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Zhang X, Han X, Li C, Cui J, Yuan X, Meng J, Han Z, Han X, Chen W, Xiong J, Xie W, Xie L. Clinical Outcomes of Hospitalized Immunocompromised Patients With COVID-19 and the Impact of Hyperinflammation: A Retrospective Cohort Study. J Inflamm Res 2025; 18:3385-3397. [PMID: 40070925 PMCID: PMC11895693 DOI: 10.2147/jir.s482940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Accepted: 01/30/2025] [Indexed: 03/14/2025] Open
Abstract
Purpose Immunocompromised patients are at increased risk for severe outcomes from COVID-19 due to their altered immune responses, yet their inflammatory profiles and the interplay between immunosuppression remain poorly understood. We aimed to illustrate the inflammation profile and clinical outcomes of hospitalized immunocompromised patients with COVID-19. Methods We conducted a retrospective study using a multicenter database and included adult hospitalized patients with Corona virus disease 2019 (COVID-19) in China's late 2022 COVID-19 wave. Crude and adjusted 28- and 60-day mortality was compared between the two groups. Inflammatory phenotypes were evaluated by serum interleukin-6 (IL-6) and C-reactive protein (CRP) level. The interplay between overt inflammation and immunosuppression was analyzed. Results Among the 4078 included patients, 348 (8.5%) were immunocompromised. Immunocompromised patients had lower crude mortality but higher adjusted mortality at 28-day (hazard ratio [HR] = 1.55; 95% CI 1.08 to 2.23) and 60-day (HR = 1.47; 95% CI 1.05 to 2.06). Besides, immunocompromised patients had a higher risk of developing hyperinflammation (odd ratio [OR] =1.92; 95% CI 1.47 to 2.50, p <0.001). Moreover, hyperinflammation mediated a major part of the deleterious survival effect of immunosuppression on COVID-19. Conclusion Immunodeficiency not only increases short-term mortality risk but also predisposes patients to hyperinflammation. The complex interplay between immunosuppression, hyperinflammation, and COVID-19 outcomes warrants more detailed profiling of inflammation and immunity in this population.
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Affiliation(s)
- Xinxin Zhang
- College of Pulmonary and Critical Care Medicine, The Eighth Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Xiaobo Han
- College of Pulmonary and Critical Care Medicine, The Eighth Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China
- Chinese PLA Medical School, Beijing, People’s Republic of China
| | - Chenglong Li
- National Institute of Health Data Science, Peking University, Beijing, People’s Republic of China
- Institute of Medical Technology, Health Science Center, Peking University, Beijing, People’s Republic of China
| | - Junchang Cui
- College of Pulmonary and Critical Care Medicine, The Eighth Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China
- Chinese PLA Medical School, Beijing, People’s Republic of China
| | - Xin Yuan
- Department of Pulmonary and Critical Care Medicine, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Jiguang Meng
- Department of Pulmonary and Critical Care Medicine, The Fourth Medical Center of PLA General Hospital, Beijing, People’s Republic of China
- Naval Clinical College, Anhui Medical University, Hefei, People’s Republic of China
| | - Zhihai Han
- Department of Pulmonary and Critical Care Medicine, The Sixth Medical Center of PLA General Hospital, Beijing, People’s Republic of China
| | - Xinjie Han
- College of Pulmonary and Critical Care Medicine, The Eighth Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Wei Chen
- Department of Pulmonary and Critical Care Medicine, The Sixth Medical Center of PLA General Hospital, Beijing, People’s Republic of China
| | - Junchen Xiong
- Department of Pulmonary and Critical Care Medicine, The Fourth Medical Center of PLA General Hospital, Beijing, People’s Republic of China
- Naval Clinical College, Anhui Medical University, Hefei, People’s Republic of China
| | - Wuxiang Xie
- Peking University Clinical Research Institute, Peking University First Hospital, Beijing, People’s Republic of China
- Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, People’s Republic of China
| | - Lixin Xie
- College of Pulmonary and Critical Care Medicine, The Eighth Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China
- Chinese PLA Medical School, Beijing, People’s Republic of China
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Polamraju V, Vachharajani N, Gage BF, Crippin JS, Chapman WC. Clinical outcomes of COVID-19 infection in liver transplant recipients based on vaccination status. FRONTIERS IN TRANSPLANTATION 2025; 3:1515964. [PMID: 39850667 PMCID: PMC11754219 DOI: 10.3389/frtra.2024.1515964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 12/13/2024] [Indexed: 01/25/2025]
Abstract
Background COVID-19 disease burden has been mitigated by vaccination; however, concerns persist regarding weakened immune responses in liver transplant (LT) recipients. This study investigates COVID-19 outcomes in LT recipients based on vaccination status. Methods This single-center retrospective study identified LT recipients with PCR-confirmed COVID-19 infection from 03/01/2020 to 07/31/2023. Logistic regression analyses were conducted, adjusting for age, race, co-morbidities, number of immunosuppressive agents, and infection date. Results Of 1,787 registered LT recipients, 361 had confirmed COVID-19 infection. Of those, 136 were unvaccinated and 225 were vaccinated. 13% had 1 vaccine dose, 31% had 2 vaccine doses, and 56% had 3 vaccine doses prior to infection. Logistic regression found higher mortality (p = 0.001) and hospitalization (p = 0.016) rates for older recipients, while those with 3 or more vaccine doses had lower mortality (p = 0.039) and hospitalization (p = 0.008) rates. Chronic kidney disease (CKD) increased risk of hospitalization (p < 0.001). Adjusting for the date when the Omicron variant became locally predominant, the protective effect from 3 or more vaccine doses declined to an OR (95% CI) of 0.58 (0.15-2.23), p = 0.39. Conclusions Three or more COVID-19 vaccine doses could decrease mortality for LT recipients, particularly older recipients and those with CKD. These individuals may benefit from vaccination and other interventions.
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Affiliation(s)
- Vinathi Polamraju
- Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
| | - Neeta Vachharajani
- Section of Transplant Surgery, Washington University School of Medicine, St. Louis, MO, United States
| | - Brian F. Gage
- Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
| | - Jeffrey S. Crippin
- Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
| | - William C. Chapman
- Section of Transplant Surgery, Washington University School of Medicine, St. Louis, MO, United States
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3
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Benotmane I, Legendre C, Caillard S. Challenges Faced by Solid Organ Transplant Recipients During the COVID-19 Pandemic in France: Historical Insights and Key Takeaways. Transplantation 2024; 108:819-822. [PMID: 38526428 DOI: 10.1097/tp.0000000000004924] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/26/2024]
Affiliation(s)
- Ilies Benotmane
- Department of Nephrology, Dialysis, and Transplantation, Strasbourg University Hospital, Strasbourg, France
- Inserm UMR S1109, LabEx Transplantex, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France
| | - Christophe Legendre
- Department of Nephrology-Transplantation, Hôpital Necker, Université de Paris, Paris, France
| | - Sophie Caillard
- Department of Nephrology, Dialysis, and Transplantation, Strasbourg University Hospital, Strasbourg, France
- Inserm UMR S1109, LabEx Transplantex, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France
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Ghadery AH, Abbasian L, Jafari F, Yazdi NA, Ahmadinejad Z. Correlation of clinical, laboratory, and short-term outcomes of immunocompromised and immunocompetent COVID-19 patients with semi-quantitative chest CT score findings: A case-control study. Immun Inflamm Dis 2024; 12:e1239. [PMID: 38577996 PMCID: PMC10996371 DOI: 10.1002/iid3.1239] [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: 07/05/2023] [Revised: 03/15/2024] [Accepted: 03/20/2024] [Indexed: 04/06/2024] Open
Abstract
BACKGROUND As the effects of immunosuppression are not still clear on COVID-19 patients, we conducted this study to identify clinical and laboratory findings associated with pulmonary involvement in both immunocompromised and immunocompetent patients. METHODS A case-control of 107 immunocompromised and 107 immunocompetent COVID-19 patients matched for age and sex with either positive RT-PCR or clinical-radiological findings suggestive of COVID-19 enrolled in the study. Their initial clinical features, laboratory findings, chest CT scans, and short-term outcomes (hospitalization time and intensive care unit [ICU] admission) were recorded. In addition, pulmonary involvement was assessed with the semi-quantitative scoring system (0-25). RESULTS Pulmonary involvement was significantly lower in immunocompromised patients in contrast to immunocompetent patients, especially in RLL (p = 0.001), LUL (p = 0.023), and both central and peripheral (p = 0.002), and peribronchovascular (p = 0.004) sites of lungs. Patchy (p < 0.001), wedged (p = 0.002), confluent (p = 0.002) lesions, and ground glass with consolidation pattern (p < 0.001) were significantly higher among immunocompetent patients. Initial signs and symptoms of immunocompromised patients including dyspnea (p = 0.008) and hemoptysis (p = 0.036), respiratory rate of over 25 (p < 0.001), and spo2 of below 93% (p = 0.01) were associated with higher pulmonary involvement. Total chest CT score was also associated with longer hospitalization (p = 0.016) and ICU admission (p = 0.04) among immunocompromised patients. CONCLUSIONS Pulmonary involvement score was not significantly different among immunocompromised and immunocompetent patients. Initial clinical findings (dyspnea, hemoptysis, higher RR, and lower Spo2) of immunocompromised patients could better predict pulmonary involvement than laboratory findings.
