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Remane Y, Klaus VC, Heinitz K, Ranft D, Kowald J, Herber A, Tautenhahn HM, Bertsche T, Ziganshyna S. Assessment of vaccination rates and motivation among transplant patients using vaccination cards and interviews. Sci Rep 2025; 15:16911. [PMID: 40374752 DOI: 10.1038/s41598-025-01491-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Accepted: 05/05/2025] [Indexed: 05/18/2025] Open
Abstract
Transplant patients are at an elevated risk for infections. Therefore, infection prevention plays a pivotal role in their care. Two different approaches were chosen to determine their vaccination status and motivation. The vaccination rate was determined by analyzing the patients' vaccination cards based on German vaccination recommendations. The vaccinations were categorized into standard, indicated, and risk-dependent vaccinations. The vaccination motivation was determined through a semi-structured interview using a self-developed questionnaire as an interview guide. Both parts were analyzed separately. A total of 126 patients were included in the study. In 115 (91.3%) patients, vaccination cards were available, 64.3% had complete standard and 0.9% indicated vaccinations. In the risk-dependent vaccinations category, 49.6% of participants had at least one of the additional vaccinations. The vaccination rate against hepatitis B was significantly higher in kidney than in liver transplant recipients (88.1% vs. 55.4%, Χ2 = 13.7, p < 0.001, n = 107). Vaccination confidence correlated significantly with willingness to vaccinate (r = 0.362, p < 0.001, n = 123). In conclusion, only a few transplant patients have complete vaccination protection. Further patient education is needed to increase patients' confidence in vaccinations and to motivate them.
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Affiliation(s)
- Yvonne Remane
- Pharmacy, University of Leipzig Medical Center and Leipzig University Medical Faculty, Leipzig, Germany.
- Drug Safety Center, Leipzig University and University of Leipzig Medical Center, Leipzig, Germany.
| | - Vincent Christoph Klaus
- Drug Safety Center, Leipzig University and University of Leipzig Medical Center, Leipzig, Germany
| | - Katrin Heinitz
- Pharmacy, University of Leipzig Medical Center and Leipzig University Medical Faculty, Leipzig, Germany
- Drug Safety Center, Leipzig University and University of Leipzig Medical Center, Leipzig, Germany
| | - Donald Ranft
- Pharmacy, University of Leipzig Medical Center and Leipzig University Medical Faculty, Leipzig, Germany
- Drug Safety Center, Leipzig University and University of Leipzig Medical Center, Leipzig, Germany
| | - Jan Kowald
- Medical Department III, Division of Nephrology, University of Leipzig Medical Center, Leipzig, Germany
| | - Adam Herber
- Medical Department II, Division of Hepatology, University of Leipzig Medical Center, Leipzig, Germany
| | - Hans-Michael Tautenhahn
- Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University of Leipzig Medical Center, Leipzig, Germany
| | - Thilo Bertsche
- Drug Safety Center, Leipzig University and University of Leipzig Medical Center, Leipzig, Germany
- Clinical Pharmacy, Institute of Pharmacy, Medical Faculty, Leipzig University, Leipzig, Germany
| | - Svitlana Ziganshyna
- Organ Donation Coordinator Unit, University of Leipzig Medical Center, Leipzig, Germany.
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Qin X, Song Y, Ding J, Qin X, Chen K, Wang H. Symptomatic central nervous system infections in kidney transplant recipients: a 20-years multicenter observational study. BMC Infect Dis 2025; 25:641. [PMID: 40312673 PMCID: PMC12044744 DOI: 10.1186/s12879-025-11039-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2025] [Accepted: 04/23/2025] [Indexed: 05/03/2025] Open
Abstract
BACKGROUND Central nervous system (CNS) infections in kidney transplant recipients (KTRs) remain poorly characterized, with current evidence largely derived from isolated case reports over the past two decades. This multicenter study aims to systematically delineate the epidemiology, clinical profiles, and outcomes of CNS infections in a large KTR cohort. METHODS We conducted a retrospective analysis of 3,602 KTRs across three transplant centers in China (May 2004-July 2024). CNS infections were defined by: 1) neurological symptoms/signs, and 2) microbiological confirmation via cerebrospinal fluid (CSF) analysis, including metagenomic next-generation sequencing (mNGS) and routine microbiologic testing (bacterial and fungal cultures). RESULTS CNS infections were diagnosed in 0.53% of KTRs (19/3602), with symptom onset occurring 2-121 months post-transplantation. Etiologies included bacterial (47%, 9/19), viral (32%, 6/19), and fungal (21%, 4/19) pathogens. Notably, 79% of cases (15/19) were exclusively identified by mNGS, whereas conventional cultures failed detection. Presenting symptoms included headache (79%) and altered mental status (42%). Mortality reached 42% (8/19) within 9-22 days of diagnosis; among survivors, 73% (8/11) exhibited neurological sequelae. CONCLUSIONS CNS infections in KTRs are rare but characterized by rapid progression and high fatality rate. While the risk of CNS infections persists throughout the post-transplant period, 1-6 months after transplantation is a higher-incidence period of CNS infections. KTRs with neurological symptoms (particularly headache and elevated CSF pressure) should undergo CSF mNGS which is critical in diagnosing such infections.
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Affiliation(s)
- Xingsong Qin
- Organ Transplant Center, Zhengzhou People's Hospital/ the Fifth Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, China. No. 33, Huanghe Road, Zhengzhou, Henan, 450003, People's Republic of China
| | - Yinsen Song
- Organ Transplant Center, Zhengzhou People's Hospital/ the Fifth Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, China. No. 33, Huanghe Road, Zhengzhou, Henan, 450003, People's Republic of China
| | - Junjie Ding
- Organ Transplant Center, Zhengzhou People's Hospital/ the Fifth Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, China. No. 33, Huanghe Road, Zhengzhou, Henan, 450003, People's Republic of China
| | - Xinglei Qin
- Organ Transplant Center, Henan Provincial People's Hospital/ People's Hospital of Zhengzhou University, Zhengzhou, No.7, Weiwu Road, Zhengzhou, Henan, 450003, People's Republic of China
| | - Kun Chen
- Organ Transplant CenterThe 7Th People's Hospital of Zhengzhou, Zhengzhou, , China. No. 17, Jingnan 5Th Road, Zhengzhou, Henan, 450011, People's Republic of China
| | - Hongyu Wang
- Organ Transplant Center, Zhengzhou People's Hospital/ the Fifth Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, China. No. 33, Huanghe Road, Zhengzhou, Henan, 450003, People's Republic of China.
- Intensive Care Unit, the Fifth Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, China, No. 33, Huanghe Road, Zhengzhou, Henan, 450003, People's Republic of China.
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Thierbach A, Di Cristanziano V, Eberhardt KA, Pirkl M, Steger G, Heger E, Kaiser R, Koch M, Klein F, Rauschning D, Malin JJ. High rate of RNAemia and impaired immunity in patients with immunodeficiency in the vaccination era. J Clin Virol 2025; 177:105774. [PMID: 39985863 DOI: 10.1016/j.jcv.2025.105774] [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: 12/19/2024] [Revised: 02/13/2025] [Accepted: 02/17/2025] [Indexed: 02/24/2025]
Abstract
BACKGROUND Immunocompromised individuals, hemato-oncologic diseases or post-transplantation included, are, due to impaired immune response, at increased risk for severe and prolonged COVID-19. Observational Studies showed that SARS-CoV-2 RNAemia has been associated with poorer prognosis and higher disease severity. OBJECTIVE The aim of this study was to investigate the occurrence of RNAemia and its association with anti-SARS-CoV-2 antibodies in immunocompromised COVID-19 patients. Risk factors for RNAemia were included in the analysis. STUDY DESIGN A retrospective study was conducted in 55 immunocompromised patients tested positive for SARS-CoV-2, who received treatment with monoclonal antibodies (mAb) between December 2021 and March 2022. Serological and virological tests were performed before mAb administration and clinical data were collected from electronic health records. RESULTS Out of 55 patients, 35 % showed SARS-CoV-2 RNAemia. RNAemia was present in the 2 reported fatal cases. It was associated with negative testing for anti-receptor binding domain (RBD) IgG, anti-S2 domain of spike protein (S2) IgG and a lower leukocyte count. No association was found between previous COVID-19 vaccinations and the risk for RNAemia in immunocompromised patients. CONCLUSION The study underscores the importance of humoral response in controlling SARS-CoV-2 replication. RNAemia can serve as a potential biomarker for disease severity in immunocompromised individuals. Therefore, it should be considered in clinical settings for appropriate therapy decisions. Further research is needed to evaluate the pathophysiology and implications of RNAemia in immunodeficient patients with COVID-19.
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Affiliation(s)
- Anne Thierbach
- Department of Anesthesiology and Intensive Care Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
| | - Veronica Di Cristanziano
- Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Kirsten A Eberhardt
- Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine & I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Martin Pirkl
- Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Gertrud Steger
- Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Eva Heger
- Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Rolf Kaiser
- Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Manuel Koch
- Institute for Dental Research and Oral Musculoskeletal Biology, Center for Biochemistry, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne CMMC, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Florian Klein
- Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne CMMC, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Dominic Rauschning
- Department I of Internal Medicine, Division of Infectious Diseases, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Jakob J Malin
- Department I of Internal Medicine, Division of Infectious Diseases, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
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Sahu M, Praharaj D, Bhadoria AS. Vaccination Strategies for a Liver Transplant Recipient. J Clin Exp Hepatol 2025; 15:102421. [PMID: 39588050 PMCID: PMC11585777 DOI: 10.1016/j.jceh.2024.102421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Accepted: 09/29/2024] [Indexed: 11/27/2024] Open
Abstract
Patients with cirrhosis and liver transplant recipients are at increased risk of infections. Malnutrition, multiple hospital admissions, immune dysfunction related to cirrhosis, and immunosuppressive agents used for liver transplantation predispose the recipient to various life-threatening infections. Some of these infections are preventable with vaccines. With the COVID-19 pandemic, there has been an accelerated research in vaccination technology and platforms, which in turn may also improve awareness of physicians regarding this healthy and often ignored aspect of management of patients with cirrhosis and transplant recipients. The organ transplant candidates should complete the recommended vaccination schedule as early as possible (especially patients with compensated cirrhosis) or at least during their pretransplant work-up so as to prevent or reduce the severity of various infections.
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Affiliation(s)
- Monalisa Sahu
- Department of Infectious Diseases, Yashoda Hospitals, Hyderabad, India
| | - Dibyalochan Praharaj
- Department of Gastroenterology, Kalinga Institute of Medical Sciences, Bhubaneswar, India
| | - Ajeet S. Bhadoria
- Department of Community and Family Medicine, All India Institute of Medical Sciences, Rishikesh, India
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Lee R, Choi J, Lee E, Lee J, Kim J, Kang S, An HI, Kim SH, Kim SM, Jwa EK, Park GC, Namgoong JM, Song GW, Yoon YI, Tak E, Lee SG. Effects of combined immunosuppressant and hepatitis B virus antiviral use on COVID-19 vaccination in recipients of living donor liver transplantation. PeerJ 2024; 12:e18651. [PMID: 39655328 PMCID: PMC11627077 DOI: 10.7717/peerj.18651] [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: 06/19/2024] [Accepted: 11/15/2024] [Indexed: 12/12/2024] Open
Abstract
Background & Aims The global pandemic caused by the highly contagious SARS-CoV-2 virus led to the emergency approval of COVID-19 vaccines to reduce rising morbidity and mortality. However, limited research exists on evaluating the impact of these vaccines on immunocompromised individuals, such as recipients of living donor liver transplantation, highlighting the need for further studies to better understand their effectiveness in this specific population. Methods From June 2021, we followed up on the effectiveness of the vaccine for patients taking immunosuppressive drugs after living-donor liver transplantation (LDLT). A total of 105 immunocompromised individuals participated, of which 50 patients with hepatitis B were taking antiviral drugs. Patients were assessed to analyze how the combination of immunosuppressive and antiviral drugs affected the efficacy of the BNT162b2, mRNA-1273, and ChAdOx1 nCoV-19 COVID-19 vaccines. Results Before and after the vaccinations, patients were monitored to establish differences between immunosuppressed patients and those additionally taking antiviral drugs. In immunocompromised patients taking antiviral drugs for hepatitis B, we confirmed that the effect of the COVID-19 vaccine was reduced when compared to immunocompromised patients. Interestingly, 23 patients (11 without and 12 additionally with hepatitis B drug administration) encountered breakthrough infections, and although there was a minor discrepancy in vaccine efficacy among the patients taking antiviral drugs for hepatitis B, it did not reach statistical significance. Conclusions Additional COVID-19 vaccination is recommended for patients taking immunosuppressive drugs and hepatitis B antiviral drugs after LDLT.
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Affiliation(s)
- Ryunjin Lee
- Department of Convergence Medicine, Asan Medical Institute of Convergence Science and Technology (AMIST), Seoul, Republic of South Korea
| | - Jiwan Choi
- Department of Convergence Medicine, Asan Medical Institute of Convergence Science and Technology (AMIST), Seoul, Republic of South Korea
| | - Eunkyeong Lee
- Department of Convergence Medicine, Asan Medical Institute of Convergence Science and Technology (AMIST), Seoul, Republic of South Korea
| | - Jooyoung Lee
- Department of Convergence Medicine, Asan Medical Institute of Convergence Science and Technology (AMIST), Seoul, Republic of South Korea
| | - Jiye Kim
- Department of Convergence Medicine, Asan Medical Institute of Convergence Science and Technology (AMIST), Seoul, Republic of South Korea
| | - Seoon Kang
- Department of Convergence Medicine, Asan Medical Institute of Convergence Science and Technology (AMIST), Seoul, Republic of South Korea
| | - Hye-In An
- Department of Convergence Medicine, Asan Medical Institute of Convergence Science and Technology (AMIST), Seoul, Republic of South Korea
| | - Sung-Han Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of South Korea
| | - Sung-Min Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Seoul, Republic of South Korea
| | - Eun-Kyoung Jwa
- Division of Hepatobiliary Surgery and Liver Transplantation, Seoul, Republic of South Korea
| | - Gil-Chun Park
- Division of Hepatobiliary Surgery and Liver Transplantation, Seoul, Republic of South Korea
| | - Jung-Man Namgoong
- Division of Pediatric Surgery, Department of Surgery, Asan Medical Center, University Ulsan College of Medicine, Seoul, Republic of South Korea
| | - Gi-Won Song
- Division of Hepatobiliary Surgery and Liver Transplantation, Seoul, Republic of South Korea
| | - Young-In Yoon
- Division of Hepatobiliary Surgery and Liver Transplantation, Seoul, Republic of South Korea
| | - Eunyoung Tak
- Department of Convergence Medicine, Asan Medical Institute of Convergence Science and Technology (AMIST), Seoul, Republic of South Korea
| | - Sung-Gyu Lee
- Division of Hepatobiliary Surgery and Liver Transplantation, Seoul, Republic of South Korea
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6
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Casotti V, Stroppa P, Bravi M, Tebaldi A, Loglio A, Viganò M, Fagiuoli S, D'Antiga L. Vaccinations in Paediatric Solid Organ Transplant Candidates and Recipients. Vaccines (Basel) 2024; 12:952. [PMID: 39339984 PMCID: PMC11435986 DOI: 10.3390/vaccines12090952] [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: 07/28/2024] [Revised: 08/19/2024] [Accepted: 08/20/2024] [Indexed: 09/30/2024] Open
Abstract
Solid organ transplant (SOT) candidates and recipients are a fragile population, in which the presence of a pre-transplant disease leading to organ insufficiency and the post-transplant immunosuppressive treatment expose them to an increased risk of infectious diseases. The best intervention to guarantee efficient prevention of infections, with optimal cost-benefit ratio, is represented by vaccination programs; however, the response to vaccines needs that the immune system maintains a good function. This is even more relevant at paediatric age, when specific immunological conditions make transplant candidates and recipients particularly vulnerable. Paediatric patients may be naïve to most infections and may have incomplete immunization status at the time of transplant listing due to their age. Moreover, the unaccomplished development of a mature immune system and the immunosuppressive regimen adopted after transplant might affect the efficacy of post-transplant vaccinations. Therefore, every effort should be made to obtain the widest vaccination coverage before the transplantation, whenever possible. This review reports the most relevant literature, providing information on the current approach to the vaccinations in paediatric SOT candidates and recipients.
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Affiliation(s)
- Valeria Casotti
- Paediatric Hepatology, Gastroenterology and Transplantation, Child Health Department, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy
| | - Paola Stroppa
- Paediatric Hepatology, Gastroenterology and Transplantation, Child Health Department, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy
| | - Michela Bravi
- Paediatric Hepatology, Gastroenterology and Transplantation, Child Health Department, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy
| | | | - Alessandro Loglio
- Division of Gastroenterology, Hepatology and Transplantation, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy
| | - Mauro Viganò
- Division of Gastroenterology, Hepatology and Transplantation, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy
| | - Stefano Fagiuoli
- Division of Gastroenterology, Hepatology and Transplantation, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy
- Department of Medicine and Surgery, University of Milano-Bicocca, 20126 Milano, Italy
| | - Lorenzo D'Antiga
- Paediatric Hepatology, Gastroenterology and Transplantation, Child Health Department, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy
- Department of Medicine and Surgery, University of Milano-Bicocca, 20126 Milano, Italy
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DeGruttola V, Aslam S. Designing and analyzing studies of coronavirus disease 2019 and post-acute sequelae of severe acute respiratory syndrome coronavirus 2 among immunocompromised individuals. Transpl Infect Dis 2024; 26:e14231. [PMID: 38375954 PMCID: PMC11009066 DOI: 10.1111/tid.14231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Accepted: 12/16/2023] [Indexed: 02/21/2024]
Abstract
Observational studies of coronavirus disease 2019 (COVID-19) among transplant candidates and recipients remain important as immunocompromised patients formed a very small proportion of patients included in COVID-19 trials and large database analyses. We discuss methods that have been used in such analyses to evaluate the impact of vaccination on the risk of symptomatic COVID-19 in such patients and on the probability of developing post-acute sequelae of severe acute respiratory syndrome coronavirus 2 after the onset of infection. We also propose future directions for research and discuss the methods that will be useful to conduct such investigations. The study design and analytical issues that we consider have the potential to be helpful not only for COVID-19 research but also for other infections as well.
