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Hu M, Oliveira APBN, Fang Z, Feng Y, Miranda M, Kowli S, Arunachalam PS, Vasudevan G, Hui HSY, Grifoni A, Sette A, Litvack M, Rouphael N, Suthar MS, Ji X, Maecker HT, Hagan T, Dhillon G, Nicolls MR, Pulendran B. Altered baseline immunological state and impaired immune response to SARS-CoV-2 mRNA vaccination in lung transplant recipients. Cell Rep Med 2025; 6:102050. [PMID: 40187358 PMCID: PMC12047491 DOI: 10.1016/j.xcrm.2025.102050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 12/08/2024] [Accepted: 03/07/2025] [Indexed: 04/07/2025]
Abstract
The effectiveness of COVID-19 mRNA vaccines is diminished in organ transplant patients. Using a multi-omics approach, we investigate the immunological state of lung transplant (LTX) recipients at baseline and after SARS-CoV-2 mRNA vaccination compared to healthy controls (HCs). LTX patients exhibit a baseline immune profile resembling severe COVID-19 and sepsis, characterized by elevated pro-inflammatory cytokines (e.g., EN-RAGE [also known as S100A12], interleukin [IL]-6), reduced human leukocyte antigen (HLA)-DR expression on monocytes and dendritic cells, impaired cytokine production, and increased plasma microbial products. Single-cell RNA sequencing identifies an enriched monocyte cluster in LTX patients marked by high S100A family expression and reduced cytokine and antigen presentation genes. Post vaccination, LTX patients show diminished antibody, B cell, and T cell responses, along with blunted innate immune signatures. Integrative analysis links these altered baseline immunological features to impaired vaccine responses. These findings provide critical insights into the immunosuppressed condition of LTX recipients and their reduced vaccine-induced adaptive and innate immune responses.
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Affiliation(s)
- Mengyun Hu
- Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA
| | - Ana Paula B N Oliveira
- Department of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Zhuoqing Fang
- Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA
| | - Yupeng Feng
- Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA; Institute of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Molly Miranda
- Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA
| | - Sangeeta Kowli
- Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA
| | - Prabhu S Arunachalam
- Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA; Department of Immunobiology, University of Arizona, Tucson, AZ, USA
| | - Gowri Vasudevan
- Division of Pulmonary, Allergy and Critical Care Medicine, Stanford University, Stanford, CA, USA
| | - Harold Sai-Yin Hui
- Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA
| | - Alba Grifoni
- Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA
| | - Alessandro Sette
- Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA; Department of Pathology, University of California, San Diego, La Jolla, CA 92093, USA
| | - Matthew Litvack
- Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA, USA
| | - Nadine Rouphael
- Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA, USA
| | - Mehul S Suthar
- Department of Pediatrics, Emory Vaccine Center, Emory National Primate Research Center, Atlanta, GA, USA
| | - Xuhuai Ji
- Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA
| | - Holden T Maecker
- Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA
| | - Thomas Hagan
- Department of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Gundeep Dhillon
- Division of Pulmonary, Allergy and Critical Care Medicine, Stanford University, Stanford, CA, USA
| | - Mark R Nicolls
- Division of Pulmonary, Allergy and Critical Care Medicine, Stanford University, Stanford, CA, USA
| | - Bali Pulendran
- Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA; Department of Pathology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
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Nowak A, Caldinelli A, Segelmark M, Rydell H, Artborg A, Bellocco R, Stendahl M, Lindholm B, Wijkström J, Evans M. COVID-19 among kidney transplant recipients: evaluating risk factors during the initial phase of the pandemic. Clin Kidney J 2025; 18:sfaf030. [PMID: 40052164 PMCID: PMC11883224 DOI: 10.1093/ckj/sfaf030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Indexed: 03/09/2025] Open
Abstract
Background Current knowledge about risk factors for severe COVID-19 among kidney transplant recipients stem from meta-analyses of small or regional studies. Methods All kidney transplant recipients in Sweden as of 1 January 2020 (n = 5824) were followed during the first 2 years of the pandemic. Data from the Swedish Renal Registry and linked health care registries were analyzed by multivariable adjusted logistic regression to identify risk factors for severe COVID-19, defined as hospitalization or death due to COVID-19. Results Male sex increased the risk of severe COVID-19. While many comorbidities were associated with increased risk, their significance diminished after adjustment for other factors. Kidney transplant recipients of working age, 49-58 years adjusted odds ratio (aOR) 2.32 (95% CI 1.53-3.51) and 59-68 years aOR (1.92; 1.26-2.91) had the highest risk compared to the youngest age group (18-38 years). Compared to recently (<1 year) transplanted patients, those transplanted >5 years ago had a lower risk of severe COVID-19 (aOR 0.52; 0.36-0.75 for 6-10 years; aOR 0.57; 0.41-0.79 for >10 years). Longer pre-transplant dialysis vintage (aOR1-year 1.04; 1.01-1.06) and deceased donor kidneys (aOR 1.41; 1.09-1.84) increased the risk. Immunosuppression with mycophenolate mofetil (aOR 1.47, 95% CI 1.08-1.99) and proton pump inhibitor use (aOR 1.58, 95% CI 1.24-2.01) were strongly associated with severe COVID-19. Conclusions While kidney transplant recipients share risk factors with the general population, working age groups were at the highest risk, unlike in the general population. These findings emphasize the need for targeted prevention and treatment strategies for kidney transplant recipients in future pandemics.
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Affiliation(s)
- Alexandra Nowak
- Division of Renal Medicine, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden
- Department of Renal Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Aurora Caldinelli
- Division of Renal Medicine, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden
- University of Milano-Bicocca, Department of Biostatistics, Milano, Italy
| | - Mårten Segelmark
- Department of Clinical Sciences, Division of Nephrology, Lund University and Department of Endocrinology, Nephrology and Rheumatology, Skane University Hospital Lund, Sweden
| | - Helena Rydell
- Division of Renal Medicine, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden
- Department of Renal Medicine, Karolinska University Hospital, Stockholm, Sweden
- Swedish Renal Registry, Jönköping, Sweden
| | - Angelica Artborg
- Division of Renal Medicine, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden
- Department of Renal Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Rino Bellocco
- University of Milano-Bicocca, Department of Biostatistics, Milano, Italy
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Maria Stendahl
- Department of Internal Medicine, Ryhov Hospital Jönköping, Sweden
- Swedish Renal Registry, Jönköping, Sweden
| | - Bengt Lindholm
- Division of Renal Medicine, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden
| | - Julia Wijkström
- Division of Renal Medicine, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden
- Department of Renal Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Marie Evans
- Division of Renal Medicine, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden
- Department of Renal Medicine, Karolinska University Hospital, Stockholm, Sweden
- Swedish Renal Registry, Jönköping, Sweden
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Francis A, Chaudhary AJ, Sohail A, Tarar ZI, Jaan A, Cavataio JP, Farooqui S, Varma A, Jafri S. Impact of Immunosuppressive Therapy, Vaccination, and Monoclonal Antibody Use With Outcomes in Liver and Kidney Transplant Recipients With COVID-19: A Retrospective Study. JGH Open 2024; 8:e70072. [PMID: 39639985 PMCID: PMC11617588 DOI: 10.1002/jgh3.70072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Revised: 11/08/2024] [Accepted: 11/19/2024] [Indexed: 12/07/2024]
Abstract
Background and Aim Patients who have undergone solid organ transplantation are at an elevated risk of severe coronavirus disease (COVID-19) because of post-transplantation immunosuppressive therapy. However, optimization of vaccination, modification of immunosuppression, and implementation of monoclonal antibody (mAb) therapy in transplant recipients with COVID-19 is uncertain. Methods A retrospective cross-sectional study was conducted on patients who underwent liver or kidney transplants and were diagnosed with COVID-19. The association of several vaccine doses, mycophenolate therapy, and mAB therapy with mortality outcomes after COVID-19 diagnosis (3 and 6 months), hospitalization, and length of hospital stay were assessed. Results This study included 255 patients with a median age of 59 (23-89) were included. Many COVID-19 vaccine doses were not associated with any outcome; however, patients with a liver transplanted with mycophenolate had higher 3-month (19% vs. 0%; p = 0.02) and 6-month (21% vs. 0%; p = 0.01) mortality rates than those who did not. In addition, transplant recipients who received mAb therapy for COVID-19 were less likely to be hospitalized (37% vs. 68%; p < 0.001). Conclusions For organ transplant recipients with COVID-19, vaccination alone may not be an optimal strategy for preventing serious outcomes. Rather, the types of organ transplant, immunosuppressive therapy (particularly mycophenolate), and COVID-19 treatment strategy should be synergistically considered to promote an optimal therapeutic dynamic for a vulnerable population.