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Affiliation(s)
- Abdolkarim Haji Ghadery
- Department of Radiology, Advanced Diagnostic and Interventional Radiology Research Center(ADIR)Tehran University of Medical SciencesTehranIran
| | - Ladan Abbasian
- Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High Risk Behaviors, Department of Infectious Diseases, Imam Khomeini Hospital Complex, School of MedicineTehran University of Medical SciencesTehranIran
| | - Fatemeh Jafari
- Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High Risk Behaviors, Department of Infectious Diseases, Imam Khomeini Hospital Complex, School of MedicineTehran University of Medical SciencesTehranIran
| | - Niloofar Ayoobi Yazdi
- Department of Radiology, Advanced Diagnostic and Interventional Radiology Research Center (ADIR)Tehran University of Medical SciencesTehranIran
| | - Zahra Ahmadinejad
- Department of Infectious Diseases, Liver Transplantation Research Center, Imam Khomeini Hospital ComplexTehran University of Medical SciencesTehranIran
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Bedo D, Beaudrey T, Florens N. Unraveling Chronic Cardiovascular and Kidney Disorder through the Butterfly Effect. Diagnostics (Basel) 2024; 14:463. [PMID: 38472936 DOI: 10.3390/diagnostics14050463] [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: 01/15/2024] [Revised: 02/14/2024] [Accepted: 02/16/2024] [Indexed: 03/14/2024] Open
Abstract
Chronic Cardiovascular and Kidney Disorder (CCKD) represents a growing challenge in healthcare, characterized by the complex interplay between heart and kidney diseases. This manuscript delves into the "butterfly effect" in CCKD, a phenomenon in which acute injuries in one organ lead to progressive dysfunction in the other. Through extensive review, we explore the pathophysiology underlying this effect, emphasizing the roles of acute kidney injury (AKI) and heart failure (HF) in exacerbating each other. We highlight emerging therapies, such as renin-angiotensin-aldosterone system (RAAS) inhibitors, SGLT2 inhibitors, and GLP1 agonists, that show promise in mitigating the progression of CCKD. Additionally, we discuss novel therapeutic targets, including Galectin-3 inhibition and IL33/ST2 pathway modulation, and their potential in altering the course of CCKD. Our comprehensive analysis underscores the importance of recognizing and treating the intertwined nature of cardiac and renal dysfunctions, paving the way for more effective management strategies for this multifaceted syndrome.
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Affiliation(s)
- Dimitri Bedo
- Nephrology Department, Hopitaux Universitaires de Strasbourg, F-67091 Strasbourg, France
- Faculté de Médecine, Université de Strasbourg, Team 3072 "Mitochondria, Oxidative Stress and Muscle Protection", Translational Medicine Federation of Strasbourg (FMTS), F-67000 Strasbourg, France
| | - Thomas Beaudrey
- Nephrology Department, Hopitaux Universitaires de Strasbourg, F-67091 Strasbourg, France
- Laboratoire d'ImmunoRhumatologie Moléculaire, INSERM UMR_S 1109, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, ITI TRANSPLANTEX NG, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, F-67000 Strasbourg, France
| | - Nans Florens
- Nephrology Department, Hopitaux Universitaires de Strasbourg, F-67091 Strasbourg, France
- Laboratoire d'ImmunoRhumatologie Moléculaire, INSERM UMR_S 1109, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, ITI TRANSPLANTEX NG, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, F-67000 Strasbourg, France
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Ghazanfar A, Abbas M, Hussain MW, Kayal M. Risk stratification of renal transplant recipients using routine parameters: Implication of learning from SARS-CoV-2 into transplant follow-up program. World J Transplant 2023; 13:344-356. [PMID: 38174144 PMCID: PMC10758680 DOI: 10.5500/wjt.v13.i6.344] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Revised: 10/21/2023] [Accepted: 11/13/2023] [Indexed: 12/15/2023] Open
Abstract
BACKGROUND Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is a global pandemic that is associated with a high risk of morbidity and mortality among recipients of solid organ transplantation. In the course of acute SARS-CoV-2 infection, various laboratory markers have been identified as predictors for high risk of mortality. AIM To risk stratify renal transplant recipients (RTxR) using general demographic parameters, comorbidities and routine laboratory markers for the severity of the disease and its outcomes. We believe that learning about these routinely moni tored parameters can help us plan better strategies for the RTxR follow-up program. METHODS This present study includes RTxR who acquired SARS-CoV-2 infection from March 2020 to February 2021. We recorded the basic demographics, comorbidities and routine laboratory markers. We investigated the impact of SARS-CoV-2 infection on RTxRs and risk-stratified the progression of disease severity and outcomes in terms of recovery or mortality. RESULTS From 505 RTxRs in our renal transplant follow-up program, 29 (7.75%) RTxRs had PCR-positive SARS-CoV-2 infection. We recorded 8 deaths from SARS-CoV-2 infection giving an overall mortality rate of 1.6% but a significant 27.6% mortality in SARS-CoV-2 positive recipients. Age more than 68 years, non-Caucasian ethnicity and male gender were associated with a significant drop in survival probability; P ≤ 0.001. < 0.001 and < 0.0001 respectively. 87.5% of the deceased were diabetic; P ≤ 0.0.0001. Estimated glomerular filtration rate of less than 26 mL/min/1.73 m2, serum albumin less than 20 g/L, Hemoglobin less than 9.6 g/L and serum calcium less than 1.70 mmol/L were all associated with significantly increased risk of mortality; P = 0.0128, < 0.001, < 0.0001 and 0.0061 respectively. CONCLUSION This study has identified some routinely used modifiable parameters in predicting a higher risk of mortality and morbidity. This knowledge can be used in RTxR follow-up programs by addressing these parameters early to help reduce the morbidity and mortality in RTxRs.
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Affiliation(s)
- Abbas Ghazanfar
- Renal and Transplant Unit, St Georges University Hospitals NHS Foundation Trust, London SW17 0QT, United Kingdom
| | - Madiha Abbas
- Department of Anesthesia and Intensive Care Medicine, Epsom and St Helier University Hospitals NHS Trust, London KT8 7EG, United Kingdom
| | - Md Walid Hussain
- Department of Renal and Transplant Surgery, St Georges University Hospitals NHS Foundation Trust, London SW17 0QT, United Kingdom
| | - Malik Kayal
- Department of Renal and Transplant Surgery, St Georges University Hospitals NHS Foundation Trust, London SW17 0QT, United Kingdom
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Duarsa GWK, Sugianto R, Yusari IGAAA, Tirtayasa PMW, Situmorang GR, Rasyid N, Rodjani A, Daryanto B, Seputra KP, Satyagraha P. Method for determining predictor factor for worse outcomes in kidney transplant recipients infected with coronavirus disease 2019 in a systematic review and meta-analysis research. MethodsX 2023; 11:102250. [PMID: 37325705 PMCID: PMC10257946 DOI: 10.1016/j.mex.2023.102250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2022] [Accepted: 06/10/2023] [Indexed: 06/17/2023] Open
Abstract
The systematic review and meta-analysis were conducted for COVID-19 infections in kidney transplant patients. Recent research on this topic was still scarce and limited meta-analysis research discussion, specific to some risks or treatment in kidney transplantation patients with COVID-19 infection. Therefore, this article demonstrated the fundamental steps to conducting systematic review and meta-analysis studies to derive a pooled estimate of predictor factors of worse outcomes in kidney transplant patients with positive for the SARS-CoV- 2 test•PICOT Framework to determine the research scope•PRISMA strategy for study selection•Forest Plot for meta-analysis study.
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Affiliation(s)
- Gede Wirya Kusuma Duarsa
- Department of Urology, Faculty of Medicine, Universitas Udayana, Prof. Dr. I.G.N.G Ngoerah General Hospital, Bali, Indonesia
| | - Ronald Sugianto
- Medical Doctor Study Program, Faculty of Medicine, Universitas Udayana, Bali, Indonesia
| | | | - Pande Made Wisnu Tirtayasa
- Department of Urology, Faculty of Medicine, Universitas Udayana, Universitas Udayana Teaching Hospital, Bali, Indonesia
| | - Gerhard Reinaldi Situmorang
- Department of Urology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo National Referral Hospital, Jakarta, Indonesia
| | - Nur Rasyid
- Department of Urology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo National Referral Hospital, Jakarta, Indonesia
| | - Arry Rodjani
- Department of Urology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo National Referral Hospital, Jakarta, Indonesia
| | - Besut Daryanto
- Department of Urology, Faculty of Medicine, Universitas Brawijaya, Saiful Anwar General Hospital, Malang, Indonesia
| | - Kurnia Penta Seputra
- Department of Urology, Faculty of Medicine, Universitas Brawijaya, Saiful Anwar General Hospital, Malang, Indonesia
| | - Paksi Satyagraha
- Department of Urology, Faculty of Medicine, Universitas Brawijaya, Saiful Anwar General Hospital, Malang, Indonesia
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Fenninger F, Sherwood KR, Wu V, Wong P, DeMarco ML, Wang M, Benedicto V, Dwarka KA, Günther OP, Tate L, Yoshida E, Keown PA, Kadatz M, Lan JH. Comprehensive immune profiling of SARS-CoV-2 infected kidney transplant patients. FRONTIERS IN TRANSPLANTATION 2023; 2:1261023. [PMID: 38993862 PMCID: PMC11235348 DOI: 10.3389/frtra.2023.1261023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Accepted: 10/23/2023] [Indexed: 07/13/2024]
Abstract
Introduction The immune responses of kidney transplant recipients against SARS-CoV-2 remains under studied. Methods In this prospective pilot study, we performed comprehensive immune profiling using cellular, proteomic, and serologic assays on a cohort of 9 kidney transplant recipients and 12 non-transplant individuals diagnosed with COVID-19. Results Our data show that in addition to having reduced SARS-CoV-2 specific antibody levels, kidney transplant recipients exhibited significant cellular differences including a decrease in naïve-but increase in effector T cells, a high number of CD28+ CD4 effector memory T cells, and increased CD8 T memory stem cells compared with non-transplant patients. Furthermore, transplant patients had lower concentrations of serum cytokine MIP-1β as well as a less diverse T cell receptor repertoire. Conclusion Overall, our results show that compared to non-transplant patients, kidney transplant recipients with SARS-CoV-2 infection exhibit an immunophenotype that is reminiscent of the immune signature observed in patients with severe COVID-19.