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Affiliation(s)
- Victor DeGruttola
- Herbert Wertheim School of Public Health and Longevity Science, University of California, San Diego. San Diego, CA, USA
| | - Saima Aslam
- Division of Infectious Disease and Global Public Health, Department of Medicine, University of California, San Diego. San Diego, CA, USA
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8
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Fraser M, Page RL, Chow S, Alexy T, Peters L. Pharmacotherapy in the heart transplant recipient: A primer for nurse clinicians and pharmacists. Clin Transplant 2024; 38:e15252. [PMID: 38341767 DOI: 10.1111/ctr.15252] [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: 10/27/2023] [Revised: 01/02/2024] [Accepted: 01/17/2024] [Indexed: 02/13/2024]
Abstract
Heart transplantation (HT) is the definitive treatment for eligible patients with end-stage heart disease. A major complication of HT is allograft rejection which can lead to graft dysfunction and death. The guiding principle of chronic immunosuppression therapy is to prevent rejection of the transplanted organ while avoiding oversuppression of the immune system, which can cause opportunistic infections and malignancy. The purpose of this review is to describe immunosuppressive management of the HT recipient-including agent-specific pharmacology and pharmacokinetics, outcomes data, adverse effects, clinical considerations, and recent guideline updates. We will also provide recommendations for medical prophylaxis of immunosuppressed patients based on the most recent clinical guidelines. Additionally, we highlight the importance of medical therapy adherence and the effect of social determinants of health on the long-term management of HT. HT recipients are a complex and high-risk population. The objective of this review is to describe basic pharmacotherapy in HT and implications for nurses and pharmacists.
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Affiliation(s)
- Meg Fraser
- Division of Cardiology, University of Minnesota, Minneapolis, Minnesota, USA
| | - Robert L Page
- Division of Cardiology, University of Colorado School of Medicine, Aurora, Colorado, USA
- Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, Colorado, USA
| | - Sheryl Chow
- Department of Pharmacy Practice and Administration, Western University of Health Sciences, Pomona, California, USA
- Department of Medicine, University of California, Irvine, USA
| | - Tamas Alexy
- Division of Cardiology, University of Minnesota, Minneapolis, Minnesota, USA
| | - Laura Peters
- Division of Cardiology, University of Colorado School of Medicine, Aurora, Colorado, USA
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Kuczaj A, Przybyłowski P, Hrapkowicz T. Torque Teno Virus (TTV)-A Potential Marker of Immunocompetence in Solid Organ Recipients. Viruses 2023; 16:17. [PMID: 38275952 PMCID: PMC10818937 DOI: 10.3390/v16010017] [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: 11/19/2023] [Revised: 12/15/2023] [Accepted: 12/20/2023] [Indexed: 01/27/2024] Open
Abstract
Torque Teno Virus (TTV), first discovered in 1997, is a non-pathogenic, highly prevalent virus with a notable presence in the human virome. TTV has garnered attention as a potential indicator of immunocompetence in recipients of solid organ transplants. In this review, we discuss the role of TTV as a potential marker for immunosuppression optimization, prediction of graft rejection, and as an indicator of opportunistic infections. We discuss TTV's behavior over the course of time after transplantation, TTV's implications in different immunosuppressive regimens, and potential utility in vaccinations. The review synthetizes findings from various studies depicting its potential clinical utility for future personalized patient care.
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Affiliation(s)
- Agnieszka Kuczaj
- Department of Cardiac, Vascular and Endovascular Surgery and Transplantology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland; (P.P.); (T.H.)
- Silesian Center for Heart Diseases, 41-800 Zabrze, Poland
| | - Piotr Przybyłowski
- Department of Cardiac, Vascular and Endovascular Surgery and Transplantology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland; (P.P.); (T.H.)
- Silesian Center for Heart Diseases, 41-800 Zabrze, Poland
| | - Tomasz Hrapkowicz
- Department of Cardiac, Vascular and Endovascular Surgery and Transplantology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland; (P.P.); (T.H.)
- Silesian Center for Heart Diseases, 41-800 Zabrze, Poland
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10
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Watschinger C, Stampfel G, Zollner A, Hoog AM, Rössler A, Reiter S, Dax K, Kimpel J, Tilg H, Antlanger M, Schwaiger E, Moschen AR. B and T Cell Responses to SARS-CoV-2 Vaccination in Kidney and Liver Transplant Recipients with and without Previous COVID-19. Viruses 2023; 16:1. [PMID: 38275936 PMCID: PMC10820906 DOI: 10.3390/v16010001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Revised: 12/09/2023] [Accepted: 12/14/2023] [Indexed: 01/27/2024] Open
Abstract
(1) Background: Vulnerable populations including transplant recipients are jeopardised by COVID-19. Herein, we report on B and T cell responses among liver and kidney organ recipients at our centre. (2) Methods: 23 liver and 45 kidney (14 thereof combined kidney/pancreas) transplanted patients were vaccinated with two doses of BNT162b2 followed by a booster dose of mRNA-1273 in 28 non-responders 4 months thereafter. Anti-SARS-CoV-2-Ig was measured by specific ELISA and virus neutralisation assay; T cell responses were measured by a spike protein-specific IFN-γ release assay. (3) Results: Compared to controls, B and T cell responses were weak in transplant recipients, particularly in those without prior exposure to SARS-CoV-2. Within this group, only 15% after the first and 58.3% after the second vaccination achieved seroconversion. A total of 14 out of 28 vaccination non-responders achieved a seroconversion after a third dose. Vaccination side effects were more frequent in healthy controls. The use of mycophenolate was associated with reduced anti-SARS-CoV-2-Ig production. (4) Conclusions: Our data confirm that vaccination responses are insufficient after standard vaccination in liver and kidney transplant recipients and are affected to a variable degree by specific immunosuppressants, particularly mycophenolate. Monitoring vaccination success and re-vaccinating those who are unresponsive seems prudent to achieve sufficient titres. Overall, prospective large-scale, multinational, multicentre studies or high-quality meta-analyses will be needed to generate personalised vaccination strategies in order to achieve protective immunity in high-risk, hard-to-immunize populations.
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Affiliation(s)
- Christina Watschinger
- Department of Internal Medicine 2 (Gastroenterology and Hepatology, Endocrinology and Metabolism, Nephrology, Rheumatology), Faculty of Medicine, Johannes Kepler University Linz, 4021 Linz, Austria
- Christian Doppler Laboratory for Mucosal Immunology, Faculty of Medicine, Johannes Kepler University Linz, 4021 Linz, Austria
| | - Gerald Stampfel
- Department of Internal Medicine 2 (Gastroenterology and Hepatology, Endocrinology and Metabolism, Nephrology, Rheumatology), Faculty of Medicine, Johannes Kepler University Linz, 4021 Linz, Austria
| | - Andreas Zollner
- Christian Doppler Laboratory for Mucosal Immunology, Faculty of Medicine, Johannes Kepler University Linz, 4021 Linz, Austria
- Department of Medicine, Division of Internal Medicine 1 (Gastroenterology and Hepatology, Endocrinology and Metabolism), Medical University of Innsbruck, 6020 Innsbruck, Austria
| | - Anna M. Hoog
- Department of Internal Medicine 2 (Gastroenterology and Hepatology, Endocrinology and Metabolism, Nephrology, Rheumatology), Faculty of Medicine, Johannes Kepler University Linz, 4021 Linz, Austria
- Christian Doppler Laboratory for Mucosal Immunology, Faculty of Medicine, Johannes Kepler University Linz, 4021 Linz, Austria
| | - Annika Rössler
- Department of Hygiene, Microbiology, and Public Health, Institute of Virology, Medical University of Innsbruck, 6020 Innsbruck, Austria
| | - Silvia Reiter
- Department of Internal Medicine 2 (Gastroenterology and Hepatology, Endocrinology and Metabolism, Nephrology, Rheumatology), Faculty of Medicine, Johannes Kepler University Linz, 4021 Linz, Austria
| | - Kristina Dax
- Department of Internal Medicine 2 (Gastroenterology and Hepatology, Endocrinology and Metabolism, Nephrology, Rheumatology), Faculty of Medicine, Johannes Kepler University Linz, 4021 Linz, Austria
| | - Janine Kimpel
- Department of Hygiene, Microbiology, and Public Health, Institute of Virology, Medical University of Innsbruck, 6020 Innsbruck, Austria
| | - Herbert Tilg
- Department of Medicine, Division of Internal Medicine 1 (Gastroenterology and Hepatology, Endocrinology and Metabolism), Medical University of Innsbruck, 6020 Innsbruck, Austria
| | - Marlies Antlanger
- Department of Internal Medicine 2 (Gastroenterology and Hepatology, Endocrinology and Metabolism, Nephrology, Rheumatology), Faculty of Medicine, Johannes Kepler University Linz, 4021 Linz, Austria
| | - Elisabeth Schwaiger
- Department of Internal Medicine 2 (Gastroenterology and Hepatology, Endocrinology and Metabolism, Nephrology, Rheumatology), Faculty of Medicine, Johannes Kepler University Linz, 4021 Linz, Austria
- Department of Internal Medicine, Brothers of Saint John of God Eisenstadt, 7000 Eisenstadt, Austria
| | - Alexander R. Moschen
- Department of Internal Medicine 2 (Gastroenterology and Hepatology, Endocrinology and Metabolism, Nephrology, Rheumatology), Faculty of Medicine, Johannes Kepler University Linz, 4021 Linz, Austria
- Christian Doppler Laboratory for Mucosal Immunology, Faculty of Medicine, Johannes Kepler University Linz, 4021 Linz, Austria
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11
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Angelico R, Romano F, Coppola L, Materazzo M, Pedini D, Santicchia MS, Cacciola R, Toti L, Sarmati L, Tisone G. Effects of Anti-COVID-19 Vaccination and Pre-Exposure Prophylaxis with Tixagevimab-Cilgavimab in Kidney and Liver Transplant Recipients. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:2101. [PMID: 38138204 PMCID: PMC10744931 DOI: 10.3390/medicina59122101] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 11/25/2023] [Accepted: 11/28/2023] [Indexed: 12/24/2023]
Abstract
Background and Objectives: Underpowered immune response to vaccines against SARS-CoV-2 was observed in solid organ transplant (SOT) recipients. A novel combination of monoclonal antibodies tixagevimab-cilgavimab (TGM/CGM) received authorization as pre-exposure prophylaxis (PrEP) in those with reduced response to vaccine. We aimed to evaluate the response rate to COVID-19 vaccination in kidney transplant (KT), compared to liver transplant (LT) recipients, and the efficacy and safety of PrEP with TGM/CGM. Material and Methods: Between March and November 2022, adult KT and LT recipients who had completed the vaccination schedule (3 doses) were tested for anti-SARS-CoV-2 antibodies titer. SOT recipients with anti-SARS-CoV-2 titer ≥ 100 IU/mL were considered protected against infection, while those with titer < 100 UI/mL were defined non-protected. Patients with inadequate response were invited to PrEP. Results: In total, 306 patients were enrolled [KT:197 (64.4%), LT:109 (35.6%)]. After the complete scheme of vaccination, 246 (80.3%) patients developed a protective titer, while 60 (19.6%) did not have a protective titer. KT recipients had a lower rate of protective anti-COVID-19 titer compared to LT patients [149 (75.6%) vs. 97 (89.0%), p = 0.004]. Recipients with non-protective anti-COVID-19 titer received mainly tacrolimus-based regimen associated with mycophenolate mofetil (MMF) (70%) e steroids (46.7%) as maintenance immunosuppression, while those treated with everolimus were associated with higher protective titer. Of 35 (58.3%) patients who received PrEP, within 12 months, 6 (17.1%) (all KT) developed pauci-symptomatic COVID-19 disease, while 15/25 (60%) of non-responders, who did not receive the prophylaxis, developed COVID-19 disease. After PrEP, hospitalization rate was lower (2.8% vs. 16%), and no adverse events, neither graft loss nor rejection, were observed. Conclusions: Despite complete COVID-19 vaccination, SOT recipients might be not protected from the SARS-CoV-2 infection, especially after KT. In non-protected SOT patients, the subsequent pre-exposure prophylaxis with combination of monoclonal antibodies (TGM/CGM) might be an efficacy and safe strategy to prevent COVID-19 severe disease and hospitalization.
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Affiliation(s)
- Roberta Angelico
- HPB and Transplant Unit, Department of Surgical Sciences, University of Rome Tor Vergata, 00133 Rome, Italy
| | - Francesca Romano
- HPB and Transplant Unit, Department of Surgical Sciences, University of Rome Tor Vergata, 00133 Rome, Italy
| | - Luigi Coppola
- Department of System Medicine, Tor Vergata University, 00133 Rome, Italy
| | - Marco Materazzo
- HPB and Transplant Unit, Department of Surgical Sciences, University of Rome Tor Vergata, 00133 Rome, Italy
| | - Domiziana Pedini
- HPB and Transplant Unit, Department of Surgical Sciences, University of Rome Tor Vergata, 00133 Rome, Italy
| | - Maria Sara Santicchia
- HPB and Transplant Unit, Department of Surgical Sciences, University of Rome Tor Vergata, 00133 Rome, Italy
| | - Roberto Cacciola
- HPB and Transplant Unit, Department of Surgical Sciences, University of Rome Tor Vergata, 00133 Rome, Italy
| | - Luca Toti
- HPB and Transplant Unit, Department of Surgical Sciences, University of Rome Tor Vergata, 00133 Rome, Italy
| | - Loredana Sarmati
- Department of System Medicine, Tor Vergata University, 00133 Rome, Italy
- Infectious Disease Clinic, Policlinico Tor Vergata, 00133 Rome, Italy
| | - Giuseppe Tisone
- HPB and Transplant Unit, Department of Surgical Sciences, University of Rome Tor Vergata, 00133 Rome, Italy
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12
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Kao CM, Michaels MG. Approach to vaccinating the pediatric solid organ transplant candidate and recipient. Front Pediatr 2023; 11:1271065. [PMID: 38027303 PMCID: PMC10663229 DOI: 10.3389/fped.2023.1271065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 10/27/2023] [Indexed: 12/01/2023] Open
Abstract
Solid organ transplantation (SOT) candidates and recipients are at increased risk for morbidity and mortality from vaccine-preventable infections. Children are at particular risk given that they may not have completed their primary immunization series at time of transplant or have acquired natural immunity to pathogens from community exposures. Multiple society guidelines exist for vaccination of SOT candidate and recipients, although challenges remain given limited safety and efficacy data available for pediatric SOT recipients, particularly for live-vaccines. After transplant, individual patient nuances regarding exposure risks and net state of immunosuppression will impact timing of immunizations. The purpose of this review is to provide readers with a concise, practical, expert-opinion on the approach to vaccinating the SOT candidate and recipient and to supplement existing guidelines. In addition, pediatric-specific knowledge gaps in the field and future research priorities will be highlighted.
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Affiliation(s)
- Carol M. Kao
- Department of Pediatrics, Washington University in St. Louis, St. Louis, MO, United States
| | - Marian G. Michaels
- Department of Pediatrics and Surgery, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA, United States
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13
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Múñez-Rubio E, Calderón-Parra J, Gutiérrez-Villanueva A, Fernández-Cruz A, Ramos-Martínez A. Clinical experience in the treatment of COVID-19 with monoclonal antibodies in solid organ transplant recipients. REVISTA ESPANOLA DE QUIMIOTERAPIA : PUBLICACION OFICIAL DE LA SOCIEDAD ESPANOLA DE QUIMIOTERAPIA 2023; 36 Suppl 1:25-28. [PMID: 37997867 PMCID: PMC10793550 DOI: 10.37201/req/s01.07.2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/25/2023]
Abstract
Solid organ transplant (SOT) recipients are at high risk for complications from coronavirus disease 2019 (COVID-19). SOT recipients mount lower immunological responses to vaccines than general population and are at high risk for breakthrough COVID-19 infections. Passive immunotherapy in the form of anti-Spike monoclonal antibodies (MoAbs) may be an alternative for the prophylaxis and treatment of COVID-19 in these patients. SARS-CoV-2 has evolved by accumulating resistance mutations that have escaped the neutralizing action of most MoAbs. However, MoAbs directed at more conserved epitopes and that maintain effector functions could maintain efficacy in the treatment of these patients. According to published data, SOT recipients with low anti-spike antibody responses to vaccination could benefit from the use of MoAbs in pre-exposure prophylaxis, in the treatment of COVID-19 mild to moderate and severe COVID-19 with less than 15 days of symptom duration and low oxygen requirements. Combination therapy could be more effective than monotherapy for the treatment of mild-to-moderate SARS-CoV-2 infection.
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Affiliation(s)
- E Múñez-Rubio
- Elena Múñez-Rubio, Infectious Diseases Unit, Department of Internal Medicine, University Hospital Puerta de Hierro, Majadahonda, Spain.
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14
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Mita A, Ohno Y, Masuda Y, Yoshizawa K, Kubota K, Notake T, Shimizu A, Matsunami H, Soejima Y. Antibody titer after administration of mRNA-based vaccine against severe acute respiratory syndrome coronavirus 2 in liver transplant recipients. Ann Gastroenterol Surg 2023; 7:800-807. [PMID: 37663964 PMCID: PMC10472375 DOI: 10.1002/ags3.12677] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Revised: 03/23/2023] [Accepted: 03/31/2023] [Indexed: 09/05/2023] Open
Abstract
Introduction The mRNA-based vaccine was released as a COVID-19 prophylactic; however, its efficacy in organ transplant recipients is unknown. This study aimed to clarify this in liver transplant recipients. Methods Herein, liver transplant recipients from two hospitals who received vaccines were included. Immunoglobulin-G antibodies against the spike and nucleocapsid proteins were measured chronologically after the second, third, and fourth vaccine doses. Results Antibody levels in 125 liver transplant recipients and 20 healthy volunteers were analyzed. The median age at transplant was 35 (interquartile range 1, 53) years, and the period between transplant and the first dose was 15.2 ± 7.7 years. After the second and third doses, 89.1% and 100% of recipients displayed a positive humoral response, respectively. Anti-spike antibodies after the second dose were significantly reduced at 3 and 6 months, compared to that at 1 month (26.0 [5.4, 59.5], 14.7 [6.5, 31.4] vs. 59.7 [18.3, 164.0] AU/mL, respectively, p < 0.0001). However, a booster vaccine significantly elevated anti-spike antibodies in LT recipients (p < 0.0001) as well as in healthy controls (p < 0.0001). Additionally, the decay rate was comparable between the transplant recipients and controls (2.1 [0.8, 4.5] vs. 2.7 [1.1, 4.1] AU/mL/day, p = 0.9359). Only 4.0% of vaccinated transplant recipients were positive for anti-nucleocapsid antibodies. Conclusion Liver transplant recipients can acquire immunity similar to that of healthy people through vaccination against SARS-CoV-2. The antibody decay rate is the same, and booster vaccinations should be administered similarly to that in healthy individuals.