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Affiliation(s)
- Ashley Francis
- School of MedicineWayne State UniversityDetroitMichiganUSA
| | | | - Abdullah Sohail
- Department of Internal MedicineUniversity of Iowa Hospitals and ClinicsIowa CityIowaUSA
| | - Zahid I. Tarar
- Department of Gastroenterology and HepatologyUniversity of MissouriColumbiaMissouriUSA
| | - Ali Jaan
- Department of Internal MedicineRochester General HospitalRochesterNew YorkUSA
| | | | - Sara Farooqui
- School of MedicineWayne State UniversityDetroitMichiganUSA
| | - Adarsh Varma
- Department of Gastroenterology and HepatologyHenry Ford HospitalDetroitMichiganUSA
| | - Syed‐Mohammed Jafri
- Department of Gastroenterology and HepatologyHenry Ford HospitalDetroitMichiganUSA
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Casas Deza D, Julián Gomara AB, Caudevilla Biota E, Beltrán B, Domènech E, Gutiérrez Casbas A, Mañosa M, Zabana Y, Roc Alfaro L, Valverde Romero E, García González E, Sicilia B, Laredo V, Alcalá Escriche MJ, Madero Velázquez L, Ferreiro-Iglesias R, Palmero Pérez A, Calafat M, Rubio Iturria S, Moraleja Yudego I, Ber Nieto Y, García Mateo S, Gisbert JP, Vicente Lidón R, Arias L, Alfambra E, Doñate Borao AB, Peña González E, Corsino Roche P, Vicuña Arregui M, Elorza A, Domínguez Cajal M, Chaparro M, Barreiro-de Acosta M, García-López S. A booster dose of SARS-COV-2 vaccine improves suboptimal seroconversion rates in patients with inflammatory bowel disease. Results of a prospective multicenter study of GETECCU (VACOVEII study). GASTROENTEROLOGIA Y HEPATOLOGIA 2024; 47:821-833. [PMID: 38007154 DOI: 10.1016/j.gastrohep.2023.11.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 11/13/2023] [Accepted: 11/17/2023] [Indexed: 11/27/2023]
Abstract
BACKGROUND The response to SARS-CoV-2 vaccination decreases in inflammatory bowel disease (IBD) patients, specially under anti-TNF treatment. However, data on medium-term effectiveness are limited, specially using new recommended seroconversion rate (>260BAU/mL). Our aim was to evaluate the 6-month>260 BAU-seroconversion rate after full vaccination and after booster-dose. METHODS VACOVEII is a Spanish multicenter, prospective study promoted by GETECCU. IBD patients full vaccinated against SARS-CoV-2 and without previous COVID-19 infection, treated or not with immunosuppressants, were included. The booster dose was administered 6 months after the full vaccination. Seroconversion was set at 260BAU/mL, according to most recent recommendations and was assessed 6 months after the full vaccination and 6 months after booster-dose. RESULTS Between October 2021 and March 2022, 313 patients were included (124 no treatment or mesalazine; 55 immunomodulators; 87 anti-TNF; 19 anti-integrin; and 28 ustekinumab). Most patients received mRNA-vaccines (86%). Six months after full vaccination, overall seroconversion rate was 44.1%, being significantly lower among patients on anti-TNF (19.5%, p<0.001) and ustekinumab (35.7%, p=0.031). The seroconversion rate after booster was 92%. Again, anti-TNF patients had a significantly lower seroconversion rate (67%, p<0.001). mRNA-vaccine improved seroconversion rate (OR 11.720 [95% CI 2.26-60.512]). CONCLUSION The full vaccination regimen achieves suboptimal response in IBD patients, specially among those anti-TNF or ustekinumab. The booster dose improves seroconversion rate in all patients, although it remains limited in those treated with anti-TNF. These results reinforce the need to prioritize future booster doses in patients on immunosuppressants therapy, specially under anti-TNF, and using mRNA-vaccines.
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Affiliation(s)
- Diego Casas Deza
- Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet de Zaragoza, Spain; Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Spain.
| | | | | | - Belén Beltrán
- Servicio de Aparato Digestivo, Hospital Universitari i Politècnic La Fe de Valencia, Spain
| | - Eugeni Domènech
- Servicio de Aparato Digestivo, Hospital Universitari Germans Trias i Pujol de Badalona, Universitat Autónoma de Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
| | - Ana Gutiérrez Casbas
- Servicio de Aparato Digestivo, Hospital General Universitario Doctor Balmis de Alicante, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain; Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Spain
| | - Miriam Mañosa
- Servicio de Aparato Digestivo, Hospital Universitari Germans Trias i Pujol de Badalona, Universitat Autónoma de Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
| | - Yamile Zabana
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain; Servicio de Aparato Digestivo, Hospital Universitari Mútua Terrassa, Spain
| | - Lourdes Roc Alfaro
- Servicio de Microbiología, Hospital Universitario Miguel Servet de Zaragoza, Spain
| | | | | | - Beatriz Sicilia
- Servicio de Aparato Digestivo, Hospital Universitario de Burgos, Spain
| | - Viviana Laredo
- Servicio de Aparato Digestivo, Hospital Clínico Lozano Blesa de Zaragoza, Spain
| | | | - Lucia Madero Velázquez
- Servicio de Aparato Digestivo, Hospital General Universitario Doctor Balmis de Alicante, Spain
| | - Rocío Ferreiro-Iglesias
- Servicio de Aparato Digestivo, Hospital Clínico Universitario de Santiago de Compostela, Instituto de Investigación Sanitaria Santiago de Compostela (IDIS), Spain
| | | | - Margalida Calafat
- Servicio de Aparato Digestivo, Hospital Universitari Germans Trias i Pujol de Badalona, Universitat Autónoma de Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
| | | | | | | | - Sandra García Mateo
- Servicio de Aparato Digestivo, Hospital Clínico Lozano Blesa de Zaragoza, Spain
| | - Javier P Gisbert
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain; Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), Spain
| | - Raquel Vicente Lidón
- Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet de Zaragoza, Spain
| | - Lara Arias
- Servicio de Aparato Digestivo, Hospital Universitario de Burgos, Spain
| | - Erika Alfambra
- Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Spain; Servicio de Aparato Digestivo, Hospital Clínico Lozano Blesa de Zaragoza, Spain
| | | | | | - Pilar Corsino Roche
- Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet de Zaragoza, Spain; Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Spain
| | | | - Ainara Elorza
- Servicio de Aparato Digestivo, Hospital Universitario de Galdakao, Spain
| | | | - María Chaparro
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain; Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), Spain
| | - Manuel Barreiro-de Acosta
- Servicio de Aparato Digestivo, Hospital Clínico Universitario de Santiago de Compostela, Instituto de Investigación Sanitaria Santiago de Compostela (IDIS), Spain
| | - Santiago García-López
- Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet de Zaragoza, Spain; Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Spain
