT) recipients completed a two-dose regimen with SARS-CoV-2 messenger RNA vaccine. Only 35.0% (n = 28) were able to mount a positive IgG immune response six weeks after the second dose of vaccine.
CONCLUSION: This emphasizes that SOT recipients need continued use of personal protective measures. Future studies need to closely examine the cellular immune response in patients with compromised antibody response to Covid-19 vaccination.
Malinis, M., et al. (2021). “Effectiveness of SARS-CoV-2 vaccination in fully vaccinated solid organ transplant recipients.” American Journal of Transplantation 21(8): 2916-2918.
The COVID‐19 pandemic has disproportionately impacted immunosuppressed patients, including solid organ transplant recipients (SOTR). COVID‐19‐associated mortality among SOTR was estimated at 20.5% in the early phase of the pandemic(1). SARS‐CoV‐2 vaccination may help reduce the morbidity and mortality of COVID‐19 among SOTR. Under emergency use authorization, the US Food Drug Administration approved two SARS‐CoV‐2 messenger RNA vaccines [BNT162b2 (Pfizer), mRNA‐1273 (Moderna)] and an adenovirus vector‐based vaccine [Ad26.COV2.S (Johnson and Johnson)].
Mazzola, A., et al. (2021). “Poor Antibody Response after Two Doses of SARS-CoV-2 vaccine in Transplant Recipients.” Clinical Infectious Diseases [record in progress].
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 COVID-19. No serious adverse events were recorded. Four severe COVID-19 cases were reported between or after the two doses. Our data suggests to change the vaccine strategy.
Narasimhan, M., et al. (2021). “Serological Response in Lung Transplant Recipients after Two Doses of SARS-CoV-2 mRNA Vaccines.” Vaccines 9(7): 708.
BACKGROUND: Lung-transplant (LT) recipients are at high risk for COVID-19 due to immunosuppression and respiratory tropism of SARS-CoV-2. The information on the effect of COVID-19 mRNA vaccines to elicit immunogenic responses after a two-dose (2D) regimen in LT recipients is sparse. Thus, we assessed the effect of Pfizer-BioNTech and Moderna mRNA vaccines’ 2D regimen on anti-spike responses in immunocompromised LT recipients.
METHODS: We utilized serum samples from LT recipients vaccinated for SARS-CoV-2 with 2D of either the Pfizer-BioNTech or Moderna vaccines and 2D-vaccinated naive (non-transplanted and non-exposed to COVID-19) group. Antibody responses were assessed using the FDA-approved SARS-CoV-2 anti-nucleocapsid protein IgG assay (IgGNC), the SARS-CoV-2 anti-spike protein IgM assay (IgMSP), and the SARS-CoV-2 anti-spike protein IgG II assay (IgGSP). CD4+ T-cell activity was assessed as a marker of immune competence using the ImmuKnow assay.
RESULTS: About 25% (18/73) of SARS-CoV-2 uninfected-LT patients generated a positive spike-IgG response following 2D of vaccines, with 36% (9/25) in the Moderna cohort and only 19% (9/48) in the Pfizer cohort. 2D in LT patients elicited a significantly lesser median IgGSP response (1.7 AU/mL, 95% CI: 0.6-7.5 AU/mL) compared to non-transplanted, uninfected naive subjects (14,209 AU/mL, 95% CI: 11,261-18,836 AU/mL; p < 0.0001). In LT patients, the Moderna-evoked seropositivity trend was higher than Pfizer.
CONCLUSION: 2D COVID-19 vaccination elicits a dampened serological response in LT patients. Whether assessing other arms of host immunity combined with a higher vaccine dose can better capture and elicit improved immunogenicity in this immunocompromised population warrants investigation.
Oehler, D., et al. (2021). “Moderate acceptance of COVID-19 vaccination in patients pre- and post-heart transplantation: Experiences from a German Transplant Centre.” Transplant Infectious Disease [record in progress]: e13681.
INTRODUCTION AND OBJECTIVES: Patients awaiting heart transplantation (HTx) are at increased risk developing severe coronavirus disease 2019 (COVID-19). Patients supported by a left ventricular assist device (LVAD) face additional risks due to coagulopathies during COVID-19. Following HTx, elevated risk factors for severe COVID-19 persist due to chronic immunosuppression and frequent comorbidities. Taken together, COVID-19 vaccination is of critical importance in all three patient cohorts. Here, we report our experience to deliver COVID-19 vaccination in a German transplant center.
METHODS AND RESULTS: We screened 211 patients for contraindications and offered the remaining 186 eligible patients COVID-19 vaccination. Of those, 133 patients (71%) accepted the offer and were vaccinated. Acceptance of vaccination differed between HTx recipients (84 of 113, 74%), patients on the waiting list (34 of 47, 72%), and patients with LVAD support (28 of 50, 56%). The LVAD cohort demonstrated lower acceptance levels for vaccination compared to HTx recipients and patients awaiting HTx (74% vs. 56%; p = 0.028).
CONCLUSION: We demonstrate for the first time only moderate acceptance levels of COVID-19 vaccination in HTx recipients and candidates on the waiting list compared to general population, despite perceived high-risk for severe disease. Additionally, those supported by LVAD have even lower adherence. Efforts may need to be made to increase acceptance in this vulnerable as well as cost-intensive patient cohort.
Rashidi-Alavijeh, J., et al. (2021). “Humoral Response to SARS-Cov-2 Vaccination in Liver Transplant Recipients-A Single-Center Experience.” Vaccines 9(7).
Vaccination against SARS-CoV-2 infection is currently approved and shows favorable outcomes, but little known about antibody responses in solid organ transplant recipients, since these patients are known to have an impaired immune response upon vaccination and have not been included in admission studies. We therefore analyzed immunogenicity in 43 liver transplant (LT) recipients in a median of 15 days (IQR, 12-24) after receiving two doses of the mRNA-based SARS-CoV-2 vaccine BNT162b2 following the standard protocol, and compared these results to a control group consisting of 20 healthcare workers (HCWs). Thirty-four of the 43 (79%) LT recipients developed antibodies, compared to 20 out of 20 (100%) in the control group (p = 0.047). The median SARS-CoV-2 IgG titer was significantly lower in the LT recipients compared to the control group (216 vs. >2080 BAU/mL, p = 0.0001). Age and sex distribution was similar in the LT patients that developed antibodies after vaccination compared to those who did not. Interestingly, the patients who received mycophenolate mofetil exhibited a reduced vaccination response compared to the other LT patients (5 of 11 (45.5%) vs. 29 of 32 (90.6%), p = 0.004). In conclusion, our data reveal lower immunogenicity of SARS-CoV-2 vaccine BNT162b2 in LT patients compared to the control group, but still show superior results compared to other solid organ transplant recipients reported so far.
Schramm, R., et al. (2021). “Poor humoral and T-cell response to two-dose SARS-CoV-2 messenger RNA vaccine BNT162b2 in cardiothoracic transplant recipients.” Clinical Research in Cardiology 110(8): 1142-1149.
AIMS: Immunocompromised patients have been excluded from studies of SARS-CoV-2 messenger RNA vaccines. The immune response to vaccines against other infectious agents has been shown to be blunted in such patients. We aimed to analyse the humoral and cellular response to prime-boost vaccination with the BNT162b2 vaccine (Pfizer-BioNTech) in cardiothoracic transplant recipients.
