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Metscher E, Meziyerh S, Arends EJ, Teng YKO, de Vries APJ, Swen JJ, Moes DJAR. Dried blood spot LC-MS/MS quantification of voclosporin in renal transplant recipients using volumetric dried blood spot sampling. J Pharm Biomed Anal 2025; 255:116647. [PMID: 39729691 DOI: 10.1016/j.jpba.2024.116647] [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: 09/04/2024] [Revised: 12/18/2024] [Accepted: 12/19/2024] [Indexed: 12/29/2024]
Abstract
Voclosporin is a potent immunosuppressive agent currently approved for treating active lupus nephritis. Based on its potential antiviral activity, it has also been investigated as immunosuppressive agent in an investigator-initiated study in SARS-CoV2 positive kidney transplant recipients. As with many immunosuppressive agents, optimizing dosing regimens to achieve therapeutic efficacy while minimizing toxicity remains a critical challenge in clinical practice. To prevent organ rejection as well as infections, the prescribed immunosuppression needs to be well balanced. Dried blood spot (DBS) sampling has enabled development of remote voclosporin therapeutic drug monitoring. Here, we report on the development and analytical validation of a liquid chromatography tandem mass spectrometry (LC-MS/MS) assay for quantification of voclosporin in dried blood spots. Method development was based on previously developed assays for the quantification of tacrolimus, everolimus, sirolimus, cyclosporin, mycophenolic acid, creatinine and iohexol in DBS and voclosporin in whole blood using LC-MS/MS. HemaXis™ volumetric blood spot devices were used for sample collection. The sample purification was based on the extraction of voclosporin from the DBS samples. Stable isotopically labeled voclosporin-D4 was used as an internal standard prior to sample purification. Bland Altman and Passing bablok analysis were performed for cross validation between whole blood and DBS samples. The method was successfully validated following the current ICH M10 guidelines. The dynamic range for the analyte was 10-600 µg/L with an excellent mean coefficient of correlation of 0.9978. The within run and between run precision and accuracy were both within the acceptance criteria. The cross-validation against the whole blood method shows that the quantified voclosporin results are promising. This developed dried blood spot LC-MS/MS method was successfully validated and provides an easy, efficient workflow for therapeutic drug monitoring in kidney transplant patients or remote pharmacokinetic studies in lupus nephritis patients treated with voclosporin.
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Affiliation(s)
- E Metscher
- Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, the Netherlands; Leiden Network for Personalized Medicine, Leiden, the Netherlands
| | - S Meziyerh
- Department of Internal Medicine, Division of Nephrology, Leiden University Medical Center, Leiden, the Netherlands
| | - E J Arends
- Department of Internal Medicine, Division of Nephrology, Leiden University Medical Center, Leiden, the Netherlands
| | - Y K O Teng
- Department of Internal Medicine, Division of Nephrology, Leiden University Medical Center, Leiden, the Netherlands
| | - A P J de Vries
- Department of Internal Medicine, Division of Nephrology, Leiden University Medical Center, Leiden, the Netherlands; Leiden Transplant Center, Leiden, the Netherlands
| | - J J Swen
- Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, the Netherlands; Leiden Network for Personalized Medicine, Leiden, the Netherlands
| | - D J A R Moes
- Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, the Netherlands; Leiden Network for Personalized Medicine, Leiden, the Netherlands.
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Abu Jawdeh BG, Vikram HR. Coronavirus Disease 2019 in Kidney Transplantation - A 2024 Update. ADVANCES IN KIDNEY DISEASE AND HEALTH 2024; 31:458-465. [PMID: 39232616 DOI: 10.1053/j.akdh.2024.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 02/29/2024] [Accepted: 03/05/2024] [Indexed: 09/06/2024]
Abstract
The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 has led to the death of about 7 million people worldwide. When infected, older individuals and those with diabetes, hypertension, cardiovascular disease, and compromised immune system are at higher risk for unfavorable outcomes. These comorbidities are prevalent in kidney transplant candidates and recipients making them inherently vulnerable to severe acute respiratory syndrome coronavirus 2 infection, hence, the significant burden the pandemic has exerted on kidney transplant programs. With the swift discovery and wide-scale availability of vaccines and therapeutics against severe acute respiratory syndrome coronavirus 2, the pandemic is currently behind us allowing transplant programs to relieve their restrictions and resume normal pre-COVID-19 operations. In the aftermath of the pandemic, we discuss the implications for immunosuppression and vaccination, COVID-19-induced kidney injury phenotypes and long COVID-19 symptoms. We also discuss some of the operational aspects the pandemic brought about - mainly the utilization of telemedicine - that are now here to stay.
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ElNahid MS, Issac MSM, Sadek KM. Outcome of COVID-19 in Egyptian living-donor kidney transplant recipients and relation to maintenance immunosuppressive drugs: a pilot study. Sci Rep 2023; 13:19002. [PMID: 37923735 PMCID: PMC10624883 DOI: 10.1038/s41598-023-45750-8] [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: 12/15/2022] [Accepted: 10/23/2023] [Indexed: 11/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) in kidney transplant recipients is a subject of much debate and became of interest to nephrologists amidst the pandemic. The main concerns are the influence of the chronic use of immunosuppressive drugs, the viral-related risk of acute rejection, and the long-term outcome of allograft function. This single-center prospective study included kidney transplant recipients with COVID-19 infection. Patients were maintained on immunosuppressive regimens. The severity of disease was defined as oxygen saturation < 94%, the need for hospitalization and/or hemodialysis, the occurrence of acute kidney injury (AKI), and mortality. Seventeen patients (54.8%) required hospital admission, four patients needed hemodialysis (12.9%), twelve patients (38.7%) had AKI, and three patients died (9.7%). Oxygen saturation < 94% showed a positive correlation with the presence of diabetes (p value 0.031) and a negative correlation with the maintenance steroid dose (p value 0.046). A negative correlation existed between the need for hemodialysis and average Cyclosporin level (p value 0.019) and between the need for hospitalization and average Tacrolimus level (p value 0.046). Severity of disease was associated with the presence of lymphopenia (p value 0.042), the cumulative steroid dose (p value 0.001), increased serum levels of LDH (p value 0.010), Ferritin (p value 0.020), AST (p value 0.047), and ALT (p value 0.006) and D-dimer levels more than 0.5 mg/L (p value 0.038). This study highlighted that the immunocompromised state of renal transplant recipients may not be regarded as a disadvantage in the setting of COVID-19 infection. Studies on a larger scale are needed to validate these results.