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Affiliation(s)
- Atsuyoshi Mita
- Division of Gastroenterological, Hepato‐Biliary‐Pancreatic, Transplantation and Pediatric Surgery, Department of SurgeryShinshu University School of MedicineMatsumotoJapan
| | - Yasunari Ohno
- Division of Gastroenterological, Hepato‐Biliary‐Pancreatic, Transplantation and Pediatric Surgery, Department of SurgeryShinshu University School of MedicineMatsumotoJapan
| | - Yuichi Masuda
- Division of Gastroenterological, Hepato‐Biliary‐Pancreatic, Transplantation and Pediatric Surgery, Department of SurgeryShinshu University School of MedicineMatsumotoJapan
| | - Kazuki Yoshizawa
- Division of Gastroenterological, Hepato‐Biliary‐Pancreatic, Transplantation and Pediatric Surgery, Department of SurgeryShinshu University School of MedicineMatsumotoJapan
| | - Koji Kubota
- Division of Gastroenterological, Hepato‐Biliary‐Pancreatic, Transplantation and Pediatric Surgery, Department of SurgeryShinshu University School of MedicineMatsumotoJapan
| | - Tsuyoshi Notake
- Division of Gastroenterological, Hepato‐Biliary‐Pancreatic, Transplantation and Pediatric Surgery, Department of SurgeryShinshu University School of MedicineMatsumotoJapan
| | - Akira Shimizu
- Division of Gastroenterological, Hepato‐Biliary‐Pancreatic, Transplantation and Pediatric Surgery, Department of SurgeryShinshu University School of MedicineMatsumotoJapan
| | | | - Yuji Soejima
- Division of Gastroenterological, Hepato‐Biliary‐Pancreatic, Transplantation and Pediatric Surgery, Department of SurgeryShinshu University School of MedicineMatsumotoJapan
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15
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Ketkar A, Willey V, Pollack M, Glasser L, Dobie C, Wenziger C, Teng CC, Dube C, Cunningham D, Verduzco-Gutierrez M. Assessing the risk and costs of COVID-19 in immunocompromised populations in a large United States commercial insurance health plan: the EPOCH-US Study. Curr Med Res Opin 2023; 39:1103-1118. [PMID: 37431293 DOI: 10.1080/03007995.2023.2233819] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 06/30/2023] [Accepted: 07/04/2023] [Indexed: 07/12/2023]
Abstract
OBJECTIVE To estimate the prevalence of patients with an immunocompromising condition at risk for COVID-19, estimate COVID-19 prevalence rate (PR) and incidence rate (IR) by immunocompromising condition, and describe COVID-19-related healthcare resource utilization (HCRU) and costs. METHODS Using the Healthcare Integrated Research Database (HIRD), patients with ≥1 claim for an immunocompromising condition of interest or ≥2 claims for an immunosuppressive (IS) treatment and COVID-19 diagnosis during the infection period (1 April 2020-31 March 2022) and had ≥12 months baseline data were included. Cohorts (other than the composite cohort) were not mutually exclusive and were defined by each immunocompromising condition. Analyses were descriptive in nature. RESULTS Of the 16,873,161 patients in the source population, 2.7% (n = 458,049) were immunocompromised (IC). The COVID-19 IR for the composite IC cohort during the study period was 101.3 per 1000 person-years and the PR was 13.5%. The highest IR (195.0 per 1000 person-years) and PR (20.1%) were seen in the end-stage renal disease (ESRD) cohort; the lowest IR (68.3 per 1000 person-years) and PR (9.4%) were seen in the hematologic or solid tumor malignancy cohort. Mean costs for hospitalizations associated with the first COVID-19 diagnosis were estimated at nearly $1 billion (2021 United States dollars [USD]) for 14,516 IC patients, with a mean cost of $64,029 per patient. CONCLUSIONS Immunocompromised populations appear to be at substantial risk of severe COVID-19 outcomes, leading to increased costs and HCRU. Effective prophylactic options are still needed for these high-risk populations as the COVID-19 landscape evolves.
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Affiliation(s)
| | | | | | - Lisa Glasser
- AstraZeneca Biopharmaceuticals Medical, Wilmington, DE, USA
| | | | | | - Chia-Chen Teng
- AstraZeneca Biopharmaceuticals Medical, Wilmington, DE, USA
| | - Christine Dube
- AstraZeneca Biopharmaceuticals Medical, Wilmington, DE, USA
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16
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Jones JM, Agarwal A, Moorman AC, Hofmeister MG, Hulse JC, Meneveau MO, Mixon-Hayden T, Ramachandran S, Jones CM, Kellner S, Ferrell D, Sifri CD. Donor-derived Transmission of Hepatitis A Virus Following Kidney Transplantation: Clinical Course of Two Cases From One Donor. Transplant Direct 2023; 9:e1506. [PMID: 37456591 PMCID: PMC10348723 DOI: 10.1097/txd.0000000000001506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Accepted: 05/09/2023] [Indexed: 07/18/2023] Open
Abstract
Donor-derived transmission of infections is a rare complication of kidney transplant. Hepatitis A virus (HAV) is a common cause of acute viral hepatitis worldwide, but donor-derived transmission to organ recipients has been reported in the literature only twice previously. The timeline for HAV incubation and clearance in transplant recipients is not well understood. Methods In 2018, 2 kidneys and a liver were procured from a deceased donor resident of Kentucky, one of many states that was experiencing an HAV outbreak associated with person-to-person transmission through close contact, primarily among people who reported drug use. Both kidney recipients, residents of Virginia, subsequently developed acute HAV infections. We report the results of an investigation to determine the source of transmission and describe the clinical course of HAV infection in the infected kidney recipients. Results The liver recipient had evidence of immunity to HAV and did not become infected. The donor and both kidney recipients were found to have a genetically identical strain of HAV using a next-generation sequencing-based cyber molecular assay (Global Hepatitis Outbreak Surveillance Technology), confirming donor-derived HAV infections in kidney recipients. At least 1 kidney recipient experienced delayed development of detectable hepatitis A anti-IgM antibodies. By 383 and 198 d posttransplant, HAV RNA was no longer detectable in stool specimens from the left and right kidney recipients, respectively. Conclusions Adherence to current guidance for hepatitis A vaccination may prevent future morbidity due to HAV among organ recipients. http://links.lww.com/TXD/A548.
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Affiliation(s)
- Jefferson M. Jones
- Division of Healthcare Quality Promotion, National Center for Emerging, Zoonotic and Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA
| | - Avinash Agarwal
- Division of Transplantation, Department of Surgery, UVA Health, Charlottesville, VA
| | - Anne C. Moorman
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA
| | - Megan G. Hofmeister
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA
| | - John C. Hulse
- University of Virginia School of Medicine, Charlottesville, VA
| | | | - Tonya Mixon-Hayden
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA
| | - Sumathi Ramachandran
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA
| | - Christopher M. Jones
- Division of Hepatobiliary and Transplant Surgery, Trager Transplant Center, University of Louisville, Louisville, KY
| | - Stephanie Kellner
- Central Shenandoah Health District, Virginia Department of Health, Richmond, VA
| | - Daniel Ferrell
- Rappahannock-Rapidan Health District, Virginia Department of Health, Richmond, VA
| | - Costi D. Sifri
- Division of Infectious Diseases and International Health, Department of Medicine, UVA Health, Charlottesville, VA
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17
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La Civita E, Zannella C, Brusa S, Romano P, Schettino E, Salemi F, Carrano R, Gentile L, Punziano A, Lagnese G, Spadaro G, Franci G, Galdiero M, Terracciano D, Portella G, Loffredo S. BNT162b2 Elicited an Efficient Cell-Mediated Response against SARS-CoV-2 in Kidney Transplant Recipients and Common Variable Immunodeficiency Patients. Viruses 2023; 15:1659. [PMID: 37632002 PMCID: PMC10459971 DOI: 10.3390/v15081659] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Revised: 07/27/2023] [Accepted: 07/28/2023] [Indexed: 08/27/2023] Open
Abstract
SARS-CoV-2 vaccination is the standard of care for the prevention of COVID-19 disease. Although vaccination triggers both humoral and cellular immune response, COVID-19 vaccination efficacy is currently evaluated by measuring antibodies only, whereas adaptative cellular immunity is unexplored. Our aim is to test humoral and cell-mediated response after three doses of BNT162b vaccine in two cohorts of fragile patients: Common Variable Immunodeficiency (CVID) patients and Kidney Transplant Recipients (KTR) patients compared to healthy donors. We enrolled 10 healthy controls (HCs), 19 CVID patients and 17 KTR patients. HC BNT162b third dose had successfully mounted humoral immune response. A positive correlation between Anti-Spike Trimeric IgG concentration and neutralizing antibody titer was also observed. CVID and KTR groups showed a lower humoral immune response compared to HCs. IFN-γ release induced by epitopes of the Spike protein in stimulated CD4+ and CD8+ T cells was similar among vaccinated HC, CVID and KTR. Patients vaccinated and infected showed a more efficient humoral and cell-mediated response compared to only vaccinated patients. In conclusion, CVID and KTR patients had an efficient cell-mediated but not humoral response to SARS-CoV-2 vaccine, suggesting that the evaluation of T cell responses could be a more sensitive marker of immunization in these subjects.
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Affiliation(s)
- Evelina La Civita
- Department of Translational Medical Sciences, University of Naples “Federico II”, 80131 Naples, Italy; (E.L.C.); (S.B.); (A.P.); (G.L.); (G.S.); (D.T.); (S.L.)
| | - Carla Zannella
- Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (C.Z.); (M.G.)
- UOC of Virology and Microbiology, University Hospital of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Stefano Brusa
- Department of Translational Medical Sciences, University of Naples “Federico II”, 80131 Naples, Italy; (E.L.C.); (S.B.); (A.P.); (G.L.); (G.S.); (D.T.); (S.L.)
| | - Paolo Romano
- Department of Public Health, Section of Nephrology, University of Naples “Federico II”, 80131 Naples, Italy; (P.R.); (E.S.); (F.S.); (R.C.)
| | - Elisa Schettino
- Department of Public Health, Section of Nephrology, University of Naples “Federico II”, 80131 Naples, Italy; (P.R.); (E.S.); (F.S.); (R.C.)
| | - Fabrizio Salemi
- Department of Public Health, Section of Nephrology, University of Naples “Federico II”, 80131 Naples, Italy; (P.R.); (E.S.); (F.S.); (R.C.)
| | - Rosa Carrano
- Department of Public Health, Section of Nephrology, University of Naples “Federico II”, 80131 Naples, Italy; (P.R.); (E.S.); (F.S.); (R.C.)
| | - Luca Gentile
- Integrated Department of Laboratory and Trasfusion Medicine, University of Naples “Federico II”, 80131 Naples, Italy;
| | - Alessandra Punziano
- Department of Translational Medical Sciences, University of Naples “Federico II”, 80131 Naples, Italy; (E.L.C.); (S.B.); (A.P.); (G.L.); (G.S.); (D.T.); (S.L.)
| | - Gianluca Lagnese
- Department of Translational Medical Sciences, University of Naples “Federico II”, 80131 Naples, Italy; (E.L.C.); (S.B.); (A.P.); (G.L.); (G.S.); (D.T.); (S.L.)
| | - Giuseppe Spadaro
- Department of Translational Medical Sciences, University of Naples “Federico II”, 80131 Naples, Italy; (E.L.C.); (S.B.); (A.P.); (G.L.); (G.S.); (D.T.); (S.L.)
- Center for Basic and Clinical Immunology Research (CISI), University of Naples “Federico II”, 80131 Naples, Italy
| | - Gianluigi Franci
- Department of Medicine, Surgery and Dentistry “ScholaMedicaSalernitana”, University of Salerno, 84081 Baronissi, Italy;
- Clinical Pathology and Microbiology Unit, San Giovanni di Dio e Ruggi D’Aragona University Hospital, 84125 Salerno, Italy
| | - Massimiliano Galdiero
- Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (C.Z.); (M.G.)
- UOC of Virology and Microbiology, University Hospital of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Daniela Terracciano
- Department of Translational Medical Sciences, University of Naples “Federico II”, 80131 Naples, Italy; (E.L.C.); (S.B.); (A.P.); (G.L.); (G.S.); (D.T.); (S.L.)
| | - Giuseppe Portella
- Department of Translational Medical Sciences, University of Naples “Federico II”, 80131 Naples, Italy; (E.L.C.); (S.B.); (A.P.); (G.L.); (G.S.); (D.T.); (S.L.)
| | - Stefania Loffredo
- Department of Translational Medical Sciences, University of Naples “Federico II”, 80131 Naples, Italy; (E.L.C.); (S.B.); (A.P.); (G.L.); (G.S.); (D.T.); (S.L.)
- Center for Basic and Clinical Immunology Research (CISI), University of Naples “Federico II”, 80131 Naples, Italy
- Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council, 80131 Naples, Italy
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18
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Tsoutsoura P, Xagas E, Roussos S, Hatzakis A, Gourzi P, Boletis IN, Marinaki S. Assessment of mRNA Vaccine Immunogenicity in Solid Organ Transplant Recipients. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1075. [PMID: 37374279 DOI: 10.3390/medicina59061075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/09/2023] [Revised: 05/29/2023] [Accepted: 05/30/2023] [Indexed: 06/29/2023]
Abstract
Background and Objectives: Solid organ transplant (SOT) recipients have a higher risk of suffering from severe Coronavirus (COVID-19) compared to the general population. Studies have shown impaired immunogenicity of mRNA vaccines in this high-risk population; thus, SOT recipients have been prioritized globally for primary and booster doses. Materials and Methods: We analyzed 144 SOT recipients who had previously received two doses of BNT162b2 or mRNA1273 vaccine, and who were subsequently vaccinated with a booster dose of the mRNA1273 vaccine. Humoral and cellular immune responses were measured 1 and 3 months after the second dose, and 1 month after the third dose. Results: One month after the second dose, 33.6% (45/134) of patients displayed a positive antibody response with a median (25th, 75th) antibody titer of 9 (7, 161) AU/mL. Three months after the second dose, 41.8% (56/134) tested positive with a median (25th, 75th) antibody titer of 18 (7, 251) AU/mL. After the booster dose, the seropositivity rate increased to 69.4% (93/134), with a median (25th, 75th) titer of 966 (10, 8027) AU/mL. The specific SARS-CoV-2 T-cell response was assessed in 44 randomly selected recipients 3 months after the second dose, and 11.4% (5/44) of them had a positive response. Following the third dose, 42% (21/50) tested positive. Side effects after the third dose were mild, with pain at the injection site being the most frequent adverse effect, reported by 73.4% of the recipients. Conclusion: Our study shows a mild delayed increase in antibody titer, three months after primary vaccination compared to one month after. It also shows a robust augmentation of humoral and specific T-cell responses after the booster dose, as well as the safety and tolerability of the mRNA vaccines in SOT recipients.
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Affiliation(s)
- Paraskevi Tsoutsoura
- Clinic of Nephrology and Renal Transplantation, Laiko General Hospital, Medical School of Athens, National and Kapodistrian University, 11527 Athens, Greece
| | - Efstathios Xagas
- Clinic of Nephrology and Renal Transplantation, Laiko General Hospital, Medical School of Athens, National and Kapodistrian University, 11527 Athens, Greece
| | - Sotirios Roussos
- Department of Hygiene, Epidemiology & Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, 15772 Athens, Greece
| | - Angelos Hatzakis
- Department of Hygiene, Epidemiology & Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, 15772 Athens, Greece
| | - Polyxeni Gourzi
- Molecular Immunopathology and Histocompatibility Unit, Onassis Cardiac Surgery Center, 17674 Athens, Greece
| | - Ioannis N Boletis
- Clinic of Nephrology and Renal Transplantation, Laiko General Hospital, Medical School of Athens, National and Kapodistrian University, 11527 Athens, Greece
| | - Smaragdi Marinaki
- Clinic of Nephrology and Renal Transplantation, Laiko General Hospital, Medical School of Athens, National and Kapodistrian University, 11527 Athens, Greece
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19
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Radcliffe C, Malinis M, Azar MM. Antiviral Treatment of Coronavirus Disease-2019 Pneumonia. Clin Chest Med 2023; 44:279-297. [PMID: 37085220 PMCID: PMC9701636 DOI: 10.1016/j.ccm.2022.11.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Direct acting antivirals and monoclonal antibodies reduce morbidity and mortality associated with severe acute respiratory syndrome coronavirus 2 infection. Persons at higher risk for disease progression and hospitalized patients with coronavirus disease-2019 (COVID-19) benefit most from available therapies. Following an emphasis on inpatient treatment of COVID-19 during the early pandemic, several therapeutic options were developed for outpatients with COVID-19. Additional clinical trials and real-world studies are needed to keep pace with the evolving pandemic.
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Affiliation(s)
- Christopher Radcliffe
- Section of Infectious Diseases, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA
| | - Maricar Malinis
- Section of Infectious Diseases, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA
| | - Marwan M Azar
- Section of Infectious Diseases, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, USA.