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Casas Deza D, Julián Gomara AB, Caudevilla Biota E, Beltrán B, Domènech E, Gutiérrez Casbas A, Mañosa M, Zabana Y, Roc Alfaro L, Valverde Romero E, García González E, Sicilia B, Laredo V, Alcalá Escriche MJ, Madero Velázquez L, Ferreiro-Iglesias R, Palmero Pérez A, Calafat M, Rubio Iturria S, Moraleja Yudego I, Ber Nieto Y, García Mateo S, Gisbert JP, Vicente Lidón R, Arias L, Alfambra E, Doñate Borao AB, Peña González E, Corsino Roche P, Vicuña Arregui M, Elorza A, Domínguez Cajal M, Chaparro M, Barreiro-de Acosta M, García-López S. Impact of mesalazine on the response to COVID-19 vaccination in patients with inflammatory bowel disease: Results of a prospective multicentre study of GETECCU (VACOVEII study). GASTROENTEROLOGIA Y HEPATOLOGIA 2024; 47:750-758. [PMID: 38219960 DOI: 10.1016/j.gastrohep.2023.12.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Revised: 12/18/2023] [Accepted: 12/29/2023] [Indexed: 01/16/2024]
Abstract
OBJECTIVE The recommendations of the Spanish Ministry of Health on vaccination in risk groups include mesalazine among the treatments with a possible negative effect on its effectiveness. However, this is not the recommendation of most experts. Our objective was to evaluate the effect of mesalazine on the humoral response to the SARS-CoV-2 vaccine in patients with inflammatory bowel disease (IBD). METHODS VACOVEII is a Spanish, prospective, multicenter study promoted by GETECCU, which evaluates the effectiveness of the SARS-CoV-2 vaccine in patients with IBD. This study includes IBD patients who have recieved the full vaccination schedule and without previous COVID-19 infection. Seroconversion was set at 260BAU/mL (centralized determination) and was assessed 6 months after full vaccination. In this subanalysis of the study, we compare the effectiveness of the vaccine between patients treated with mesalazine and patients without treatment. RESULTS A total of 124 patients without immunosuppressive therapy were included, of which 32 did not receive any treatment and 92 received only mesalazine. Six months after full vaccination, no significant differences are observed in the mean concentrations of IgG anti-S between both groups. In the multivariate analysis, antibody titers were independently associated with the use of mRNA vaccines and with SARS-CoV-2 infection. CONCLUSION Mesalazine does not have a negative effect on the response to SARS-CoV-2 vaccines in IBD patients.
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Affiliation(s)
- Diego Casas Deza
- Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet de Zaragoza, España; Instituto de Investigación Sanitaria de Aragón (IIS Aragón), España
| | | | | | - Belén Beltrán
- Servicio de Aparato Digestivo, Hospital Universitari i Politècnic La Fe de Valencia, España
| | - Eugeni Domènech
- Servicio de Aparato Digestivo, Hospital Universitari Germans Trias i Pujol de Badalona, Universitat Autónoma de Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España
| | - Ana Gutiérrez Casbas
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España; Servicio de Aparato Digestivo, Hospital General Universitario Doctor Balmis de Alicante, España; Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), España
| | - Miriam Mañosa
- Servicio de Aparato Digestivo, Hospital Universitari Germans Trias i Pujol de Badalona, Universitat Autónoma de Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España
| | - Yamile Zabana
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España; Servicio de Aparato Digestivo, Hospital Universitari Mútua Terrassa, España
| | - Lourdes Roc Alfaro
- Servicio de Microbiología, Hospital Universitario Miguel Servet de Zaragoza, España
| | | | | | - Beatriz Sicilia
- Servicio de Aparato Digestivo, Hospital Universitario de Burgos, España
| | - Viviana Laredo
- Servicio de Aparato Digestivo, Hospital Clínico Lozano Blesa de Zaragoza, España
| | | | - Lucia Madero Velázquez
- Servicio de Aparato Digestivo, Hospital General Universitario Doctor Balmis de Alicante, España
| | - Rocío Ferreiro-Iglesias
- Servicio de Aparato Digestivo, Hospital Clínico Universitario de Santiago de Compostela, Instituto de Investigación Sanitaria Santiago de Compostela (IDIS), España
| | | | - Margalida Calafat
- Servicio de Aparato Digestivo, Hospital Universitari Germans Trias i Pujol de Badalona, Universitat Autónoma de Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España
| | | | | | | | - Sandra García Mateo
- Servicio de Aparato Digestivo, Hospital Clínico Lozano Blesa de Zaragoza, España
| | - Javier P Gisbert
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España; Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, Madrid, España; Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), España
| | - Raquel Vicente Lidón
- Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet de Zaragoza, España
| | - Lara Arias
- Servicio de Aparato Digestivo, Hospital Universitario de Burgos, España
| | - Erika Alfambra
- Instituto de Investigación Sanitaria de Aragón (IIS Aragón), España; Servicio de Aparato Digestivo, Hospital Clínico Lozano Blesa de Zaragoza, España
| | | | | | - Pilar Corsino Roche
- Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet de Zaragoza, España; Instituto de Investigación Sanitaria de Aragón (IIS Aragón), España
| | | | - Ainara Elorza
- Servicio de Aparato Digestivo, Hospital Universitario de Galdakao, España
| | | | - María Chaparro
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España; Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, Madrid, España; Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), España
| | - Manuel Barreiro-de Acosta
- Servicio de Aparato Digestivo, Hospital Clínico Universitario de Santiago de Compostela, Instituto de Investigación Sanitaria Santiago de Compostela (IDIS), España
| | - Santiago García-López
- Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet de Zaragoza, España; Instituto de Investigación Sanitaria de Aragón (IIS Aragón), España
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Liu FC, Xie M, Rao W. Clinical application of COVID-19 vaccine in liver transplant recipients. Hepatobiliary Pancreat Dis Int 2024; 23:339-343. [PMID: 37620225 DOI: 10.1016/j.hbpd.2023.08.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Accepted: 08/07/2023] [Indexed: 08/26/2023]
Abstract
BACKGROUND Solid organ transplant (SOT) activities, such as liver transplant, have been greatly influenced by the pandemic of coronavirus disease 2019 (COVID-19), a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Immunosuppressed individuals of liver transplant recipients (LTRs) tend to have a high risk of COVID-19 infection and related complications. Therefore, COVID-19 vaccination has been recommended to be administered as early as possible in LTRs. DATA SOURCES The keywords "liver transplant", "SARS-CoV-2", and "vaccine" were used to retrieve articles published in PubMed. RESULTS The antibody response following the 1st and 2nd doses of vaccination was disappointingly low, and the immune responses among LTRs remarkably improved after the 3rd or 4th dose of vaccination. Although the 3rd or 4th dose of COVID-19 vaccine increased the antibody titer, a proportion of patients remained unresponsive. Furthermore, recent studies showed that SARS-CoV-2 vaccine could trigger adverse events in LTRs, including allograft rejection and liver injury. CONCLUSIONS This review provides the recently reported data on the antibody response of LTRs following various doses of vaccine, risk factors for poor serological response and adverse events after vaccination.