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Affiliation(s)
- Franz Fenninger
- Department of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Karen R. Sherwood
- Department of Medicine, University of British Columbia, Vancouver, BC, Canada
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Vivian Wu
- Department of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Paaksum Wong
- Department of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Mari L. DeMarco
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
- Department of Pathology and Laboratory Medicine, Providence Health Care, Vancouver, BC, Canada
| | - Meng Wang
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Vincent Benedicto
- BC Provincial Immunology Laboratory, Vancouver Coastal Health, Vancouver, BC, Canada
| | - Krishna A. Dwarka
- Department of Medicine, University of British Columbia, Vancouver, BC, Canada
| | | | - Logan Tate
- Department of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Eric Yoshida
- Department of Medicine, University of British Columbia, Vancouver, BC, Canada
- Division of Gastroenterology, University of British Columbia, Vancouver, BC, Canada
| | - Paul A. Keown
- Department of Medicine, University of British Columbia, Vancouver, BC, Canada
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Matthew Kadatz
- Department of Medicine, University of British Columbia, Vancouver, BC, Canada
- Division of Nephrology, University of British Columbia, Vancouver, BC, Canada
| | - James H. Lan
- Department of Medicine, University of British Columbia, Vancouver, BC, Canada
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
- Division of Nephrology, University of British Columbia, Vancouver, BC, Canada
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Maiese K. Cellular Metabolism: A Fundamental Component of Degeneration in the Nervous System. Biomolecules 2023; 13:816. [PMID: 37238686 PMCID: PMC10216724 DOI: 10.3390/biom13050816] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Revised: 05/05/2023] [Accepted: 05/10/2023] [Indexed: 05/28/2023] Open
Abstract
It is estimated that, at minimum, 500 million individuals suffer from cellular metabolic dysfunction, such as diabetes mellitus (DM), throughout the world. Even more concerning is the knowledge that metabolic disease is intimately tied to neurodegenerative disorders, affecting both the central and peripheral nervous systems as well as leading to dementia, the seventh leading cause of death. New and innovative therapeutic strategies that address cellular metabolism, apoptosis, autophagy, and pyroptosis, the mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), growth factor signaling with erythropoietin (EPO), and risk factors such as the apolipoprotein E (APOE-ε4) gene and coronavirus disease 2019 (COVID-19) can offer valuable insights for the clinical care and treatment of neurodegenerative disorders impacted by cellular metabolic disease. Critical insight into and modulation of these complex pathways are required since mTOR signaling pathways, such as AMPK activation, can improve memory retention in Alzheimer's disease (AD) and DM, promote healthy aging, facilitate clearance of β-amyloid (Aß) and tau in the brain, and control inflammation, but also may lead to cognitive loss and long-COVID syndrome through mechanisms that can include oxidative stress, mitochondrial dysfunction, cytokine release, and APOE-ε4 if pathways such as autophagy and other mechanisms of programmed cell death are left unchecked.
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Affiliation(s)
- Kenneth Maiese
- Cellular and Molecular Signaling, New York, NY 10022, USA
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10
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Elalouf A. Infections after organ transplantation and immune response. Transpl Immunol 2023; 77:101798. [PMID: 36731780 DOI: 10.1016/j.trim.2023.101798] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 01/08/2023] [Accepted: 01/26/2023] [Indexed: 01/31/2023]
Abstract
Organ transplantation has provided another chance of survival for end-stage organ failure patients. Yet, transplant rejection is still a main challenging factor. Immunosuppressive drugs have been used to avoid rejection and suppress the immune response against allografts. Thus, immunosuppressants increase the risk of infection in immunocompromised organ transplant recipients. The infection risk reflects the relationship between the nature and severity of immunosuppression and infectious diseases. Furthermore, immunosuppressants show an immunological impact on the genetics of innate and adaptive immune responses. This effect usually reactivates the post-transplant infection in the donor and recipient tissues since T-cell activation has a substantial role in allograft rejection. Meanwhile, different infections have been found to activate the T-cells into CD4+ helper T-cell subset and CD8+ cytotoxic T-lymphocyte that affect the infection and the allograft. Therefore, the best management and preventive strategies of immunosuppression, antimicrobial prophylaxis, and intensive medical care are required for successful organ transplantation. This review addresses the activation of immune responses against different infections in immunocompromised individuals after organ transplantation.
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Affiliation(s)
- Amir Elalouf
- Bar-Ilan University, Department of Management, Ramat Gan 5290002, Israel.
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Berger B, Hazzan M, Kamar N, Francois H, Matignon M, Greze C, Gatault P, Frimat L, Westeel PF, Goutaudier V, Snanoudj R, Colosio C, Sicard A, Bertrand D, Mousson C, Bamoulid J, Thierry A, Anglicheau D, Couzi L, Chemouny JM, Duveau A, Moal V, Le Meur Y, Blancho G, Tourret J, Malvezzi P, Mariat C, Rerolle JP, Bouvier N, Caillard S, Thaunat O, the French Solid Organ Transplant (SOT) COVID Registry 34. Absence of Mortality Differences Between the First and Second COVID-19 Waves in Kidney Transplant Recipients. Kidney Int Rep 2022; 7:2617-2629. [PMID: 36159445 PMCID: PMC9489985 DOI: 10.1016/j.ekir.2022.09.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Accepted: 09/05/2022] [Indexed: 12/15/2022] Open
Abstract
Introduction SARS-CoV-2 pandemic evolved in 2 consecutive waves during 2020. Improvements in the management of COVID-19 led to a reduction in mortality rates among hospitalized patients during the second wave. Whether this progress benefited kidney transplant recipients (KTRs), a population particularly vulnerable to severe COVID-19, remained unclear. Methods In France, 957 KTRs were hospitalized for COVID-19 in 2020 and their data were prospectively collected into the French Solid Organ Transplant (SOT) COVID registry. The presentation, management, and outcomes of the 359 KTRs diagnosed during the first wave were compared to those of the 598 of the second wave. Results Baseline comorbidities were similar between KTRs of the 2 waves. Maintenance immunosuppression was reduced in most patients but withdrawal of antimetabolite (73.7% vs. 58.4%, P < 0.001) or calcineurin inhibitor (32.1% vs. 16.6%, P < 0.001) was less frequent during the second wave. Hydroxychloroquine and azithromycin that were commonly used during the first wave (21.7% and 30.9%, respectively) but were almost abandoned during the second wave. In contrast, the use of high dose corticosteroids doubled (19.5% vs. 41.6%, P < 0.001). Despite these changing trends in COVID-19 management, 60-day mortality was not statistically different between the 2 waves (25.3% vs. 23.9%; Log Rank, P = 0.48) and COVID-19 hospitalization period was not associated with death due to COVID-19 in multivariate analysis (Hazard ratio 0.89, 95% confidence interval 0.67-1.17, P = 0.4). Conclusion We conclude that changing of therapeutic trends during 2020 did not reduce COVID-19 related mortality among KTRs. Our data indirectly support the importance of vaccination and neutralizing monoclonal anti-SARS-CoV-2 antibodies to protect KTRS from severe COVID-19.
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Affiliation(s)
- Bastien Berger
- Department of Transplantation, Nephrology and Clinical Immunology, Edouard Herriot Hospital, Hospices civils de Lyon, Lyon, France
| | - Marc Hazzan
- Department of Nephrology and Transplantation, University of Lille, Lille, France
| | - Nassim Kamar
- Department of Nephrology and Transplantation, University of Toulouse, Toulouse, France
| | - Hélène Francois
- Department of Nephrology and Renal Transplantation, Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Paris, France
| | - Marie Matignon
- Department of Nephrology and Renal Transplantation, Assistance Publique-Hôpitaux de Paris, Institut Francilien de Recherche en Néphrologie et Transplantation IFRNT, Groupe Hospitalier Henri-Mondor/Albert-Chenevier, Université Paris-Est-Créteil, Département Hospitalo-Universitaire, Virus-Immunité-Cancer, Institut Mondor de Recherche Biomédicale, Equipe 21, INSERM U 955, Créteil, France
| | - Clarisse Greze
- Department of Nephrology and Transplantation, Hôpital Bichat, Paris, France
| | - Philippe Gatault
- Department of Nephrology and Transplantation, University of Tours, Tours, France
| | - Luc Frimat
- Department of Nephrology, University of Lorraine, CHRU-Nancy, Vandoeuvre, France, INSERM CIC-EC CIE6, Nancy, France
| | - Pierre F. Westeel
- Department of Nephrology and Transplantation, University of Amiens, Amiens, France
| | - Valentin Goutaudier
- Department of Nephrology and Transplantation, University of Montpellier, Montpellier, France
| | - Renaud Snanoudj
- Nephrology and Renal Transplantation Department, Hôpital Foch, Paris, France
| | - Charlotte Colosio
- Department of Nephrology and Transplantation, University of Reims, Reims, France
| | - Antoine Sicard
- Service de Néphrologie-Dialyse-Transplantation, Hôpital Pasteur 2, CHU de Nice, Unité de Recherche Clinique Côte d'Azur, Université Côte d'Azur, Nice, France
| | - Dominique Bertrand
- Department of Nephrology and Transplantation, University of Rouen, Rouen, France
| | - Christiane Mousson
- Department of Nephrology and Transplantation, University of Dijon, Dijon, France
| | - Jamal Bamoulid
- Department of Nephrology, University of Besançon, Besançon, France
| | - Antoine Thierry
- Department of Nephrology and Transplantation, University of Poitiers, Poitiers, France
| | - Dany Anglicheau