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20
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Ziv N, Gimelraikh Y, Ashkenazi-Hoffnung L, Alfandary H, Borovitz Y, Dagan A, Levi S, Hamdani G, Levy-Erez D, Landau D, Koren G, Talgam-Horshi E, Haskin O. Serologic response to COVID-19 infection or vaccination in pediatric kidney transplant recipients compared to healthy children. Transpl Immunol 2023; 78:101839. [PMID: 37076050 PMCID: PMC10110277 DOI: 10.1016/j.trim.2023.101839] [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: 12/10/2022] [Revised: 04/15/2023] [Accepted: 04/16/2023] [Indexed: 04/21/2023]
Abstract
BACKGROUND Differences in serologic response to COVID-19 infection or vaccination were reported in adult kidney transplant recipients (KTR) compared to non-immunocompromised patients. This study aims to compare the serologic response of naturally infected or vaccinated pediatric KTR to that of controls. METHODS Thirty-eight KTR and 42 healthy children were included; aged ≤18 years, with a previously confirmed COVID-19 infection or post COVID-19 vaccination. Serological response was measured by anti-spike protein IgG antibody titers. Response post third vaccine was additionally assessed in KTR. RESULTS Fourteen children in each group had previously confirmed infection. KTR were significantly older and developed a 2-fold higher antibody titer post-infection compared to controls [median (interquartile range [IQR]) age: 14.9 (7.8, 17.5) vs. 6.3 (4.5, 11.5) years, p = 0.02; median (IQR) titer: 1695 (982, 3520) vs. 716 (368, 976) AU/mL, p = 0.03]. Twenty-four KTR and 28 controls were vaccinated. Antibody titer was lower in KTR than in controls [median (IQR): 803 (206, 1744) vs. 8023 (3032, 30,052) AU/mL, p < 0.001]. Fourteen KTR received third vaccine. Antibody titer post booster in KTR reached similar levels to those of controls post two doses [median (IQR) 5923 (2295, 12,278) vs. 8023 (3034, 30,052) AU/mL, p = 0.37] and to KTR post natural infection [5282 AU/mL (2583, 13,257) p = 0.8]. CONCLUSION Serologic response to COVID-19 infection was significantly higher in KTR than in controls. Antibody level in KTR was higher in response to infection vs. vaccination, contrary to reports in the general population. Response to vaccination in KTR reached levels comparable to controls only after third vaccine.
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Affiliation(s)
- Noa Ziv
- Department of Pediatrics "C", Schneider Children's Medical Center of Israel, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
| | - Yulia Gimelraikh
- Department of Pediatric Emergency Medicine, Schneider Children's Medical Center of Israel, Petah Tikva, Israel
| | - Liat Ashkenazi-Hoffnung
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Pediatric Infectious Disease Unit, Day Hospitalization Department, Schneider Children's Medical Center of Israel, Petah Tikva, Israel
| | - Hadas Alfandary
- Institute of Nephrology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel
| | - Yael Borovitz
- Institute of Nephrology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel
| | - Amit Dagan
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Institute of Nephrology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel
| | - Shelly Levi
- Institute of Nephrology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel
| | - Gilad Hamdani
- Institute of Nephrology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel
| | - Daniella Levy-Erez
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Institute of Nephrology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel
| | - Daniel Landau
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Institute of Nephrology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel
| | - Gili Koren
- Institute of Nephrology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel
| | - Efrat Talgam-Horshi
- Institute of Nephrology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel
| | - Orly Haskin
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Institute of Nephrology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel
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21
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Roberto P, Cinti L, Napoli A, Paesani D, Riveros Cabral RJ, Maggi F, Garofalo M, Pretagostini R, Centofanti A, Carillo C, Venuta F, Gaeta A, Antonelli G. Torque teno virus (TTV): A gentle spy virus of immune status, predictive marker of seroconversion to COVID-19 vaccine in kidney and lung transplant recipients. J Med Virol 2023; 95:e28512. [PMID: 36661060 PMCID: PMC10108096 DOI: 10.1002/jmv.28512] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 01/11/2023] [Accepted: 01/16/2023] [Indexed: 01/21/2023]
Abstract
To date, no comprehensive marker to monitor the immune status of patients is available. Given that Torque teno virus (TTV), a known human virome component, has previously been identified as a marker of immunocompetence, it was retrospectively investigated whether TTV viral load may also represent a marker of ability to develop antibody in response to COVID-19-BNT162B2 vaccine in solid organ transplant recipients (SOT). Specifically, 273 samples from 146 kidney and 26 lung transplant recipients after successive doses of vaccine were analyzed. An inverse correlation was observed within the TTV copy number and anti-Spike IgG antibody titer with a progressive decrease in viremia the further away from the transplant date. Analyzing the data obtained after the second dose, a significant difference in TTV copy number between responsive and nonresponsive patients was observed, considering a 5 log10 TTV copies/mL threshold to discriminate between the two groups. Moreover, for 86 patients followed in their response to the second and third vaccination doses a 6 log10 TTV copies/mL threshold was used to predict responsivity to the booster dose. Although further investigation is necessary, possibly extending the analysis to other patient categories, this study suggests that TTV can be used as a good marker of vaccine response in transplant patients.
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Affiliation(s)
- Piergiorgio Roberto
- Department of Molecular Medicine, Laboratory of Microbiology and Virology, Sapienza University of Rome, Rome, Italy
| | - Lilia Cinti
- Department of Molecular Medicine, Laboratory of Microbiology and Virology, Sapienza University of Rome, Rome, Italy
| | - Anna Napoli
- Department of Molecular Medicine, Laboratory of Microbiology and Virology, Sapienza University of Rome, Rome, Italy
| | | | - Rodolfo J Riveros Cabral
- Department of Molecular Medicine, Laboratory of Microbiology and Virology, Sapienza University of Rome, Rome, Italy
| | - Fabrizio Maggi
- Laboratory of Virology, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, Rome, Italy
| | - Manuela Garofalo
- General Surgery and Organ Transplantation Unit, Sapienza University of Rome, Rome, Italy
| | - Renzo Pretagostini
- General Surgery and Organ Transplantation Unit, Sapienza University of Rome, Rome, Italy
| | - Anastasia Centofanti
- Department of General and Specialistic Surgery "Paride Stefanini", Sapienza University of Rome, Rome, Italy
| | - Carolina Carillo
- Department of General and Specialistic Surgery "Paride Stefanini", Sapienza University of Rome, Rome, Italy
| | - Federico Venuta
- Department of General and Specialistic Surgery "Paride Stefanini", Sapienza University of Rome, Rome, Italy
| | - Aurelia Gaeta
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
| | - Guido Antonelli
- Department of Molecular Medicine, Laboratory of Microbiology and Virology, Sapienza University of Rome, Rome, Italy.,Microbiology and Virology Unit, Sapienza University Hospital Policlinico Umberto I, Rome, Italy
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22
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Vaccine Effectiveness Against the SARS-CoV-2 B.1.1.529 Omicron Variant in Solid Organ and Islet Transplant Recipients in England: A National Retrospective Cohort Study. Transplantation 2023; 107:1124-1135. [PMID: 36727724 PMCID: PMC10125014 DOI: 10.1097/tp.0000000000004535] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
BACKGROUND The effectiveness of vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 Omicron variant in immunosuppressed solid organ and islet transplant (SOT) recipients is unclear. METHODS National registries in England were linked to identify SARS-CoV-2 positive tests, noninjury hospitalization within 14 d, and deaths within 28 d between December 7, 2020, and March 31, 2022 in adult SOT recipients. Incidence rate ratios (IRRs) for infection, and hospitalization or death, were adjusted for recipient demographics and calendar month for the Omicron-dominant period (December 20, 2021, to March 31, 2022). Mortality risk following SARS-CoV-2 infection was adjusted for recipient demographics and dominant variant using a Cox proportional-hazards model for the entire time period. RESULTS During the Omicron-dominant period, infection IRRs (95% confidence intervals) were higher in those receiving 2, 3, and 4 vaccine doses than in unvaccinated patients (1.25 [1.08-1.45], 1.46 [1.28-1.67], and 1.79 [1.54-2.06], respectively). However, hospitalization or death IRRs during this period were lower in those receiving 3 or 4 vaccine doses than in unvaccinated patients (0.62 [0.45-0.86] and 0.39 [0.26-0.58], respectively). Risk-adjusted analyses for deaths after SARS-CoV-2 infection between December 7, 2020, and March 31, 2022, found hazard ratios (95% confidence intervals) of 0.67 (0.46-0.98), 0.46 (0.30-0.69), and 0.18 (0.09-0.35) for those with 2, 3, and 4 vaccine doses, respectively, when compared with the unvaccinated group. CONCLUSIONS In immunosuppressed SOT recipients, vaccination is associated with incremental, dose-dependent protection against hospitalization or death after SARS-CoV-2 infection, including against the Omicron variant.
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23
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Gleeson S, Martin P, Thomson T, Spensley KJ, Goodall D, Bedi R, Thind AK, Seneschall C, Gan J, McAdoo S, Lightstone L, Kelleher P, Prendecki M, Willicombe M. Lack of seroresponse to SARS-CoV-2 booster vaccines given early post-transplant in patients primed pre-transplantation. Front Immunol 2023; 13:1083167. [PMID: 36726970 PMCID: PMC9885043 DOI: 10.3389/fimmu.2022.1083167] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 12/16/2022] [Indexed: 01/19/2023] Open
Abstract
SARS-CoV-2 vaccines are recommended pre-transplantation, however, waning immunity and evolving variants mandate booster doses. Currently there no data to inform the optimal timing of booster doses post-transplant, in patients primed pre-transplant. We investigated serial serological samples in 204 transplant recipients who received 2 or 3 SARS-CoV-2 vaccines pre-transplant. Spike protein antibody concentrations, [anti-S], were measured on the day of transplantation and following booster doses post-transplant. In infection-naïve patients, post-booster [anti-S] did not change when V3 (1st booster) was given at 116(78-150) days post-transplant, falling from 122(32-574) to 111(34-682) BAU/ml, p=0.78. Similarly, in infection-experienced patients, [anti-S] on Day-0 and post-V3 were 1090(133-3667) and 2207(650-5618) BAU/ml respectively, p=0.26. In patients remaining infection-naïve, [anti-S] increased post-V4 (as 2nd booster) when given at 226(208-295) days post-transplant, rising from 97(34-1074) to 5134(229-5680) BAU/ml, p=0.0016. Whilst in patients who had 3 vaccines pre-transplant, who received V4 (as 1st booster) at 82(49-101) days post-transplant, [anti-S] did not change, falling from 981(396-2666) to 871(242-2092) BAU/ml, p=0.62. Overall, infection pre-transplant and [anti-S] at the time of transplantation predicted post-transplant infection risk. As [Anti-S] fail to respond to SARS-CoV-2 booster vaccines given early post-transplant, passive immunity may be beneficial to protect patients during this period.
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Affiliation(s)
- Sarah Gleeson
- Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom,Imperial College Renal and Transplant Centre, Imperial College Healthcare National Healthcare Service Trust, Hammersmith Hospital, London, United Kingdom
| | - Paul Martin
- Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom,Imperial College Renal and Transplant Centre, Imperial College Healthcare National Healthcare Service Trust, Hammersmith Hospital, London, United Kingdom
| | - Tina Thomson
- Imperial College Renal and Transplant Centre, Imperial College Healthcare National Healthcare Service Trust, Hammersmith Hospital, London, United Kingdom
| | - Katrina J. Spensley
- Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom,Imperial College Renal and Transplant Centre, Imperial College Healthcare National Healthcare Service Trust, Hammersmith Hospital, London, United Kingdom
| | - Dawn Goodall
- Imperial College Renal and Transplant Centre, Imperial College Healthcare National Healthcare Service Trust, Hammersmith Hospital, London, United Kingdom
| | - Rachna Bedi
- Imperial College Renal and Transplant Centre, Imperial College Healthcare National Healthcare Service Trust, Hammersmith Hospital, London, United Kingdom
| | - Amarpreet Kaur Thind
- Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom,Imperial College Renal and Transplant Centre, Imperial College Healthcare National Healthcare Service Trust, Hammersmith Hospital, London, United Kingdom
| | - Charlotte Seneschall
- Imperial College Renal and Transplant Centre, Imperial College Healthcare National Healthcare Service Trust, Hammersmith Hospital, London, United Kingdom
| | - Jaslyn Gan
- Imperial College Renal and Transplant Centre, Imperial College Healthcare National Healthcare Service Trust, Hammersmith Hospital, London, United Kingdom
| | - Stephen McAdoo
- Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom,Imperial College Renal and Transplant Centre, Imperial College Healthcare National Healthcare Service Trust, Hammersmith Hospital, London, United Kingdom
| | - Liz Lightstone
- Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom,Imperial College Renal and Transplant Centre, Imperial College Healthcare National Healthcare Service Trust, Hammersmith Hospital, London, United Kingdom
| | - Peter Kelleher
- Department of Infection and Immunity Sciences Northwest London Pathology NHS Trust, Charing Cross Hospital, London, United Kingdom,Department of Infectious Diseases, Imperial College London, London, United Kingdom
| | - Maria Prendecki
- Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom,Imperial College Renal and Transplant Centre, Imperial College Healthcare National Healthcare Service Trust, Hammersmith Hospital, London, United Kingdom
| | - Michelle Willicombe
- Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom,Imperial College Renal and Transplant Centre, Imperial College Healthcare National Healthcare Service Trust, Hammersmith Hospital, London, United Kingdom,*Correspondence: Michelle Willicombe,
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24
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Fatima I, Duong N. The impact of COVID-19 on liver transplantation: challenges and perspectives. Therap Adv Gastroenterol 2023; 16:17562848231171452. [PMID: 37180361 PMCID: PMC10172841 DOI: 10.1177/17562848231171452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Accepted: 04/06/2023] [Indexed: 05/16/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic presented unique challenges to patients with decompensated cirrhosis awaiting transplant, with respect to accessing medical facilities for routine clinic visits, imaging, laboratory workup, or endoscopies. There was a delay in organ procurement that led to a decrease in the number of liver transplants (LTs) and an increase in the morality of waitlisted patients at the beginning of the pandemic. LT numbers later equalized to pre-pandemic numbers due to combined efforts and adaptability of transplant centers as well as dynamic guidelines. Due to being immunosuppressed, the demographics of LT patients were at an increased risk of infection. Although there is a higher rate of mortality and morbidity in patients with chronic liver disease, LT itself is not a risk factor for mortality in COVID-19. There was no difference in overall mortality in LT patients compared to non-LT patients, and mortality risk factors were the same: age, hypertension, diabetes, obesity, and chronic kidney disease. The most common causes of death were respiratory complications. Liver-related deaths were reported in 1.6% of patients. The optimal timing of liver transplantation post-infection depends on various factors, such as the severity of liver injury, the presence of comorbidities, and the progression of the underlying liver disease. There is not enough data available on COVID-19 cholangiopathy and the number of cases that will be seen in the future that will require LT. There are some concerns of lower immunogenicity of COVID-19 vaccines in LT patients but available evidence suggests that the vaccines are safe and well-tolerated.
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Affiliation(s)
| | - Nikki Duong
- Department of Gastroenterology, Hepatology and
Nutrition, Virginia Commonwealth University Medical Center, Richmond, VA,
USA
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25
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Pinto-Álvarez M, Fernández-Niño JA, Arregocés-Castillo L, Rojas-Botero ML, Palacios AF, Galvis-Pedraza M, Ruiz-Gomez F. Real-world Evidence of COVID-19 Vaccines Effectiveness in Solid-organ Transplant Recipient Population in Colombia: A Study Nested in the Esperanza Cohort. Transplantation 2023; 107:216-224. [PMID: 36228269 PMCID: PMC9746232 DOI: 10.1097/tp.0000000000004411] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 08/23/2022] [Accepted: 09/09/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND Solid-organ transplant recipients (SOTRs) have a higher risk of coronavirus disease 2019 (COVID-19) complications and death and a less powerful and lasting response to vaccines and to natural infection. In Colombia, this population was prioritized in the National Vaccination Plan against COVID-19 and received vaccines from different platforms. The aim of this study was to estimate the effectiveness of the complete vaccination schedule and of the vaccine booster for COVID-19 administered to SOTRs in Colombia. METHODS A nested-cohort was assembled within the population-based ESPERANZA cohort and included the subset of 16 y and older SOTRs (n = 6963); the follow-up period spanned March 11, 2021, to May 11, 2022. The vaccine effectiveness was estimated with Cox proportional-hazards models so that the overall effectiveness of the complete vaccination schedule, the vaccine booster, each used vaccine, and the homologous and heterologous schedules were estimated, adjusting by the main confounders. RESULTS The overall effectiveness of being fully vaccinated was 73.7% (95% confidence interval [CI], 68.9%-77.0%) to prevent COVID-19 infection, 83.7% (95% CI, 78.7%-87.5%) to prevent hospitalization, and 92.1% (95% CI, 88.8%-94.4%) to prevent death due to COVID-19. Similarly, the effectiveness of the vaccine booster was 76.7% (95% CI, 70.6%-81.5%), 86.9% (95% CI, 79.4%-91.6%), and 94.5% (95% CI, 89.8%-97.1%) to prevent confirmed COVID-19 infection, hospitalization, and death due to COVID-19, respectively. In both cases, there were no statistically significant differences across age groups. CONCLUSIONS Findings from this work show a high protection of vaccination against infection, hospitalization, and death due to COVID-19 in SOTRs, which increases with the vaccine booster.