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Affiliation(s)
- Feng-Chao Liu
- Division of Hepatology, Liver Disease Center, The Affiliated Hospital of Qingdao University, Qingdao 266000, China; Organ Transplantation Center, The Affiliated Hospital of Qingdao University, Qingdao 266000, China; Institute of Organ Donation and Transplantation of Qingdao University, Qingdao 266000, China
| | - Man Xie
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266000, China
| | - Wei Rao
- Division of Hepatology, Liver Disease Center, The Affiliated Hospital of Qingdao University, Qingdao 266000, China; Organ Transplantation Center, The Affiliated Hospital of Qingdao University, Qingdao 266000, China; Institute of Organ Donation and Transplantation of Qingdao University, Qingdao 266000, China.
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7
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Luo X, Lessomo FYN, Yu Z, Xie Y. Factors influencing immunogenicity and safety of SARS-CoV-2 vaccine in liver transplantation recipients: a systematic review and meta-analysis. Front Immunol 2023; 14:1145081. [PMID: 37731498 PMCID: PMC10508849 DOI: 10.3389/fimmu.2023.1145081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Accepted: 08/22/2023] [Indexed: 09/22/2023] Open
Abstract
Background This review summarizes the factors influencing the efficacy and safety of the COVID-19 vaccine in LTR through meta-analysis, hoping to provide strategies for vaccine use. Methods Electronic databases were screened for studies on mRNA vaccines in LTR. The primary outcome was the pooled seroconversion rate, and the secondary outcome was the incidence of adverse events+breakthrough infections. Subgroup analyses were made based on BMI, associated comorbidities, presence of baseline leukopenia, time since transplant, and drugs used. Result In total, 31 articles got included. The pooled seroconversion rate after at least two doses of SARS-CoV-2 vaccination was 72% (95% CI [0.52-0.91). With significant heterogeneity among studies I2 = 99.9%, the seroconversion rate was about 72% (95%CI [0.66-0.75]), from the studies reporting two doses of vaccine slightly higher around 75%(95%CI [0.29-1.22]) from studies reporting three doses. The pooled seroconversion rate within the lower to normal BMI group was 74% (95% CI [0.22-1.27], Pi=0.005) against 67% (95% CI [0.52-0.81], Pi=0.000) in the high BMI group. The pooled seroconversion rate in the ''positive leukopenia'' group was the lowest, 59%. Leukopenia could influence the vaccine seroconversion rate in LTR. From the time since transplant analysis after setting seven years as cut off point, the pooled seroconversion rate after at least two doses of COVID-19 vaccination was 53% (95% CI [0.18-0.83], P=0.003, I2 = 99.6%) in <7years group and 83% (95% CI [0.76-0.90], P=0.000 I2 = 95.7%) in > 7years group. The only time since transplantation had reached statistical significance to be considered a risk factor predictor of poor serological response (OR=1.27 95%CI [1.03-1.55], P=0.024). The breakthrough infection rate after vaccination was very low2% (95% CI 0.01-0.03, I2 = 63.0%), and the overall incidence of adverse events, which included mainly pain at the injection site and fatigue, was 18% (95%CI [0.11-0.25], I2 = 98.6%, Pi=0.000). Conclusion The seroconversion rate in LTR vaccinated with at least two doses of mRNA COVID-19 vaccine could be significantly affected by the vaccine type, immunosuppressant used, BMI, leukopenia, associated comorbidities, and time since transplantation. Nevertheless, booster doses are still recommended for LTR.
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Affiliation(s)
- Xinyi Luo
- Queen Mary School, Nanchang University, Nanchang, Jiangxi, China
- Department of Gastroenterology, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | | | - Zhimin Yu
- Department of Gastroenterology, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Yong Xie
- Department of Gastroenterology, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
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8
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Luxenburger H, Thimme R. SARS-CoV-2 and the liver: clinical and immunological features in chronic liver disease. Gut 2023; 72:1783-1794. [PMID: 37316169 PMCID: PMC10423489 DOI: 10.1136/gutjnl-2023-329623] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 05/24/2023] [Indexed: 06/16/2023]
Abstract
SARS-CoV-2 infection may affect the liver in healthy individuals but also influences the course of COVID-19 in patients with chronic liver disease (CLD). As described in healthy individuals, a strong SARS-CoV-2-specific adaptive immune response is important for the outcome of COVID-19, however, knowledge on the adaptive immune response in CLD is limited.Here, we review the clinical and immunological features of SARS-CoV-2 infection in individuals with CLD. Acute liver injury occurs in many cases of SARS-CoV-2 infection and may be induced by multiple factors, such as cytokines, direct viral infection or toxic effects of COVID-19 drugs. In individuals with CLD, SARS-CoV-2 infection may have a more severe course and promote decompensation and particularly in patients with cirrhosis. Compared with healthy individuals, the SARS-CoV-2-specific adaptive immune responses is impaired in patients with CLD after both, natural infection and vaccination but improves at least partially after booster vaccination.Following SARS-CoV-2 vaccination, rare cases of acute vaccine-induced liver injury and the development of autoimmune-like hepatitis have been reported. However, the concomitant elevation of liver enzymes is reversible under steroid treatment.
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Affiliation(s)
- Hendrik Luxenburger
- Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Robert Thimme
- Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
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9
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Toniutto P, Cussigh A, Cmet S, Fabris M, Curcio F, Bitetto D, Fornasiere E, Fumolo E, Falleti E. Mycophenolate Interruption Restores Anti-SARS-CoV-2 Vaccine Immunogenicity in Unresponsive Liver Transplant Recipients. Vaccines (Basel) 2023; 11:1165. [PMID: 37514981 PMCID: PMC10383127 DOI: 10.3390/vaccines11071165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 06/19/2023] [Accepted: 06/24/2023] [Indexed: 07/30/2023] Open
Abstract
BACKGROUND & AIMS The fourth dose of anti-SARS-CoV-2 vaccine slightly improved the humoral response among previously seronegative liver transplant (LT) recipients. Mycophenolate (MMF) treatment worsens the vaccination response. This study aimed to evaluate whether temporary MMF interruption might improve the immunogenicity of the fourth anti-SARS-CoV-2 BNT16b2 vaccine dose in nonresponsive LT recipients. METHODS LT recipients negative for anti-spike glycoprotein-specific immunoglobulin G receptor-binding domain (s-RBD) antibodies after the third vaccine dose were enrolled. Anti-SARS-CoV-2 spike-specific T-cell responses were measured before and 2 months following the fourth vaccine dose, and anti-SARS-CoV-2 s-RBD antibodies also 6 months thereafter. MMF was suspended two weeks before and after vaccination. RESULTS Five LT recipients were enrolled. After a mean of 78 days after vaccination, all patients tested positive for anti-SARS-CoV-2 s-RBD antibodies. The mean antibody titer was 8944 UI/mL. The positive antibody response was maintained during a mean of 193 days of follow-up. Three patients developed a positive T-cell response. Two patients (one positive for T-cell response) developed a self-limited SARS-CoV-2 infection. CONCLUSIONS Suspending MMF prior to the fourth dose of the anti-SARS-CoV-2 mRNA vaccine seems feasible and safe. This procedure could restore vaccine-induced immunogenicity in a large portion of previously nonresponsive LT recipients.