METHODS AND RESULTS: A total of 50 transplant patients [1-3 years post heart (42), lung (7), or heart-lung (1) transplant, mean age 55 +/- 10 years] and a control group of 50 healthy staff members were included. Blood samples were analysed 21 days after the prime and the boosting dose, respectively, to quantify anti-SARS-CoV-2 spike protein (S) immunoglobulin titres (tested by Abbott, Euroimmun and RocheElecsys Immunoassays, each) and the functional inhibitory capacity of neutralizing antibodies (Genscript). To test for a specific T-cell response, heparinized whole blood was stimulated with SARS-CoV-2 specific peptides, covering domains of the viral spike, nucleocapsid and membrane protein, and the interferon-gamma release was measured (QuantiFERON Monitor ELISA, Qiagen). The vast majority of transplant patients (90%) showed neither a detectable humoral nor a T-cell response three weeks after the completed two-dose BNT162b2 vaccination; these results are in sharp contrast to the robust immunogenicity seen in the control group: 98% exhibited seroconversion after the prime dose already, with a further significant increase of IgG titres after the booster dose (average > tenfold increase), a more than 90% inhibition capability of neutralizing antibodies as well as evidence of a T-cell responsiveness.
CONCLUSIONS: The findings of poor immune responses to a two-dose BNT162b2 vaccination in cardiothoracic transplant patients have a significant impact for organ transplant recipients specifically and possibly for immunocompromised patients in general. It urges for a review of future vaccine strategies in these patients.
Tsapepas, D., et al. (2021). “Perspectives on COVID-19 vaccination among kidney and pancreas transplant recipients living in New York City.” American Journal of Health System Pharmacy [record in progress].
PURPOSE: Solid 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.
METHODS: This 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.
RESULTS: Of 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.
CONCLUSION: Our 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.
Werbel, W. A., et al. (2021). “Safety and Immunogenicity of a Third Dose of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: A Case Series.” Annals of Internal Medicine [record in progress].
Anjan, S., et al. (2021). “Breakthrough COVID-19 infections after mRNA vaccination in Solid Organ Transplant Recipients in Miami, Florida.” Transplantation [record in progress].
Aslam, S., et al. (2021). “Clinical effectiveness of COVID-19 vaccination in solid organ transplant recipients.” Transplant Infectious Disease [record in progress]: e13705.
GOAL: We aimed to assess the incidence rate of coronavirus disease 2019 (COVID-19) in vaccinated versus unvaccinated solid organ transplant recipients (SOTR) at our center.
METHODS: We abstracted the following clinical data from our transplant registry from 1/1/2021 to 6/2/2021: demographics, details of COVID-19 vaccination, incidence of COVID-19, and related mortality. We calculated incidence of symptomatic COVID-19 per 1000/person days at risk and incidence rate ratio (IRR).
RESULTS: Among 2151 SOTRs, 912 were fully vaccinated, and 1239 were controls (1151 unvaccinated, 88 partially vaccinated). Almost 70% of vaccinated subjects received the mRNA-1273 vaccine. There were 65 cases of COVID-19 that occurred during the study period – four occurred among fully vaccinated individuals and 61 among controls (including two in partially vaccinated individuals). Incidence rate for COVID-19 was 0.065 (95% CI 0.024-0.17) per 1000 person days in vaccinated versus 0.34 (95% CI 0.26-0.44) per 1000/person days in the control group; IRR was 0.19 (95% CI 0.049 -0.503, p < 0.005). There were no COVID-19 related deaths in the four breakthrough infections and two of 61 (3.3%) among controls.
CONCLUSION: We demonstrate real world clinical effectiveness of COVID-19 vaccination in SOTRs with an almost 80% reduction in the incidence of symptomatic COVID-19 versus unvaccinated SOTRs during the same time.
Axelrod, D. A., et al. (2021). “Operational challenges in the COVID era: Asymptomatic infections and vaccination timing.” Clinical Transplantation [record in progress].
The coronavirus disease 2019 (COVID-19) pandemic has created unprecedented challenges for solid organ transplant programs. While transplant activity has largely recovered, appropriate management of deceased donor candidates who are asymptomatic but have positive nucleic acid test (NAT) for COVID-19 is unclear as this may reflect active infection or prolonged viral shedding. Furthermore, candidates who are unvaccinated or partially vaccinated continue to receive donor offers. In the absence of prospective data, transplant professionals at U.S. adult kidney transplant centers were surveyed to determine community practice (N: 92 centers, capturing 40.8% of centers and 56.6% of transplants performed). The majority (96.8%) of responding centers declined organs for asymptomatic NAT+ patients without documented prior infection. However, 31.6% of centers proceeded with kidney transplant in NAT+ patients who were at least 30 days from initial diagnosis with negative chest imaging. Less than 7% of programs reported inactivating patients who were unvaccinated or partially vaccinated. In conclusion, despite national recommendations to wait for negative testing, many centers are proceeding with transplant in patients with positive tests due to presumed viral shedding. Furthermore, very few centers are requiring COVID-19 vaccination prior to transplantation despite early evidence suggesting reduced immunogenicity in transplant patients on immunosuppression. This article is protected by copyright. All rights reserved.
Benotmane, I., et al. (2021). “Antibody Response After a Third Dose of the mRNA-1273 SARS-CoV-2 Vaccine in Kidney Transplant Recipients With Minimal Serologic Response to 2 Doses.” JAMA [record in progress].
Cao, J., et al. (2021). “Poor Humoral Response in Solid Organ Transplant Recipients following Complete mRNA SARS-CoV-2 Vaccination.” Clinical Chemistry [record in progress].
Del Bello, A., et al. (2021). “Efficiency of a boost with a third dose of anti-SARS-CoV-2 messenger RNA-based vaccines in solid organ transplant recipients.” American Journal of Transplantation [record in progress].
A weak humoral response to two-doses of SARS-CoV-2 vaccine was observed in solid organ transplant (SOT) patients (1,2). Preliminary reports suggested the usefulness of a boost with a third dose (3) (4). Herein, we report the humoral response in 396 SOT patients (mean age 59 +/- 15 years, 65 % men) who were given 3 doses messenger RNA-based vaccine (BNT162b2 vaccine [Pfizer-BioNTech]) (Table S1). Of these, 101 were included in our previous report (3). The two first doses were given one month apart, and the third dose was administered 59 (IQR<sub>25-75</sub> : 47-67) days after the second dose, i.e. once the third dose was recommended by the French National Authority for Health.
Guarino, M., et al. (2021). “Effectiveness of SARS-Cov-2 vaccination in liver transplanted patients: the debate is open!” Journal of Hepatology [record in progress].
Hall, V. G., et al. (2021). “Humoral and cellular immune response and safety of two-dose SARS-CoV-2 mRNA-1273 vaccine in solid organ transplant recipients.” American Journal of Transplantation [record in progress].
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).
Haskin, O., et al. (2021). “Serological Response to the BNT162b2 COVID-19 mRNA Vaccine in Adolescent and Young Adult Kidney Transplant Recipients.” Transplantation [record in progress].
BACKGROUND: Initial reports in adult kidney transplant recipients (KTR) indicate low immunogenicity after 2 doses of the BNT162b2 COVID-19 mRNA vaccine. We describe the immunogenicity of this vaccine compared to the serologic response in naturally infected COVID-19 positive adolescent and young adult KTR.
METHODS: For this prospective observational study, the study group included 38 KTR who received 2 doses of the tested vaccine; the control group included 14 KTR who had a previous PCR-confirmed COVID-19 infection.