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Affiliation(s)
- Mariana Pinto-Álvarez
- Dirección de Medicamentos y Tecnologías de Salud, Ministerio de Salud y Protección Social, Bogotá DC, Colombia
| | - Julián A. Fernández-Niño
- Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
- Departamento de Salud Pública, Universidad del Norte, Barranquilla, Colombia
| | - Leonardo Arregocés-Castillo
- Dirección de Medicamentos y Tecnologías de Salud, Ministerio de Salud y Protección Social, Bogotá DC, Colombia
| | | | - Andrés F. Palacios
- Dirección de Medicamentos y Tecnologías de Salud, Ministerio de Salud y Protección Social, Bogotá DC, Colombia
| | - Maryory Galvis-Pedraza
- Dirección de Medicamentos y Tecnologías de Salud, Ministerio de Salud y Protección Social, Bogotá DC, Colombia
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26
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Balsby D, Nilsson AC, Petersen I, Lindvig SO, Davidsen JR, Abazi R, Poulsen MK, Holden IK, Justesen US, Bistrup C, Johansen IS. Humoral immune response following a third SARS-CoV-2 mRNA vaccine dose in solid organ transplant recipients compared with matched controls. Front Immunol 2022; 13:1039245. [PMID: 36569919 PMCID: PMC9780530 DOI: 10.3389/fimmu.2022.1039245] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Accepted: 11/23/2022] [Indexed: 12/14/2022] Open
Abstract
Background Solid organ transplant (SOT) recipients have shown suboptimal antibody response following COVID-19 vaccination. Several risk factors for the diminished response have been identified including immunosuppression and older age, but the influence of different comorbidities is not fully elucidated. Method This case-control study consisted of 420 Danish adult SOT recipients and 840 sex- and age-matched controls, all vaccinated with a third homologous dose of either BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine. The primary outcome was differences in humoral immune response. The secondary outcome was breakthrough infections. Additionally, we looked for factors that could predict possible differences between the two groups. Results Response rate increased from 186/382 (49%) to 275/358 (77%) in SOT recipients and remained on 781/790 (99%) to 601/609 (99%) in controls following a third vaccine dose. SOT recipients had significantly lower median antibody concentrations after third dose compared to controls (332.6 BAU/ml vs 46,470.0 BAU/ml, p <0.001). Lowest median antibody concentrations were seen in SOT recipients with liver disease (10.3 BAU/ml, IQR 7.1-319) and diabetes (275.3 BAU/ml, IQR 7.3-957.4). Breakthrough infections occurred similarly frequent, 150 (40%) among cases and 301 (39%) among controls (p = 0.80). Conclusion A third COVID-19 vaccine dose resulted in a significant increase in humoral immunogenicity in SOT recipients and maintained high response rate in controls. Furthermore, SOT recipients were less likely to produce antibodies with overall lower antibody concentrations and humoral immunity was highly influenced by the presence of liver disease and diabetes. The prevalence of breakthrough infections was similar in the two groups.
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Affiliation(s)
- Daniel Balsby
- Department of Infectious Diseases, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Anna Christine Nilsson
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- Department of Clinical Immunology, Odense University Hospital, Odense, Denmark
| | - Inge Petersen
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- Open Patient data Explorative Network, Odense University Hospital, Odense, Denmark
| | - Susan O. Lindvig
- Department of Infectious Diseases, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Jesper Rømhild Davidsen
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- Department of Respiratory Medicine, Odense University Hospital, Odense, Denmark
| | - Rozeta Abazi
- Department of Gastroenterology, Odense University Hospital, Odense, Denmark
| | - Mikael K. Poulsen
- Department of Cardiology, Odense University Hospital, Odense, Denmark
| | - Inge K. Holden
- Department of Infectious Diseases, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Ulrik S. Justesen
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- Department of Clinical Microbiology, Odense University Hospital, Odense, Denmark
| | - Claus Bistrup
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- Department of Nephrology, Odense University Hospital, Odense, Denmark
| | - Isik Somuncu Johansen
- Department of Infectious Diseases, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
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27
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Gulmez R, Ozbey D, Agbas A, Aksu B, Yildiz N, Uckardes D, Saygili S, Yilmaz EK, Yildirim ZY, Tasdemir M, Kiykim A, Cokugras H, Canpolat N, Nayir A, Kocazeybek B, Caliskan S. Humoral and cellular immune response to SARS-CoV-2 mRNA BNT162b2 vaccine in pediatric kidney transplant recipients compared with dialysis patients and healthy children. Pediatr Nephrol 2022:10.1007/s00467-022-05813-w. [PMID: 36459243 PMCID: PMC9716124 DOI: 10.1007/s00467-022-05813-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 10/10/2022] [Accepted: 10/31/2022] [Indexed: 12/04/2022]
Abstract
BACKGROUND Compared with the general population, the immune response to COVID-19 mRNA vaccines is lower in adult kidney transplant recipients (KTRs). However, data is limited for pediatric KTRs. In this study, we aimed to assess humoral and cellular immune responses to the COVID-19 mRNA vaccine in pediatric KTRs. METHODS This multicenter, prospective, case-control study included 63 KTRs (37 male, aged 12-21 years), 19 dialysis patients, and 19 controls. Humoral (anti-SARS-CoV2 IgG, neutralizing Ab (nAb)) and cellular (interferon-gamma release assay (IGRA)) immune responses were assessed at least one month after two doses of BNT162b2 mRNA vaccine. RESULTS Among COVID-19 naïve KTRs (n = 46), 76.1% tested positive for anti-SARS-CoV-2 IgG, 54.3% for nAb, and 63% for IGRA. Serum levels of anti-SARS-CoV-2 IgG and nAb activity were significantly lower in KTRs compared to dialysis and control groups (p < 0.05 for all). Seropositivity in KTRs was independently associated with shorter transplant duration (p = 0.005), and higher eGFR (p = 0.007). IGRA titer was significantly lower than dialysis patients (p = 0.009). Twenty (43.4%) KTRs were positive for all immune parameters. Only four of 11 seronegative KTRs were IGRA-positive. COVID-19 recovered KTRs had significantly higher anti-SARS-CoV-2 IgG and nAb activity levels than COVID-19 naïve KTRs (p = 0.018 and p = 0.007, respectively). CONCLUSIONS The humoral and cellular immune responses to SARS-CoV-2 mRNA BNT162b2 vaccine are lower in pediatric KTRs compared to dialysis patients. Further prospective studies are required to demonstrate the clinical efficacy of the mRNA vaccine in KTRs. This prospective study was registered in ClinicalTrials.gov (NCT05465863, registered retrospectively at 20.07.2022). A higher resolution version of the Graphical abstract is available as Supplementary information.
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Affiliation(s)
- Ruveyda Gulmez
- grid.506076.20000 0004 1797 5496Department of Pediatric Nephrology, Cerrahpasa School of Medicine, IU-Cerrahpasa, Istanbul, Turkey
| | - Dogukan Ozbey
- grid.506076.20000 0004 1797 5496Department of Microbiology, Cerrahpasa School of Medicine, IU-Cerrahpasa, Istanbul, Turkey
| | - Ayse Agbas
- Department of Pediatric Nephrology, Cerrahpasa School of Medicine, IU-Cerrahpasa, Istanbul, Turkey.
| | - Bagdagul Aksu
- grid.9601.e0000 0001 2166 6619Department of Pediatric Nephrology, Istanbul University School of Medicine, Istanbul, Turkey ,grid.9601.e0000 0001 2166 6619Institute of Child Health, Istanbul University, Istanbul, Turkey
| | - Nurdan Yildiz
- grid.16477.330000 0001 0668 8422Department of Pediatric Nephrology, Marmara University School of Medicine, Istanbul, Turkey
| | - Diana Uckardes
- grid.411776.20000 0004 0454 921XDepartment of Pediatric Nephrology, Medeniyet University School of Medicine, Istanbul, Turkey
| | - Seha Saygili
- grid.506076.20000 0004 1797 5496Department of Pediatric Nephrology, Cerrahpasa School of Medicine, IU-Cerrahpasa, Istanbul, Turkey
| | - Esra Karabag Yilmaz
- grid.506076.20000 0004 1797 5496Department of Pediatric Nephrology, Cerrahpasa School of Medicine, IU-Cerrahpasa, Istanbul, Turkey
| | - Zeynep Yuruk Yildirim
- grid.9601.e0000 0001 2166 6619Department of Pediatric Nephrology, Istanbul University School of Medicine, Istanbul, Turkey
| | - Mehmet Tasdemir
- grid.459708.70000 0004 7553 3311Department of Pediatric Nephrology, Istinye University School of Medicine, Liv Hospital, Istanbul, Turkey
| | - Ayca Kiykim
- grid.506076.20000 0004 1797 5496Department of Pediatric Immunology and Allergy, Cerrahpasa School of Medicine, IU-Cerrahpasa, Istanbul, Turkey
| | - Haluk Cokugras
- grid.506076.20000 0004 1797 5496Department of Pediatric Immunology and Allergy, Cerrahpasa School of Medicine, IU-Cerrahpasa, Istanbul, Turkey
| | - Nur Canpolat
- grid.506076.20000 0004 1797 5496Department of Pediatric Nephrology, Cerrahpasa School of Medicine, IU-Cerrahpasa, Istanbul, Turkey
| | - Ahmet Nayir
- grid.9601.e0000 0001 2166 6619Department of Pediatric Nephrology, Istanbul University School of Medicine, Istanbul, Turkey ,Department of Pediatric Nephrology, Memorial Hospital, Istanbul, Turkey
| | - Bekir Kocazeybek
- grid.506076.20000 0004 1797 5496Department of Microbiology, Cerrahpasa School of Medicine, IU-Cerrahpasa, Istanbul, Turkey
| | - Salim Caliskan
- grid.506076.20000 0004 1797 5496Department of Pediatric Nephrology, Cerrahpasa School of Medicine, IU-Cerrahpasa, Istanbul, Turkey
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Infantino M, Tsalouchos A, Russo E, Laudicina S, Grossi V, Lari B, Benucci M, Stacchini L, Amedei A, Casprini P, Villalta D, Dattolo PC, Manfredi M. Assessing T-Cell Immunity in Kidney Transplant Recipients with Absent Antibody Production after a 3rd Dose of the mRNA-1273 Vaccine. Int J Mol Sci 2022; 23:12333. [PMID: 36293190 PMCID: PMC9604095 DOI: 10.3390/ijms232012333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Revised: 09/30/2022] [Accepted: 10/13/2022] [Indexed: 11/07/2022] Open
Abstract
The vulnerable population of kidney transplant recipients (KTRs) are low responders to COVID-19 vaccines, so specific immune surveillance is needed. The interferon-gamma (IFN-γ) release assay (IGRA) is effective in assessing T cell-mediated immunity. We assessed SARS-CoV-2-directed T cell responses in KTRs with absent antibody production after a third dose of the mRNA-1273 vaccine, using two different IGRAs. A cohort of 57 KTRs, who were actively followed up, received a third dose of the mRNA-1273 vaccine. After the evaluation of humoral immunity to SARS-CoV-2, 14 seronegative patients were tested with two commercial IGRAs (SD Biosensor and Euroimmun). Out of 14 patients, one and three samples were positive by IGRAs with Euroimmun and SD Biosensor, respectively. The overall agreement between the two assays was 85.7% (κ = 0.444). In addition, multivariate linear regression analysis showed no statistically significant association between the IFN-γ concentration, and the independent variables analyzed (age, gender, years since transplant, total lymphocytes cells/mcl, CD3+ cells/mcl, CD3+ CD4+ cells/mcl, CD3+ CD8+ cells/mcl, CD19+ cells/mcl, CD3-CD16+CD56+ cells/mcl) (p > 0.01). In a vulnerable setting, assessing cellular immune response to complement the humoral response may be advantageous. Since the two commercial IGRAs showed a good agreement on negative samples, the three discordant samples highlight the need for further investigations.
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Affiliation(s)
- Maria Infantino
- Immunology and Allergology Laboratory Unit, S. Giovanni di Dio Hospital, 50143 Florence, Italy
| | - Aris Tsalouchos
- Nephrology and Dialysis Unit Firenze II, Santa Maria Annunziata Hospital, 50139 Florence, Italy
| | - Edda Russo
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
| | - Selene Laudicina
- Nephrology and Dialysis Unit Firenze II, Santa Maria Annunziata Hospital, 50139 Florence, Italy
| | - Valentina Grossi
- Immunology and Allergology Laboratory Unit, S. Giovanni di Dio Hospital, 50143 Florence, Italy
| | - Barbara Lari
- Immunology and Allergology Laboratory Unit, S. Giovanni di Dio Hospital, 50143 Florence, Italy
| | - Maurizio Benucci
- Rheumatology Unit, S. Giovanni di Dio Hospital, 50143 Florence, Italy
| | - Lorenzo Stacchini
- Department of Health Science, University of Florence, 50134 Florence, Italy
| | - Amedeo Amedei
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
| | - Patrizia Casprini
- Clinical Pathology Laboratory, S. Giovanni di Dio Hospital, 50143 Florence, Italy
| | - Danilo Villalta
- Immunology and Allergology Laboratory Unit, S-Maria degli Angeli Hospital, 33170 Pordenone, Italy
| | - Pietro Claudio Dattolo
- Nephrology and Dialysis Unit Firenze II, Santa Maria Annunziata Hospital, 50139 Florence, Italy
| | - Mariangela Manfredi
- Immunology and Allergology Laboratory Unit, S. Giovanni di Dio Hospital, 50143 Florence, Italy
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Thümmler L, Konik M, Lindemann M, Fisenkci N, Koldehoff M, Gäckler A, Horn PA, Theodoropoulos F, Taube C, Zettler M, Anastasiou OE, Braß P, Jansen S, Witzke O, Rohn H, Krawczyk A. Long-term cellular immune response in immunocompromised unvaccinated COVID-19 patients undergoing monoclonal antibody treatment. Front Immunol 2022; 13:980698. [PMID: 36311723 PMCID: PMC9606643 DOI: 10.3389/fimmu.2022.980698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Accepted: 09/26/2022] [Indexed: 11/17/2022] Open
Abstract
Immunocompromised patients are at increased risk for a severe course of COVID-19. Treatment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection with anti-SARS-CoV-2 monoclonal antibodies (mAbs) has become widely accepted. However, the effects of mAb treatment on the long-term primary cellular response to SARS-CoV-2 are unknown. In the following study, we investigated the long-term cellular immune responses to SARS-CoV-2 Spike S1, Membrane (M) and Nucleocapsid (N) antigens using the ELISpot assay in unvaccinated, mAb-treated immunocompromised high-risk patients. Anti-SARS-CoV-2 mAb untreated though vaccinated COVID-19 immunocompromised patients, vaccinated SARS-CoV-2 immunocompromised patients without COVID-19 and vaccinated healthy control subjects served as control groups. The cellular immune response was determined at a median of 5 months after SARS-CoV-2 infection. Our data suggest that immunocompromised patients develop an endogenous long-term cellular immune response after COVID-19, although at low levels. A better understanding of the cellular immune response will help guide clinical decision making for these vulnerable patient cohorts.
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Affiliation(s)
- Laura Thümmler
- Department of Infectious Diseases, West German Centre of Infectious Diseases, University Medicine Essen, University Hospital Essen, University Duisburg-Essen, Essen, Germany
- Institute for Transfusion Medicine, University Medicine Essen, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Margarethe Konik
- Department of Infectious Diseases, West German Centre of Infectious Diseases, University Medicine Essen, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Monika Lindemann
- Institute for Transfusion Medicine, University Medicine Essen, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Neslinur Fisenkci
- Institute for Transfusion Medicine, University Medicine Essen, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Michael Koldehoff
- Department of Hematology and Stem Cell Transplantation, University Medicine Essen, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Department of Hygiene and Environmental Medicine, University Medicine Essen, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Anja Gäckler
- Department of Nephrology, University Medicine Essen, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Peter A. Horn
- Institute for Transfusion Medicine, University Medicine Essen, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Fotis Theodoropoulos
- Department of Pneumology, University Medicine Essen-Ruhrlandklinik, University Duisburg- Essen, Essen, Germany
| | - Christian Taube
- Department of Pneumology, University Medicine Essen-Ruhrlandklinik, University Duisburg- Essen, Essen, Germany
| | - Markus Zettler
- Department of Infectious Diseases, West German Centre of Infectious Diseases, University Medicine Essen, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Olympia Evdoxia Anastasiou
- Institute for Virology, University Medicine Essen, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Peer Braß
- Department of Infectious Diseases, West German Centre of Infectious Diseases, University Medicine Essen, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Sarah Jansen
- Department of Infectious Diseases, West German Centre of Infectious Diseases, University Medicine Essen, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Oliver Witzke
- Department of Infectious Diseases, West German Centre of Infectious Diseases, University Medicine Essen, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Hana Rohn
- Department of Infectious Diseases, West German Centre of Infectious Diseases, University Medicine Essen, University Hospital Essen, University Duisburg-Essen, Essen, Germany
- *Correspondence: Adalbert Krawczyk, ; Hana Rohn,
| | - Adalbert Krawczyk
- Department of Infectious Diseases, West German Centre of Infectious Diseases, University Medicine Essen, University Hospital Essen, University Duisburg-Essen, Essen, Germany
- Institute for Virology, University Medicine Essen, University Hospital Essen, University Duisburg-Essen, Essen, Germany
- *Correspondence: Adalbert Krawczyk, ; Hana Rohn,
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30
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Feldman C, Dlamini S, Richards GA, Black J, Butler ILC, Cutland C, Hefer E, Hodkinson B, Kok A, Manga P, Meiring S, Molaudzi M, Moosa MYS, Parker S, Peter J, van Vuuren C, Verburgh E, Watermeyer G. A comprehensive overview of pneumococcal vaccination recommendations for adults in South Africa, 2022. J Thorac Dis 2022; 14:4150-4172. [PMID: 36389298 PMCID: PMC9641319 DOI: 10.21037/jtd-22-287] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Accepted: 07/28/2022] [Indexed: 09/08/2024]
Abstract
Pneumococcal infections remain a common global cause of significant morbidity and mortality. The first recommendations for adult pneumococcal vaccination, published in South Africa in 1999, contained information only on the 23-valent polysaccharide vaccine (PPV23). With the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) for use in adults and the perceived uncertainty that most clinicians had regarding use of these vaccines in adults, these vaccine recommendations were updated in 2022. A Working Group, which consisted of individuals in various fields of medical practice in South Africa, who were from different areas of the country, and included clinicians from both the public and private sectors, was assembled to revise the recommendations. The expertise of the participants varied widely, dependent on their training and specialty, and encompassed different organ systems, disease conditions, and/or practice types. Each participant was allocated a different section, based on their expertise, for which they were required to do an extensive review of the current literature and write their section. The entire working group then reviewed the complete document several times, following additional comments and recommendations. This update contains recommendations for the use of both PPV23 and PCV13, either alone, or in sequence, both in vaccine naïve and in previously vaccinated individuals. It includes both age and risk categories, and encompasses the elderly (≥65 years), as well as younger adults (<65 years) with comorbid conditions or with high-risk conditions and/or immunocompromise. It is hoped that this review and its associated vaccine recommendations will clarify for clinicians, from all spheres of practice in South Africa, how, where, and when pneumococcal vaccines should be used in adults, with the ultimate goal of significantly increasing the appropriate use of these vaccines, in order to decrease the substantial morbidity and mortality associated with pneumococcal infections in adults in South Africa. Furthermore, it is hoped that this review of local epidemiological data and the manner in which this information was interpreted in the development of these local vaccine recommendations, could be used as an example for other regions of the world, to tailor their recommendations to locally available epidemiological data.