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Affiliation(s)
- Pierluigi Toniutto
- Hepatology and Liver Transplantation Unit, Department of Specialized Medicine, Udine University Hospital, 33100 Udine, Italy
| | - Annarosa Cussigh
- Clinical Pathology, Udine University Hospital, 33100 Udine, Italy
| | - Sara Cmet
- Clinical Pathology, Udine University Hospital, 33100 Udine, Italy
| | - Martina Fabris
- Clinical Pathology, Udine University Hospital, 33100 Udine, Italy
| | - Francesco Curcio
- Clinical Pathology, Udine University Hospital, 33100 Udine, Italy
| | - Davide Bitetto
- Hepatology and Liver Transplantation Unit, Department of Specialized Medicine, Udine University Hospital, 33100 Udine, Italy
| | - Ezio Fornasiere
- Hepatology and Liver Transplantation Unit, Department of Specialized Medicine, Udine University Hospital, 33100 Udine, Italy
| | - Elisa Fumolo
- Hepatology and Liver Transplantation Unit, Department of Specialized Medicine, Udine University Hospital, 33100 Udine, Italy
| | - Edmondo Falleti
- Hepatology and Liver Transplantation Unit, Department of Specialized Medicine, Udine University Hospital, 33100 Udine, Italy
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10
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Thompson MA, Martinez-Barbini F, Mendizabal M. SARS-CoV-2 vaccination in liver transplant recipients: We still haven't found what we are looking for. Ann Hepatol 2023; 28:101081. [PMID: 36882137 PMCID: PMC9985536 DOI: 10.1016/j.aohep.2023.101081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Accepted: 02/24/2023] [Indexed: 03/07/2023]
Affiliation(s)
- Marcos A Thompson
- Laboratorio de hemodinámica Hepática, Unidad de Hepatologia, Hospital Clinic, Barcelona, Spain
| | | | - Manuel Mendizabal
- Unidad de Hígado y Trasplante Hepático, Hospital Universitario Austral, Pilar, Argentina.
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11
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Reeg DB, Hofmann M, Neumann-Haefelin C, Thimme R, Luxenburger H. SARS-CoV-2-Specific T Cell Responses in Immunocompromised Individuals with Cancer, HIV or Solid Organ Transplants. Pathogens 2023; 12:pathogens12020244. [PMID: 36839516 PMCID: PMC9966413 DOI: 10.3390/pathogens12020244] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 01/30/2023] [Accepted: 01/31/2023] [Indexed: 02/05/2023] Open
Abstract
Adaptive immune responses play an important role in the clinical course of SARS-CoV-2 infection. While evaluations of the virus-specific defense often focus on the humoral response, cellular immunity is crucial for the successful control of infection, with the early development of cytotoxic T cells being linked to efficient viral clearance. Vaccination against SARS-CoV-2 induces both CD4+ and CD8+ T cell responses and permits protection from severe COVID-19, including infection with the currently circulating variants of concern. Nevertheless, in immunocompromised individuals, first data imply significantly impaired SARS-CoV-2-specific immune responses after both natural infection and vaccination. Hence, these high-risk groups require particular consideration, not only in routine clinical practice, but also in the development of future vaccination strategies. In order to assist physicians in the guidance of immunocompromised patients, concerning the management of infection or the benefit of (booster) vaccinations, this review aims to provide a concise overview of the current knowledge about SARS-CoV-2-specific cellular immune responses in the vulnerable cohorts of cancer patients, people living with HIV (PLWH), and solid organ transplant recipients (SOT). Recent findings regarding the virus-specific cellular immunity in these differently immunocompromised populations might influence clinical decision-making in the future.
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12
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Herting A, Jahnke-Triankowski J, Harberts A, Schaub GM, Lütgehetmann M, Ruether DF, Fischer L, Addo MM, Lohse AW, Schulze zur Wiesch J, Sterneck M. Clinical Outcomes of SARS-CoV-2 Breakthrough Infections in Liver Transplant Recipients during the Omicron Wave. Viruses 2023; 15:v15020297. [PMID: 36851510 PMCID: PMC9958724 DOI: 10.3390/v15020297] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Revised: 01/11/2023] [Accepted: 01/16/2023] [Indexed: 01/26/2023] Open
Abstract
At the start of the pandemic, liver transplant recipients (LTR) were at high risk of developing severe COVID-19. Here, the outcomes of breakthrough infections in fully vaccinated LTR (n = 98) during the Omicron wave were assessed. In most patients, a mild disease course was observed, but 11 LTR (11.2%) required hospitalization for COVID-19-related complications. All patients survived. The LTR requiring hospitalization were older (67 years vs. 54 years; p < 0.001), had a higher Charlson comorbidity index (9 vs. 5; p < 0.001), and a lower anti-S RBD titer (Roche Elecsys) prior to infection (508.3 AU/mL vs. 2044 AU/mL; p = 0.03). Long-lasting symptoms for ≥4 weeks were reported by 37.5% of LTR (30/80). Risk factors in LTR included female sex (p = 0.01; Odds Ratio (OR) = 4.92 (95% confidence interval (CI) (1.5-16.5)) and dyspnea (p = 0.009; OR = 7.2 (95% CI (1.6-31.6)) during infection. Post-infection high anti-S RBD antibody levels were observed in LTR, and healthy controls (HC), while the cellular immune response, assessed by interferon-gamma release assay (EUROIMMUN), was significantly lower in LTR compared with HC (p < 0.001). In summary, in fully vaccinated LTR, SARS-CoV-2 breakthrough infections during the Omicron wave led to mild disease courses in the majority of patients and further boosted the humoral and cellular hybrid anti-SARS-CoV-2-directed immune response. While all patients survived, older and multimorbid LTR with low baseline antibody titers after vaccination still had a substantial risk for a disease course requiring hospitalization due to COVID-19-related complications.
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Affiliation(s)
- Anna Herting
- I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Jacqueline Jahnke-Triankowski
- Department of Visceral Transplantation, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
- University Transplant Center, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Aenne Harberts
- I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Golda M. Schaub
- I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
- German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, 38124 Braunschweig, Germany
| | - Marc Lütgehetmann
- German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, 38124 Braunschweig, Germany
- Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Darius F. Ruether
- I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Lutz Fischer
- Department of Visceral Transplantation, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
- University Transplant Center, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Marylyn M. Addo
- I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
- German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, 38124 Braunschweig, Germany
- Bernhard-Nocht-Institute for Tropical Medicine, Department for Clinical Immunology of Infectious Diseases, 20359 Hamburg, Germany
- University Medical Center Hamburg-Eppendorf, Institute for Infection Research and Vaccine Development (IIRVD), 20246 Hamburg, Germany
| | - Ansgar W. Lohse
- I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
- German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, 38124 Braunschweig, Germany
| | - Julian Schulze zur Wiesch
- I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
- German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, 38124 Braunschweig, Germany
- Correspondence: ; Tel.: +49-152-228-16113
| | - Martina Sterneck
- I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
- University Transplant Center, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
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13
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Khazaaleh S, Suarez ZK, Alomari M, Rashid MU, Handa A, Gonzalez AJ, Zervos XB, Kapila N. Liver transplantation amidst the COVID-19 era: Our center’s experience. World J Clin Cases 2023; 11:316-321. [PMID: 36686357 PMCID: PMC9850982 DOI: 10.12998/wjcc.v11.i2.316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Revised: 12/08/2022] [Accepted: 01/05/2023] [Indexed: 01/12/2023] Open
Abstract
Coronavirus disease 2019 significantly impacted the liver transplant process worldwide. Consequently, it brought significant challenges and limitations to transplant policies and organ allocation forcing liver transplant centers to adjust their protocols to ensure maximum benefit and avoid harm to their patients. Our center, like many others, was obliged to adapt to the challenges. This paper provided an overview of the effects of coronavirus disease 2019 on liver transplantations and detailed our center’s experience and efforts during this unprecedented pandemic to serve as a guide for future public health crises.