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Affiliation(s)
- Maggie Said ElNahid
- Department of Internal Medicine and Nephrology, Faculty of Medicine, Cairo University, Cairo, Egypt.
| | | | - Khaled Marzouk Sadek
- Department of Internal Medicine and Nephrology, Faculty of Medicine, Cairo University, Cairo, Egypt
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Lemaitre F, Budde K, Van Gelder T, Bergan S, Lawson R, Noceti O, Venkataramanan R, Elens L, Moes DJAR, Hesselink DA, Pawinski T, Johnson-Davis KL, De Winter BCM, Pattanaik S, Brunet M, Masuda S, Langman LJ. Therapeutic Drug Monitoring and Dosage Adjustments of Immunosuppressive Drugs When Combined With Nirmatrelvir/Ritonavir in Patients With COVID-19. Ther Drug Monit 2023; 45:191-199. [PMID: 35944126 DOI: 10.1097/ftd.0000000000001014] [Citation(s) in RCA: 39] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 07/20/2022] [Indexed: 11/25/2022]
Abstract
ABSTRACT Nirmatrelvir/ritonavir (Paxlovid) consists of a peptidomimetic inhibitor (nirmatrelvir) of the SARS-CoV-2 main protease and a pharmacokinetic enhancer (ritonavir). It is approved for the treatment of mild-to-moderate COVID-19. This combination of nirmatrelvir and ritonavir can mediate significant and complex drug-drug interactions (DDIs), primarily due to the ritonavir component. Indeed, ritonavir inhibits the metabolism of nirmatrelvir through cytochrome P450 3A (CYP3A) leading to higher plasma concentrations and a longer half-life of nirmatrelvir. Coadministration of nirmatrelvir/ritonavir with immunosuppressive drugs (ISDs) is particularly challenging given the major involvement of CYP3A in the metabolism of most of these drugs and their narrow therapeutic ranges. Exposure of ISDs will be drastically increased through the potent ritonavir-mediated inhibition of CYP3A, resulting in an increased risk of adverse drug reactions. Although a decrease in the dosage of ISDs can prevent toxicity, an inappropriate dosage regimen may also result in insufficient exposure and a risk of rejection. Here, we provide some general recommendations for therapeutic drug monitoring of ISDs and dosing recommendations when coadministered with nirmatrelvir/ritonavir. Particularly, tacrolimus should be discontinued, or patients should be given a microdose on day 1, whereas cyclosporine dosage should be reduced to 20% of the initial dosage during the antiviral treatment. Dosages of mammalian target of rapamycin inhibitors (m-TORis) should also be adjusted while dosages of mycophenolic acid and corticosteroids are expected to be less impacted.
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Affiliation(s)
- Florian Lemaitre
- Department of Pharmacology, Univ Rennes, CHU Rennes, Inserm, EHESP, IRSET-UMR S 1085, Rennes, France
- INSERM, Centre d'Investigation Clinique 1414, Rennes, France
| | - Klemens Budde
- Department of Nephrology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Teun Van Gelder
- Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, the Netherlands
| | - Stein Bergan
- Department of Pharmacology, Oslo University Hospital and Department of Pharmacy, University of Oslo, Norway
| | - Roland Lawson
- University of Limoges, Inserm U1248, Pharmacology & Transplantation, Limoges, France
| | - Ofelia Noceti
- National Center for Liver Transplantation and Liver Diseases, Army Forces Hospital, Montevideo, Uruguay
| | - Raman Venkataramanan
- Department of Pharmaceutical Sciences, School of Pharmacy and Department of Pathology, Starzl Transplantation Institute, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Laure Elens
- Integrated Pharmacometrics, Pharmacogenetic and Pharmacokinetics Research Group (PMGK), Louvain Drug for Research Institute (LDRI), Catholic University of Louvain (UCLouvain), Brussels, Belgium
| | - Dirk Jan A R Moes
- Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, the Netherlands
| | - Dennis A Hesselink
- Erasmus MC Transplant Institute, University Medical Center, Rotterdam, the Netherlands
| | - Tomasz Pawinski
- Department of Drug Chemistry, Faculty of Pharmacy, Medical University of Warsaw, Warsaw, Poland
| | | | - Brenda C M De Winter
- Department of Hospital Pharmacy, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Smita Pattanaik
- Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh, INDIA
| | - Mercè Brunet
- Pharmacology and Toxicology Laboratory, Biochemistry and Molecular Genetics Department, Biomedical Diagnostic Center, Hospital Clinic of Barcelona, University of Barcelona, IDIBAPS, CIBERehd, Spain
| | - Satohiro Masuda
- Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Japan; and
| | - Loralie J Langman
- Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
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Meziyerh S, Bouwmans P, van Gelder T, van der Helm D, Messchendorp L, van der Boog PJM, de Fijter JW, Moes DJAR, de Vries APJ. Mycophenolic Acid Exposure Determines Antibody Formation Following SARS-CoV-2 Vaccination in Kidney Transplant Recipients: A Nested Cohort Study. Clin Pharmacol Ther 2023. [PMID: 36789469 DOI: 10.1002/cpt.2872] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 02/07/2023] [Indexed: 02/16/2023]
Abstract
Despite (repeated) boosting, kidney transplant recipients (KTRs) may remain at increased risk of severe COVID-19 since a substantial number of individuals remain seronegative or with low antibody titers. In particular, mycophenolic acid use has been shown to affect antibody formation negatively and may be an important modifiable risk factor. We investigated the exposure-response relationship between mycophenolic acid 12-hour area under the curve (AUC0-12h ) exposure and seroconversion including antibody titers after vaccination using mRNA-1273 SARS-CoV-2 vaccine (Moderna) in 316 KTRs from our center that participated in the national Dutch renal patients COVID-19 vaccination - long term efficacy and safety of SARS-CoV-2 vaccination in kidney disease patients vaccination study. After two vaccination doses, 162 (51%) KTRs seroconverted. KTRs treated with mycophenolic acid showed less seroconversion and lower antibody titers compared with KTRs without mycophenolic acid (44% vs. 77%, and 36 binding antibody units (BAU)/mL vs. 340 BAU/mL; P < 0.001). The mean mycophenolic acid AUC0-12h exposure was significantly lower in KTRs who seroconverted compared with KTRs who did not (39 vs. 29 mg⋅h/L; P < 0.001). High mycophenolic acid exposure (±90 mg⋅h/L) and no exposure to mycophenolic acid resulted in a seroconversion rate ranging from 10% to 80%. Every 10 mg⋅h/L increase in mycophenolic acid AUC0-12h gave an adjusted odds ratio for seroconversion of 0.87 (95% confidence interval (CI), 0.79-0.97; P = 0.010) and 0.89 (95% CI, 0.85-0.93; P < 0.001) for KTRs on dual and triple maintenance immunosuppressive therapy, respectively. Higher mycophenolic acid AUC0-12h correlated with lower antibody titers (R = 0.44, P < 0.001). This study demonstrates the exposure-response relationship between gold standard mycophenolic acid exposure and antibody formation to support interventional studies investigating mycophenolic acid adjustment to improve antibody formation after further boosting.