RESULTS: The mean age was 18+/-3 years. Positive serologic responses were observed in 63% and 100% of the study and control groups, respectively (p=0.01). Antibody titers were almost 30-fold higher in the control than the study group [median, interquartile range (IQR): 2782 (1908-11 000) vs. 100.3 (4.7-1744) U/mL, p<0.001), despite the longer time from the COVID-19 infection to serologic testing compared to time from vaccination [median (IQR): 157.5 (60-216) vs 37 (20.5-53) days, p=0.011]. Among vaccinated patients, higher proportions of those seronegative than seropositive were previously treated with rituximab (50% vs. 8%, p=0.01). Time from the second vaccine dose to serologic testing was longer in seropositive than seronegative patients [median, (IQR) 24.5 (15, 40) vs. 46 (27, 56) days, p=0.05]. No patient developed symptomatic COVID-19 disease postvaccination.
CONCLUSIONS: The BNT162b2 COVID-19 mRNA vaccine yielded higher positive antibody response in adolescent and young adult KTR than previously reported for adult KTR. Antibody titers after vaccination were significantly lower than following COVID-19 infection. Longer time may be required to mount appropriate humoral immunity to vaccination in KTR.
Midtvedt, K., et al. (2021). “Low Immunization Rate in Kidney Transplant Recipients Also After Dose 2 of the BNT162b2 Vaccine: Continue to Keep Your Guard up!” Transplantation 105(8): e80-e81.
Montagud-Marrahi, E., et al. (2021). “SARS-CoV-2 Infection After Full Vaccination in Kidney Transplant Recipients.” Transplantation [record in progress].
Qin, C. X., et al. (2021). “Risk of Breakthrough SARS-CoV-2 Infections in Adult Transplant Recipients.” Transplantation [record in progress].
Ravanan, R., et al. (2021). “Two Doses of SARS-CoV-2 Vaccines Reduce Risk of Death Due to COVID-19 in Solid Organ Transplant Recipients: Preliminary Outcomes From a UK Registry Linkage Analysis.” Transplantation [record in progress].
Silvariño, R., et al. (2021). “Recommendations on vaccination against SARS-CoV-2 / COVID-19 in patients with kidney disease and kidney transplantation.” Revista Médica del Uruguay 37(2): e901-e901.
The objective of this document of recommendations is to guide nephrologists and non-nephrologists who assist patients with chronic kidney disease (CKD) at all stages of the disease in the vaccination process against SARS-CoV-2. As a consequence of the epidemiological situation and the timing of the preparation process for the available vaccines, sufficiently powerful evidence has not been generated, so the recommendations are not accompanied by their level of evidence. The need to prioritize vaccination in this group of patients is based on the highest risk of acquiring the SARS-CoV-2 infection, developing the COVID-19 disease with greater severity and presenting a higher mortality than the general population. The recommendations are organized by groups of patients, considering patients with non-dialytic CKD, dialysis and kidney transplantation, and patients under immunosuppressive treatment.
Stumpf, J., et al. (2021). “Humoral and cellular immunity to SARS-CoV-2 vaccination in renal transplant versus dialysis patients: A prospective, multicenter observational study using mRNA-1273 or BNT162b2 mRNA vaccine.” The Lancet Regional Health [record in progress]: 100178.
Background: Dialysis and kidney transplant patients are vulnerable populations for COVID-19 related disease and mortality.
Methods: We conducted a prospective study exploring the eight week time course of specific cellular (interferon-gamma release assay and flow cytometry) or/and humoral immune responses (ELISA) to SARS-CoV-2 boost vaccination in more than 3100 participants including medical personnel, dialysis patients and kidney transplant recipients using mRNA vaccines BNT162b2 or mRNA-1273.
Results: SARS-CoV-2-vaccination induced seroconversion efficacy in dialysis patients was similar to medical personnel (> 95%), but markedly impaired in kidney transplant recipients (42%). T-cellular immunity largely mimicked humoral results. Major risk factors of seroconversion failure were immunosuppressive drug number and type (belatacept, MMF-MPA, calcineurin-inhibitors) as well as vaccine type (BNT162b2 mRNA). Seroconversion rates induced by mRNA-1273 compared to BNT162b2 vaccine were 97% to 88% (p < 0.001) in dialysis and 49% to 26% in transplant patients, respectively. Specific IgG directed against the new binding domain of the spike protein (RDB) were significantly higher in dialysis patients vaccinated by mRNA-1273 (95%) compared to BNT162b2 (85%, p < 0.001). Vaccination appeared safe and highly effective demonstrating an almost complete lack of symptomatic COVID-19 disease after boost vaccination as well as ceased disease incidences during third pandemic wave in dialysis patients.
Conclusion: Dialysis patients exhibit a remarkably high seroconversion rate of 95% after boost vaccination, while humoral response is impaired in the majority of transplant recipients. Immunosuppressive drug number and type as well as vaccine type (BNT162b2) are major determinants of seroconversion failure in both dialysis and transplant patients suggesting immune monitoring and adaption of vaccination protocols.
Stumpf, J., et al. (2021). “Cellular And Humoral Immune Responses after Three Doses of BNT162b2 mRNA SARS-Cov-2 Vaccine in Kidney Transplant.” Transplantation [record in progress].
Boyarsky, B. J., et al. (2021). “Antibody Response to 2-Dose SARS-CoV-2 mRNA Vaccine Series in Solid Organ Transplant Recipients.” JAMA [record in progress].
Caillard, S., et al. (2021). “Occurrence of severe Covid-19 in vaccinated transplant patients.” Kidney International [record in progress].
Cucchiari, D., et al. (2021). “Cellular and humoral response after mRNA-1273 SARS-CoV-2 vaccine in kidney transplant recipients.” American Journal of Transplantation [record in progress].
According to preliminary data, seroconversion after mRNA SARS-CoV-2 vaccination might be unsatisfactory in Kidney Transplant Recipients (KTRs). However, it is unknown if seronegative patients develop at least a cellular response that could offer a certain grade of protection against SARS-CoV-2. To answer this question, we prospectively studied 148 recipients of either kidney (133) or kidney-pancreas (15) grafts with assessment of IgM/IgG spike (S) antibodies and ELISpot against the nucleocapside (N) and the S protein at baseline and two weeks after receiving the second dose of the mRNA-1273 (Moderna) vaccine. At baseline, 31 patients (20.9%) had either IgM/IgG or ELISpot positivity and were considered to be SARS-CoV-2-pre-immunized, while 117 (79.1%) patients had no signs of either cellular or humoral response and were considered SARS-CoV-2-naive. After vaccination, naive patients who developed either humoral or cellular response were finally 65.0%, of which 29.9% developed either IgG or IgM and 35.0% S-ELISpot positivity. Factors associated with vaccine unresponsiveness were diabetes and treatment with anti-thymocytes globulins during the last year. Side effects were consistent with that of the pivotal trial and no DSAs developed after vaccination. In conclusion, mRNA-1273 SARS-CoV-2 vaccine elicits either cellular or humoral response in almost two thirds of KTRs.
Kho, M. M. L., et al. (2021). “The RECOVAC IR study: the immune response and safety of the mRNA-1273 COVID-19 vaccine in patients with chronic kidney disease, on dialysis, or living with a kidney transplant – a prospective, controlled, multicenter observational cohort by the REnal patients COVID-19 VACcination (RECOVAC) consortium COVID-19 VACcination (RECOVAC) consortium.” Nephrology Dialysis Transplantation [record in progress].
Marion, O., et al. (2021). “Safety and Immunogenicity of Anti-SARS-CoV-2 Messenger RNA Vaccines in Recipients of Solid Organ Transplants.” Annals of Internal Medicine [record in progress].