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Affiliation(s)
- Shrouq Khazaaleh
- Department of Internal Medicine, Cleveland Clinic Fairview Hospital, Cleveland, OH 44126, United States
| | - Zoilo Karim Suarez
- Department of Internal Medicine, Florida Atlantic University Charles E. Schmidt College of Medicine, Boca Raton, FL 33431, United States
| | - Mohammad Alomari
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, FL 33331, United States
| | - Mamoon Ur Rashid
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, FL 33331, United States
| | - Armaan Handa
- Royal College of Surgeons, Dublin 11111, United Kingdom
| | - Adalberto Jose Gonzalez
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, FL 33331, United States
| | - Xaralambos Bobby Zervos
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, FL 33331, United States
| | - Nikhil Kapila
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, FL 33331, United States
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14
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Rezahosseini O, Hamm SR, Heftdal LD, Pérez-Alós L, Møller DL, Perch M, Madsen JR, Hald A, Hansen CB, Armenteros JJA, Pries-Heje MM, Hasselbalch RB, Fogh K, Frikke-Schmidt R, Hilsted LM, Sørensen E, Ostrowski SR, Harboe ZB, Iversen K, Bundgaard H, Sørensen SS, Rasmussen A, Garred P, Nielsen SD. Humoral and T-cell response 12 months after the first BNT162b2 vaccination in solid organ transplant recipients and controls: Kinetics, associated factors, and role of SARS-CoV-2 infection. Front Immunol 2023; 13:1075423. [PMID: 36713395 PMCID: PMC9880190 DOI: 10.3389/fimmu.2022.1075423] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Accepted: 12/29/2022] [Indexed: 01/15/2023] Open
Abstract
Introduction We investigated humoral and T-cell responses within 12 months after first BNT162b2 vaccine in solid organ transplant (SOT) recipients and controls who had received at least three vaccine doses. Furthermore, we compared the immune response in participants with and without previous SARS-CoV-2 infection. Methods We included adult liver, lung, and kidney transplant recipients, and controls were selected from a parallel cohort of healthcare workers. Results At 12th-month, the IgG geometric mean concentrations (GMCs) (P<0.001), IgA GMCs (P=0.003), and median IFN-γ (P<0.001) were lower in SOT recipients than in controls. However, in SOT recipients and controls with previous infection, the neutralizing index was 99%, and the IgG, and IgA responses were comparable. After adjustment, female-sex (aOR: 3.6, P<0.009), kidney (aOR: 7.0, P= 0.008) or lung transplantation (aOR: 7.5, P= 0.014), and use of mycophenolate (aOR: 5.2, P=0.03) were associated with low IgG non response. Age (OR:1.4, P=0.038), time from transplantation to first vaccine (OR: 0.45, P<0.035), and previous SARS-CoV-2 infection (OR: 0.14, P<0.001), were associated with low IgA non response. Diabetes (OR:2.4, P=0.044) was associated with T-cell non response. Conclusion In conclusion, humoral and T-cell responses were inferior in SOT recipients without previous SARS-CoV-2 infection but comparable to controls in SOT recipients with previous infection.
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Affiliation(s)
- Omid Rezahosseini
- Viro-immunology Research Unit, Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Sebastian Rask Hamm
- Viro-immunology Research Unit, Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Line Dam Heftdal
- Viro-immunology Research Unit, Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Laura Pérez-Alós
- Laboratory of Molecular Medicine, Department of Clinical Immunology, Section 7631, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Dina Leth Møller
- Viro-immunology Research Unit, Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Michael Perch
- Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Johannes Roth Madsen
- Laboratory of Molecular Medicine, Department of Clinical Immunology, Section 7631, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Annemette Hald
- Viro-immunology Research Unit, Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Cecilie Bo Hansen
- Laboratory of Molecular Medicine, Department of Clinical Immunology, Section 7631, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Jose Juan Almagro Armenteros
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Mia Marie Pries-Heje
- Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Rasmus Bo Hasselbalch
- Department of Cardiology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark,Department of Emergency Medicine, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark
| | - Kamille Fogh
- Department of Cardiology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark,Department of Emergency Medicine, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark
| | - Ruth Frikke-Schmidt
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark,Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Linda Maria Hilsted
- Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Erik Sørensen
- Department of Clinical Immunology, Section 2034, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Sisse Rye Ostrowski
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark,Department of Clinical Immunology, Section 2034, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Zitta Barrella Harboe
- Viro-immunology Research Unit, Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark,Department of Pulmonary and Infectious Diseases, Hospital of North Zealand, Copenhagen University Hospital, Hillerød, Denmark
| | - Kasper Iversen
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark,Department of Cardiology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark,Department of Emergency Medicine, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark
| | - Henning Bundgaard
- Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Søren Schwartz Sørensen
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark,Department of Nephrology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Allan Rasmussen
- Department of Surgical Gastroenterology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Peter Garred
- Laboratory of Molecular Medicine, Department of Clinical Immunology, Section 7631, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Susanne Dam Nielsen
- Viro-immunology Research Unit, Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark,*Correspondence: Susanne Dam Nielsen,
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15
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Immunogenicity, Immune Dynamics, and Subsequent Response to the Booster Dose of Heterologous versus Homologous Prime-Boost Regimens with Adenoviral Vector and mRNA SARS-CoV-2 Vaccine among Liver Transplant Recipients: A Prospective Study. Vaccines (Basel) 2022; 10:vaccines10122126. [PMID: 36560535 PMCID: PMC9781301 DOI: 10.3390/vaccines10122126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 12/02/2022] [Accepted: 12/08/2022] [Indexed: 12/15/2022] Open
Abstract
Background: Heterologous prime-boost vaccination potentially augments the immune response against SARS-CoV-2 in liver transplant (LT) recipients. We investigated immunogenicity induced by different primary prime-boost vaccination protocols and the subsequent response to the booster vaccine among LT recipients. Methods: LT recipients, who received primary immunisation with ChAdOx1/ChAdOx1 or ChAdOx1/BNT162b2, were administered the third dose of mRNA-1273 three months following the primary vaccination. Blood samples were collected before and after primary vaccination and post-booster. The levels of receptor binding domain antibody (anti-RBD) and neutralising antibody (sVNT) and spike-specific T-cell responses were assessed. Results: Among the 89 LT recipients, patients receiving ChAdOx1/BNT162b2 had significantly higher anti-RBD titres, sVNT, and cellular response after primary vaccination than those receiving ChAdOx1/ChAdOx1 (p < 0.05). The antibody response decreased 12 weeks after the primary vaccination. After the booster, humoral and cellular responses significantly improved, with comparable seroconversion rates between the heterologous and homologous groups. Positive sVNT against the wild type occurred in >90% of LT patients, with only 12.3% positive against the Omicron variant. Conclusions: ChAdOx1/BNT162b2 evoked a significantly higher immunological response than ChAdOx1/ChAdOx1 in LT recipients. The booster strategy substantially induced robust immunity against wild type in most patients but was less effective against the Omicron strain.