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Affiliation(s)
- Soufian Meziyerh
- Department of Medicine, Division of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.,Leiden University Medical Center Transplant Center, Leiden University Medical Center, Leiden, The Netherlands
| | - Pim Bouwmans
- Department of Internal Medicine, Division of Nephrology, Maastricht University Medical Center, Maastricht, The Netherlands.,Cardiovascular Research Institute Maastricht School for Cardiovascular Disease, University of Maastricht, Maastricht, The Netherlands
| | - Teun van Gelder
- Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands
| | - Danny van der Helm
- Leiden University Medical Center Transplant Center, Leiden University Medical Center, Leiden, The Netherlands
| | - Lianne Messchendorp
- Department of Nephrology, University Medical Center Groningen, Groningen, The Netherlands
| | - Paul J M van der Boog
- Department of Medicine, Division of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.,Leiden University Medical Center Transplant Center, Leiden University Medical Center, Leiden, The Netherlands
| | - Johan W de Fijter
- Department of Medicine, Division of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.,Leiden University Medical Center Transplant Center, Leiden University Medical Center, Leiden, The Netherlands
| | - Dirk Jan A R Moes
- Cardiovascular Research Institute Maastricht School for Cardiovascular Disease, University of Maastricht, Maastricht, The Netherlands
| | - Aiko P J de Vries
- Department of Medicine, Division of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.,Leiden University Medical Center Transplant Center, Leiden University Medical Center, Leiden, The Netherlands
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6
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Gonzalez-García R, Roma JR, Rodríguez-García M, Arranz N, Ambrosioni J, Bodro M, Castel MÁ, Cofan F, Crespo G, Diekmann F, Farrero M, Forner A, LLigoña A, Marcos MÁ, Moreno A, Ruiz P, Soy D, Brunet M, Miró JM, Tuset M. Drug-drug interactions of ritonavir-boosted SARS-CoV-2 protease inhibitors in solid organ transplant recipients: experience from the initial use of lopinavir-ritonavir. Clin Microbiol Infect 2023; 29:655.e1-655.e4. [PMID: 36641051 PMCID: PMC9831976 DOI: 10.1016/j.cmi.2023.01.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 01/02/2023] [Accepted: 01/03/2023] [Indexed: 01/13/2023]
Abstract
OBJECTIVES To review the drug-drug interactions between tacrolimus and lopinavir/ritonavir in 23 patients who received solid organ transplant during the first wave of COVID-19 and to determine the efficacy as well as safety of prednisone monotherapy. METHODS Observational study performed between March and June 2020 in solid organ transplant recipients admitted with an established diagnosis of SARS-CoV-2 infection who received lopinavir/ritonavir (≥2 doses). Once lopinavir/ritonavir therapy was initiated, calcineurin inhibitor treatment was temporarily switched to prednisone monotherapy (15-20 mg/d) to avoid drug-drug interactions and toxicity. After lopinavir/ritonavir treatment completion, immunosuppressive treatment was restarted with reduced doses of prednisone-tacrolimus (target minimum blood concentration -C0- approximately 5 ng/mL). Patients were observed for 3 months to confirm the absence of rejection. RESULTS The median time from discontinuation of tacrolimus to initiation of lopinavir/ritonavir was 14 hours (interquartile range [IQR], 12-15) and from discontinuation of lopinavir/ritonavir to resumption of tacrolimus 58 hours (IQR, 47-81). The duration of lopinavir/ritonavir treatment was 7 days (IQR, 5-7). Nine of the 21 (42.8%) patients on tacrolimus treatment had C0 above the cutoff point after lopinavir/ritonavir initiation, despite having been substituted with prednisone before lopinavir/ritonavir initiation. Three patients had very high concentrations (>40 ng/mL) and developed toxicity. No episodes of acute rejection were diagnosed. DISCUSSION We did not observe toxicity in patients for whom tacrolimus was discontinued 24 hours before starting lopinavir/ritonavir and reintroduced at half dose 48 to 72 hours after lopinavir/ritonavir discontinuation. Prednisone monotherapy during lopinavir/ritonavir therapy was safe with no episodes of acute rejection. Experience with lopinavir/ritonavir may be applicable to the use of nirmatrelvir/ritonavir, but larger multicentre studies are needed to confirm these findings.
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Affiliation(s)
- Ruben Gonzalez-García
- Pharmacy Service, Division of Medicines, Hospital Clínic Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Joan-Ramon Roma
- Pharmacy Service, Division of Medicines, Hospital Clínic Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - María Rodríguez-García
- Pharmacology and Toxicology Laboratory, Biochemistry and Molecular Genetics Department, Biomedical Diagnostic Center, Hospital Clinic Barcelona, Barcelona, Spain
| | - Natalia Arranz
- Pharmacy Service, Division of Medicines, Hospital Clínic Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Juan Ambrosioni
- Infectious Diseases Service, Hospital Clínic Barcelona - IDIBAPS, University of Barcelona, Barcelona, Spain,Centro de Investigación Biomédica en Red. Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain
| | - Marta Bodro
- Infectious Diseases Service, Hospital Clínic Barcelona - IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Maria-Ángeles Castel
- Heart Failure and Heart Transplant Unit, Cardiology Department, Cardiovascular Institute, Hospital Clinic Barcelona - IDIBAPS, Barcelona, Spain
| | - Federic Cofan
- Department of Nephrology and kidney Transplantation, Hospital Clínic Barcelona - IDIBAPS, Barcelona, Spain
| | - Gonzalo Crespo
- Liver Transplant Section, Liver Unit, Hospital Clínic Barcelona - IDIBAPS, University of Barcelona, Barcelona, Spain,Centro de Investigación Biomédica en Red. Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain
| | - Fritz Diekmann
- Department of Nephrology and kidney Transplantation, Hospital Clínic Barcelona - IDIBAPS, Barcelona, Spain
| | - Marta Farrero
- Heart Failure and Heart Transplant Unit, Cardiology Department, Cardiovascular Institute, Hospital Clinic Barcelona - IDIBAPS, Barcelona, Spain
| | - Alejandro Forner
- Barcelona Clinic Liver Cancer Group, Liver Unit, Hospital Clínic Barcelona - IDIBAPS, University of Barcelona, Centro de Investigación Biomédica en Red. Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Barcelona, Madrid, Spain
| | - Ana LLigoña
- Addictive Behavior Unit, Hospital Clínic Barcelona, Barcelona, Spain
| | - Maria Ángeles Marcos
- Microbiology Service (CDB), Hospital Clínic Barcelona, Centro de Investigación Biomédica en Red. Enfermedades Hepáticas y Digestivas, IDIBAPS, Instituto de Salud Global de Barcelona, University of Barcelona, Barcelona, Spain
| | - Asunción Moreno
- Infectious Diseases Service, Hospital Clínic Barcelona - IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Pablo Ruiz
- Liver Transplant Section, Liver Unit, Hospital Clínic Barcelona - IDIBAPS, University of Barcelona, Barcelona, Spain,Centro de Investigación Biomédica en Red. Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain
| | - Dolors Soy
- Pharmacy Service, Division of Medicines, Hospital Clínic Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Mercè Brunet
- Pharmacology and Toxicology Laboratory, Biochemistry and Molecular Genetics Department, Biomedical Diagnostic Center, Hospital Clinic Barcelona - IDIBAPS, Centro de Investigación Biomédica en Red. Enfermedades Hepáticas y Digestivas, Network Biomedical Research Center, Liver and Digestive Diseases, University of Barcelona, Barcelona, Spain
| | - Jose M. Miró
- Infectious Diseases Service, Hospital Clínic Barcelona - IDIBAPS, University of Barcelona, Barcelona, Spain,Centro de Investigación Biomédica en Red. Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain
| | - Montse Tuset
- Pharmacy Service, Division of Medicines, Hospital Clínic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
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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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8
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Clinically Relevant Interactions Between Ritonavir-Boosted Nirmatrelvir and Concomitant Antiseizure Medications: Implications for the Management of COVID-19 in Patients with Epilepsy. Clin Pharmacokinet 2022; 61:1219-1236. [PMID: 35895276 PMCID: PMC9325946 DOI: 10.1007/s40262-022-01152-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/26/2022] [Indexed: 01/06/2023]
Abstract
Ritonavir-boosted nirmatrelvir (RBN) has been authorized recently in several countries as an orally active anti-SARS-CoV-2 treatment for patients at high risk of progressing to severe COVID-19 disease. Nirmatrelvir is the active component against the SARS-CoV-2 virus, whereas ritonavir, a potent CYP3A inhibitor, is intended to boost the activity of nirmatrelvir by increasing its concentration in plasma to ensure persistence of antiviral concentrations during the 12-hour dosing interval. RBN is involved in many clinically important drug–drug interactions both as perpetrator and as victim, which can complicate its use in patients treated with antiseizure medications (ASMs). Interactions between RBN and ASMs are bidirectional. As perpetrator, RBN may increase the plasma concentration of a number of ASMs that are CYP3A4 substrates, possibly leading to toxicity. As victims, both nirmatrelvir and ritonavir are subject to metabolic induction by concomitant treatment with potent enzyme-inducing ASMs (carbamazepine, phenytoin, phenobarbital and primidone). According to US and European prescribing information, treatment with these ASMs is a contraindication to the use of RBN. Although remdesivir is a valuable alternative to RBN, it may not be readily accessible in some settings due to cost and/or need for intravenous administration. If remdesivir is not an appropriate option, either bebtelovimab or molnupiravir may be considered. However, evidence about the clinical efficacy of bebtelovimab is still limited, and molnupiravir, the only orally active alternative, is deemed to have appreciably lower efficacy than RBN and remdesivir.