Ou, M. T., et al. (2021). “Immunogenicity and Reactogenicity After SARS-CoV-2 mRNA Vaccination in Kidney Transplant Recipients Taking Belatacept.” Transplantation [record in progress].
BACKGROUND: 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.
METHODS: Participants were recruited between 12/9/2020 – 4/1/2021. 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 (IPTW) was used to compare immunogenicity and a weighted logistics regression was used to calculate fold change of positive response.
RESULTS: Among the 609 participants studied, 24 (4%) were taking belatacept. After dose 1, 0/24 (0%) belatacept patients had detectable antibodies, compared to 77/568 (14%) among the equivalent nonbelatacept population (p=0.06). After dose 2, 1/19 (5%) belatacept patients had detectable antibodies, compared to 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).
CONCLUSIONS: Additional measures need to be explored in order to protect kidney transplant recipients taking belatacept. Best safety practices should be continued despite vaccination among this population.
Rozen-Zvi, B., et al. (2021). “Antibody response to SARS-CoV-2 mRNA vaccine among kidney transplant recipients: a prospective cohort study.” Clinical Microbiology & Infection [record in progress].
OBJECTIVES: We aimed to evaluate the rates of antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine among kidney transplant recipients, and to identify factors associated with reduced immunogenicity.
METHODS: This was a prospective cohort study including consecutive kidney transplant recipients in a single referral transplant centre. Participants were tested for anti-spike (anti-S) antibodies 2-4 weeks after a second vaccine dose. Primary outcome was rate of seropositivity. Univariate and multivariate analyses were conducted to identify factors associated with seropositivity.
RESULTS: Of 308 kidney transplant recipients included, only 112 (36.4%) tested positive for anti-S antibodies 2-4 weeks after receiving the second dose of BNT162b2 vaccine. Median antibody titre was 15.5 AU/mL (interquartile range (IQR) 3.5-163.6). Factors associated with antibody response were higher estimated glomerular filtration rate (eGFR) (odds ratio (OR) 1.025 per mL/min/1.73 m2, 95% confidence interval (CI) 1.014-1.037, p < 0.001), lower mycophenolic acid dose (OR 2.347 per 360 mg decrease, 95%CI 1.782-3.089, p < 0.001), younger age (OR 1.032 per year decrease, 95%CI 1.015-1.05, p < 0.001) and lower calcineurin inhibitor (CNI) blood level (OR 1.987, 95%CI 1.146-3.443, p 0.014). No serious adverse events resulting from the vaccine were reported.
CONCLUSIONS: Kidney transplant recipients demonstrated an inadequate antibody response to SARS-CoV-2 mRNA vaccination. Immunosuppression level was a significant factor in this response. Strategies to improve immunogenicity should be examined in future studies.
Tsapepas, D., et al. (2021). “Clinically Significant COVID-19 Following SARS-CoV-2 Vaccination in Kidney Transplant Recipients.” American Journal of Kidney Diseases [record in progress].
Benotmane, I., et al. (2021). “Weak anti-SARS-CoV-2 antibody response after the first injection of an Mrna COVID-19 vaccine in kidney transplant recipients.” Kidney International [record in progress].
Boyarsky, B. J., et al. (2021). “Immunogenicity of a Single Dose of SARS-CoV-2 Messenger RNA Vaccine in Solid Organ Transplant Recipients.” JAMA [record in progress].
Yi, S. G., et al. (2021). “Kidney Transplant Recipients Rarely Show an Early Antibody Response Following the First COVID-19 Vaccine Administration.” Transplantation [record in progress].
Benotmane, I., et al. (2021). “Low immunization rates among kidney transplant recipients who received two doses of the mRNA-1273 SARS-CoV-2 vaccine.” Kidney International [record in progress].
Blumberg, E. A., et al. (2021). “The future of SARS-CoV-2 vaccines in transplant recipients: To be determined.” Am J Transplant.
Chavarot, N., et al. (2021). “Poor Anti-SARS-CoV-2 Humoral and T-cell Responses After 2 Injections of mRNA Vaccine in Kidney Transplant Recipients Treated with Belatacept.” Transplantation [record in progress].
Grupper, A., et al. (2021). “Reduced humoral response to mRNA SARS-Cov-2 BNT162b2 vaccine in kidney transplant recipients without prior exposure to the virus.” American Journal of Transplantation [record in progress].
COVID-19 is associated with increased morbidity and mortality in transplant recipients. There are no efficacy data available regarding these patients with any of the available SARS-CoV-2 vaccines. We analyzed the humoral response following full vaccination with the BNT162b2 (Pfizer-BioNTech) in 136 kidney transplant recipients, and compared it to 25 controls. In order to exclude prior exposure to the virus, only participants with negative serology to SARS-CoV-2 nucleocapsid protein were included. All controls developed a positive response to spike protein, while only 51/136 transplant recipients (37.5%) had positive serology (p<0.001). Mean IgG anti-spike level was higher in the controls (31.05 (41.8) vs 200.5 (65.1) AU/mL, study vs control, respectively, p<0.001). Variables associated with null humoral response were older age [odds ratio 1.66 (95% confidence interval 1.17-2.69)], high dose corticosteroids in the last 12 months [1.3 (1.09-1.86)], maintenance with triple immunosuppression [1.43 (1.06-2.15)], and regimen that includes mycophenolate [1.47 (1.26-2.27)]. There was a similar rate of side effects between controls and recipients, and no correlation was found between presence of symptoms to seroconversion. Our findings suggest that most kidney transplant recipients remain at high risk for COVID-19 despite vaccination. Further studies regarding possible measures to increase recipient’s response to vaccination are required.
Husain, S. A., et al. (2021). “Post-vaccine anti-SARS-CoV-2 spike protein antibody development in kidney transplants recipients.” KI Reports [record in progress].
Korth, J., et al. (2021). “Impaired Humoral Response in Renal Transplant Recipients to SARS-CoV-2 Vaccination with BNT162b2 (Pfizer-BioNTech).” Viruses 13(5): 756-756.
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has a major impact on transplant recipients, with mortality rates up to 20%. Therefore, the effect of established messenger RNA (mRNA)-based SARS-CoV-2 vaccines have to be evaluated for solid organ transplant patients (SOT) since they are known to have poor responses after vaccination. We investigated the SARS-CoV-2 immune response via SARS-CoV-2 IgG detection in 23 renal transplant recipients after two doses of the mRNA-based SARS-CoV-2 vaccine BNT162b2 following the standard protocol. The antibody response was evaluated once with an anti-SARS-CoV-2 IgG CLIA 15.8 +/− 3.0 days after the second dose. As a control, SARS-CoV-2 IgG was determined in 23 healthcare workers (HCW) and compared to the patient cohort. Only 5 of 23 (22%) renal transplant recipients were tested positive for SARS-CoV-2 IgG antibodies after the second dose of vaccine. In contrast, all 23 (100%) HCWs were tested positive for antibodies after the second dose. Thus, the humoral response of renal transplant recipients after two doses of the mRNA-based vaccine BNT162b2 (Pfizer-BioNTech, Kronach, Germany) is impaired and significantly lower compared to healthy controls (22% vs. 100%; p = 0.0001). Individual vaccination strategies might be beneficial in these vulnerable patients.
Marinaki, S., et al. (2021). “Immunogenicity of SARS-CoV-2 BNT162b2 vaccine in solid organ transplant recipients.” American Journal of Transplantation [record in progress].