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16
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Theocharidou E, Adebayo D. Challenges in liver transplantation in the context of a major pandemic. World J Transplant 2022; 12:347-358. [PMID: 36437846 PMCID: PMC9693897 DOI: 10.5500/wjt.v12.i11.347] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 08/27/2022] [Accepted: 09/22/2022] [Indexed: 11/17/2022] Open
Abstract
Coronavirus disease-2019 (COVID-19) has led to a temporary suspension of liver transplant activity across the world and the remodeling of care for patients on the waiting list and transplant recipients with the increasing use of remote consultations. Emerging evidence shows that patients with more advanced liver disease are at increased risk of severe COVID-19 and death, whereas transplant recipients have similar risk with the general population which is mainly driven by age and metabolic comorbidities. Tacrolimus immunosuppression might have a protective role in the post-transplant population. Vaccines that have become rapidly available seem to be safe in liver patients, but the antibody response in transplant patients is likely suboptimal. Most transplant centers were gradually able to resume activity soon after the onset of the pandemic and after modifying their pathways to optimize safety for patients and workforce. Preliminary evidence regarding utilizing grafts from positive donors and/or transplanting recently recovered or infected recipients under certain circumstances is encouraging and may allow offering life-saving transplant to patients at the greatest need. This review summarizes the currently available data on liver transplantation in the context of a major pandemic and discusses areas of uncertainty and future challenges. Lessons learnt from the COVID-19 pandemic might provide invaluable guidance for future pandemics.
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Affiliation(s)
- Eleni Theocharidou
- 2nd Department of Internal Medicine, Aristotle University of Thessaloniki, Konstantinoupoleos 49, 54642, Thessaloniki, Greece
| | - Danielle Adebayo
- Department of Gastroenterology and Hepatology, Royal Berkshire NHS Foundation Trust, London Road, Reading, RG1 5AN, United Kingdom
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Harberts A, Schaub GM, Ruether DF, Duengelhoef PM, Brehm TT, Karsten H, Fathi A, Jahnke-Triankowski J, Fischer L, Addo MM, Haag F, Luetgehetmann M, Lohse AW, Schulze Zur Wiesch J, Sterneck M. Humoral and Cellular Immune Response After Third and Fourth SARS-CoV-2 mRNA Vaccination in Liver Transplant Recipients. Clin Gastroenterol Hepatol 2022; 20:2558-2566.e5. [PMID: 35850415 PMCID: PMC9287575 DOI: 10.1016/j.cgh.2022.06.028] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 06/16/2022] [Accepted: 06/21/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Liver transplant recipients (LTRs) show a decreased immune response after 2 severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccinations compared with healthy controls (HCs). Here, we investigated the immunogenicity of additional vaccinations. METHODS In this prospective study, humoral (anti-SARS-CoV-2 receptor-binding domain [anti-S RBD]) and cellular (interferon-gamma release assay) immune responses were determined after mRNA-based SARS-CoV-2 vaccination in 106 LTRs after a third vaccination and in 36 LTRs after a fourth vaccination. Patients with anti-S RBD antibody levels >0.8 arbitrary unit (AU)/mL after vaccination were defined as responders. RESULTS After 3 vaccinations, 92% (97/106) of LTRs compared with 100% (28/28) of HCs were responders. However, the antibody titer of LTRs was lower compared with HCs (1891.0 vs 21,857.0 AU/mL; P < .001). Between a second and third vaccination (n = 75), the median antibody level increased 67-fold in LTRs. In patients seronegative after 2 vaccinations, a third dose induced seroconversion in 76% (19/25), whereas all HCs were already seropositive after 2 vaccinations. A spike-specific T-cell response was detected in 72% (28/39) after a third vaccination compared with 32% (11/34) after a second vaccination. Independent risk factors for a low antibody response (anti-S RBD <100 AU/mL) were first vaccination within the first year after liver transplant (odds ratio [OR], 8.00; P = .023), estimated glomular filtration rate <45 mL/min (OR, 4.72; P = .006), and low lymphocyte counts (OR, 5.02; P = .008). A fourth vaccination induced a 9-fold increase in the median antibody level and seroconversion in 60% (3/5) of previous non-responders. CONCLUSIONS A third and fourth SARS-CoV-2 vaccination effectively increases the humoral and cellular immune response of LTRs, but to a lesser extent than in HCs. A fourth vaccination should be generally considered in LTRs.
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Affiliation(s)
- Aenne Harberts
- Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Golda M Schaub
- Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Germany
| | - Darius F Ruether
- Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Paul M Duengelhoef
- Institute of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Thomas T Brehm
- Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Germany
| | - Hendrik Karsten
- Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Anahita Fathi
- Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Germany; Bernhard-Nocht-Institute for Tropical Medicine, Department for Clinical Immunology of Infectious Diseases, Hamburg, Germany; University Medical Center Hamburg-Eppendorf, Institute for Infection Research and Vaccine Development (IIRVD), Hamburg, Germany
| | - Jacqueline Jahnke-Triankowski
- Department of Visceral Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; University Transplant Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Lutz Fischer
- Department of Visceral Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; University Transplant Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Marylyn M Addo
- Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Germany; Bernhard-Nocht-Institute for Tropical Medicine, Department for Clinical Immunology of Infectious Diseases, Hamburg, Germany; University Medical Center Hamburg-Eppendorf, Institute for Infection Research and Vaccine Development (IIRVD), Hamburg, Germany
| | - Friedrich Haag
- Institute of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Marc Luetgehetmann
- German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Germany; Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ansgar W Lohse
- Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Germany
| | - Julian Schulze Zur Wiesch
- Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Germany.
| | - Martina Sterneck
- Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; University Transplant Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Cheng CH, Hung HC, Lee JC, Huang PW, Gu PW, Lai Y, Wang YC, Wu TH, Lee CF, Wu TJ, Chou HS, Chan KM, Huang CG, Lee WC. Determinants of Antibody Response to SARS-CoV-2 Vaccines in Liver Transplant Recipients: The Role of Immunosuppression Reduction. Vaccines (Basel) 2022; 10:1827. [PMID: 36366336 PMCID: PMC9692368 DOI: 10.3390/vaccines10111827] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 10/23/2022] [Accepted: 10/25/2022] [Indexed: 11/29/2022] Open
Abstract
Liver transplant recipients on chronic immunosuppression show an attenuated antibody response after SARS-CoV-2 vaccination. Adjusting immunosuppressants during vaccination remains debated. We enrolled 380 liver transplant recipients receiving 2 doses of a protein subunit, mRNA, or a vector vaccine. The patients were informed to temporarily suspend immunosuppression for 2 weeks for both vaccination doses. We measured anti-live-SARS-CoV-2 spike neutralizing antibody levels at 1−2 months after the second vaccination; 83.9% of patients had humoral responses (SARS-CoV-2 NT50 ≥ 9.62 IU/mL) to 2 doses of vaccines. The mRNA (86.7%) and protein subunit vaccines (85%) yielded higher response rates than the vector vaccines (40.9%). Immunosuppression suspension during the two vaccinations yielded a higher response rate (91.5% vs. 57.7%). Only eight patients (2.1%) experienced transaminase level elevation of thrice the normal value (>110 IU/L) after the second vaccination. Most recovered spontaneously after resuming immunosuppression. Multivariate analysis revealed ABO incompatibility, white blood cell count <4000, lymphocyte count <20%, tacrolimus trough level >6.5 ng/mL, and no immunosuppression adjustment as independent risk factors to nonresponse. The mRNA and protein subunit vaccines yielded a higher response rate. Immunosuppression suspension for 2 weeks enhanced the antibody response. ABO incompatibility, leukopenia, lymphopenia, a high tacrolimus trough level, and no immunosuppression adjustment are associated with nonresponse.