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9
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Conti V, Sellitto C, Torsiello M, Manzo V, De Bellis E, Stefanelli B, Bertini N, Costantino M, Maci C, Raschi E, Sabbatino F, Corbi G, Pagliano P, Filippelli A. Identification of Drug Interaction Adverse Events in Patients With COVID-19: A Systematic Review. JAMA Netw Open 2022; 5:e227970. [PMID: 35438752 PMCID: PMC9020212 DOI: 10.1001/jamanetworkopen.2022.7970] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
IMPORTANCE During the COVID-19 pandemic, urgent clinical management of patients has mainly included drugs currently administered for other diseases, referred to as repositioned drugs. As a result, some of these drugs have proved to be not only ineffective but also harmful because of adverse events associated with drug-drug interactions (DDIs). OBJECTIVE To identify DDIs that led to adverse clinical outcomes and/or adverse drug reactions in patients with COVID-19 by systematically reviewing the literature and assessing the value of drug interaction checkers in identifying such events. EVIDENCE REVIEW After identification of the drugs used during the COVID-19 pandemic, the drug interaction checkers Drugs.com, COVID-19 Drug Interactions, LexiComp, Medscape, and WebMD were consulted to analyze theoretical DDI-associated adverse events in patients with COVID-19 from March 1, 2020, through February 28, 2022. A systematic literature review was performed by searching the databases PubMed, Scopus, and Cochrane for articles published from March 1, 2020, through February 28, 2022, to retrieve articles describing actual adverse events associated with DDIs. The drug interaction checkers were consulted again to evaluate their potential to assess such events. FINDINGS The DDIs identified in the reviewed articles involved 46 different drugs. In total, 575 DDIs for 58 drug pairs (305 associated with at least 1 adverse drug reaction) were reported. The drugs most involved in DDIs were lopinavir and ritonavir. Of the 6917 identified studies, 20 met the inclusion criteria. These studies, which enrolled 1297 patients overall, reported 115 DDI-related adverse events: 15 (26%) were identifiable by all tools analyzed, 29 (50%) were identifiable by at least 1 of them, and 14 (24%) remained nonidentifiable. CONCLUSIONS AND RELEVANCE The main finding of this systematic review is that the use of drug interaction checkers could have identified several DDI-associated adverse drug reactions, including severe and life-threatening events. Both the interactions between the drugs used to treat COVID-19 and between the COVID-19 drugs and those already used by the patients should be evaluated.
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Affiliation(s)
- Valeria Conti
- Department of Medicine, Surgery, and Dentistry, Scuola Medica Salernitana, University of Salerno, Baronissi, Italy
- Clinical Pharmacology Unit, San Giovanni di Dio e Ruggi d’Aragona University Hospital, Salerno, Italy
| | - Carmine Sellitto
- Department of Medicine, Surgery, and Dentistry, Scuola Medica Salernitana, University of Salerno, Baronissi, Italy
- Doctoral School, Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana,” University of Salerno, Baronissi, Italy
| | - Martina Torsiello
- Department of Medicine, Surgery, and Dentistry, Scuola Medica Salernitana, University of Salerno, Baronissi, Italy
- Clinical Pharmacology Unit, San Giovanni di Dio e Ruggi d’Aragona University Hospital, Salerno, Italy
| | - Valentina Manzo
- Department of Medicine, Surgery, and Dentistry, Scuola Medica Salernitana, University of Salerno, Baronissi, Italy
- Clinical Pharmacology Unit, San Giovanni di Dio e Ruggi d’Aragona University Hospital, Salerno, Italy
| | - Emanuela De Bellis
- Clinical Pharmacology Unit, San Giovanni di Dio e Ruggi d’Aragona University Hospital, Salerno, Italy
- Postgraduate Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana,” University of Salerno, Baronissi, Italy
| | - Berenice Stefanelli
- Clinical Pharmacology Unit, San Giovanni di Dio e Ruggi d’Aragona University Hospital, Salerno, Italy
- Postgraduate Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana,” University of Salerno, Baronissi, Italy
| | - Nicola Bertini
- Clinical Pharmacology Unit, San Giovanni di Dio e Ruggi d’Aragona University Hospital, Salerno, Italy
- Postgraduate Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana,” University of Salerno, Baronissi, Italy
| | - Maria Costantino
- Department of Medicine, Surgery, and Dentistry, Scuola Medica Salernitana, University of Salerno, Baronissi, Italy
| | - Chiara Maci
- Department of Medicine, Surgery, and Dentistry, Scuola Medica Salernitana, University of Salerno, Baronissi, Italy
| | - Emanuel Raschi
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Francesco Sabbatino
- Department of Medicine, Surgery, and Dentistry, Scuola Medica Salernitana, University of Salerno, Baronissi, Italy
- Oncology Unit, San Giovanni di Dio e Ruggi d’Aragona University Hospital, Salerno, Italy
| | - Graziamaria Corbi
- Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy
| | - Pasquale Pagliano
- Department of Medicine, Surgery, and Dentistry, Scuola Medica Salernitana, University of Salerno, Baronissi, Italy
- Infectious Diseases Unit, San Giovanni di Dio e Ruggi d’Aragona University Hospital, Salerno, Italy
| | - Amelia Filippelli
- Department of Medicine, Surgery, and Dentistry, Scuola Medica Salernitana, University of Salerno, Baronissi, Italy
- Clinical Pharmacology Unit, San Giovanni di Dio e Ruggi d’Aragona University Hospital, Salerno, Italy
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10