Solid organ transplant (SOT) recipients represent a high-risk group for all SARS-COV-2 infection-related adverse outcomes. Therefore, most European countries have established prioritization of SOTrecipients in their vaccination programs. Suboptimal vaccine efficacy to the SARS-COV-2 vaccines is anticipated; however, they have been excluded from vaccination trials. Overall response rates to other vaccines as influenza have demonstrated high, though acceptable, variability.
Ou, M. T., et al. (2021). “Safety and Reactogenicity of 2 Doses of SARS-CoV-2 Vaccination in Solid Organ Transplant Recipients.” Transplantation [record in progress].
BACKGROUND: We studied the safety and reactogenicity SARS-CoV-2 mRNA vaccines in transplant recipients because immunosuppressed patients were excluded from vaccine trials.
METHODS: US transplant recipients were recruited into this prospective cohort study through social media; those who completed the full vaccine series between 12/9/2020-3/1/2021 were included. We collected demographics, medical history, and safety information within 7 days after doses 1 and 2 (D1, D2). Associations between characteristics and reactions were evaluated using modified Poisson regression.
RESULTS: We studied 741 transplant recipients who underwent BNT162b2 (54%) or mRNA-1273 (46%) vaccination. Median (IQR) age was 60 (44-69) years, 57% were female, and 10% were nonwhite. While local site reactions decreased after D2 (85% D1 vs. 78% D2, p<0.001), systemic reactions increased (49% D1 vs. 69% D2, p<0.001). Younger participants were more likely to develop systemic symptoms after D1 (adjusted incidence rate ratio [aIRR] per 10 years= 0.850.900.94, p<0.001) and D2 (aIRR per 10 years= 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.
CONCLUSIONS: In SOTRs 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.
Peled, Y., et al. (2021). “BNT162b2 vaccination in heart transplant recipients: clinical experience and antibody response.” The Journal of Heart and Lung Transplantation [record in progress].
Data on the safety and efficacy of SARS-CoV-2 vaccines in immunocompromised populations are sparse. We conducted a prospective study of 77 heart transplant (HT) recipients vaccinated with two doses of BNT162b2 vaccine and monitored for adverse events following both doses, the receptor-binding domain (RBD) IgG response, and neutralizing antibodies. BNT162b2 vaccination was associated with a low rate of adverse events, characterized mostly by pain at the injection site. By a mean 41 days post second dose there were no clinical episodes of rejection, as suggested by a troponin leak or allograft dysfunction. At a mean 21 days following the second dose, IgG anti-RBD antibodies were detectable in 14 (18%) HT recipients. Immune sera neutralized SARS-CoV-2 pseudo-virus in 8 (57%) of those with IgG anti-RBD antibodies. Immunosuppressive regimen containing mycophenolic acid was associated with lower odds of an antibody response (OR=0.12, P=0.042). Whether a longer time-frame for observation of an antibody response is required after vaccination in immunosuppressed individuals remains unknown.
Rabinowich, L., et al. (2021). “Low immunogenicity to SARS-CoV-2 vaccination among liver transplant recipients.” Journal of Hepatology [record in progress].
BACKGROUND AND AIMS: Two SARS-CoV-2 mRNA vaccines were approved to prevent COVID-19 infection, with reported vaccine efficacy of 95%. Liver transplant (LT) recipients are at risk for lower vaccine immunogenicity and were not included in the registration trials. We assessed vaccine immunogenicity and safety in this special population.
METHODS: LT recipients followed at the Tel-Aviv Sourasky Medical Center and healthy volunteers were tested for SARS-CoV-2 IgG antibodies directed against the Spike-protein (S) and Nucleocapsid-protein (N) 10-20 days after receiving the second Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine dose. Information regarding vaccine side effects and clinical data was collected from patients and medical records.
RESULTS: Eighty LT recipients were enrolled. Mean age was 60 years and 30% were female. Twenty-five healthy volunteer controls were younger (mean age 52.7 years, p=0.013) and mostly female (68%, p=0.002). All participants were negative for IgG N-protein serology, indicating immunity did not result from prior COVID-19 infection. All controls were positive for IgG S-protein serology. Immunogenicity among LT recipients was significantly lower with positive serology in only 47.5% (p<0.001). Antibody titer was also significantly lower in this group (mean 95.41 AU/mL vs. 200.5 AU/mL in controls, p<0.001). Predictors for negative response among LT recipients were older age, lower eGFR, and treatment with high dose steroids and MMF. No serious adverse events were reported in both groups.
CONCLUSION: LT recipients developed substantially lower immunological response to Pfizer-BioNTech SARS-CoV-2 mRNA-based vaccine. Factors influencing serological antibodies response include age, renal function and immunosuppressive medications. The findings require re-evaluation of vaccine regimens in this population.
LAY SUMMARY: Liver Transplant recipients had a substantially inferior immunity to the Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine. Less than half of the patients developed sufficient levels of antibodies against the virus, and in those who were positive, average antibody levels were two times less compared to healthy controls. Factors predicting non-response were older age, renal function and immunosuppressive medications.
Wadei, H. M., et al. (2021). “COVID-19 infection in Solid Organ Transplant Recipients after SARS-CoV-2 vaccination.” American Journal of Transplantation [record in progress].
The prevalence and mortality of COVID-19 are higher in solid organ transplant recipients (SOTs) compared to the general population (1-3). Two SARS-CoV-2 messenger RNA (mRNA) vaccines have been approved by the FDA, both are 95% efficient in preventing COVID-19 in the general population. The efficacy of these vaccines in SOTs remains to be unknown as immunocompromised patients have been excluded from the vaccine studies.
(2021). “Booster Dose of COVID-19 Vaccine for Kidney Transplant Recipients Without Adequate Humoral Response (WHO).” Clinicaltrials.gov.
Introduction: Inadequate antibody response to mRNA SARS-CoV-2 vaccination has been described among kidney transplant recipients. Immunosuppression level and specifically, use of antimetabolite in the maintenance immunosuppressive regimen, are associated with inadequate response. In light of the severe consequences of COVID-19 in solid organ transplant recipients, we believe it is justified to examine new vaccination strategies in these patients.
Methods and analysis: BECAME is a single center, open label, investigator-initiated randomised controlled, superiority trial, aiming to compare immunosuppression reduction combined with a third BNT162b2 vaccine dose versus third dose alone. The primary outcome will be seropositivity rate against SARS-CoV-2. A sample size of 154 patients was calculated for the seropositivity endpoint assuming 25% seropositivity in the control group and 50% in the intervention group. A sample of participant per arm will be also teste for T-cell response. We also plan to perform a prospective observational study, evaluating seropositivity among ~500 kidney transplant recipients consenting to receive a third vaccine dose, who are not eligible for the randomised controlled trial.
Ethics and dissemination: The trial is approved by local ethics committee of Rabin medical center (RMC-0192- 21). Results of this trial will be published; trial data will be available. Protocol amendments will be submitted to the local ethics committee.
(2021). “COVID-19 Protection After Transplant Pilot Study (CPAT).” Clinicaltrials.gov.
Antibodies are an important part of the body’s defense against infection. Individuals who have no antibodies or very low antibody levels are considered less well protected from Coronavirus Disease 2019 (COVID-19) than those who have higher antibody levels. What level of antibodies is necessary for protection is currently unknown.
Inadequate antibody response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccination has been described among kidney transplant recipients. The aim of this study is to elicit an antibody response to vaccination against SARS-CoV-2 in kidney transplant recipients who have failed to respond to two doses of either the Moderna COVID-19 vaccine or Pfizer-BioNTech Coronavirus Disease 2019 (COVID-19) vaccine.