- Service de Néphrologie et Transplantation Adultes, Hôpital Universitaire Necker- APHP Centre-Université de Paris INEM INSERM U 1151 - CNRS UMR 8253, Paris, France
| | - Lionel Couzi
- Service de Néphrologie-Transplantation-Dialyse-Aphérèse, Hôpital Pellegrin, CHU de Bordeaux Pellegrin, Unité Mixte de Recherche “ImmunoConcEpT” 5164 - Université de Bordeaux, Bordeaux, France
| | - Jonathan M. Chemouny
- University of Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085, CIC-P 1414, Rennes, France
| | - Agnes Duveau
- Department of Nephrology and Transplantation, University of Angers, Angers, France
| | - Valerie Moal
- Centre de Néphrologie et Transplantation Rénale, Aix Marseille Université, Hôpitaux Universitaires de Marseille, Hôpital Conception, Marseille, France
| | - Yannick Le Meur
- Department of Nephrology, CHU de Brest, UMR1227, Lymphocytes B et Autoimmunité, Université de Brest, Inserm, Labex IGO, Brest, France
| | - Gilles Blancho
- Department of Nephrology and Transplantation, Centre Hospitalier Universitaire de Nantes, Nantes, France
| | - Jérôme Tourret
- Nephrology and Renal Transplantation Department, Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié Salpétrière, Paris, France
| | - Paolo Malvezzi
- Department of Nephrology, University of Grenoble, Grenoble, France
| | - Christophe Mariat
- Department of Nephrology and Transplantation, University of St Etienne, St Etienne, France
| | - Jean-Philippe Rerolle
- Department of Nephrology and Transplantation, University of Limoges, Limoges, France
| | - Nicolas Bouvier
- Department of Nephrology and Transplantation, University of Caen, Caen, France
| | - Sophie Caillard
- Department of Nephrology and Transplantation, Strasbourg University Hospital, Strasbourg, France
- INSERM, IRM UMR-S 1109, University of Strasbourg, Strasbourg, France
| | - Olivier Thaunat
- Department of Transplantation, Nephrology and Clinical Immunology, Edouard Herriot Hospital, Hospices civils de Lyon, Lyon, France
- CIRI, INSERM U1111, University Claude Bernard Lyon I, Lyon, France
- Claude Bernard University (Lyon 1), Villeurbanne, France
| | - the French Solid Organ Transplant (SOT) COVID Registry34
- Department of Transplantation, Nephrology and Clinical Immunology, Edouard Herriot Hospital, Hospices civils de Lyon, Lyon, France
- Department of Nephrology and Transplantation, University of Lille, Lille, France
- Department of Nephrology and Transplantation, University of Toulouse, Toulouse, France
- Department of Nephrology and Renal Transplantation, Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Paris, France
- Department of Nephrology and Renal Transplantation, Assistance Publique-Hôpitaux de Paris, Institut Francilien de Recherche en Néphrologie et Transplantation IFRNT, Groupe Hospitalier Henri-Mondor/Albert-Chenevier, Université Paris-Est-Créteil, Département Hospitalo-Universitaire, Virus-Immunité-Cancer, Institut Mondor de Recherche Biomédicale, Equipe 21, INSERM U 955, Créteil, France
- Department of Nephrology and Transplantation, Hôpital Bichat, Paris, France
- Department of Nephrology and Transplantation, University of Tours, Tours, France
- Department of Nephrology, University of Lorraine, CHRU-Nancy, Vandoeuvre, France, INSERM CIC-EC CIE6, Nancy, France
- Department of Nephrology and Transplantation, University of Amiens, Amiens, France
- Department of Nephrology and Transplantation, University of Montpellier, Montpellier, France
- Nephrology and Renal Transplantation Department, Hôpital Foch, Paris, France
- Department of Nephrology and Transplantation, University of Reims, Reims, France
- Service de Néphrologie-Dialyse-Transplantation, Hôpital Pasteur 2, CHU de Nice, Unité de Recherche Clinique Côte d'Azur, Université Côte d'Azur, Nice, France
- Department of Nephrology and Transplantation, University of Rouen, Rouen, France
- Department of Nephrology and Transplantation, University of Dijon, Dijon, France
- Department of Nephrology, University of Besançon, Besançon, France
- Department of Nephrology and Transplantation, University of Poitiers, Poitiers, France
- Service de Néphrologie et Transplantation Adultes, Hôpital Universitaire Necker- APHP Centre-Université de Paris INEM INSERM U 1151 - CNRS UMR 8253, Paris, France
- Service de Néphrologie-Transplantation-Dialyse-Aphérèse, Hôpital Pellegrin, CHU de Bordeaux Pellegrin, Unité Mixte de Recherche “ImmunoConcEpT” 5164 - Université de Bordeaux, Bordeaux, France
- University of Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085, CIC-P 1414, Rennes, France
- Department of Nephrology and Transplantation, University of Angers, Angers, France
- Centre de Néphrologie et Transplantation Rénale, Aix Marseille Université, Hôpitaux Universitaires de Marseille, Hôpital Conception, Marseille, France
- Department of Nephrology, CHU de Brest, UMR1227, Lymphocytes B et Autoimmunité, Université de Brest, Inserm, Labex IGO, Brest, France
- Department of Nephrology and Transplantation, Centre Hospitalier Universitaire de Nantes, Nantes, France
- Nephrology and Renal Transplantation Department, Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié Salpétrière, Paris, France
- Department of Nephrology, University of Grenoble, Grenoble, France
- Department of Nephrology and Transplantation, University of St Etienne, St Etienne, France
- Department of Nephrology and Transplantation, University of Limoges, Limoges, France
- Department of Nephrology and Transplantation, University of Caen, Caen, France
- Department of Nephrology and Transplantation, Strasbourg University Hospital, Strasbourg, France
- INSERM, IRM UMR-S 1109, University of Strasbourg, Strasbourg, France
- CIRI, INSERM U1111, University Claude Bernard Lyon I, Lyon, France
- Claude Bernard University (Lyon 1), Villeurbanne, France
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12
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Firket L, Bouquegneau A, Seidel L, Bonvoisin C, Grosch S, Hayette MP, Jouret F, Weekers L. The prospective screening for SARS-CoV-2 S1/S2 antibodies delineates the factual incidence of COVID-19 and shows a sustained serological response post COVID-19 in kidney transplant recipients. Acta Clin Belg 2022; 78:200-205. [PMID: 35938938 DOI: 10.1080/17843286.2022.2108978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/15/2022]
Abstract
BACKGROUND The impact of immunosuppression on the occurrence of Coronavirus Disease 2019 (COVID-19) remains unclear. METHODS We conducted a prospective screening of anti-S1/S2 IgGs against SARS-CoV-2 Spike protein from March, 1 2020 to May, 15 2021 (prior to the vaccination campaign) in a cohort of 713 kidney transplant recipients (KTRs). In a first phase, the factual incidence and seroprevalence of COVID-19 was established in this cohort: cases diagnosed by serology were added to RT-PCR-based diagnoses to obtain the overall incidence of COVID-19 in both symptomatic and asymptomatic KTRs. In the second phase, the kinetics of the post-COVID-19 humoral response were studied, taking into account the severity of the disease defined by the need for oxygen therapy (group S, "severe") or not (group nS, "not severe"). RESULTS The combined diagnostic approaches identified 138 COVID-19 cases (19.2%), with 37 diagnoses by serology (26.8%). The rate of asymptomatic KTRs reached 20.3% (28/138). Thirteen patients (9.4%) died from COVID-19. The seroconversion rate was 91.7% (99/108). The peak anti-S1/S2 IgG level was 85 [30-150] AU/ml and was similar between the S and nS groups (117 [38; 186] AU/ml versus 73 [23; 140] AU/ml). A high probability of persistence of anti-S1/S2 IgG post-COVID-19 was observed, with only 10.1% (7/69) of the patients having negated their serology during the 9-month follow-up. CONCLUSION Our pragmatic serological screening combined with RT-PCR tests provides a better estimation of the real incidence of COVID-19 in KTRs. A significant proportion of KTRs develop humoral immunity post COVID-19, which most often persists beyond 9 months.
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Affiliation(s)
- Louis Firket
- Division of Nephrology, University of Liege Hospital (ULiege CHU), Liege, Belgium
| | - Antoine Bouquegneau
- Division of Nephrology, University of Liege Hospital (ULiege CHU), Liege, Belgium
| | - Laurence Seidel
- Division of Biostatistics, University of Liege Hospital (ULiege CHU), Liege, Belgium
| | - Catherine Bonvoisin
- Division of Nephrology, University of Liege Hospital (ULiege CHU), Liege, Belgium
| | - Stéphanie Grosch
- Division of Nephrology, University of Liege Hospital (ULiege CHU), Liege, Belgium
| | - Marie-Pierre Hayette
- Division of Microbiology, University of Liege Hospital (ULiege CHU), Liege, Belgium
| | - François Jouret
- Division of Nephrology, University of Liege Hospital (ULiege CHU), Liege, Belgium.,Laboratory of Translational Research in Nephrology, University of Liege GIGA Research Center, ULiege, Belgium
| | - Laurent Weekers
- Division of Nephrology, University of Liege Hospital (ULiege CHU), Liege, Belgium
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13
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El-Saber Batiha G, Al-Gareeb AI, Saad HM, Al-kuraishy HM. COVID-19 and corticosteroids: a narrative review. Inflammopharmacology 2022; 30:1189-1205. [PMID: 35562628 PMCID: PMC9106274 DOI: 10.1007/s10787-022-00987-z] [Citation(s) in RCA: 52] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Accepted: 03/30/2022] [Indexed: 02/06/2023]
Abstract
It has been reported that corticosteroid therapy was effective in the management of severe acute respiratory syndrome (SARS) and the Middle East Respiratory Syndrome (MERS), and recently in coronavirus disease 2019 (COVID-19). Corticosteroids are potent anti-inflammatory drugs that mitigate the risk of acute respiratory distress syndrome (ARDS) in COVID-19 and other viral pneumonia, despite a reduction of viral clearance; corticosteroids inhibit the development of cytokine storm and multi-organ damage. The risk-benefit ratio should be assessed for critical COVID-19 patients. In conclusion, corticosteroid therapy is an effective way in the management of COVID-19, it reduces the risk of complications primarily acute lung injury and the development of ARDS. Besides, corticosteroid therapy mainly dexamethasone and methylprednisolone are effective in reducing the severity of COVID-19 and associated comorbidities such as chronic obstructive pulmonary diseases (COPD), rheumatoid arthritis, and inflammatory bowel disease (IBD).