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Karastaneva A, Gasparella P, Tschauner S, Crazzolara R, Kropshofer G, Modl M, Pfleger A, Burmas A, Pocivalnik M, Ulreich R, Zenz W, Schwinger W, Beqo BP, Urban C, Haxhija EQ, Lackner H, Benesch M. Indications and Limitations of Sirolimus in the Treatment of Vascular Anomalies-Insights From a Retrospective Case Series. Front Pediatr 2022; 10:857436. [PMID: 35676905 PMCID: PMC9168223 DOI: 10.3389/fped.2022.857436] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Accepted: 04/07/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Despite recent developments, the role of sirolimus in the heterogeneous spectrum of vascular anomalies is yet to be defined, in terms of indication, dosage, and therapy duration, recognizing both its potential and limitations. METHODS We retrospectively analyzed 16 children with vascular anomalies treated with sirolimus in two pediatric centers between 2014 and 2020 [male: n = 7, the median age at diagnosis: 4.6 months (range, 0-281.4)]. In addition, repetitive volumetric analyses of the vascular anomalies were performed when possible (11 cases). RESULTS Ten patients were diagnosed with vascular malformations and 6 with vascular tumors. The mean therapy duration was 27.2 months (range, 3.5-65). The mean sirolimus level was 8.52 ng/ml (range, 5.38-12.88). All patients except one with central conducting lymphatic anomaly responded to sirolimus, with the most noticeable volume reduction in the first 4-6 months. Additional administration of vincristine was needed in five patients with kaposiform hemangioendothelioma and yielded a response, even in cases, refractory to sirolimus monotherapy. As a single agent, sirolimus led to impressive improvement in a patient with another vascular tumor-advanced epithelioid hemangioendothelioma. Complicated vascular malformations required long-term sirolimus therapy. Side effects of sirolimus included mucositis and laboratory abnormalities. No major infectious episodes were recorded. An infant with COVID-19, diagnosed while on sirolimus therapy, presented with a mild course. CONCLUSION In the current series, we reported limitations of sirolimus as monotherapy, addressing the need to redefine its indications, and explore combination regimens and multimodal treatment strategies. Tools for objective evaluation of response trends over time could serve as a basis for the establishment of future therapeutic algorithms.
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Affiliation(s)
- Anna Karastaneva
- Division of Pediatric Hematology and Oncology, Department of Pediatric and Adolescent Medicine, Medical University of Graz, Graz, Austria
| | - Paolo Gasparella
- Department of Pediatric and Adolescent Surgery, Medical University of Graz, Graz, Austria
| | | | - Roman Crazzolara
- Department of Pediatrics, Medical University of Innsbruck, Innsbruck, Austria
| | - Gabriele Kropshofer
- Department of Pediatrics, Medical University of Innsbruck, Innsbruck, Austria
| | - Manfred Modl
- Division of Pediatric Pulmonology and Allergology, Department of Pediatric and Adolescent Medicine, Medical University of Graz, Graz, Austria
| | - Andreas Pfleger
- Division of Pediatric Pulmonology and Allergology, Department of Pediatric and Adolescent Medicine, Medical University of Graz, Graz, Austria
| | - Ante Burmas
- Division of Pediatric Cardiology, Department of Pediatric and Adolescent Medicine, Medical University of Graz, Graz, Austria
| | - Mirjam Pocivalnik
- Pediatric Intensive Care Unit, Department of Pediatric and Adolescent Medicine, Medical University of Graz, Graz, Austria
| | - Raphael Ulreich
- Pediatric Intensive Care Unit, Department of Pediatric and Adolescent Medicine, Medical University of Graz, Graz, Austria
| | - Werner Zenz
- Division of General Pediatrics, Department of Pediatric and Adolescent Medicine, Medical University of Graz, Graz, Austria
| | - Wolfgang Schwinger
- Division of Pediatric Hematology and Oncology, Department of Pediatric and Adolescent Medicine, Medical University of Graz, Graz, Austria
| | - Besiana P Beqo
- Department of Pediatric and Adolescent Surgery, Medical University of Graz, Graz, Austria.,Global Clinical Scholars Research Training, Department of Postgraduate Medical Education, Harvard Medical School, Boston, MA, United States
| | - Christian Urban
- Division of Pediatric Hematology and Oncology, Department of Pediatric and Adolescent Medicine, Medical University of Graz, Graz, Austria
| | - Emir Q Haxhija
- Department of Pediatric and Adolescent Surgery, Medical University of Graz, Graz, Austria
| | - Herwig Lackner
- Division of Pediatric Hematology and Oncology, Department of Pediatric and Adolescent Medicine, Medical University of Graz, Graz, Austria
| | - Martin Benesch
- Division of Pediatric Hematology and Oncology, Department of Pediatric and Adolescent Medicine, Medical University of Graz, Graz, Austria
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11
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Sheikhalipour Z, Faghihdinevari M, Salehi-Pourmehr H, Khameneh M, Vahedi L. Covid-19 in kidney transplant recipients with immunosuppressive therapy. CASPIAN JOURNAL OF INTERNAL MEDICINE 2022; 13:161-172. [PMID: 35872680 PMCID: PMC9272967 DOI: 10.22088/cjim.12.4.509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/01/2020] [Revised: 12/15/2020] [Accepted: 12/30/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Since the outbreak of COVID-19, various treatments have been frequently reported for patients infected with this virus, especially in transplant patients/recipients. Objective: Investigating of kidney transplant patients under immunosuppressive therapy infected with COVID-19 can pave the way to understanding, handling, and treatment of COVID-19. METHODS We had a brief review of the literature on immunosuppressive therapy in kidney transplants infected with COVID-19. This was based on the PubMed Database with keywords "kidney, transplant, COVID-19, and immunosuppress" after hospitalization of kidney transplantation infected with COVID-19. He had already been recorded in the Organ Transplant Registry (ID≠ 64510) of Tabriz University of Medical Sciences /Iran. RESULTS We reported the clinical course of a 45-year-old man with a history of kidney transplantation and immunotherapy who was infected with COVID-19 with respiratory infections and positive RT-PCR (Real-time polymerase chain reaction). He was treated with hydroxychloroquine, Kaletra, CellCept, and prednisolone for 5 days, and finally discharged from the hospital. In addition, reviewing of 47 papers with 851 samples showed that immunosuppressant medications alone could be a therapeutic choice in kidney transplants infected with COVID-19 with careful management. CONCLUSION Patients with organ transplantation infected with COVID-19 may show different clinical signs, clinical course, and prognosis due to underlying diseases and the use of immunosuppressant medications. It might be best to continue taking the immunosuppressant medications but modify them based on the patients' conditions such as clinical symptoms, laboratory results, paraclinical examinations.