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Affiliation(s)
- Charles Feldman
- Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Sipho Dlamini
- Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| | - Guy A. Richards
- Department of Critical Care, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - John Black
- Department of Internal Medicine, Walter Sisulu University, Gqeberha, South Africa
| | - India L. C. Butler
- Division of Geriatric Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Clare Cutland
- African Leadership in Vaccinology Expertise, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Eric Hefer
- General Practitioner in Private Practice, Forest Town, Johannesburg, South Africa
| | - Bridget Hodkinson
- Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| | - Adri Kok
- Private Practice Physician and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Pravin Manga
- Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Susan Meiring
- Division of Public Health Surveillance and Response, National Institute for Communicable Diseases, a Division of the National Health Laboratory Service, Johannesburg, South Africa
| | | | - Mahomed-Yunus S. Moosa
- Division of Internal Medicine, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa
| | - Salim Parker
- Division of Infectious Diseases and HIV Medicine, University of Cape Town, Cape Town, South Africa
| | - Jonny Peter
- Division of Allergy and Clinical Immunology, University of Cape Town, Cape Town, South Africa
| | - Cloete van Vuuren
- Department Internal Medicine, University of the Free State and Department of Internal Medicine, 3 Military Hospital, Bloemfontein, South Africa
| | - Estelle Verburgh
- Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| | - Gill Watermeyer
- Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
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Biagio P, Rosa C, Nicola SM, Fabrizio S, Amerigo P, Giulia Z, Riccardo S, Riccardo V, Paolo R, Lorenzo S, Ivan G, Federico II COVID Team. Serological Response and Clinical Protection of Anti-SARS-CoV-2 Vaccination and the Role of Immunosuppressive Drugs in a Cohort of Kidney Transplant Patients. Viruses 2022; 14:v14091951. [PMID: 36146758 PMCID: PMC9503455 DOI: 10.3390/v14091951] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 08/31/2022] [Accepted: 09/01/2022] [Indexed: 11/16/2022] Open
Abstract
Vaccination against SARS-CoV2 represents a key weapon to prevent COVID-19, but lower response rates to vaccination have frequently been reported in solid organ transplant recipients. The aim of our study was to evaluate the rate of seroconversion to SARS-CoV-2 mRNA vaccines in a cohort of kidney transplant recipients and the potential role of the different immunosuppressive regimens. We conducted an observational retrospective cohort study in kidney transplant patients vaccinated for COVID-19. For each patient, we evaluated IgG anti-S-RBD SARS-CoV-2 titers immediately before the administration of first COVID-19 vaccination dose, 20 days after the first dose and 40 days after the second dose. Moreover, we evaluated the type of immunosuppressive treatment and the incidence of vaccine breakthrough SARS-CoV-2 infection. We enrolled 121 kidney transplant patients vaccinated for COVID-19. At the time of administration of the first vaccine dose, all patients had a negative antibody titer; only 4.1% had positive antibody titers 20 days after the first dose. More than half patients 62 (51%) had protective antibody titers 40 days after the second dose. A total of 18 Solid Organ Transplant Recipients (SOTRs) (14.9%) got a SARS-CoV-2 breakthrough infection during the study period. With regard to immunosuppressive regimen, patients on mycophenolate-based regimen (48.7%) showed the lowest antibody response rates (27.5%) compared to other regimens. Our study confirms that kidney transplant patients show a poor response to two doses of COVID-19 vaccination. Moreover, in our study the use of mycophenolate is significantly associated with a non-response to COVID-19 m-RNA vaccines.
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Affiliation(s)
- Pinchera Biagio
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy
- Correspondence:
| | - Carrano Rosa
- Section of Nephrology, Department of Public Health, University of Naples Federico II, 80131 Naples, Italy
| | - Schiano Moriello Nicola
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy
| | - Salemi Fabrizio
- Section of Nephrology, Department of Public Health, University of Naples Federico II, 80131 Naples, Italy
| | - Piccione Amerigo
- Section of Nephrology, Department of Public Health, University of Naples Federico II, 80131 Naples, Italy
| | - Zumbo Giulia
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy
| | - Scotto Riccardo
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy
| | - Villari Riccardo
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy
| | - Romano Paolo
- Section of Nephrology, Department of Public Health, University of Naples Federico II, 80131 Naples, Italy
| | - Spirito Lorenzo
- Section of Urology, Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, 80131 Naples, Italy
| | - Gentile Ivan
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy
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Hirama T, Akiba M, Shundo Y, Watanabe T, Watanabe Y, Oishi H, Niikawa H, Okada Y. Efficacy and safety of mRNA SARS-CoV-2 vaccines in lung transplant recipients. J Infect Chemother 2022; 28:1153-1158. [PMID: 35599079 PMCID: PMC9110371 DOI: 10.1016/j.jiac.2022.04.019] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 04/15/2022] [Accepted: 04/19/2022] [Indexed: 11/21/2022]
Abstract
BACKGROUND To date, reports addressing the antibody response following mRNA SARS-CoV-2 vaccination in lung transplant (LTX) recipients are limited. Thus, the aim of this clinical study was to investigate the efficacy and safety of the vaccines in LTX recipients compared to controls. METHODS An open-label, nonrandomized prospective study was conducted at Tohoku University Hospital. LTX recipients and controls who received either the BNT162b2 vaccine or the mRNA-1273 vaccine were recruited, and SARS-CoV-2 IgG was measured before and after vaccination. The adverse events were reviewed. Predictors of negative serology after vaccination were evaluated with logistic regression. RESULTS Forty-one LTX recipients and 24 controls were analyzed. Although all controls had a positive antibody response to a SARS-CoV-2 mRNA vaccine, antibody response was found in 24.4% of LTX recipients (p < .0001). The amount of SARS-CoV-2 IgG following the 2nd dose significantly climbed to 6557 AU/mL in controls, whereas the increase in IgG in LTX recipients was 8.3 AU/mL (p < .0001). Fewer LTX recipients developed systemic fever than controls (p < .0001) despite equivalent overall adverse event percentages in both groups. A higher plasma concentration of mycophenolate was a significant predictor of negative serology (p = .032). CONCLUSIONS An impaired antibody response to mRNA vaccines was significantly found in LTX recipients compared to controls and was associated with the plasma concentration of mycophenolate. While repeating mRNA vaccination may be one of the strategies to improve antibody response given the safety of the vaccines, emerging data on humoral immune responses based on immunosuppression regimens in LTX recipients should be studied (jRCT1021210009).
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Affiliation(s)
- Takashi Hirama
- Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan; Division of Organ Transplantation, Tohoku University Hospital, Sendai, Miyagi, Japan.
| | - Miki Akiba
- Division of Organ Transplantation, Tohoku University Hospital, Sendai, Miyagi, Japan.
| | - Yuki Shundo
- Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan.
| | - Tatsuaki Watanabe
- Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan.
| | - Yui Watanabe
- Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan.
| | - Hisashi Oishi
- Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan.
| | - Hiromichi Niikawa
- Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan.
| | - Yoshinori Okada
- Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan; Division of Organ Transplantation, Tohoku University Hospital, Sendai, Miyagi, Japan.
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33
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Moss P, Berenbaum F, Curigliano G, Grupper A, Berg T, Pather S. Benefit-risk evaluation of COVID-19 vaccination in special population groups of interest. Vaccine 2022; 40:4348-4360. [PMID: 35718592 PMCID: PMC9135663 DOI: 10.1016/j.vaccine.2022.05.067] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 05/06/2022] [Accepted: 05/22/2022] [Indexed: 11/29/2022]
Abstract
Several population groups display an increased risk of severe disease and mortality following SARS-CoV-2 infection. These include those who are immunocompromised (IC), have a cancer diagnosis, human immunodeficiency virus (HIV) infection or chronic inflammatory disease including autoimmune disease, primary immunodeficiencies, and those with kidney or liver disease. As such, improved understanding of the course of COVID-19 disease, as well as the efficacy, safety, and benefit-risk profiles of COVID-19 vaccines in these vulnerable groups is paramount in order to inform health policy makers and identify evidence-based vaccination strategies. In this review, we seek to summarize current data, including recommendations by national health authorities, on the impact and benefit-risk profiles of COVID-19 vaccination in these populations. Moving forward, although significant efforts have been made to elucidate and characterize COVID-19 disease course and vaccine responses in these groups, further larger-scale and longer-term evaluation will be instrumental to help further guide management and vaccination strategies, particularly given concerns about waning of vaccine-induced immunity and the recent surge of transmission with SARS-CoV-2 variants of concern.
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Affiliation(s)
- Paul Moss
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK; Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2TH, UK
| | - Francis Berenbaum
- Sorbonne University, INSERM, AP-HP Saint-Antoine Hospital, Paris, France
| | - Giuseppe Curigliano
- Istituto Europeo di Oncologia, IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - Ayelet Grupper
- Department of Nephrology, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Thomas Berg
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, 04103 Leipzig, Germany
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34
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Kueht M, Kirk K, Scott Lea A, Stevenson HL, Fair J, Kathleen Gamilla-Crudo A, Hussain S, Mujtaba M. Donor-directed immunologic safety of COVID-19 vaccination in renal transplant recipients. Hum Immunol 2022; 83:607-612. [PMID: 35871882 PMCID: PMC9279300 DOI: 10.1016/j.humimm.2022.07.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 06/22/2022] [Accepted: 07/11/2022] [Indexed: 11/25/2022]
Abstract
Infection risk and COVID-19 outcomes make SARS-CoV-2 vaccination essential forsolid-organ transplant recipients. Reports of immune activation after vaccination causing graft failure raise concerns, but data are limited. Here, we document graft function, donor-derived-cell-free-DNA(dd-cfDNA), and donor-specific antibodies (DSA) in solid-organ renal transplant recipients after vaccination. Retrospective demographics, graft function, and immunologic parameters were collected in 96 renal transplant patients one month after their second vaccine dose. For-cause biopsies were performed based on clinician judgment. Similar proportions of subjects experienced increases (39.6 %) and decreases (44.8 %) in serum creatinine in the post-vaccination period, p = 0.56. Similar proportions of subjects experienced increases (23 %) and decreases (25 %) in serum ddcfDNA in the post-vaccination period, p = 0.87. Post-vaccination changes in serum creatinine and ddcfDNA (r(95) = -0.04, p = 0.71), serum creatinine and cumulative DSA MFI (r(95) = 0.07, p = 0.56), and ddcfDNA and cumulative DSA MFI(r(95) = 0.13, p = 0.21) were not significantly correlated. Five subjects had increased cumulativeDSA MFI, but there were no de novo cases. Biopsies on three subjects confirmed pre-existing diagnoses. Our study found minimal evidence ofdonor-directed immunologic activity post-vaccination, and all immunologic changesdid not correlate to graft dysfunction. We believe these findings do not amount to evidence ofpost-vaccination deleterious donor-directed activation. SARS-CoV-2 vaccination is immunologically safe and should continue for renal transplant recipients.
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Affiliation(s)
- Michael Kueht
- Department of Surgery, Division of Transplant Surgery, University of Texas Medical Branch, Galveston, TX, United States.
| | - Katie Kirk
- School of Medicine, University of Texas Medical Branch, Galveston, TX, United States
| | - A Scott Lea
- Department of Internal Medicine, Division of Infectious Disease, University of Texas Medical Branch, Galveston, TX, United States
| | | | - Jeff Fair
- Department of Surgery, Division of Transplant Surgery, University of Texas Medical Branch, Galveston, TX, United States
| | - A Kathleen Gamilla-Crudo
- Department of Medicine, Division of Transplant Nephrology, University of Texas Medical Branch, Galveston, TX, United States
| | - Syed Hussain
- Department of Medicine, Division of Transplant Nephrology, University of Texas Medical Branch, Galveston, TX, United States
| | - Muhammad Mujtaba
- Department of Medicine, Division of Transplant Nephrology, University of Texas Medical Branch, Galveston, TX, United States
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35
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Nimmo A, Gardiner D, Ushiro-Lumb I, Ravanan R, Forsythe JLR. The Global Impact of COVID-19 on Solid Organ Transplantation: Two Years Into a Pandemic. Transplantation 2022; 106:1312-1329. [PMID: 35404911 PMCID: PMC9213067 DOI: 10.1097/tp.0000000000004151] [Citation(s) in RCA: 59] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Revised: 02/23/2022] [Accepted: 02/24/2022] [Indexed: 02/06/2023]
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has had a major global impact on solid organ transplantation (SOT). An estimated 16% global reduction in transplant activity occurred over the course of 2020, most markedly impacting kidney transplant and living donor programs, resulting in substantial knock-on effects for waitlisted patients. The increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection risk and excess deaths in transplant candidates has resulted in substantial effort to prioritize the safe restart and continuation of transplant programs over the second year of the pandemic, with transplant rates returning towards prepandemic levels. Over the past 2 y, COVID-19 mortality in SOT recipients has fallen from 20%-25% to 8%-10%, attributed to the increased and early availability of SARS-CoV-2 testing, adherence to nonpharmaceutical interventions, development of novel treatments, and vaccination. Despite these positive steps, transplant programs and SOT recipients continue to face challenges. Vaccine efficacy in SOT recipients is substantially lower than the general population and SOT recipients remain at an increased risk of adverse outcomes if they develop COVID-19. SOT recipients and transplant teams need to remain vigilant and ongoing adherence to nonpharmaceutical interventions appears essential. In this review, we summarize the global impact of COVID-19 on transplant activity, donor evaluation, and patient outcomes over the past 2 y, discuss the current strategies aimed at preventing and treating SARS-CoV-2 infection in SOT recipients, and based on lessons learnt from this pandemic, propose steps the transplant community could consider as preparation for future pandemics.
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Affiliation(s)
- Ailish Nimmo
- Renal Department, Southmead Hospital, North Bristol NHS Trust, Bristol, United Kingdom
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36
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Opsomer R, Kuypers D. COVID-19 and solid organ transplantation: Finding the right balance. Transplant Rev (Orlando) 2022; 36:100710. [PMID: 35809422 PMCID: PMC9251959 DOI: 10.1016/j.trre.2022.100710] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 06/20/2022] [Accepted: 06/23/2022] [Indexed: 11/29/2022]
Affiliation(s)
- Roxanne Opsomer
- Catholic University of Leuven, Faculty of Medicine, Herestraat 49, 3000 Leuven, Belgium.
| | - Dirk Kuypers
- University Hospitals Leuven, Department of Nephrology and Renal Transplantation; Catholic University Leuven, Department of Microbiology, Immunology and Transplantation, Herestraat 49, 3000 Leuven, Belgium.
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Guarino M, Esposito I, Portella G, Cossiga V, Loperto I, Tortora R, Cennamo M, Capasso M, Terracciano D, Galeota Lanza A, Di Somma S, Picciotto FP, Morisco F. Humoral Response to 2-dose BNT162b2 mRNA COVID-19 Vaccination in Liver Transplant Recipients. Clin Gastroenterol Hepatol 2022; 20:1534-1541.e4. [PMID: 35066136 PMCID: PMC8770248 DOI: 10.1016/j.cgh.2022.01.012] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Revised: 01/09/2022] [Accepted: 01/11/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS In the context of the Italian severe acute respiratory syndrome coronavirus 2 vaccination program, liver transplant (LT) recipients were prioritized for vaccine administration, although the lower response to vaccines is a well-known problem in this population. We aimed to evaluate immunogenicity of BNT162b2 mRNA vaccine in LT recipients and healthy controls and to identify factors associated with negative response to vaccine. METHODS In a cohort of adult patients with LT, we prospectively evaluated the humoral response (with anti-Spike protein IgG-LIAISON SARS-CoV-2 S1/S2-IgG chemiluminescent assay) at 1 and 3 months after 2-dose vaccination. A group of 307 vaccinated health care workers, matched by age and sex, served as controls. RESULTS Overall, 492 LT patients were enrolled (75.41% male; median age, 64.85 years). Detectable antibodies were observed in the 75% of patients, with a median value of 73.9 AU/mL after 3 months from 2-dose vaccination. At multivariable analysis, older age (>40 years; P = .016), shorter time from liver transplantation (<5 years; P = .004), and immunosuppression with antimetabolites (P = .029) were significantly associated with non-response to vaccination. Moreover, the LT recipients showed antibody titers statistically lower than the control group (103 vs 261 AU/mL; P < .0001). Finally, in both controls and LT patients, we found a trend of inverse correlation between age and antibody titers (correlation coefficients: -0.2023 and -0.2345, respectively). CONCLUSIONS Three months after vaccination, LT recipients showed humoral response in 75% of cases. Older age, shorter time from transplantation, and use of antimetabolites were factors associated with non-response to vaccination, and LT recipients at risk of non-response to vaccination needed to be kept under close monitoring.