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Affiliation(s)
- Gaber El-Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511 AlBeheira Egypt
| | - Ali I. Al-Gareeb
- Department of Clinical Pharmacology and Medicine, College of Medicine, Mustansiriyiah University, Baghdad, Iraq
| | - Hebatallah M. Saad
- Department of Pathology, Faculty of Veterinary Medicine, Matrouh University, Matrouh, 51744 Matrouh Egypt
| | - Hayder M. Al-kuraishy
- Department of Clinical Pharmacology and Medicine, College of Medicine, Mustansiriyiah University, Baghdad, Iraq
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14
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Mahalingasivam V, Su G, Iwagami M, Davids MR, Wetmore JB, Nitsch D. COVID-19 and kidney disease: insights from epidemiology to inform clinical practice. Nat Rev Nephrol 2022; 18:485-498. [PMID: 35418695 PMCID: PMC9006492 DOI: 10.1038/s41581-022-00570-3] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/30/2022] [Indexed: 01/08/2023]
Abstract
Over the course of the COVID-19 pandemic, numerous studies have aimed to address the challenges faced by patients with kidney disease and their caregivers. These studies addressed areas of concern such as the high infection and mortality risk of patients on in-centre haemodialysis and transplant recipients. However, the ability to draw meaningful conclusions from these studies has in some instances been challenging, owing to barriers in aspects of usual care, data limitations and problematic methodological practices. In many settings, access to SARS-CoV-2 testing differed substantially between patient groups, whereas the incidence of SARS-CoV-2 infection varied over time and place because of differences in viral prevalence, targeted public health policies and vaccination rates. The absence of baseline kidney function data posed problems in the classification of chronic kidney disease and acute kidney injury in some studies, potentially compromising the generalizability of findings. Study findings also require attentive appraisal in terms of the effects of confounding, collider bias and chance. As this pandemic continues and in the future, the implementation of sustainable and integrated research infrastructure is needed in settings across the world to minimize infection transmission and both prevent and plan for the short-term and long-term complications of infectious diseases. Registries can support the real-world evaluation of vaccines and therapies in patients with advanced kidney disease while enabling monitoring of rare complications.
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Affiliation(s)
- Viyaasan Mahalingasivam
- Department of Non-Communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK
| | - Guobin Su
- Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital, The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou City, Guangdong Province, China
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Clinical Research Center for Kidney Disease, Department of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou City, Guangdong Province, China
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Masao Iwagami
- Department of Non-Communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK
- Department of Health Services Research, University of Tsukuba, Ibaraki, Japan
| | - Mogamat Razeen Davids
- Division of Nephrology, Stellenbosch University, Cape Town, South Africa
- South African Renal Registry, Cape Town, South Africa
- African Renal Registry, African Association of Nephrology, Durban, South Africa
| | - James B Wetmore
- Division of Nephrology, Hennepin Healthcare, Minneapolis, MN, USA
- Chronic Disease Research Group, Hennepin Healthcare, Minneapolis, USA
| | - Dorothea Nitsch
- Department of Non-Communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK.
- UK Renal Registry, Bristol, UK.
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15
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Benotmane I, Gautier-Vargas G, Cognard N, Olagne J, Heibel F, Braun-Parvez L, Martzloff J, Perrin P, Pszczolinski R, Moulin B, Fafi-Kremer S, Caillard S. Prediction of Vaccine Response and Development of a Personalized Anti-SARS-CoV-2 Vaccination Strategy in Kidney Transplant Recipients: Results from a Large Single-Center Study. J Pers Med 2022; 12:jpm12071107. [PMID: 35887604 PMCID: PMC9317479 DOI: 10.3390/jpm12071107] [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: 05/05/2022] [Revised: 06/18/2022] [Accepted: 07/04/2022] [Indexed: 12/11/2022] Open
Abstract
Kidney transplant recipients (KTRs) displays marked inter-individual variations in magnitude of immune responses to anti-SARS-CoV-2 vaccination. The aim of this large single-center study was to identify the predictive factors for serological response to the mRNA-1273 vaccine in KTRs. We also devised a score to optimize prediction with the goal of implementing a personalized vaccination strategy. The study population consisted of 564 KTRs who received at least two doses of the mRNA-1273 vaccine. Anti-RBD IgG titers were quantified one month after each vaccine dose and until six months thereafter. A third dose vaccine was given when the antibody titer after the second dose was <143 BAU/mL. A score to optimize prediction of vaccine response was devised using the independent predictors identified in multivariate analysis. The seropositivity rate after the second dose was 46.6% and 22.2% of participants were classified as good responders (titers ≥ 143 BAU/mL). On analyzing the 477 patients for whom serology testing was available after the second or third dose, the global seropositivity rate was 69% (good responders: 46.3%). Immunosuppressive drugs, graft function, age, interval from transplantation, body mass index, and sex were associated with vaccine response. The devised score was strongly associated with the seropositivity rate (AUC = 0.752, p < 0.0001) and the occurrence of a good antibody response (AUC = 0.785, p < 0.0001). Notably, antibody titers declined over time both after the second and third vaccine doses. In summary, a high burden of comorbidities and immunosuppression was correlated with a weaker antibody response. A fourth vaccine dose and/or pre-exposure prophylaxis with monoclonal antibodies should be considered for KTRs who remain unprotected.
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Affiliation(s)
- Ilies Benotmane
- Department of Nephrology, Dialysis and Transplantation, Strasbourg University Hospital, 1 Place de l’Hopital, BP 426, 67091 Strasbourg, France; (G.G.-V.); (N.C.); (J.O.); (F.H.); (L.B.-P.); (J.M.); (P.P.); (R.P.); (B.M.); (S.C.)
- Fédération de Médecine Translationnelle (FMTS), 67000 Strasbourg, France;
- Correspondence:
| | - Gabriela Gautier-Vargas
- Department of Nephrology, Dialysis and Transplantation, Strasbourg University Hospital, 1 Place de l’Hopital, BP 426, 67091 Strasbourg, France; (G.G.-V.); (N.C.); (J.O.); (F.H.); (L.B.-P.); (J.M.); (P.P.); (R.P.); (B.M.); (S.C.)
| | - Noëlle Cognard
- Department of Nephrology, Dialysis and Transplantation, Strasbourg University Hospital, 1 Place de l’Hopital, BP 426, 67091 Strasbourg, France; (G.G.-V.); (N.C.); (J.O.); (F.H.); (L.B.-P.); (J.M.); (P.P.); (R.P.); (B.M.); (S.C.)
| | - Jérôme Olagne
- Department of Nephrology, Dialysis and Transplantation, Strasbourg University Hospital, 1 Place de l’Hopital, BP 426, 67091 Strasbourg, France; (G.G.-V.); (N.C.); (J.O.); (F.H.); (L.B.-P.); (J.M.); (P.P.); (R.P.); (B.M.); (S.C.)
- Fédération de Médecine Translationnelle (FMTS), 67000 Strasbourg, France;
| | - Françoise Heibel
- Department of Nephrology, Dialysis and Transplantation, Strasbourg University Hospital, 1 Place de l’Hopital, BP 426, 67091 Strasbourg, France; (G.G.-V.); (N.C.); (J.O.); (F.H.); (L.B.-P.); (J.M.); (P.P.); (R.P.); (B.M.); (S.C.)
| | - Laura Braun-Parvez
- Department of Nephrology, Dialysis and Transplantation, Strasbourg University Hospital, 1 Place de l’Hopital, BP 426, 67091 Strasbourg, France; (G.G.-V.); (N.C.); (J.O.); (F.H.); (L.B.-P.); (J.M.); (P.P.); (R.P.); (B.M.); (S.C.)
| | - Jonas Martzloff
- Department of Nephrology, Dialysis and Transplantation, Strasbourg University Hospital, 1 Place de l’Hopital, BP 426, 67091 Strasbourg, France; (G.G.-V.); (N.C.); (J.O.); (F.H.); (L.B.-P.); (J.M.); (P.P.); (R.P.); (B.M.); (S.C.)
| | - Peggy Perrin
- Department of Nephrology, Dialysis and Transplantation, Strasbourg University Hospital, 1 Place de l’Hopital, BP 426, 67091 Strasbourg, France; (G.G.-V.); (N.C.); (J.O.); (F.H.); (L.B.-P.); (J.M.); (P.P.); (R.P.); (B.M.); (S.C.)
- Fédération de Médecine Translationnelle (FMTS), 67000 Strasbourg, France;
| | - Romain Pszczolinski
- Department of Nephrology, Dialysis and Transplantation, Strasbourg University Hospital, 1 Place de l’Hopital, BP 426, 67091 Strasbourg, France; (G.G.-V.); (N.C.); (J.O.); (F.H.); (L.B.-P.); (J.M.); (P.P.); (R.P.); (B.M.); (S.C.)
| | - Bruno Moulin
- Department of Nephrology, Dialysis and Transplantation, Strasbourg University Hospital, 1 Place de l’Hopital, BP 426, 67091 Strasbourg, France; (G.G.-V.); (N.C.); (J.O.); (F.H.); (L.B.-P.); (J.M.); (P.P.); (R.P.); (B.M.); (S.C.)
- Fédération de Médecine Translationnelle (FMTS), 67000 Strasbourg, France;
| | - Samira Fafi-Kremer
- Fédération de Médecine Translationnelle (FMTS), 67000 Strasbourg, France;
- Department of Virology, Strasbourg University Hospital, BP 426, 67091 Strasbourg, France
| | - Sophie Caillard
- Department of Nephrology, Dialysis and Transplantation, Strasbourg University Hospital, 1 Place de l’Hopital, BP 426, 67091 Strasbourg, France; (G.G.-V.); (N.C.); (J.O.); (F.H.); (L.B.-P.); (J.M.); (P.P.); (R.P.); (B.M.); (S.C.)