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Affiliation(s)
- Zahra Sheikhalipour
- Medical and Surgical Department, Nursing and Midwifery School, Organ Transplant Registry, Tabriz University of Medical Sciences, Iran
| | - Masood Faghihdinevari
- Liver and Gastrointestinal Diseases Research Center, Organ Transplant Registry, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hanieh Salehi-Pourmehr
- Research Center for Evidence-Based Medicine, Iranian EBM Centre: A Joanna Briggs Institute (JBI) Center of Excellence, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Maryam Khameneh
- Student Research Committee, Islamic Azad University of Tabriz, Tabriz, Iran
| | - Leila Vahedi
- Liver and Gastrointestinal Diseases Research Center, Organ Transplant Registry, Tabriz University of Medical Sciences, Tabriz, Iran,Correspondence: Leila Vahedi, Liver and Gastrointestinal Diseases Research Center, Organ Transplant Registry, Tabriz University of Medical Sciences, Tabriz, Iran. E-mail: , Tel: 0098 4133351688, Fax: 0098 4133373741
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12
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Daoud A, Alqassieh A, Alkhader D, Posadas Salas MA, Rao V, Fülöp T, Soliman KM. Immunosuppression in kidney transplant recipients with COVID-19 infection - where do we stand and where are we heading? Ren Fail 2021; 43:273-280. [PMID: 33491531 PMCID: PMC7850379 DOI: 10.1080/0886022x.2021.1876730] [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: 11/30/2020] [Revised: 01/02/2021] [Accepted: 01/10/2021] [Indexed: 12/15/2022] Open
Abstract
The appropriate immunosuppressive regimen in kidney transplant recipients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2/COVID-19) infection remains unclear. The impact of direct virus injury complicated by dysregulated hyperimmune response with overwhelming release of various cytokines in COVID-19 infected subjects contributes to the complexity of management. The largest concern of the practicing clinicians at current time is how to tailor maintenance immune-modulating therapy during active viral infection and the efficacy of the soon-to-be upcoming immunization for COVID-19. This targeted review aims to cover most of the current evidence on the effect of key maintenance immunosuppressive agents in COVID-19 infection and proposes a line of management to specific scenarios on this very rapidly evolving subject.
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Affiliation(s)
- Ahmed Daoud
- Nephrology Unit, Internal Medicine Department, Kasr Alainy School of Medicine, Cairo University, Cairo, Egypt
| | - Ahmad Alqassieh
- Department of Surgery, Medical University of South Carolina, Charleston, SC, USA
| | - Duaa Alkhader
- Department of Surgery, Medical University of South Carolina, Charleston, SC, USA
| | - Maria Aurora Posadas Salas
- Department of Surgery, Medical University of South Carolina, Charleston, SC, USA
- Department of Medicine, Division of Nephrology, Medical University of South Carolina, Charleston, SC, USA
| | - Vinaya Rao
- Department of Surgery, Medical University of South Carolina, Charleston, SC, USA
- Department of Medicine, Division of Nephrology, Medical University of South Carolina, Charleston, SC, USA
| | - Tibor Fülöp
- Department of Medicine, Division of Nephrology, Medical University of South Carolina, Charleston, SC, USA
- Medicine Service, Ralph H. Johnson VA Medical Center, Charleston, SC, USA
| | - Karim M. Soliman
- Department of Surgery, Medical University of South Carolina, Charleston, SC, USA
- Department of Medicine, Division of Nephrology, Medical University of South Carolina, Charleston, SC, USA
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13
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Sagnelli C, Sica A, Gallo M, Peluso G, Varlese F, D'Alessandro V, Ciccozzi M, Crocetto F, Garofalo C, Fiorelli A, Iannuzzo G, Reginelli A, Schonauer F, Santangelo M, Sagnelli E, Creta M, Calogero A. Renal involvement in COVID-19: focus on kidney transplant sector. Infection 2021; 49:1265-1275. [PMID: 34611792 PMCID: PMC8491762 DOI: 10.1007/s15010-021-01706-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 09/22/2021] [Indexed: 01/08/2023]
Abstract
INTRODUCTION Kidney transplant recipients and patients on the waiting list for kidney transplant who acquire SARS-CoV-2 infection are at serious risk of developing severe COVID-19, with an increased risk of mortality for the their immunosuppressive state; other risk factors for mortality have been identified in some comorbidities such as obesity, diabetes, asthma and chronic lung disease. MATERIALS AND METHODS The COVID-19 pandemic has led to a sharp reduction in kidney transplants in most countries, mainly due to the concern of patients on the waiting list for their potential increased susceptibility to acquire SARS-CoV-2 infection in healthcare facilities and for the difficulties of transplant centers to ensure full activity as hospitals have had to focus most of their attention on COVID-19 patients. Indeed, while the infection curve continued its exponential rise, there was a vertical decline in kidney donation/transplant activity. CONCLUSION This review article focuses on the damage induced by SARS-CoV-2 infection on kidney and on the adverse effect of this pandemic on the entire kidney transplant sector.
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Affiliation(s)
- Caterina Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania "Luigi Vanvitelli", Largo Madonna delle Grazie n. 1, 80138, Naples, Italy
| | - Antonello Sica
- Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80131, Naples, Italy
| | - Monica Gallo
- Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131, Naples, Italy
| | - Gaia Peluso
- Department of Advanced Biomedical Sciences, University of Naples Federico II, via Pansini, 5, 80131, Naples, Italy
| | - Filippo Varlese
- Department of Advanced Biomedical Sciences, University of Naples Federico II, via Pansini, 5, 80131, Naples, Italy
| | - Vincenzo D'Alessandro
- UOSD Centro Trapianti di rene e Chirurgia del Retroperitoneo, AOU-University of Naples Federico II, 80131, Naples, Italy
| | - Massimo Ciccozzi
- Unit of Medical Statistics and Molecular Epidemiology, University Campus Bio-Medico of Rome, 80128, Rome, Italy
| | - Felice Crocetto
- Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples "Federico II", 80131, Naples, Italy
| | - Carlo Garofalo
- Division of Nephrology, University of Campania "Luigi Vanvitelli", 80137, Naples, Italy
| | - Alfonso Fiorelli
- Department of Thoracic Surgery, University of Campania "Luigi Vanvitelli", 80137, Naples, Italy
| | - Gabriella Iannuzzo
- Department of Clinical Medicine and Surgery, Federico II University Naples, Naples, Italy
| | - Alfonso Reginelli
- Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80131, Naples, Italy
| | - Fabrizo Schonauer
- Division of Plastic, Reconstructive and Aesthetic Surgery, University of Naples Federico II, 80131, Naples, Italy
| | - Michele Santangelo
- Department of Advanced Biomedical Sciences, University of Naples Federico II, via Pansini, 5, 80131, Naples, Italy
| | - Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania "Luigi Vanvitelli", Largo Madonna delle Grazie n. 1, 80138, Naples, Italy.