(2021). “Safety and Immunogenicity of 2-dose Inactivated COVID-19 Vaccine in Kidney Transplant Recipients.” Clinicaltrials.gov.
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has a major impact on transplant recipients, with mortality rates up to 20%. However, immunocompromised individuals have been excluded from studies of SARS-CoV-2 vaccines. In such patients, the immune response to vaccination may be blunted. To better understand the immunogenicity of SARS-CoV-2 vaccines in transplant recipients, we quantified the humoral response to SARS-CoV-2 vaccine in kidney transplant recipients.
This is an observational cohort study assessing the serological response to COVID-19 vaccination in kidney and kidney pancreas transplant recipients and patients treated with maintenance dialysis at Auckland City Hospital. Three analyses will be undertaken:
1. Vaccine immunogenicity based on humoral and cellular responses. Serological testing for the antibody to SARS-CoV-2 will be done prior to vaccination and again at 1 and 3 weeks and 6 months after the booster vaccination in dialysis and transplant recipients. Cellular responses will be assessed at 3 weeks after the booster vaccination.
2. Development of anti-HLA antibodies in dialysis patients on the kidney transplant waiting list in the first 12 months after vaccination.
3. Development of acute rejection episodes at 1, 4, 8 and 12 weeks after vaccination in recipients of kidney and kidney-pancreas transplants.
Describe the antibody response in clinically stable patients after successful kidney transplantation 28 days after the first dose of a registered mRNA-vaccine against COVID-19 disease (Moderna vaccine).
At the same time interval, ie 28 days after the first dose of Moderna, characterize the basic cellular immune response and evaluate the results in relation to the measured antibody values and to other routinely monitored clinical data (available from routine regular medical examinations).
(2020). “Corona-NTx – Living with a Kidney Transplant during the Corona Virus.” NTR (Dutch Trial Register).
1. How do transplant recipients describe the impact of the Corona virus and the associated societal restrictions on their lives, emotions and behaviours in their own words?
2. To what extent do transplant recipients report symptoms of anxiety, depression, loneliness and social support during the Corona crisis? How does this level compare to levels measured in previous studies (prior to the Corona pandemic)?
3. To what extent do transplant recipients report medication nonadherence during the Corona crisis? How does this level compare to levels measured in previous studies (prior to the Corona pandemic)?
4. To what extent does time since transplantation play a role in the impact of Corona on transplant recipients?
5. To what extent do results differ on symptoms of anxiety, depression, loneliness and social support between baseline measure and six months after baseline measure? (Follow-up)
(2021). “Third Dose of Moderna in Transplant Recipients.” ClinicalTrials.gov.
Solid organ transplant (SOT) recipients are at high risk of COVID-19 complications. The Moderna vaccine (mRNA-1273) has proven highly efficacious and safe in a phase III large, randomized controlled trial of 30,420 persons in the general population, and has been in use in Canada since December 2020. SOT patients show diminished response to mRNA vaccines in several studies with approximately 40-50% positive antibody after the second dose. In positive patients, antibody titers are lower than the general population and adverse events mirror the general population. The current study will recruit 120 SOT recipients who have received both scheduled doses of the Moderna vaccine at 0 and 1 months. The hypothesis is that a third dose of vaccine will significantly increase antibody titers. SOT participants will be recruited and randomized 1:1 to receive an additional dose of Moderna COVID-19 vaccine two months after the last dose vs saline placebo. The outcomes will measure anti-RBD antibody titer, T-cell immunity, local/systemic side effects, and rejection events.
(2021). “Vaccination of kidney transplant and dialysis patients and their close household contacts against COVID-19.” ANZCTR.
This study aims to measure the efficacy of the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) and BNT162b2 mRNA (Pfizer-BioNTech) COVID-19 vaccines in transplant recipients and patients on dialysis, and in their close household contacts. Early reports indicate that kidney transplant recipients receiving immunosuppressive medications have a reduced protective immune response to COVID-19 vaccines. This is of concern as these are the individuals most at risk. These patient groups are adept at avoiding exposure to pathogens out in the world, and are therefore most likely to be exposed to the SARS-CoV-2 virus via a close household contact e.g. a spouse.
In this study, transplant recipients and dialysis patients will receive their vaccination at the same time as a close household contact. By comparing the immune response of patient and cohabitant, we will develop an understanding of whether priority vaccination of household contacts is a worthwhile strategy for protecting transplant and dialysis patients from COVID-19 in the future.
(2021). “Immunological Follow-up After SARS CoV2 Vaccination in Kidney Transplant Recipients.” ClinicalTrials.gov.
The investigators goal is to assess the vaccine response of kidney transplant patients following vaccination against SARS-CoV-2. The study population will be derived from cohorts of kidney transplant patients who have been transplanted for more than 3 months and have no contraindications to vaccination. These patients will be vaccinated as part of routine care with a CoV-2 SARS vaccine licensed in France. In this cohort, the investigators wish to study the post-vaccination humoral response by assaying neutralizing antibodies against SARS CoV-2 and the specific cellular response of SARS Cov-2 by quantiferon and in vitro lymphocyte stimulation assays.
(2021). “SARS-CoV-2 Vaccination in Chronic Kidney Disease.” ClinicalTrials.gov.
Patients on dialysis and kidney transplant patients infected with SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2) have an increased risk to develop a more severe course of disease or die from COVID-19 (coronavirus disease 2019). SARS-CoV-2 vaccination can increase protection against COVID-19. Kidney transplant patients and patients requiring dialysis suffer from an acquired immune deficiency. Due to the dysfunctional immune response, the general vaccine response in dialysis patients and kidney transplant patients is in many cases insufficient.
Until now, the vaccination response in dialysis patients and kidney-transplanted patients is unpredictable. Verification of vaccine response can provide important information on how to treat and protect these patients from a COVID-19. Therefore, there is a medical need to monitor vaccine protection after SARS-CoV-2 vaccination in clinical practice. In this observational study, data of the SARS-CoV-2 vaccination response collected in clinical routine will be analyzed from these patients. Based on this observational study, the investigators aim to get first evidence whether and to what extent vaccination against COVID-19 causes a vaccine response in immunocompromised patients with kidney disease.
(2021). “Evaluate the Impact, Safety, Tolerability and Immunogenicity of the Coronavac Vaccine in Kidney Transplant Recipients (TXCoronavac).” ClinicalTrials.gov.
Since the beginning of the SARS-CoV-2 pandemic, 1031 (8.7%) of the 11875 kidney transplant recipients being followed up at Hospital do Rim have been infected. The overall lethality rate was 24%, reaching 53% among those over 70 years old. Among the survivors, there is also a high incidence of renal dysfunction with loss of the renal graft and definitive return to dialysis. Patients receiving pharmacological immunosuppression, including transplant recipients, have not been included in the studies carried out to date. In addition, kidney transplant recipients may have reduced vaccine responses compared to the general population. The severity, the high incidence of renal dysfunction and loss of renal graft, and the high lethality associated with COVD-19 justify the investigation of the epidemiological impact and immunogenicity of the vaccine against SARS-CoV-2 infection.
(2021). “IgG Antibodies After SARS-CoV-2 mRNA Vaccine in Kidney Transplantation (TASMANIA).” ClinicalTrials.gov.
The aim of this study is to assess humoral immune response in kidney transplant recipients after SARS-CoV-2 mRNA vaccine.