- Fédération de Médecine Translationnelle (FMTS), 67000 Strasbourg, France;
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16
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An W, Wang Q, Kim TE, Kang JS. Clinical characteristics and outcome of coronavirus disease 2019 infection in patients with solid organ transplants: A systematic review and meta-analysis. J Infect Public Health 2022; 15:365-372. [PMID: 35193818 PMCID: PMC8857642 DOI: 10.1016/j.jiph.2022.02.002] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 01/03/2022] [Accepted: 02/06/2022] [Indexed: 12/24/2022] Open
Affiliation(s)
- Wen An
- Department of Pharmacology & Clinical Pharmacology, College of Medicine, Hanyang University, Seoul, South Korea.
| | - Qiuyang Wang
- Department of Central China Research Institute of Health, Xinxiang Medical University, Xinxiang, China.
| | - Tae-Eun Kim
- Department of Clinical Pharmacology, Konkuk University Hospital, Seoul, South Korea.
| | - Ju-Seop Kang
- Department of Pharmacology & Clinical Pharmacology, College of Medicine, Hanyang University, Seoul, South Korea.
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Padmanabhan P, Desikan R, Dixit NM. Modeling how antibody responses may determine the efficacy of COVID-19 vaccines. NATURE COMPUTATIONAL SCIENCE 2022; 2:123-131. [PMID: 38177523 DOI: 10.1038/s43588-022-00198-0] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Accepted: 01/20/2022] [Indexed: 01/06/2024]
Abstract
Predicting the efficacy of COVID-19 vaccines would aid vaccine development and usage strategies, which is of importance given their limited supplies. Here we develop a multiscale mathematical model that proposes mechanistic links between COVID-19 vaccine efficacies and the neutralizing antibody (NAb) responses they elicit. We hypothesized that the collection of all NAbs would constitute a shape space and that responses of individuals are random samples from this space. We constructed the shape space by analyzing reported in vitro dose-response curves of ~80 NAbs. Sampling NAb subsets from the space, we recapitulated the responses of convalescent patients. We assumed that vaccination would elicit similar NAb responses. We developed a model of within-host SARS-CoV-2 dynamics, applied it to virtual patient populations and, invoking the NAb responses above, predicted vaccine efficacies. Our predictions quantitatively captured the efficacies from clinical trials. Our study thus suggests plausible mechanistic underpinnings of COVID-19 vaccines and generates testable hypotheses for establishing them.
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Affiliation(s)
- Pranesh Padmanabhan
- Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
| | - Rajat Desikan
- Department of Chemical Engineering, Indian Institute of Science, Bangalore, India
- Certara QSP, Certara UK Limited, Sheffield, UK
| | - Narendra M Dixit
- Department of Chemical Engineering, Indian Institute of Science, Bangalore, India.
- Centre for Biosystems Science and Engineering, Indian Institute of Science, Bangalore, India.
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18
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Panigrahi D, Bagai S, Singh K, Gandhi K, Prasad P, Chhabra G, Grover R, Khullar D. Clinical profile and outcome of coronavirus disease-2019 in kidney transplant recipients admitted to a tertiary care center: A retrospective study. INDIAN JOURNAL OF MEDICAL SPECIALITIES 2022. [DOI: 10.4103/injms.injms_112_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
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19
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Monfared A, Akhondzadeh L, Mousazadeh M, Jafari A, Khosravi M, Lebadi M, Aghajanzadeh P, Haghdar-Saheli Y, Movassaghi A, Ramezanzadeh E, Shobeirian F, Kazemnezhad E, Esmaeili S. COVID-19 in renal transplant recipients and general population: a comparative study of clinical, laboratory, and radiological features, severity, and outcome. Virol J 2021; 18:243. [PMID: 34876176 PMCID: PMC8649678 DOI: 10.1186/s12985-021-01713-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2021] [Accepted: 11/27/2021] [Indexed: 12/15/2022] Open
Abstract
INTRODUCTION Coronavirus disease 2019 (COVID-19), a novel disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to millions of deaths worldwide. Kidney transplant recipients (KTRs) are a fragile population due to their immunosuppressed status. However, there are limited studies available comparing this population with the general population regarding clinical symptoms, and laboratory and imaging features as well as disease severity and clinical outcomes. METHODS A total of 24 KTRs and 40 patients from the general population (control group) were enrolled after applying exclusion criteria. Clinical symptoms, laboratory values, and lung involvement patterns in high-resolution computed tomography (HRCT) were compared between KTRs with COVID-19 and their counterparts from the general population. Moreover, the category of disease severity and adverse outcomes such as intensive care unit (ICU) admission, mechanical ventilation (MV), and mortality rate were also compared between these two groups. RESULTS Hypertension was significantly higher among KTRs. Dyspnea was significantly more among the control group (P = 0.045). There was no significant difference in the rest of clinical symptoms (P > 0.05). There was no significant difference in CT features as well, except pleural effusion, which was more prevalent in the control group. A lower absolute lymphocytic count (ALC) and platelet count were observed in KTRs. Renal transplant recipients (RTRs) had a higher elevation in creatinine level than their counterparts. The ICU admission, MV, duration of hospital stay, and mortality as adverse outcomes were not significantly different between the KTR and control groups. CONCLUSION In conclusion, there was no significant difference in the severity and risk of adverse outcomes, including MV, ICU admission, and mortality between KTRs under chronic immunosuppression and the control group.
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Affiliation(s)
- Ali Monfared
- Urology Research Center, School of Medicine, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Leila Akhondzadeh
- Urology Research Center, School of Medicine, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Mahsa Mousazadeh
- School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Atefeh Jafari
- Department of Clinical Pharmacy, School of Pharmacy, Guilan University of Medical Sciences, Rasht, Iran
| | - Masoud Khosravi
- Urology Research Center, School of Medicine, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Mohammadkazem Lebadi
- Urology Research Center, School of Medicine, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Pegah Aghajanzadeh
- Urology Research Center, School of Medicine, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Yalda Haghdar-Saheli
- Urology Research Center, School of Medicine, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Ali Movassaghi
- Urology Research Center, School of Medicine, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Elham Ramezanzadeh
- Urology Research Center, School of Medicine, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | | | - Ehsan Kazemnezhad
- Urology Research Center, School of Medicine, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Samaneh Esmaeili
- Urology Research Center, School of Medicine, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran
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20
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Chen JJ, Kuo G, Lee TH, Yang HY, Wu HH, Tu KH, Tian YC. Incidence of Mortality, Acute Kidney Injury and Graft Loss in Adult Kidney Transplant Recipients with Coronavirus Disease 2019: Systematic Review and Meta-Analysis. J Clin Med 2021; 10:jcm10215162. [PMID: 34768682 PMCID: PMC8584628 DOI: 10.3390/jcm10215162] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 10/26/2021] [Accepted: 10/28/2021] [Indexed: 02/07/2023] Open
Abstract
The adverse impact of Coronavirus disease 2019 (COVID-19) on kidney function has been reported since the global pandemic. The burden of COVID-19 on kidney transplant recipients, however, has not been systematically analyzed. A systematic review and meta-analysis with a random-effect model was conducted to explore the rate of mortality, intensive care unit admission, invasive mechanical ventilation, acute kidney injury, kidney replacement therapy and graft loss in the adult kidney transplant population with COVID-19. Sensitivity analysis, subgroup analysis and meta-regression were also performed. Results: we demonstrated a pooled mortality rate of 21% (95% CI: 19−23%), an intensive care unit admission rate of 26% (95% CI: 22–31%), an invasive ventilation rate among those who required intensive care unit care of 72% (95% CI: 62–81%), an acute kidney injury rate of 44% (95% CI: 39–49%), a kidney replacement therapy rate of 12% (95% CI: 9–15%), and a graft loss rate of 8% (95% CI: 5–15%) in kidney transplant recipients with COVID-19. The meta-regression indicated that advancing age is associated with higher mortality; every increase in age by 10 years was associated with an increased mortality rate of 3.7%. Regional differences in outcome were also detected. Further studies focused on treatments and risk factor identification are needed.
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Affiliation(s)
- Jia-Jin Chen
- Department of Nephrology, Chang Gung Memorial Hospital, Linkou Main Branch, Taoyuan City 33305, Taiwan; (J.-J.C.); (G.K.); (T.H.L.); (H.-Y.Y.); (H.H.W.); (K.-H.T.)
| | - George Kuo
- Department of Nephrology, Chang Gung Memorial Hospital, Linkou Main Branch, Taoyuan City 33305, Taiwan; (J.-J.C.); (G.K.); (T.H.L.); (H.-Y.Y.); (H.H.W.); (K.-H.T.)
| | - Tao Han Lee
- Department of Nephrology, Chang Gung Memorial Hospital, Linkou Main Branch, Taoyuan City 33305, Taiwan; (J.-J.C.); (G.K.); (T.H.L.); (H.-Y.Y.); (H.H.W.); (K.-H.T.)
| | - Huang-Yu Yang
- Department of Nephrology, Chang Gung Memorial Hospital, Linkou Main Branch, Taoyuan City 33305, Taiwan; (J.-J.C.); (G.K.); (T.H.L.); (H.-Y.Y.); (H.H.W.); (K.-H.T.)
- Department of Nephrology, Kidney Research Center, Chang Gung Memorial Hospital, Taoyuan City 33305, Taiwan
| | - Hsin Hsu Wu
- Department of Nephrology, Chang Gung Memorial Hospital, Linkou Main Branch, Taoyuan City 33305, Taiwan; (J.-J.C.); (G.K.); (T.H.L.); (H.-Y.Y.); (H.H.W.); (K.-H.T.)
- Department of Nephrology, Kidney Research Center, Chang Gung Memorial Hospital, Taoyuan City 33305, Taiwan
| | - Kun-Hua Tu
- Department of Nephrology, Chang Gung Memorial Hospital, Linkou Main Branch, Taoyuan City 33305, Taiwan; (J.-J.C.); (G.K.); (T.H.L.); (H.-Y.Y.); (H.H.W.); (K.-H.T.)