| | - Massimiliano Creta
- Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples "Federico II", 80131, Naples, Italy
| | - Armando Calogero
- Department of Advanced Biomedical Sciences, University of Naples Federico II, via Pansini, 5, 80131, Naples, Italy
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14
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Dedinská I, Skálová P, Graňák K, Vnučák M, Baltesová T, Žilinská Z, Jeseňák M. The Role of HLA Antigens and Steroid Dose on the Course of COVID-19 of Patients After Kidney Transplantation. Front Med (Lausanne) 2021; 8:730156. [PMID: 34790673 PMCID: PMC8591240 DOI: 10.3389/fmed.2021.730156] [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: 06/24/2021] [Accepted: 09/17/2021] [Indexed: 12/12/2022] Open
Abstract
Background: Kidney transplant recipients appear to be at higher risk for critical COVID-19. Our analysis aimed to identify the possible risk factors for a severe course of the COVID-19 disease and to determine the influence of selected human leukocyte antigens (HLAs) on the course of the disease. Methods: This is a retrospective, multicenter analysis that included patients that were confirmed to be severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) positive after kidney transplantation (KT). The group of patients was divided into two subgroups according to the course of the infection, as follows: non-hospitalized and hospitalized. Results: A total of 186 patients (men, 69.4%) with confirmed SARS-CoV-2 positivity were included in the group. The following independent risk factors for the outcome of hospitalization were identified: the age at the time of infection [odds ratio (OR) = 1.19, P < 0.0001], a body mass index (BMI) >29.9 kg/m2 (OR = 7.21, P < 0.0001), <7.5-mg prednisone dose/day (OR = 2.29, P = 0.0008), and HLA-DQ2 with a protective nature (OR = 0.05, P = 0.0034). Conclusions: Higher doses of corticosteroids (>7.5 mg/kg) in standard immunosuppressive regimes and HLA-DQ2 appear to be protective factors in our analysis.
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Affiliation(s)
- Ivana Dedinská
- Jessenius Faculty of Medicine, Transplantation Center, University Hospital, Comenius University, Martin, Slovakia
| | - Petra Skálová
- Jessenius Faculty of Medicine, Transplantation Center, University Hospital, Comenius University, Martin, Slovakia
| | - Karol Graňák
- Jessenius Faculty of Medicine, Transplantation Center, University Hospital, Comenius University, Martin, Slovakia
| | - Matej Vnučák
- Jessenius Faculty of Medicine, Transplantation Center, University Hospital, Comenius University, Martin, Slovakia
| | - Tatiana Baltesová
- Transplant Department, L. Pasteur's University Hospital, Košice, Slovakia
| | - Zuzana Žilinská
- Department of Urology, Medical Faculty, Renal Transplantation Center, University Hospital, Comenius University, Bratislava, Slovakia
| | - Miloš Jeseňák
- Department of Pediatrics, Department of Pneumology and Phthisiology, Department of Clinical Immunology and Allergology, Jessenius Faculty of Medicine, University Hospital, Comenius University, Martin, Slovakia
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15
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Ahmadian E, Zununi Vahed S, Mammadova S, Abediazar S. Immunosuppressant Management in Renal Transplant Patients with COVID-19. BIOMED RESEARCH INTERNATIONAL 2021; 2021:9318725. [PMID: 34692845 PMCID: PMC8531766 DOI: 10.1155/2021/9318725] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 08/31/2021] [Accepted: 10/05/2021] [Indexed: 11/18/2022]
Abstract
The coronavirus disease 2019 (COVID-19) pandemic poses a special risk for both immunosuppressed patients, especially transplant recipients. Although the knowledge about this infection is growing, many uncertainties remain, particularly regarding the kidney. Kidney transplant recipients (KDRs) should be considered immunocompromised hosts since a potential risk for infection, comorbidity, and immunosuppression exposure exists. Additionally, the management of immunosuppressive agents in KDRs remains challenging. Potential drug interactions with immunosuppressive treatment escalated the risk of unwanted side effects. In this review, we aimed to attain an augmented awareness and improved management immunosuppressant for COVID-19 KDRs.
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Affiliation(s)
- Elham Ahmadian
- Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Shakar Mammadova
- Department of Physical Geography, Baku State University, Baku, Azerbaijan
| | - Sima Abediazar
- Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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16
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Cajamarca-Baron J, Guavita-Navarro D, Buitrago-Bohorquez J, Gallego-Cardona L, Navas A, Cubides H, Arredondo AM, Escobar A, Rojas-Villarraga A. [SARS-CoV-2 (COVID-19) in Patients with some Degree of Immunosuppression]. ACTA ACUST UNITED AC 2021; 17:408-419. [PMID: 34630575 PMCID: PMC7486041 DOI: 10.1016/j.reuma.2020.08.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Accepted: 08/06/2020] [Indexed: 01/08/2023]
Abstract
Antecedentes No es claro si los pacientes con algún grado de inmunosupresión tienen peores desenlaces en la infección por SARS-CoV-2, en comparación con la población sana. Objetivo Realizar una revisión narrativa de la información disponible sobre infección por SARS-CoV-2 en pacientes inmunosuprimidos, especialmente pacientes con cáncer, trasplantados, con patologías neurológicas, inmunodeficiencias primarias y secundarias. Resultados Los pacientes con cáncer y tratamiento reciente del mismo (quimioterapia o cirugía) e infección por SARS-CoV-2 tienen mayor riesgo de peores desenlaces. En los pacientes trasplantados (renal, cardiaco y hepático), con patologías neurológicas (esclerosis múltiple [EM], neuromielitis óptica [NMODS], miastenia grave [MG]), inmunodeficiencias primarias e infección por virus de inmunodeficiencia humana (VIH) en asociación con uso de inmunosupresores, los estudios no han mostrado tendencia a peores desenlaces. Conclusión Dada la poca evidencia con que contamos hasta el momento no es claro el comportamiento de la infección por SARS-CoV-2 en pacientes con inmunosupresión, pero los estudios actuales no han mostrado peores desenlaces en este tipo de pacientes, a excepción de los pacientes con cáncer.