TASMANIA is a single-center prospective observational study with 1000 kidney transplant recipients from Institute for Clinical and Experimental Medicine (IKEM), Prague. The primary objective of the study is to assess humoral and cellular immune response to SARS-CoV-2 mRNA vaccines in SARS-CoV-2-naive kidney transplant recipients using immunochemiluminescent and Enzyme Linked Immuno Spot (ELISPOT) assays. As comparator several cohorts will be evaluated:
The secondary objective is to determine clinical variables affecting antibody levels. SARS-CoV-2 anti S1/2 antibodies will be tested ≥ 15 days after the second dose of mRNA vaccines and in 3 months after the first blood sampling. In subanalysis 50 kidney transplant recipients will be examined for a cell-mediated immune response after SARS-CoV-2 mRNA vaccine.
(2021). “Immunocompromised Swiss Cohorts Based Trial Platform (COVERALL).” ClinicalTrials.gov.
This study is to set up a flexible trial platform using two existing national cohorts of immunocompromised patients (i.e. Swiss HIV Cohort Study [SHCS] and Swiss Transplant Cohort Study [STCS]) to assess the comparative effectiveness and safety of approved SARS-CoV-2 vaccines in immunocompromised patients. This platform will be tested in the frame of an exploratory pilot trial and a framework will be set up to conduct a larger, flexible, randomized controlled trial (RCT) to test approved SARS-CoV-2 vaccines to prevent SARS-CoV-2 infections.
(2021). “Monitoring of COVID-19 Vaccine Response in Organ Transplant Patients (COVATRANS).” ClinicalTrials.gov.
Vaccination against SARS CoV-2 appears to be the best strategy today to control the COVID-19 pandemic. The first published studies with Pfizer, Moderna and Astra-Zeneca vaccines show very good vaccine protection in the general population and good short-term tolerance. The efficacy of these vaccines ranges from 62 to 95%, which is particularly remarkable, especially for mRNA vaccines. Nevertheless, these studies do not report the vaccine response in organ transplant patients. It is known that transplant patients have lower vaccine responses than immunocompetent patients due to some degree of immunosuppression. Therefore, the investigators are interested in evaluating the vaccine response of organ transplant recipients after vaccination against SARS- CoV-2.
(2021). “Saxon SARS-CoV-2 Infection and Vaccination Study in Dialysis Patients, Solid Organ Recipients and Staff (DIA-Vacc).” ClinicalTrials.gov.
To investigate short- (3 and 8 weeks) and long-term (6, 9, 12, and 18 months) immune protection or response at the humoral and cellular levels before and after SARS-CoV-2 infection or vaccination in patients with moderately reduced immune status (dialysis patients) and severely reduced immune status (organ transplant recipients, mostly kidney transplant recipients) and immunocompetent subjects (medical staff) in Saxony, Germany.
(2021). “Long Term Efficacy and Safety of COVID-19 (SARS-CoV-2) Vaccination in Kidney Disease Patients.” ClinicalTrials.gov.
Rationale: COVID-19 is associated with severely increased morbidity and mortality in patients with chronic kidney disease stage G4-G5 and patients on dialysis or after kidney transplantation. Therefore, effective SARS-CoV-2 vaccination would be of great clinical importance in these patients. However, SARS-CoV-2 vaccination studies have excluded these patients so-far. Literature data indicate that vaccination may be less effective in these patient groups. Objective: To assess the efficacy and safety of SARS-CoV-2 vaccination in patients with chronic kidney disease stage G4-G5, patients on dialysis or after kidney transplantation during two years follow-up after vaccination. Study design: prospective single center observational cohort study. Study population: – all Dutch patients on dialysis with data registered in the Dutch Dialysis registry (RENINE) – all Dutch patients after kidney transplantation with data registered in the Dutch national kidney transplant registry (NOTR). – All Dutch patients with chronic kidney disease stage G4-G5 registered in the Santeon hospitals. Intervention: After SARS-CoV-2 vaccination according to standard of care, blood will be drawn for antibody response measurements at day 28 and month 6 after 2nd vaccination at by mailer-based finger-prick in 3400 hemodialysis patients, 600 peritoneal dialysis patients, 4000 patients after kidney transplantation and 4000 patients with chronic kidney disease stage G4-G5 Main study parameters/endpoints: The primary endpoint is efficacy of SARS-CoV-2 vaccination determined as: – the incidence of COVID-19 after vaccination. Secondary endpoints are – the antibody based immune response at 28 days after completion of vaccination. – the duration of antibody based immune response at 6 months compared to at 28 days after completion of vaccination. – mortality – adverse events of specific interest according to (inter)national authorities in collaboration with LAREB – presence of HLA-antibodies in dialysis patients on the waiting list for a first kidney transplantation – acute rejection and graft failure in patients after kidney transplantation The incidence of these endpoints will be compared, if applicable, to those: – in the general population who are vaccinated – in patients on dialysis or after kidney transplant who are not vaccinated Within these patient groups endpoints will be compared between recipients of different vaccines.
(2021). “Protective vaccination against coronavirus SARS-CoV-2 in patients after heart transplantation: tolerability – effectiveness – documentation of antibody progression/ immunity.” German Clinical Trials Register.
INTERVENTION: Intervention 1: Patients after heart transplantation and vaccination receive a questionnaire (mainly questions about the tolerability of the vaccination). In addition, serum for the determination of antibodies against SARS-COV-2 is serially collected as part of routine blood collections (over a period of one year after vaccination). CONDITION: heart transplant U07.1 – Emergency use of U07.1 PRIMARY OUTCOME: The aim is to assess the tolerability and efficacy of the vaccine as well as the antibody progression/immunity after vaccination against SARS-CoV-2 in a collective of heart transplanted patients.; It needs to be clarified wheather under chronic immunosuppression a immunity comparable to the normal population can be achieved.; In addition, the tolerability and efficacy of the vaccination will be assessed in this previously unstudied population. SECONDARY OUTCOME: Not defined INCLUSION CRITERIA: Patients after heart transplantation and protective vaccination against coronavirus SARS-CoV-2
(2021). “A Study to Evaluate Safety and Immunogenicity of mRNA-1273 Vaccine in Adult Organ Transplant Recipients and in Healthy Adult Participants.” ClinicalTrials.gov.
This is an open-label study to evaluate the safety, reactogenicity, and immunogenicity of mRNA-1273 Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) vaccine in adults with a kidney or liver transplant and in healthy adult participants. The primary goal of the study is to evaluate the safety of mRNA-1273 and the serum antibody (Ab) responses obtained 28 days after the second dose of mRNA-1273.
(2021). “A Study to Evaluate Safety, Reactogenicity and Immunogenicity of the SARS-CoV-2 mRNA Vaccine CVnCoV in Adults With Co-morbidities for COVID-19.” ClinicalTrials.gov.
The primary objectives of this study are to evaluate the safety and reactogenicity profile after 1 and 2 dose administrations of investigational SARS-CoV-2 mRNA vaccine CVnCoV, and to evaluate the humoral immune responses 14 days after 2 dose administrations of CVnCoV.
Preprints are preliminary reports of work that have not been certified by peer review. They should not be relied on to guide clinical practice or health-related behaviour and should not be reported in news media as established information (https://www.medrxiv.org/).
Sattler A., et al. “Impaired Humoral and Cellular Immunity after SARS-CoV2 BNT162b2 (Tozinameran) Prime-Boost Vaccination in Kidney Transplant Recipients”. medRxiv 2021.04.06.21254963
Schrezenmeier E., et al. “Immunogenicity of COVID-19 Tozinameran Vaccination in Patients on Chronic Dialysis”. medRxiv 2021.03.31.21254683
Lentine, K. L., et al. (2020). “Practicing With Uncertainty: Kidney Transplantation During the COVID-19 Pandemic.” Am J Kidney Dis [record in progress].