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Affiliation(s)
- Chih-Hsien Cheng
- Department of General Surgery, Division of Liver and Transplantation Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 333, Taiwan
| | - Hao-Chien Hung
- Department of General Surgery, Division of Liver and Transplantation Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 333, Taiwan
| | - Jin-Chiao Lee
- Department of General Surgery, Division of Liver and Transplantation Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 333, Taiwan
| | - Po-Wei Huang
- Department of Laboratory Medicine, Chang-Gung Memorial Hospital, Taoyuan 333, Taiwan
| | - Po-Wen Gu
- Department of Laboratory Medicine, Chang-Gung Memorial Hospital, Taoyuan 333, Taiwan
| | - Yin Lai
- Department of General Surgery, Division of Liver and Transplantation Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 333, Taiwan
| | - Yu-Chao Wang
- Department of General Surgery, Division of Liver and Transplantation Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 333, Taiwan
| | - Tsung-Han Wu
- Department of General Surgery, Division of Liver and Transplantation Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 333, Taiwan
| | - Chen-Fang Lee
- Department of General Surgery, Division of Liver and Transplantation Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 333, Taiwan
| | - Ting-Jung Wu
- Department of General Surgery, Division of Liver and Transplantation Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 333, Taiwan
| | - Hong-Shiue Chou
- Department of General Surgery, Division of Liver and Transplantation Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 333, Taiwan
| | - Kun-Ming Chan
- Department of General Surgery, Division of Liver and Transplantation Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 333, Taiwan
| | - Chung-Guei Huang
- Department of Laboratory Medicine, Chang-Gung Memorial Hospital, Taoyuan 333, Taiwan
- Department of Medical Biotechnology and Laboratory Science, Chang-Gung University College of Medicine, Taoyuan 333, Taiwan
| | - Wei-Chen Lee
- Department of General Surgery, Division of Liver and Transplantation Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 333, Taiwan
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19
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Li P, Liu Y, Cheng Z, Yu X, Li Y. COVID-19-associated liver injury: Clinical characteristics, pathophysiological mechanisms and treatment management. Biomed Pharmacother 2022; 154:113568. [PMID: 36029543 PMCID: PMC9381432 DOI: 10.1016/j.biopha.2022.113568] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Revised: 08/14/2022] [Accepted: 08/15/2022] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a global epidemic and poses a major threat to public health. In addition to COVID-19 manifesting as a respiratory disease, patients with severe disease also have complications in extrapulmonary organs, including liver damage. Abnormal liver function is relatively common in COVID-19 patients; its clinical manifestations can range from an asymptomatic elevation of liver enzymes to decompensated hepatic function, and liver injury is more prevalent in severe and critical patients. Liver injury in COVID-19 patients is a comprehensive effect mediated by multiple factors, including liver damage directly caused by SARS-CoV-2, drug-induced liver damage, hypoxia reperfusion dysfunction, immune stress and inflammatory factor storms. Patients with chronic liver disease (especially alcohol-related liver disease, nonalcoholic fatty liver disease, cirrhosis and hepatocellular carcinoma) are at increased risk of severe disease and death after infection with SARS-CoV-2, and COVID-19 aggravates liver damage in patients with chronic liver disease. This article reviews the latest SARS-CoV-2 reports, focusing on the liver damage caused by COVID-19 and the underlying mechanism, and expounds on the risk, treatment and vaccine safety of SARS-CoV-2 in patients with chronic liver disease and liver transplantation.
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Affiliation(s)
- Penghui Li
- Center for Health Research, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; University of Chinese Academy of Sciences, Beijing, China; Key Laboratory of Stem Cell and Regenerative Medicine, CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
| | - Ying Liu
- Center for Health Research, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; University of Chinese Academy of Sciences, Beijing, China; Key Laboratory of Stem Cell and Regenerative Medicine, CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
| | - Ziqi Cheng
- Center for Health Research, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; University of Chinese Academy of Sciences, Beijing, China; Key Laboratory of Stem Cell and Regenerative Medicine, CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
| | - Xiaorui Yu
- Center for Health Research, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; University of Chinese Academy of Sciences, Beijing, China; Key Laboratory of Stem Cell and Regenerative Medicine, CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
| | - Yinxiong Li
- Center for Health Research, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; University of Chinese Academy of Sciences, Beijing, China; Key Laboratory of Stem Cell and Regenerative Medicine, CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; State Key Laboratory of Respiratory Disease, Guangzhou, China; China-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou, China.
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20
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Solid Organ Rejection following SARS-CoV-2 Vaccination or COVID-19 Infection: A Systematic Review and Meta-Analysis. Vaccines (Basel) 2022; 10:vaccines10081289. [PMID: 36016180 PMCID: PMC9412452 DOI: 10.3390/vaccines10081289] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 08/06/2022] [Accepted: 08/08/2022] [Indexed: 02/06/2023] Open
Abstract
Background: Solid organ rejection post-SARS-CoV-2 vaccination or COVID-19 infection is extremely rare but can occur. T-cell recognition of antigen is the primary and central event that leads to the cascade of events that result in rejection of a transplanted organ. Objectives: To describe the results of a systematic review for solid organ rejections following SARS-CoV-2 vaccination or COVID-19 infection. Methods: For this systematic review and meta-analysis, we searched Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines for studies on the incidence of solid organ rejection post-SARS-CoV-2 vaccination or COVID-19 infection, published from 1 December 2019 to 31 May 2022, with English language restriction. Results: One hundred thirty-six cases from fifty-two articles were included in the qualitative synthesis of this systematic review (56 solid organs rejected post-SARS-CoV-2 vaccination and 40 solid organs rejected following COVID-19 infection). Cornea rejection (44 cases) was the most frequent organ observed post-SARS-CoV-2 vaccination and following COVID-19 infection, followed by kidney rejection (36 cases), liver rejection (12 cases), lung rejection (2 cases), heart rejection (1 case) and pancreas rejection (1 case). The median or mean patient age ranged from 23 to 94 years across the studies. The majority of the patients were male (n = 51, 53.1%) and were of White (Caucasian) (n = 51, 53.7%) and Hispanic (n = 15, 15.8%) ethnicity. A total of fifty-six solid organ rejections were reported post-SARS-CoV-2 vaccination [Pfizer-BioNTech (n = 31), Moderna (n = 14), Oxford Uni-AstraZeneca (n = 10) and Sinovac-CoronaVac (n = 1)]. The median time from SARS-CoV-2 vaccination to organ rejection was 13.5 h (IQR, 3.2–17.2), while the median time from COVID-19 infection to organ rejection was 14 h (IQR, 5–21). Most patients were easily treated without any serious complications, recovered and did not require long-term allograft rejection therapy [graft success (n = 70, 85.4%), graft failure (n = 12, 14.6%), survived (n = 90, 95.7%) and died (n = 4, 4.3%)]. Conclusion: The reported evidence of solid organ rejections post-SARS-CoV-2 vaccination or COIVD-19 infection should not discourage vaccination against this worldwide pandemic. The number of reported cases is relatively small in relation to the hundreds of millions of vaccinations that have occurred, and the protective benefits offered by SARS-CoV-2 vaccination far outweigh the risks.
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21
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Arenas-De Larriva M, Rodríguez-Perálvarez ML. Mycophenolate and SARS-CoV-2 vaccination: Mixing oil and water. Liver Int 2022; 42:1218-1221. [PMID: 35678038 DOI: 10.1111/liv.15265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Accepted: 03/29/2022] [Indexed: 02/13/2023]
Affiliation(s)
- Marisol Arenas-De Larriva
- Department of Interventional Pulmonology, Hospital Universitario Reina Sofía, IMIBIC, Córdoba, Spain
| | - Manuel L Rodríguez-Perálvarez
- Department of Hepatology and Liver Transplantation, Hospital Universitario Reina Sofía, Universidad de Córdoba, IMIBIC, Córdoba, Spain
- CIBER de enfermedades hepáticas y digestivas, Madrid, Spain
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