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Affiliation(s)
- Maria Guarino
- The Department of Clinical Medicine and Surgery, Gastroenterology and Hepatology Unit, University of Naples "Federico II," Naples, Italy.
| | | | - Giuseppe Portella
- the Department of Translational Medical Science, University of Naples "Federico II", Naples, Italy
| | - Valentina Cossiga
- The Department of Clinical Medicine and Surgery, Gastroenterology and Hepatology Unit, University of Naples "Federico II," Naples, Italy
| | - Ilaria Loperto
- the UOC Epidemiologia e Prevenzione e Registro Tumori, ASL Napoli 1 Centro, Naples, Italy
| | | | - Michele Cennamo
- the Department of Translational Medical Science, University of Naples "Federico II", Naples, Italy
| | - Mario Capasso
- The Department of Clinical Medicine and Surgery, Gastroenterology and Hepatology Unit, University of Naples "Federico II," Naples, Italy
| | - Daniela Terracciano
- the Department of Translational Medical Science, University of Naples "Federico II", Naples, Italy
| | | | - Sarah Di Somma
- the Department of Translational Medical Science, University of Naples "Federico II", Naples, Italy
| | | | - Filomena Morisco
- The Department of Clinical Medicine and Surgery, Gastroenterology and Hepatology Unit, University of Naples "Federico II," Naples, Italy
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38
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Cho K, Park S, Kim EY, Koyanagi A, Jacob L, Yon DK, Lee SW, Kim MS, Radua J, Elena D, Il Shin J, Smith L. Immunogenicity of COVID-19 Vaccines in Patients with Diverse Health Conditions: a Comprehensive Systematic Review. J Med Virol 2022; 94:4144-4155. [PMID: 35567325 PMCID: PMC9347877 DOI: 10.1002/jmv.27828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 04/05/2022] [Accepted: 05/03/2022] [Indexed: 11/08/2022]
Abstract
It remains unclear how effective COVID-19 vaccinations will be in patients with weakened immunity due to diseases, transplantation, and dialysis. We conducted a systematic review comparing the efficacy of COVID-19 vaccination in patients with solid tumor, hematologic malignancy, autoimmune disease, inflammatory bowel disease, and patients who received transplantation or dialysis. A literature search was conducted twice using the Medline/PubMed database. As a result, 21 papers were included in the review, and seropositivity rate was summarized by specific type of disease, transplantation, and dialysis. When different papers studied the same type of patient group, a study with a higher number of participants was selected. Most of the solid tumor patients showed a seropositivity rate of more than 80% after the second inoculation, but a low seropositivity was found in certain tumors such as breast cancer. Research in patients with certain types of hematological malignancy and autoimmune diseases has also reported low seropositivity, and this may have been affected by the immunosuppressive treatment these patients receive. Research in patients receiving dialysis or transplantation has reported lower seropositivity rates than the general population, while all patients with inflammatory bowel disease have converted to be seropositive. Meta-analysis validating these results will be needed, and studies will also be needed on methods to protect patients with reduced immunity from COVID-19. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Kyuyeon Cho
- Yonsei University, College of Medicine, Seoul, Republic of Korea
| | - Seoyeon Park
- Yonsei University, College of Medicine, Seoul, Republic of Korea
| | - Eun-Young Kim
- Evidence-Based and Clinical Research Laboratory, Department of Health, Social and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, Seoul, 06974, Korea
| | - Ai Koyanagi
- ICREA, Pg. Lluis Companys 23, 08010, Barcelona, Spain.,Research and Development Unit, Parc Sanitari Sant Joan de Déu, CIBERSAM, 08830, Barcelona, Spain
| | - Louis Jacob
- Research and Development Unit, Parc Sanitari Sant Joan de Déu, CIBERSAM, 08830, Barcelona, Spain.,Faculty of Medicine, University of Versailles Saint-Quentin-en-Yvelines, 78180, Montigny-le-Bretonneux, France
| | - Dong Keon Yon
- Department of Pediatrics, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Seung Won Lee
- Department of Data Science, Sejong University College of Software Convergence, Seoul, Republic of Korea
| | - Min Seo Kim
- Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Samsung Medical Center, Seoul, Republic of Korea
| | - Joaquim Radua
- Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, SE5 8AB, UK.,Mental Health Networking Biomedical Research Centre (CIBERSAM), 08036, Barcelona, Spain.,Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institute, 11330, Stockholm, Sweden.,Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036, Barcelona, Spain
| | - Dragioti Elena
- Pain and Rehabilitation Centre, and Department of Health, Medicine and Caring Sciences, Linköping University, SE-581 85 Linköping, Sweden
| | - Jae Il Shin
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Lee Smith
- Centre for Health, Performance and Wellbeing, Anglia Ruskin University, Cambridge, UK
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Alukal JJ, Naqvi HA, Thuluvath PJ. Vaccination in Chronic Liver Disease: An Update. J Clin Exp Hepatol 2022; 12:937-947. [PMID: 34975241 PMCID: PMC8710401 DOI: 10.1016/j.jceh.2021.12.003] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 12/04/2021] [Indexed: 12/12/2022] Open
Abstract
Patients with chronic liver disease (CLD) with or without cirrhosis remain at risk of developing hepatic decompensation when infected with viral or bacterial pathogens. The Advisory Committee on Immunization Practices (ACIP) currently recommends vaccination in CLD against hepatitis A virus (HAV), hepatitis B virus (HBV), influenza, pneumococcus, herpes zoster, tetanus, diphtheria, pertussis, and SARS-CoV-2. Inactivated vaccines are preferred over live attenuated ones, especially in transplant recipients where live vaccines are contraindicated. As the severity of the liver disease progresses, vaccine efficacy declines, and therefore, vaccines should be ideally administered early in the disease course for optimal immune response. Despite the strong recommendations, overall vaccination coverage in CLD remains poor; however, it is encouraging to note that in recent years coverage against influenza and pneumococcus has shown some improvement. Inadequate access to healthcare, lack of information on vaccine safety, poor financial reimbursement for healthcare providers, and vaccine misinformation are often responsible for low immunization rates. This review summarizes the impact of vaccine-preventable illness in those with CLD, updated vaccine guidelines, seroconversion rates in the vaccinated, and barriers faced by healthcare professionals in immunizing those with liver disease.
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Key Words
- ACIP, Advisory Committee on Immunization Practices
- ACLF, acute on chronic liver failure
- ALD, alcohol-related liver disease
- CLD, Chronic liver disease
- CLIF-C, Chronic Liver Failure Consortium
- DAA, direct-acting antiviral drugs
- HAV, hepatitis A virus
- HBV, hepatitis B virus
- HCV, hepatitis C virus
- LT, liver transplant
- NAFLD, nonalcoholic fatty liver disease
- SARS-CoV-2
- SOFA, sequential organ failure assessment
- chronic liver disease
- immunization
- vaccines
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Affiliation(s)
- Joseph J. Alukal
- Institute of Digestive Health & Liver Diseases, Mercy Medical Center, Baltimore MD, USA
| | | | - Paul J. Thuluvath
- Institute of Digestive Health & Liver Diseases, Mercy Medical Center, Baltimore MD, USA
- Department of Medicine, University of Maryland School of Medicine, Baltimore MD, USA
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40
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Netti GS, Infante B, Troise D, Mercuri S, Panico M, Spadaccino F, Catalano V, Gigante M, Simone S, Pontrelli P, Gesualdo L, Ranieri E, Castellano G, Stallone G. mTOR inhibitors improve both humoral and cellular response to SARS-CoV-2 messenger RNA BNT16b2 vaccine in kidney transplant recipients. Am J Transplant 2022; 22:1475-1482. [PMID: 35038362 PMCID: PMC9303518 DOI: 10.1111/ajt.16958] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 01/10/2022] [Accepted: 01/11/2022] [Indexed: 01/25/2023]
Abstract
Kidney transplant recipients (KTRs) have been considered as patients at higher risk of SARS-CoV-2-related disease severity, thus COVID-19 vaccination was highly recommended. However, possible interferences of different immunosuppression with development of both humoral and T cell-mediated immune response to COVID-19 vaccination have not been determined. Here we evaluated the association between mTOR-inhibitors (mTOR-I) and immune response to mRNA BNT162b2 (Pfizer-BioNTech) vaccine in KTR. To this aim 132 consecutive KTR vaccinated against COVID-19 in the early 2021 were enrolled, and humoral and T cell-mediated immune response were assessed after 4-5 weeks. Patients treated with mTOR-I showed significantly higher anti-SARS-CoV-2 IgG titer (p = .003) and higher percentages of anti-SARS-CoV-2 S1/RBD Ig (p = .024), than those without. Moreover, SARS-CoV-2-specific T cell-derived IFNγ release was significantly increased in patients treated with mTOR-I (p < .001), than in those without. Multivariate analysis confirmed that therapy with mTOR-I gained better humoral (p = .005) and T cell-mediated immune response (p = .005) in KTR. The presence of mTOR-I is associated with a better immune response to COVID-19 vaccine in KTR compared to therapy without mTOR-I, not only by increasing vaccine-induced antibodies but also by stimulating anti-SARS-CoV-2 T cell response. These finding are consistent with a potential beneficial role of mTOR-I as modulators of immune response to COVID-19 vaccine in KTR.
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Affiliation(s)
- Giuseppe S. Netti
- Clinical Pathology Unit, Department of Medical and Surgical Sciences, Advanced Research Center on Kidney Aging (A.R.K.A.), University of Foggia, Foggia, Italy,Correspondence Giuseppe S. Netti, Clinical Pathology Unit and Center for Molecular Medicine, Department of Medical and Surgical Sciences, University of Foggia, Viale L. Pinto, 71122 Foggia, Italy.
| | - Barbara Infante
- Nephrology Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, Advanced Research Center on Kidney Aging (A.R.K.A.), University of Foggia, Foggia, Italy
| | - Dario Troise
- Nephrology Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, Advanced Research Center on Kidney Aging (A.R.K.A.), University of Foggia, Foggia, Italy
| | - Silvia Mercuri
- Nephrology Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, Advanced Research Center on Kidney Aging (A.R.K.A.), University of Foggia, Foggia, Italy
| | - Maddalena Panico
- Nephrology Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, Advanced Research Center on Kidney Aging (A.R.K.A.), University of Foggia, Foggia, Italy
| | - Federica Spadaccino
- Clinical Pathology Unit, Department of Medical and Surgical Sciences, Advanced Research Center on Kidney Aging (A.R.K.A.), University of Foggia, Foggia, Italy
| | - Valeria Catalano
- Clinical Pathology Unit, Department of Medical and Surgical Sciences, Advanced Research Center on Kidney Aging (A.R.K.A.), University of Foggia, Foggia, Italy
| | - Margherita Gigante
- Clinical Pathology Unit, Department of Medical and Surgical Sciences, Advanced Research Center on Kidney Aging (A.R.K.A.), University of Foggia, Foggia, Italy
| | - Simona Simone
- Nephrology Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation (DETO), University of Bari “Aldo Moro”, Bari, Italy
| | - Paola Pontrelli
- Nephrology Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation (DETO), University of Bari “Aldo Moro”, Bari, Italy
| | - Loreto Gesualdo
- Nephrology Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation (DETO), University of Bari “Aldo Moro”, Bari, Italy
| | - Elena Ranieri
- Clinical Pathology Unit, Department of Medical and Surgical Sciences, Advanced Research Center on Kidney Aging (A.R.K.A.), University of Foggia, Foggia, Italy
| | - Giuseppe Castellano
- Nephrology, Dialysis and Renal Transplant Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
| | - Giovanni Stallone
- Nephrology Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, Advanced Research Center on Kidney Aging (A.R.K.A.), University of Foggia, Foggia, Italy
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Søfteland JM, Gisslén M, Liljeqvist JÅ, Friman V, de Coursey E, Karason K, Ekelund J, Felldin M, Magnusson J, Baid-Agrawal S, Wallquist C, Schult A, Jacobsson H, Bergdahl A, Bemark M, Andersson LM, Holm Gunnarsson I, Stenström J, Leach S. Longevity of anti-spike and anti-nucleocapsid antibodies after COVID-19 in solid organ transplant recipients compared to immunocompetent controls. Am J Transplant 2022; 22:1245-1252. [PMID: 34860447 PMCID: PMC9906230 DOI: 10.1111/ajt.16909] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2021] [Revised: 11/01/2021] [Accepted: 11/28/2021] [Indexed: 01/25/2023]
Abstract
Solid organ transplant recipients (SOTRs) are on lifelong immunosuppression, which may interfere with adaptive immunity to COVID-19. The data on dynamics and duration of antibody response in SOTRs are limited. This longitudinal study examined the longevity of both anti-spike (S)- and anti-nucleocapsid (N)-specific IgG antibodies after COVID-19 in SOTRs compared to matched immunocompetent persons. SOTRs (n = 65) were matched with controls (n = 65) for COVID-19 disease severity, age, and sex in order of priority. Serum-IgG antibodies against N and S antigens of SARS-CoV-2 were analyzed. At 1 and 9 months after COVID-19, anti-S-IgG detectability decreased from 91% to 82% in SOTRs versus 100% to 95% in controls, whereas the anti-N-IgG decreased from 63% to 29% in SOTRs versus 89% to 46% in controls. A matched paired analysis showed SOTRs having significantly lower levels of anti-N-IgG at all time points (1 month p = .007, 3 months p < .001, 6 months p = .019, and 9 months p = .021) but not anti-S-IgG at any time points. A mixed-model analysis confirmed these findings except for anti-S-IgG at 1 month (p = .005) and identified severity score as the most important predictor of antibody response. SOTRs mount comparable S-specific, but not N-specific, antibody responses to SARS-CoV-2 infection compared to immunocompetent controls.
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Affiliation(s)
- John M. Søfteland
- The Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden,Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden,Correspondence John M. Søfteland, The Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden.
| | - Magnus Gisslén
- Department of Infectious Diseases, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden,Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Jan-Åke Liljeqvist
- Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Vanda Friman
- Department of Infectious Diseases, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden,Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Emily de Coursey
- The Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Kristjan Karason
- The Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Jan Ekelund
- Centre of Registers, Västra Götaland, Gothenburg, Sweden
| | - Marie Felldin
- The Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Jesper Magnusson
- The Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Seema Baid-Agrawal
- The Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Carin Wallquist
- Department of Nephrology, Skåne University Hospital, Malmö, Sweden
| | - Andreas Schult
- The Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden,Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Hanna Jacobsson
- The Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden,Biobank West, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Anders Bergdahl
- Department of Nephrology, Northern Älvsborg County Hospital, Trollhättan, Sweden
| | - Mats Bemark
- Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden,Department of Clinical Immunology and Transfusion Medicine, Sahlgrenska University Hospital, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Lars-Magnus Andersson
- Department of Infectious Diseases, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden,Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | | | - Jan Stenström
- Department of Nephrology, Capio Lundby Specialist Hospital, Gothenburg, Sweden
| | - Susannah Leach
- Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden,Department of Clinical Pharmacology, Sahlgrenska University Hospital, Gothenburg, Sweden
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Schuller M, Pfeifer V, Kirsch AH, Klötzer KA, Mooslechner AA, Rosenkranz AR, Stiegler P, Schemmer P, Sourij H, Eller P, Prietl B, Eller K. B Cell Composition Is Altered After Kidney Transplantation and Transitional B Cells Correlate With SARS-CoV-2 Vaccination Response. Front Med (Lausanne) 2022; 9:818882. [PMID: 35187002 PMCID: PMC8847739 DOI: 10.3389/fmed.2022.818882] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Accepted: 01/13/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND The COVID-19 pandemic has major implications on kidney transplant recipients (KTRs) since they show increased mortality due to impaired immune responses to SARS-CoV-2 infection and a reduced efficacy of SARS-CoV-2 vaccination. Surprisingly, dialysis patients have shown superior seroconversion rates after vaccination compared to KTRs. Therefore, we investigated peripheral blood B cell (BC) composition before and after kidney transplantation (KT) and aimed to screen the BC compartment to explain impaired antibody generation. METHODS A total of 105 patients were recruited, and multicolor flow cytometric phenotyping of peripheral venous blood BC subpopulations was performed before and 1 year after KT. Complete follow-up was available for 71 individuals. Anti-SARS-CoV-2 antibodies were collected retrospectively and were available for 40 subjects, who had received two doses of an mRNA-based vaccine (BNT162b2 or mRNA-1273). RESULTS Overall, relative BC frequencies within lymphocytes decreased, and their absolute counts trended in the same direction 1 year after KT as compared to CKD G5 patients. Frequencies and absolute numbers of naïve BCs remained stable. Frequencies of double negative BCs, a heterogeneous subpopulation of antigen experienced BCs lacking CD27 expression, were increased after KT, yet their absolute counts were similar at both time points. Transitional BCs (TrBCs) and plasmablasts were significantly reduced after KT in absolute and relative terms. Memory BCs were affected differently since class-switched and IgM-only subsets decreased after KT, but unswitched and IgD-only memory BCs remained unchanged. CD86+ and CD5+ expression on BCs was downregulated after KT. Correlational analysis revealed that TrBCs were the only subset to correlate with titer levels after SARS-CoV-2 vaccination. Responders showed higher TrBCs, both absolute and relative, than non-responders. CONCLUSION Together, after 1 year, KTRs showed persistent and profound compositional changes within the BC compartment. Low TrBCs, 1 year after KT, may account for the low serological response to SARS-CoV-2 vaccination in KTRs compared to dialysis patients. Our findings need confirmation in further studies as they may guide vaccination strategies.