- Department of Nephrology, Kidney Research Center, Chang Gung Memorial Hospital, Taoyuan City 33305, Taiwan
| | - Ya-Chung Tian
- Department of Nephrology, Chang Gung Memorial Hospital, Linkou Main Branch, Taoyuan City 33305, Taiwan; (J.-J.C.); (G.K.); (T.H.L.); (H.-Y.Y.); (H.H.W.); (K.-H.T.)
- Department of Nephrology, Kidney Research Center, Chang Gung Memorial Hospital, Taoyuan City 33305, Taiwan
- Correspondence:
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21
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Dęborska-Materkowska D, Kamińska D. The Immunology of SARS-CoV-2 Infection and Vaccines in Solid Organ Transplant Recipients. Viruses 2021; 13:1879. [PMID: 34578460 PMCID: PMC8473113 DOI: 10.3390/v13091879] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 09/13/2021] [Accepted: 09/17/2021] [Indexed: 12/12/2022] Open
Abstract
Since its outbreak in December 2019, the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), led to an enormous rise in scientific response with an excess of COVID-19-related studies on the pathogenesis and potential therapeutic approaches. Solid organ transplant (SOT) recipients are a heterogeneous population with long-lasting immunosuppression as a joining element. Immunocompromised patients are a vulnerable population with a high risk of severe infections and an increased infection-related mortality rate. It was postulated that the hyperinflammatory state due to cytokine release syndrome during severe COVID-19 could be alleviated by immunosuppressive therapy in SOT patients. On the other hand, it was previously established that T cell-mediated immunity, which is significantly weakened in SOT recipients, is the main component of antiviral immune responses. In this paper, we present the current state of science on COVID-19 immunology in relation to solid organ transplantation with prospective therapeutic and vaccination strategies in this population.
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Affiliation(s)
- Dominika Dęborska-Materkowska
- Department of Transplantation Medicine, Nephrology and Internal Diseases, Medical University of Warsaw, Nowogrodzka 59, 02-006 Warsaw, Poland;
| | - Dorota Kamińska
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland
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22
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Yin S, Wang X, Song T. Tacrolimus Use and COVID-19 Infection in Patients After Solid Organ Transplantation. Gastroenterology 2021; 161:728-730.e1. [PMID: 33539863 PMCID: PMC7848533 DOI: 10.1053/j.gastro.2021.01.223] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Revised: 01/24/2021] [Accepted: 01/27/2021] [Indexed: 02/08/2023]
Affiliation(s)
- Saifu Yin
- Organ Transplant Center, Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, China
| | - Xianding Wang
- Organ Transplant Center, Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, China
| | - Turun Song
- Organ Transplant Center, Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, China
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23
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Clinical utility of biochemical markers for the prediction of COVID-19-related mortality in kidney transplant recipients. Kidney Int Rep 2021; 6:2689-2693. [PMID: 34254049 PMCID: PMC8264524 DOI: 10.1016/j.ekir.2021.06.034] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 06/22/2021] [Indexed: 12/21/2022] Open
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Azzi Y, Brooks A, Yaffe H, Greenstein S. COVID-19 and the Response of Transplant Centers: the Global Response with an Emphasis on the Kidney Recipient. CURRENT TRANSPLANTATION REPORTS 2021; 8:163-182. [PMID: 34221847 PMCID: PMC8241407 DOI: 10.1007/s40472-021-00330-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/22/2021] [Indexed: 12/12/2022]
Abstract
PURPOSE OF THE REVIEW In response to the COVID-19 pandemic, vulnerable populations, such as transplant patients, were at greater risk than the regular population. In order to protect these populations, transplant centers enacted new guidelines. We approach this review by looking at how different transplant regions responded to COVID-19 and analyze the unifying themes that have proven invaluable in the subsequent waves. RECENT FINDINGS We noticed that most elective surgeries including living donor transplant operations were suspended in most countries. The response to deceased donor transplants varied between countries: in some deceased donor transplants continued with modified donor and recipient criteria, while in other countries this surgery was suspended. There was a general trend of decreasing or holding antimetabolites, treating the virus with hydroxychloroquine and/or azithromycin, and converting outpatient clinics to virtual clinics. SUMMARY We learned how to carefully select donors and recipients, tailor immunosuppressant regiments, and implement telemedicine. The kidney recipient population can be effectively managed in times of crisis with appropriate accommodations and measures. This review can be a model for the transplant community for future pandemics.
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Affiliation(s)
- Yorg Azzi
- Albert Einstein College of Medicine, Bronx, NY USA
- Montefiore-Einstein Center for Transplantation, Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467-2401 USA
| | - Abigail Brooks
- Albert Einstein College of Medicine, Bronx, NY USA
- Montefiore-Einstein Center for Transplantation, Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467-2401 USA
| | - Hillary Yaffe
- Albert Einstein College of Medicine, Bronx, NY USA
- Montefiore-Einstein Center for Transplantation, Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467-2401 USA
| | - Stuart Greenstein
- Albert Einstein College of Medicine, Bronx, NY USA
- Montefiore-Einstein Center for Transplantation, Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467-2401 USA
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25
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Kute VB, Bhalla AK, Guleria S, Ray DS, Bahadur MM, Shingare A, Hegde U, Gang S, Raju S, Patel HV, Jain S, Godara S, Modi P, Gumber M, Engineer DP, Dalal S, Darji P, Balwani M, Patel AH, Mishra VV. Clinical Profile and Outcome of COVID-19 in 250 Kidney Transplant Recipients: A Multicenter Cohort Study From India. Transplantation 2021; 105:851-860. [PMID: 33350674 PMCID: PMC7993652 DOI: 10.1097/tp.0000000000003593] [Citation(s) in RCA: 74] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 11/17/2020] [Accepted: 11/21/2020] [Indexed: 12/23/2022]
Abstract
BACKGROUND There is a scarcity of data on the consequences of coronavirus disease-19 (COVID-19) infections in kidney transplant recipients (KTRs) from emerging countries. METHODS Here, we present a cohort study of 13 transplant centers in India including 250 KTR (226 living and 24 deceased donors) with polymerase chain reaction-confirmed COVID-19 positivity from March 23, 2020, until September 15, 2020. We detailed demographics, immunosuppression regimen, clinical profile, treatment, and outcomes. RESULTS Median age of transplant recipients was 43 years, and recipients presented at a median of 3.5 years after transplant. Most common comorbidities (94%) included arterial hypertension (84%) and diabetes (32%); presenting symptoms at the time of COVID-19 included fever (88%), cough (72%), and sputum production (52%). Clinical severity ranged from asymptomatic (6%), mild (60%), and moderate (20%) to severe (14%). Strategies to modify immunosuppressants included discontinuation of antimetabolites without changes in calcineurin inhibitors and steroids (60%). Risk factors for mortality included older age; dyspnea; severe disease; obesity; allograft dysfunction before COVID-19 infection; acute kidney injury; higher levels of inflammatory markers including C-reactive protein, interleukin-6 level, and procalcitonin; chest X-ray abnormality, and intensive care unit/ventilator requirements. Overall patient mortality was 11.6% (29 of 250), 14.5% (29 of 200) in hospitalized patients, 47% (25 of 53) in intensive care unit patients, and 96.7% (29 of 30) in patients requiring ventilation. KTRs with mild COVID-19 symptoms (n = 50) were managed as outpatients to optimize the utilization of scarce resources during the COVID-19 pandemic. CONCLUSIONS Mortality rates in COVID-19-positive KTR appear to be higher than those in nonimmunosuppressed patients, and high mortality was noted among those requiring intensive care and those on ventilator.