The coronavirus disease 2019 (COVID-19) pandemic required transplant nephrologists, surgeons, and care teams to make decisions about the full spectrum of transplant program operations and clinical practices, in the absence of experience or data. Initially, across the country, there was a reduction in kidney transplant procedures, and a striking pause in the conduct of living donation and living donor transplant surgeries. Aspects of candidate evaluation and follow-up rapidly converted to telehealth. Months into the pandemic, much has been learned from experiences world-wide, yet many questions remain. In this Perspective, we reflect on some of the practice decisions made by the transplant community in the initial response to the pandemic, and consider lessons learned, including related to the risks, benefits, and logistical considerations of proceeding with versus delaying deceased donor transplantation, living donation, and living donor transplantation during the pandemic. We review the evolution of therapeutic strategies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and their use in transplant recipients, current consensus related to immunosuppression management in infected transplant recipients, and emerging information on vaccination against SARS-CoV-2. We share our thoughts on research priorities, discuss the areas in which we are still practicing with uncertainty, and look ahead to the next phase of the pandemic response.
Kute, V. B., et al. (2021). “NOTTO COVID-19 Vaccine Guidelines for Transplant Recipients.” Indian Journal of Nephrology 31(2): 89-91.
In December 2019, novel coronavirus (SARS-CoV-2) infection started in Wuhan and resulted in a pandemic within a few weeks’ time. Organ transplant recipients being at a risk for more severe COVID-19 if they get SARS CoV-2 viral infection, COVID-19 vaccine has a significant role in these patients. The vaccine is a safer way to help build protection and would either prevent COVID-19 infection or at least diminish the severity of the disease. It would also reduce the risk of the continuing transmission and enhance herd immunity. Immuno-compromised patients should not receive live vaccines as they can cause vaccine-related disease and hence the guidelines suggest that all transplant recipients should receive age-appropriate ‘inactivated vaccine’ as recommended for general population. Though trials have not been undertaken on transplant recipients, efficacy and safety of COVID-19 vaccine have been scientifically documented for few vaccines among the general population.
Sánchez-Álvarez, E., et al. (2021). “[Position statement of the Spanish Society of Nephrology on the SARS-CoV-2 vaccines][Spanish].” Nefrologia.;S0211-6995(20)30211-3.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide over the last year causing more than one million deaths. Several treatments have tried to modify the natural history of the coronavirus disease 2019 (COVID-19) but only corticosteroids have demonstrated to be effective in moderate or severe affectation. In that situation, the development of vaccines for preventing the SARS-CoV-2 infection has focused the attention of the scientific community. At present, available messenger RNA-based technology vaccines have received the approval of local and international sanitary authorities. In this position statement, the Spanish Society of Nephrology wants to state that patients with chronic kidney disease and healthcare workers are at high-risk for contagion and complications of COVID-19 so they must have priority in the vaccine administration.
Cornberg, M., et al. (2021). “EASL position paper on the use of COVID-19 vaccines in patients with chronic liver diseases, hepatobiliary cancer and liver transplant recipients.”- J Hepatol;74(4):944-951
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.
Fix, O. K., et al. (2021). “AASLD Expert Panel Consensus Statement: Vaccines to Prevent COVID-19 Infection in Patients with Liver Disease.” Hepatology [record in progress].
BACKGROUND AND RATIONALE: The aim of this document is to provide a concise scientific review of the currently available COVID-19 vaccines and those in development, including mRNA, adenoviral vectors, and recombinant protein approaches. The anticipated use of COVID-19 vaccines in patients with chronic liver disease and liver transplant recipients is reviewed and practical guidance is provided for health care providers involved in the care of patients with liver disease and liver transplantation about vaccine prioritization and administration.
MAIN RESULTS: The Pfizer and Moderna mRNA COVID-19 vaccines are associated with a 94%-95% vaccine efficacy compared to placebo against COVID-19. Local site reactions of pain and tenderness were reported in 70%-90% of clinical trial participants, and systemic reactions of fever and fatigue were reported in 40%-70% of participants, but these reactions were generally mild and self-limited and occurred more frequently in younger individuals. Severe hypersensitivity reactions related to the mRNA COVID-19 vaccines are rare and more commonly seen in women and individuals with a history of prior drug reactions for unclear reasons. Because patients with advanced liver disease and immunosuppressed patients were excluded from the vaccine licensing trials, additional data regarding the safety and efficacy of COVID-19 vaccines are eagerly awaited in these and other subgroups CONCLUSIONS: Remarkably safe and highly effective mRNA COVID-19 vaccines are now available for widespread use and should be given to all adult patients with chronic liver disease and liver transplant recipients. The online companion document located at https://www.aasld.org/about-aasld/covid-19-resources will be updated as additional data become available regarding the safety and efficacy of other COVID-19 vaccines in development.
British Transplantation Society. Position Statement on Vaccination against COVID-19 in Solid Organ and Islet Transplant Recipients (adults, children and young people)
Kute, V., et al. (2021). “NOTTO COVID-19 vaccine guidelines for transplant recipients.” Indian Journal of Transplantation 15(1): 1-3.
In December 2019 Novel corona virus (SARS-CoV-2) infection started in Wuhan and resulted in a pandemic within few weeks’ time. Organ transplant recipients being at a risk for more severe COVID-19 if they get SARS CoV-2 viral infection, COVID 19 Vaccine has a significant role in these patients. The vaccine is a safer way to help build protection and would either prevent COVID -19 infection or atleast diminish the severity of the disease. It would also reduce the risk of the continuing transmission and enhance herd immunity. Immuno compromised patients should not receive live vaccines as they can cause vaccine related disease and hence the guidelines suggest that all transplant recipients should receive age appropriate ‘inactivated vaccine’ as recommended for general population. Though trials have not been undertaken on transplant recipients, efficacy and safety of COVID-19 vaccine have been scientifically documented for few vaccines among the general population.
Aslam S, et al (2021). COVID-19 vaccination in our transplant recipients: The time is now. J Heart Lung Transplant.; 40(3):169-171
We are entering 2021 with an expanding and effective COVID-19 vaccine armamentarium. Recent interim results from COVID-19 vaccine trials, including more than 80,000 participants worldwide, demonstrate remarkable efficacy and low rate of serious adverse events. Based on experience with other vaccines in transplant recipients and knowing the risk of severe COVID-19 in this population, we believe that COVID-19 vaccines provide potential benefit with minimal risk. We strongly support and encourage COVID-19 vaccination of our transplant recipients.
Combe, C., et al. (2021). “At least 156 reasons to prioritise COVID-19 vaccination in patients receiving in-centre haemodialysis.” Nephrol Dial Transplant.;36(4):571-574.
Fishman, J. (2021). “Commentary: The Advisory Committee on Immunization Practices’ ethical principles for allocating initial supplies of COVID-19 vaccine – United States, 2020.” Am J Transplant 21(1): 419.
Heldman M.R., Limaye, A.P. (2021). SARS-CoV-2 Vaccines in Kidney Transplant Recipients: Will They Be Safe and Effective and How Will We Know? J Am Soc Nephrol. [record in progress]
Ison M.G., et al. (2021). SARS-CoV-2 Vaccination and Solid Organ Transplant Patients: Data Needed to Inform Safety and Efficacy. Transplantation [record in progress]