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Affiliation(s)
- Max Schuller
- Division of Nephrology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Verena Pfeifer
- Center for Biomarker Research in Medicine, CBmed GmbH, Graz, Austria
- Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Alexander H. Kirsch
- Division of Nephrology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Konstantin A. Klötzer
- Division of Nephrology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Agnes A. Mooslechner
- Division of Nephrology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Alexander R. Rosenkranz
- Division of Nephrology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Philipp Stiegler
- General, Visceral, and Transplant Surgery, Department of Surgery, Medical University of Graz, Graz, Austria
| | - Peter Schemmer
- General, Visceral, and Transplant Surgery, Department of Surgery, Medical University of Graz, Graz, Austria
| | - Harald Sourij
- Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Philipp Eller
- Intensive Care Unit, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Barbara Prietl
- Center for Biomarker Research in Medicine, CBmed GmbH, Graz, Austria
- Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Kathrin Eller
- Division of Nephrology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
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43
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Aslam S, Ison MG. SARS-CoV-2 vaccination in heart transplantation: What we do and do not know. J Heart Lung Transplant 2022; 41:158-160. [PMID: 34876356 PMCID: PMC8566197 DOI: 10.1016/j.healun.2021.10.017] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Revised: 10/25/2021] [Accepted: 10/28/2021] [Indexed: 01/06/2023] Open
Affiliation(s)
- Saima Aslam
- Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, California
| | - Michael G. Ison
- Divisions of Infectious Diseases and Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, Illinois,Reprint requests: Michael G. Ison, MD, MS, Divisions of Infectious Diseases & Organ Transplantation, Northwestern University Feinberg School of Medicine, 645 N Michigan Avenue Suite 900, Chicago, IL. Telephone: 60611. 312-695-4186. Fax: 312-695-5088
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Yanis A, Haddadin Z, Spieker AJ, Waqfi D, Rankin DA, Talj R, Thomas L, Birdwell KA, Ezzell L, Blair M, Eason J, Varjabedian R, Warren CM, Nochowicz CH, Olson EC, Simmons JD, Yoder S, Guy M, Thomsen I, Chappell JD, Kalams SA, Halasa NB. Humoral and cellular immune responses to the SARS-CoV-2 BNT162b2 vaccine among a cohort of solid organ transplant recipients and healthy controls. Transpl Infect Dis 2022; 24:e13772. [PMID: 34905653 DOI: 10.1111/tid.13772] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 11/09/2021] [Accepted: 11/16/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with increased morbidity and mortality in solid organ transplant (SOT) recipients. Despite exclusion from SARS-CoV-2 vaccine clinical trials, these individuals were identified as high-risk and prioritized for vaccination in public health guidelines. METHODS We prospectively evaluated humoral and cellular immune responses to two doses of the SARS-CoV-2 mRNA vaccine, BNT162b2, in 56 SOT recipients and 26 healthy controls (HCs). Blood specimens collected from participants prior to each dose and following the second dose were tested for SARS-CoV-2-specific antibodies, as well as CD4+ and CD8+ T-cell responses. RESULTS SOT recipients demonstrated lower mean anti-SARS-CoV-2 antibody levels compared to HCs after each dose, and only 21.6% achieved an antibody response after the second dose within the range of HC responses. Similarly, the percentage of responsive CD4+ and CD8+ T cells in SOT recipients was lower than in HCs. While most HCs showed notable humoral and cellular responses, responses were less concordant in SOT recipients, with some showing evidence of either humoral or cellular response, but not both. CONCLUSION Humoral and cellular immune responses to the BNT162b2 vaccine are markedly reduced in SOT recipients as compared to HCs, suggesting that SOT recipients may benefit from more tailored regimens such as higher dose and/or additional vaccinations.
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Affiliation(s)
- Ahmad Yanis
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Zaid Haddadin
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Andrew J Spieker
- Department of Biostatistics, Vanderbilt University, Nashville, Tennessee, USA
| | - Danya Waqfi
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Danielle A Rankin
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
- Vanderbilt Epidemiology PhD Program, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
| | - Rana Talj
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Lora Thomas
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Kelly A Birdwell
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Lauren Ezzell
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Marcia Blair
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Joan Eason
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Rebekkah Varjabedian
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Christian M Warren
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Cynthia H Nochowicz
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Eric C Olson
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Joshua D Simmons
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Sandra Yoder
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Madeline Guy
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Isaac Thomsen
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - James D Chappell
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Spyros A Kalams
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, Tennessee, USA
| | - Natasha B Halasa
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
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45
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Sun J, Zheng Q, Madhira V, Olex AL, Anzalone AJ, Vinson A, Singh JA, French E, Abraham AG, Mathew J, Safdar N, Agarwal G, Fitzgerald KC, Singh N, Topaloglu U, Chute CG, Mannon RB, Kirk GD, Patel RC. Association Between Immune Dysfunction and COVID-19 Breakthrough Infection After SARS-CoV-2 Vaccination in the US. JAMA Intern Med 2022; 182:153-162. [PMID: 34962505 PMCID: PMC8715386 DOI: 10.1001/jamainternmed.2021.7024] [Citation(s) in RCA: 202] [Impact Index Per Article: 67.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Accepted: 10/09/2021] [Indexed: 12/30/2022]
Abstract
Importance Persons with immune dysfunction have a higher risk for severe COVID-19 outcomes. However, these patients were largely excluded from SARS-CoV-2 vaccine clinical trials, creating a large evidence gap. Objective To identify the incidence rate and incidence rate ratio (IRR) for COVID-19 breakthrough infection after SARS-CoV-2 vaccination among persons with or without immune dysfunction. Design, Setting, and Participants This retrospective cohort study analyzed data from the National COVID Cohort Collaborative (N3C), a partnership that developed a secure, centralized electronic medical record-based repository of COVID-19 clinical data from academic medical centers across the US. Persons who received at least 1 dose of a SARS-CoV-2 vaccine between December 10, 2020, and September 16, 2021, were included in the sample. Main Outcomes and Measures Vaccination, COVID-19 diagnosis, immune dysfunction diagnoses (ie, HIV infection, multiple sclerosis, rheumatoid arthritis, solid organ transplant, and bone marrow transplantation), other comorbid conditions, and demographic data were accessed through the N3C Data Enclave. Breakthrough infection was defined as a COVID-19 infection that was contracted on or after the 14th day of vaccination, and the risk after full or partial vaccination was assessed for patients with or without immune dysfunction using Poisson regression with robust SEs. Poisson regression models were controlled for a study period (before or after [pre- or post-Delta variant] June 20, 2021), full vaccination status, COVID-19 infection before vaccination, demographic characteristics, geographic location, and comorbidity burden. Results A total of 664 722 patients in the N3C sample were included. These patients had a median (IQR) age of 51 (34-66) years and were predominantly women (n = 378 307 [56.9%]). Overall, the incidence rate for COVID-19 breakthrough infection was 5.0 per 1000 person-months among fully vaccinated persons but was higher after the Delta variant became the dominant SARS-CoV-2 strain (incidence rate before vs after June 20, 2021, 2.2 [95% CI, 2.2-2.2] vs 7.3 [95% CI, 7.3-7.4] per 1000 person-months). Compared with partial vaccination, full vaccination was associated with a 28% reduced risk for breakthrough infection (adjusted IRR [AIRR], 0.72; 95% CI, 0.68-0.76). People with a breakthrough infection after full vaccination were more likely to be older and women. People with HIV infection (AIRR, 1.33; 95% CI, 1.18-1.49), rheumatoid arthritis (AIRR, 1.20; 95% CI, 1.09-1.32), and solid organ transplant (AIRR, 2.16; 95% CI, 1.96-2.38) had a higher rate of breakthrough infection. Conclusions and Relevance This cohort study found that full vaccination was associated with reduced risk of COVID-19 breakthrough infection, regardless of the immune status of patients. Despite full vaccination, persons with immune dysfunction had substantially higher risk for COVID-19 breakthrough infection than those without such a condition. For persons with immune dysfunction, continued use of nonpharmaceutical interventions (eg, mask wearing) and alternative vaccine strategies (eg, additional doses or immunogenicity testing) are recommended even after full vaccination.
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Affiliation(s)
- Jing Sun
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Qulu Zheng
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | | | - Amy L. Olex
- Wright Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond
| | - Alfred J. Anzalone
- Department of Neurological Sciences, University of Nebraska Medical Center, Omaha
| | - Amanda Vinson
- Division of Nephrology, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Jasvinder A. Singh
- Department of Medicine at the School of Medicine, University of Alabama at Birmingham (UAB), Birmingham
- Department of Epidemiology at the UAB School of Public Health, Birmingham
| | - Evan French
- Wright Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond
| | - Alison G. Abraham
- Department of Epidemiology, University of Colorado, Anschutz Medical Campus, Denver
| | - Jomol Mathew
- Department of Population Health Sciences, University of Wisconsin−Madison School of Medicine and Public Health, Madison
| | - Nasia Safdar
- Department of Medicine, University of Wisconsin−Madison, Madison
| | - Gaurav Agarwal
- Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham
| | - Kathryn C. Fitzgerald
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
- Department of Neurology, Johns Hopkins University, Baltimore, Maryland
| | - Namrata Singh
- Division of Rheumatology, Department of Medicine, University of Washington, Seattle
| | - Umit Topaloglu
- Wake Forest School of Medicine, Winston-Salem, North Carolina
| | - Christopher G. Chute
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
- School of Medicine, Public Health and Nursing, Johns Hopkins University, Baltimore, Maryland
| | - Roslyn B. Mannon
- Department of Medicine, University of Nebraska Medical Center, Omaha
| | - Gregory D. Kirk
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
- School of Medicine, Johns Hopkins University, Baltimore, Maryland
| | - Rena C. Patel
- Division of Allergy and Infectious Diseases, Departments of Medicine and Global Health, University of Washington, Seattle
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46
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Wang AX, Busque S, Kuo J, Singh U, Röeltgen K, Pinsky BA, Chertow GM, Scandling JD, Lenihan CR. SARS-CoV-2 Neutralizing Monoclonal Antibodies for the Treatment of COVID-19 in Kidney Transplant Recipients. KIDNEY360 2022; 3:133-143. [PMID: 35368573 PMCID: PMC8967616 DOI: 10.34067/kid.0005732021] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Accepted: 10/15/2021] [Indexed: 01/10/2023]
Abstract
Background Morbidity and mortality associated with coronavirus disease 2019 (COVID-19) infection in kidney transplant recipients are high and early outpatient interventions to prevent progression to severe disease are needed. SARS-CoV-2 neutralizing mAbs, including bamlanivimab and casirivimab-imdevimab, received emergency use authorization in the United States in November 2020 for treatment of mild to moderate COVID-19 disease. Methods We performed a retrospective analysis of 27 kidney transplant recipients diagnosed with COVID-19 between July 2020 and February 2021 who were treated with bamlanivimab or casirivimab-imdevimab and immunosuppression reduction. We additionally identified 13 kidney transplant recipients with COVID-19 who had mild to moderate disease at presentation, who did not receive mAbs, and had SARS-CoV-2 serology testing available. Results There were no deaths or graft failures in either group. Both infusions were well tolerated. Four of the 27 patients treated with mAbs required hospitalization due to COVID-19. Four of 13 patients who did not receive mAbs required hospitalization due to COVID-19. Patients who received mAbs demonstrated measurable anti-SARS-CoV-2 IgG with angiotensin-converting enzyme 2 (ACE2) receptor blocking activity at the highest level detectable at 90 days postinfusion, whereas ACE2 blocking activity acquired from natural immunity in the mAb-untreated group was weak. Conclusions Bamlanivimab and casirivimab-imdevimab combined with immunosuppression reduction were well tolerated and associated with favorable clinical outcomes in kidney transplant recipients diagnosed with mild to moderate COVID-19.
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Affiliation(s)
- Aileen X Wang
- Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, California
| | - Stephan Busque
- Division of Abdominal Transplantation, Department of Surgery, Stanford University School of Medicine, Stanford, California
| | - Jamie Kuo
- Pharmacy Manager of Clinical Effectiveness, Department of Pharmacy, Stanford Health Care, Stanford, California
| | - Upinder Singh
- Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California
- Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California
| | - Katharina Röeltgen
- Department of Pathology, Stanford University School of Medicine, Stanford, California
| | - Benjamin A Pinsky
- Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California
- Department of Pathology, Stanford University School of Medicine, Stanford, California
| | - Glenn M Chertow
- Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, California
- Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, California
| | - John D Scandling
- Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, California
| | - Colin R Lenihan
- Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, California
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Marinaki S, Degiannis D, Roussos S, Xagas E, Tsoutsoura P, Adamopoulos S, Sypsa V, Chaidaroglou A, Pavlopoulou ID, Hatzakis A, Boletis IN. Head-to-Head Comparison of Response Rates to the Two mRNA SARS-CοV-2 Vaccines in a Large Cohort of Solid Organ Transplant (SOT) Recipients. Vaccines (Basel) 2022; 10:190. [PMID: 35214649 PMCID: PMC8876597 DOI: 10.3390/vaccines10020190] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Revised: 01/17/2022] [Accepted: 01/24/2022] [Indexed: 02/04/2023] Open
Abstract
Due to their higher risk of developing life-threatening COVID-19 disease, solid organ transplant (SOT) recipients have been prioritized in the vaccination programs of many countries. However, there is increasing evidence of reduced immunogenicity to SARS-CοV-2 vaccination. The present study investigated humoral response, safety, and effectiveness after the two mRNA vaccines in 455 SOT recipients. Overall, the antibody response rate was low, at 39.6%. Higher immunogenicity was detected among individuals vaccinated with the mRNA1273 compared to those with the BNT162b2 vaccine (47% vs. 36%, respectively, p = 0.025) as well as higher median antibody levels of 31 (7, 372) (AU/mL) vs. 11 (7, 215) AU/mL, respectively. Among the covariates assessed, vaccination with the BNT162b2 vaccine, antimetabolite- and steroid-containing immunosuppression, female gender, the type of transplanted organ and older age were factors that negatively influenced immune response. Only mild adverse effects were observed. Our findings confirm poor immunogenicity after vaccination, implicating a reevaluation of vaccination policy in SOT recipients.
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Affiliation(s)
- Smaragdi Marinaki
- Clinic of Nephrology and Renal Transplantation, Laiko General Hospital, Medical School of Athens, National and Kapodistrian University, 11527 Athens, Greece; (E.X.); (P.T.); (I.N.B.)
| | - Dimitrios Degiannis
- Molecular Immunopathology and Histocompatibility Unit, Onassis Cardiac Surgery Center, 17674 Athens, Greece; (D.D.); (A.C.)
| | - Sotirios Roussos
- Department of Hygiene, Epidemiology & Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, 15772 Athens, Greece; (S.R.); (V.S.); (A.H.)
| | - Efstathios Xagas
- Clinic of Nephrology and Renal Transplantation, Laiko General Hospital, Medical School of Athens, National and Kapodistrian University, 11527 Athens, Greece; (E.X.); (P.T.); (I.N.B.)
| | - Paraskevi Tsoutsoura
- Clinic of Nephrology and Renal Transplantation, Laiko General Hospital, Medical School of Athens, National and Kapodistrian University, 11527 Athens, Greece; (E.X.); (P.T.); (I.N.B.)
| | - Stamatis Adamopoulos
- Heart Failure and Transplant Units, Onassis Cardiac Surgery Center, 17674 Athens, Greece;
| | - Vana Sypsa
- Department of Hygiene, Epidemiology & Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, 15772 Athens, Greece; (S.R.); (V.S.); (A.H.)
| | - Antigoni Chaidaroglou
- Molecular Immunopathology and Histocompatibility Unit, Onassis Cardiac Surgery Center, 17674 Athens, Greece; (D.D.); (A.C.)
| | - Ioanna D. Pavlopoulou
- Pediatric Research Laboratory, Faculty of Nursing, National and Kapodistrian University of Athens, 15772 Athens, Greece;
| | - Angelos Hatzakis
- Department of Hygiene, Epidemiology & Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, 15772 Athens, Greece; (S.R.); (V.S.); (A.H.)
| | - Ioannis N. Boletis
- Clinic of Nephrology and Renal Transplantation, Laiko General Hospital, Medical School of Athens, National and Kapodistrian University, 11527 Athens, Greece; (E.X.); (P.T.); (I.N.B.)
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48
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Grupper A, Katchman H. SARS-CoV-2 Vaccines: Safety and Immunogenicity in Solid Organ Transplant Recipients and Strategies for Improving Vaccine Responses. CURRENT TRANSPLANTATION REPORTS 2022; 9:35-47. [PMID: 35096509 PMCID: PMC8783189 DOI: 10.1007/s40472-022-00359-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/27/2021] [Indexed: 12/20/2022]
Abstract
Purpose of Review While solid organ transplant (SOT) recipients are at the highest risk for severe complications and increased mortality from COVID19 disease, their vaccination against SARS-CoV-2 remains challenging due to fear of immune-mediated adverse events and suboptimal immune response. Our current review is aimed to summarize current knowledge about the safety and efficacy of SARS-CoV-2 vaccines, describe factors that are correlated with immune response, and discuss strategies to improve vaccine immunogenicity in SOT recipients. Recent Findings SARS-CoV-2 vaccines are safe in SOT recipients and not related to rejection or other major adverse events. The immune response to two doses of vaccine is suboptimal and correlated to age and magnitude of immunosuppression. Administration of a third vaccine dose brings to significant amplification of immune response. Summary This review strengthens the existing recommendation of vaccination by three doses of vaccine in all SOT recipients and completion of vaccination before transplantation if possible.
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49
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Acute Kidney Allograft Rejection Following Coronavirus mRNA Vaccination: A Case Report. Transplant Direct 2022; 8:e1274. [PMID: 35047661 PMCID: PMC8759614 DOI: 10.1097/txd.0000000000001274] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 11/13/2021] [Accepted: 11/16/2021] [Indexed: 11/26/2022] Open
Abstract
Supplemental Digital Content is available in the text.
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50
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Chen JK, Cheng J, Liverman R, Serluco A, Corbo H, Yildirim I. Vaccination in pediatric solid organ transplant: A primer for the immunizing clinician. Clin Transplant 2022; 36:e14577. [PMID: 34997642 DOI: 10.1111/ctr.14577] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 12/20/2021] [Accepted: 12/21/2021] [Indexed: 11/29/2022]
Abstract
Pediatric solid organ transplant (SOT) recipients are at a uniquely elevated risk for vaccine preventable illness (VPI) secondary to a multitude of factors including incomplete immunization at the time of transplant, inadequate response to vaccines with immunosuppression, waning antibody titers observed post-SOT, and uncertainty among providers on the correct immunization schedule to utilize post-SOT. Multiple guidelines are in existence from the Infectious Diseases Society of America and the American Society of Transplantation, which require use in adjunct with additional published references. We summarize the present state of SOT vaccine recommendations from relevant resources in tandem with the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices guidance utilizing both routine and rapid catch-up schedules. The purpose of this all-inclusive review is to provide improved clarity on the most optimal pre- and post-transplant vaccine management within a one-stop-shop for the immunizing clinician. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Justin K Chen
- Department of Pharmacy, NewYork-Presbyterian, Columbia University Irving Medical Center, New York, New York, USA
| | - Jennifer Cheng
- Department of Pharmacy, NewYork-Presbyterian, Columbia University Irving Medical Center, New York, New York, USA
| | - Rochelle Liverman
- Department of Pharmacy, Children's Healthcare of Atlanta, Atlanta, Georgia, USA
| | - Anastacia Serluco
- Department of Pharmacy, Children's Healthcare of Atlanta, Atlanta, Georgia, USA
| | - Heather Corbo
- Department of Pharmacy, NewYork-Presbyterian, Columbia University Irving Medical Center, New York, New York, USA
| | - Inci Yildirim
- Section of Infectious Diseases and Global Health, Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut, USA.,Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, USA.,Yale Institute of Global Health, Yale University, New Haven, Connecticut, USA
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