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Affiliation(s)
- Vivek B. Kute
- Department of Nephrology, Institute of Kidney Diseases and Research Center, Dr. HL Trivedi Institute of Transplantation Sciences (IKDRC-ITS), Ahmedabad, Gujrat, India
| | - Anil K. Bhalla
- Department of Nephrology, Sir Ganga Ram Hospital, New Delhi, Delhi, India
| | - Sandeep Guleria
- Department of Transplantation Surgery, Indraprastha Apollo Hospital, New Delhi, Delhi, India
| | - Deepak S. Ray
- Department of Nephrology, Rabindranath Tagore International Institute of Cardiac Sciences, Kolkata, West Bengal, India
| | - Madan M. Bahadur
- Department of Nephrology, Jaslok Hospital and Research Centre, Mumbai, Maharashtra, India
| | - Ashay Shingare
- Department of Nephrology, Jaslok Hospital and Research Centre, Mumbai, Maharashtra, India
| | - Umapati Hegde
- Department of Nephrology, Muljibhai Patel Urological Hospital, Nadiad, Gujarat, India
| | - Sishir Gang
- Department of Nephrology, Muljibhai Patel Urological Hospital, Nadiad, Gujarat, India
| | - Sreebhushan Raju
- Department of Nephrology, Nizam’s Institute of Medical Sciences, Hyderabad, Telangana, India
| | - Himanshu V. Patel
- Department of Nephrology, Institute of Kidney Diseases and Research Center, Dr. HL Trivedi Institute of Transplantation Sciences (IKDRC-ITS), Ahmedabad, Gujrat, India
| | - Siddharth Jain
- Department of Nephrology, Kidney Care Clinic, Surat, Gujarat, India
| | - Suraj Godara
- Department of Nephrology, Mahatma Gandhi Medical College & Hospital, Jaipur, Rajasthan, India
| | - Pranjal Modi
- Department of Transplantation Surgery, IKDRC-ITS, Ahmedabad, Gujrat, India
| | - Manoj Gumber
- Department of Nephrology, Apollo Hospitals International Limited, Gandhi Nagar, Ahmedabad, Gujarat, India
| | - Divyesh P. Engineer
- Department of Nephrology, Institute of Kidney Diseases and Research Center, Dr. HL Trivedi Institute of Transplantation Sciences (IKDRC-ITS), Ahmedabad, Gujrat, India
| | - Sonal Dalal
- Department of Nephrology, Gujarat Kidney Foundation, Ahmedabad, Gujarat, India
| | - Prakash Darji
- Department of Nephrology, Zydus Hospitals, Ahmedabad, Gujarat, India
| | - Manish Balwani
- Department of Nephrology, Jawaharlal Nehru Medical College, Wardha, Maharashtra, India
| | - Ansy H. Patel
- BJ Medical College, Civil Hospital, Ahmedabad, Gujarat, India
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26
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Kute VB, Godara S, Guleria S, Ray DS, Aziz F, Hegde U, Sharma A, Nayak KS, Siddini V, Sarkar P, Thukral S, Mondal RRS, Goswami J, Patel HV, Abraham M A, Pathak V, Anandh U, Jha PK, Bavikar S, Bonu RS, Gulati S, B T AK, Yadav DK. Is it Safe to Be Transplanted From Living Donors Who Recovered From COVID-19? Experience of 31 Kidney Transplants in a Multicenter Cohort Study From India. Transplantation 2021; 105:842-850. [PMID: 33394992 PMCID: PMC7993648 DOI: 10.1097/tp.0000000000003609] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 12/18/2020] [Accepted: 12/19/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND There is lack of data on feasibility and safety of kidney transplants from living donors who recovered from COVID-19. METHODS Here, we present a retrospective cohort study of 31 kidney transplant recipients (KTR) from living donors who recovered from polymerase chain reaction confirmed COVID-19 across 19 transplant centers in India from July 3, 2020, to December 5, 2020. We detailed demographics, clinical manifestations, immunosuppression regimen, treatment, and outcomes. Donors with a previous diagnosis of COVID-19 were accepted after documenting 2 negative polymerase chain reaction tests with complete symptom resolution for at least 28 days and significant social distancing for 14 days before surgery. RESULTS COVID-19 clinical severity in donors ranged from completely asymptomatic (71%, n = 22) to mild infection (29%, n = 9). None progressed to moderate or severe stages of the disease in the entire clinical course of home treatment. Patient and graft survival was 100%, respectively, with acute cellular rejection being reported in 6.4% (n = 2) recipient. All recipients and donors were asymptomatic with normal creatinine at median follow-up of 44 days after surgery without any complications relating to surgery and COVID-19. CONCLUSIONS Our data support safety of proceeding with living donation for asymptomatic individuals with comprehensive donor, recipients screening before surgery, using a combination of clinical, radiologic, and laboratory criteria. It could provide new insights into the management of KTR from living donors who have recovered from COVID-19 in India. To the best of our knowledge, this remains the largest cohort of KTR from living donors who recovered from COVID-19.
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Affiliation(s)
- Vivek B Kute
- Department of Nephrology, Institute of Kidney Diseases and Research Center, Dr H.L. Trivedi Institute of Transplantation Sciences (IKDRC-ITS), Ahmedabad, India
| | - Suraj Godara
- Department of Nephrology, Mahatma Gandhi Medical College & Hospital, Jaipur, India
| | - Sandeep Guleria
- Department of Transplantation Surgery, Indraprastha Apollo Hospital, New Delhi, India
| | - Deepak S Ray
- Department of Nephrology, IQRAA International Hospital and Research Centre Calicut, Aster MIMS Hospital, Kozhikode, Kerala, India
| | - Feroz Aziz
- Department of Nephrology, Rabindranath Tagore International Institute of Cardiac Sciences, Kolkata, West Bengal, India
| | - Umapati Hegde
- Department of Nephrology, Muljibhai Patel Urological Hospital, Nadiad, Gujarat, India
| | - Ashish Sharma
- Department of Transplantation Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh (PGIMER), Chandigarh, India
| | - K S Nayak
- Department of Nephrology, Virinchi Hospitals, Hyderabad, Telangana, India
| | | | - Piyali Sarkar
- Department of Nephrology, Charnock Hospital, Kolkata, West Bengal, India
| | - Sharmila Thukral
- Department of Nephrology, Rabindranath Tagore International Institute of Cardiac Sciences, Kolkata, West Bengal, India
| | - Rabi Ranjan Sow Mondal
- Department of Nephrology, Rabindranath Tagore International Institute of Cardiac Sciences, Kolkata, West Bengal, India
| | | | - Himanshu V Patel
- Department of Nephrology, Institute of Kidney Diseases and Research Center, Dr H.L. Trivedi Institute of Transplantation Sciences (IKDRC-ITS), Ahmedabad, India
| | - Abi Abraham M
- Nephrology and Renal Transplant Services, VPS Lakeshore Hospital, Kochi, India
| | - Vivek Pathak
- Department of Nephrology, Kovai Medical Center and Hospital, Coimbatore, Tamil Nadu, India
| | - Urmila Anandh
- Institute of Nephrology, Yashoda Hospital, Secunderabad, India
| | - Pranaw Kumar Jha
- Department of Nephrology, Medanta Institute of Kidney and Urology, Medanta-The Medicity, Gurugram, Haryana, India
| | - Suhas Bavikar
- Department of Nephrology, MIT Hospital and Research Institute, Aurangabad, India
| | - Ravi Shankar Bonu
- Department of Nephrology, Manipal Hospital Whitefield, Bangalore, India
| | - Sanjeev Gulati
- Nephrology and Kidney Transplant, Fortis Group of Hospitals, New Delhi, India
| | - Anil Kumar B T
- Department of Nephrology, BGS Global Hospital, Bengaluru, Karnataka, India
| | - Dinesh Kumar Yadav
- Department of Nephrology, Medanta Institute of Kidney and Urology, Medanta-The Medicity, Gurugram, Haryana, India
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27
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Phadke VK, Scanlon N, Jordan SC, Rouphael NG. Immune Responses to SARS-CoV-2 in Solid Organ Transplant Recipients. CURRENT TRANSPLANTATION REPORTS 2021; 8:127-139. [PMID: 33688459 PMCID: PMC7931983 DOI: 10.1007/s40472-021-00322-5] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/21/2021] [Indexed: 12/15/2022]
Abstract
PURPOSE OF REVIEW Coronavirus disease 2019 (COVID-19) is caused by a complex interplay between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dynamics and host immune responses. Hosts with altered immunity, including solid organ transplant recipients, may be at increased risk of complications and death due to COVID-19. A synthesis of the available data on immune responses to SARS-CoV-2 infection is needed to inform therapeutic and preventative strategies in this special population. RECENT FINDINGS Few studies have directly compared immune responses to SARS-CoV-2 between transplant recipients and the general population. Like non-transplant patients, transplant recipients mount an exuberant inflammatory response following initial SARS-CoV2 infection, with IL-6 levels correlating with disease severity in some, but not all studies. Transplant recipients display anti-SARS-CoV-2 antibodies and activated B cells in a time frame and magnitude similar to non-transplant patients-limited data suggest these antibodies can be detected within 15 days of symptom onset and may be durable for several months. CD4+ and CD8+ T lymphopenia, a hallmark of COVID-19, is more profound in transplant recipients, but SARS-CoV-2-reactive T cells can be detected among patients with both mild and severe disease. SUMMARY The limited available data indicate that immune responses to SARS-CoV-2 are similar between transplant recipients and the general population, but no studies have been sufficiently comprehensive to understand nuances between organ types or level of immunosuppression to meaningfully inform individualized therapeutic decisions. The ongoing pandemic provides an opportunity to generate higher-quality data to support rational treatment and vaccination strategies in this population.
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Affiliation(s)
- Varun K. Phadke
- Emory University Vaccine and Treatment Evaluation Unit (VTEU), Division of Infectious Diseases, The Hope Clinic of the Emory Vaccine Center, 500 Irvin Court, Suite 200, Decatur, GA 30030 USA
- The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Emory University, Decatur, GA USA
| | - Nicholas Scanlon
- The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Emory University, Decatur, GA USA
| | - Stanley C. Jordan
- Department of Medicine, Division of Nephrology, Transplant Immunology Laboratory, Transplant Immunotherapy Program, Cedars-Sinai Medical Center, Los Angeles, CA USA
| | - Nadine G. Rouphael
- The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Emory University, Decatur, GA USA
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Abstract
Nierentransplantierte Patienten stellen während der COVID-19(„coronavirus disease 2019“)-Pandemie eine spezielle Risikogruppe dar. Dies liegt sowohl an den häufig bestehenden Komorbiditäten als auch an der therapeutischen Immunsuppression. Letzterer kommt auch angesichts der stark zu Morbidität und Mortalität beitragenden Hyperinflammation eine komplexe Rolle zu. Bislang publizierte Fallserien zeigen eine hohe Hospitalisierungsrate und eine Mortalität zwischen 13 und 23 % in dieser Population. Die klinische Symptomatik sowie bislang etablierte Risikofaktoren scheinen jenen der Allgemeinbevölkerung zu ähneln. Eine heikle Frage in der Behandlung von an COVID-19 erkrankten Nierentransplantierten ist der Umgang mit der Immunsuppression, welche gemäß aktuellen Empfehlungen stufenweise und in Abhängigkeit vom klinischen Verlauf reduziert werden sollte. Auf der Suche nach wirksamen Therapien gegen SARS-CoV‑2 („severe acute respiratory syndrome coronavirus 2“) wurden zahlreiche in anderen Indikationen etablierte antivirale und antiinflammatorische Substanzen untersucht, wobei bislang nur für die Therapie mit Dexamethason bei Patienten mit Sauerstoffbedarf eine überzeugende Evidenz zu bestehen scheint. Zahllose Studien zu teils auch neuentwickelten Therapien laufen derzeit.
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Affiliation(s)
- Florina Regele
- Univ. Klinik für Innere Medizin III, Klinische Abteilung für Nephrologie und Dialyse, Medizinische Universität Wien, Währinger Gürtel 18–20, 1090 Wien, Österreich
| | - Rainer Oberbauer
- Univ. Klinik für Innere Medizin III, Klinische Abteilung für Nephrologie und Dialyse, Medizinische Universität Wien, Währinger Gürtel 18–20, 1090 Wien, Österreich
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