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Affiliation(s)
- Jairo Cajamarca-Baron
- Fundación Universitaria de Ciencias de la Salud (FUCS), Hospital San José, Bogotá, Colombia
| | - Diana Guavita-Navarro
- Fundación Universitaria de Ciencias de la Salud (FUCS), Hospital San José, Bogotá, Colombia
| | | | - Laura Gallego-Cardona
- Fundación Universitaria de Ciencias de la Salud (FUCS), Hospital San José, Bogotá, Colombia
| | - Angela Navas
- Servicio de Neurología, Fundación Universitaria de Ciencias de la Salud (FUCS), Hospital San José, Bogotá, Colombia
| | - Hector Cubides
- Servicio de Reumatología, Hospital San José, Bogotá, Colombia
| | | | | | - Adriana Rojas-Villarraga
- Servicio de Reumatología, Instituto de Investigaciones, Fundación Universitaria de Ciencias de la Salud (FUCS), Bogotá, Colombia
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17
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Quante M, Brake L, Tolios A, Della Penna A, Steidle C, Gruendl M, Grishina A, Haeberle H, Guthoff M, Tullius SG, Königsrainer A, Nadalin S, Löffler MW. SARS-CoV-2 in Solid Organ Transplant Recipients: A Structured Review of 2020. Transplant Proc 2021; 53:2421-2434. [PMID: 34551880 PMCID: PMC8364801 DOI: 10.1016/j.transproceed.2021.08.019] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Revised: 08/04/2021] [Accepted: 08/10/2021] [Indexed: 01/31/2023]
Abstract
BACKGROUND The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is challenging health systems all over the world. Particularly high-risk groups show considerable mortality rates after infection. In 2020, a huge number of case reports, case series, and consecutively various systematic reviews have been published reporting on morbidity and mortality risk connected with SARS-CoV-2 in solid organ transplant (SOT) recipients. However, this vast array of publications resulted in an increasing complexity of the field, overwhelming even for the expert reader. METHODS We performed a structured literature review comprising electronic databases, transplant journals, and literature from previous systematic reviews covering the entire year 2020. From 164 included articles, we identified 3451 cases of SARS-CoV-2-infected SOT recipients. RESULTS Infections resulted in a hospitalization rate of 84% and 24% intensive care unit admissions in the included patients. Whereas 53.6% of patients were reported to have recovered, cross-sectional overall mortality reported after coronavirus disease 2019 (COVID-19) was at 21.1%. Synoptic data concerning immunosuppressive medication attested to the reduction or withdrawal of antimetabolites (81.9%) and calcineurin inhibitors (48.9%) as a frequent adjustment. In contrast, steroids were reported to be increased in 46.8% of SOT recipients. CONCLUSIONS COVID-19 in SOT recipients is associated with high morbidity and mortality worldwide. Conforming with current guidelines, modifications of immunosuppressive therapies mostly comprised a reduction or withdrawal of antimetabolites and calcineurin inhibitors, while frequently maintaining or even increasing steroids. Here, we provide an accessible overview to the topic and synoptic estimates of expectable outcomes regarding in-hospital mortality of SOT recipients with COVID-19.
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Affiliation(s)
- Markus Quante
- Department of General, Visceral, and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany
| | - Linda Brake
- Department of General, Visceral, and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany
| | - Alexander Tolios
- Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria; Center for Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria; Center for Medical Statistics, Informatics, and Intelligent Systems, Institute of Artificial Intelligence, Medical University of Vienna, Vienna, Austria
| | - Andrea Della Penna
- Department of General, Visceral, and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany
| | - Christoph Steidle
- Department of General, Visceral, and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany
| | - Magdalena Gruendl
- Department of Epidemiology, Technical University Munich, Munich, Germany
| | - Anna Grishina
- Department of Pediatrics I, University Medicine Essen, Essen, Germany
| | - Helene Haeberle
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Tübingen, Tübingen, Germany
| | - Martina Guthoff
- Department of Diabetology, Endocrinology, Nephrology, Section of Nephrology and Hypertension, University Hospital Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich, University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
| | - Stefan G Tullius
- Division of Transplant Surgery and Transplant Surgery Research Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Alfred Königsrainer
- Department of General, Visceral, and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany; Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies," University of Tübingen, Tübingen, Germany
| | - Silvio Nadalin
- Department of General, Visceral, and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany
| | - Markus W Löffler
- Department of General, Visceral, and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany; Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies," University of Tübingen, Tübingen, Germany; Department of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, Tübingen, Germany; Department of Clinical Pharmacology, University Hospital Tübingen, Tübingen, Germany.
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18
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Granata S, Carratù P, Stallone G, Zaza G. mTOR-Inhibition and COVID-19 in Kidney Transplant Recipients: Focus on Pulmonary Fibrosis. Front Pharmacol 2021; 12:710543. [PMID: 34497515 PMCID: PMC8419255 DOI: 10.3389/fphar.2021.710543] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Accepted: 08/11/2021] [Indexed: 12/24/2022] Open
Abstract
Kidney transplant recipients are at high risk of developing severe COVID-19 due to the coexistence of several transplant-related comorbidities (e.g., cardiovascular disease, diabetes) and chronic immunosuppression. As a consequence, a large part of SARS-CoV-2 infected patients have been managed with a reduction of immunosuppression. The mTOR-I, together with antimetabolites, have been often discontinued in order to minimize the risk of pulmonary toxicity and to antagonize pharmacological interaction with antiviral/anti-inflammatory drugs. However, at our opinion, this therapeutic strategy, although justified in kidney transplant recipients with severe COVID-19, should be carefully evaluated in asymptomatic/paucisymptomatic patients in order to avoid the onset of acute allograft rejections, to potentially exploit the mTOR-I antiviral properties, to reduce proliferation of conventional T lymphocytes (which could mitigate the cytokine storm) and to preserve Treg growth/activity which could reduce the risk of progression to severe disease. In this review, we discuss the current literature regarding the therapeutic potential of mTOR-Is in kidney transplant recipients with COVID-19 with a focus on pulmonary fibrosis.
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Affiliation(s)
- Simona Granata
- Renal Unit, Department of Medicine, University-Hospital of Verona, Verona, Italy
| | - Pierluigi Carratù
- Division of Internal Medicine, Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, "Aldo Moro" University of Bari, Bari, Italy
| | - Giovanni Stallone
- Nephrology, Dialysis and Transplantation Unit, Department of Medical and Surgical Science, University of Foggia, Foggia, Italy
| | - Gianluigi Zaza
- Renal Unit, Department of Medicine, University-Hospital of Verona, Verona, Italy
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19
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Alfishawy M, Nso N, Nassar M, Ariyaratnam J, Bhuiyan S, Siddiqui RS, Li M, Chung H, Al Balakosy A, Alqassieh A, Fülöp T, Rizzo V, Daoud A, Soliman KM. Liver transplantation during global COVID-19 pandemic. World J Clin Cases 2021; 9:6608-6623. [PMID: 34447809 PMCID: PMC8362541 DOI: 10.12998/wjcc.v9.i23.6608] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 06/02/2021] [Accepted: 07/06/2021] [Indexed: 02/06/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory disease respiratory syndrome coronavirus-2 has significantly impacted the health care systems globally. Liver transplantation (LT) has faced an unequivocal challenge during this unprecedented time. This targeted review aims to cover most of the clinical issues, challenges and concerns about LT during the COVID-19 pandemic and discuss the most updated literature on this rapidly emerging subject.
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Affiliation(s)
- Mostafa Alfishawy
- Infectious Diseases, Infectious Diseases Consultants and Academic Researchers of Egypt IDCARE, Cairo 0000, Egypt
| | - Nso Nso
- Department of Medicine, Icahn School of Medicine at Mount Sinai (NYC Health and Hospitals: Queens), New York, NY 11373, United States
| | - Mahmoud Nassar
- Department of Medicine, Icahn School of Medicine at Mount Sinai (NYC Health and Hospitals: Queens), New York, NY 11373, United States
| | - Jonathan Ariyaratnam
- Department of Medicine, Icahn School of Medicine at Mount Sinai (NYC Health and Hospitals: Queens), New York, NY 11373, United States
| | - Sakil Bhuiyan
- Department of Medicine, Icahn School of Medicine at Mount Sinai (NYC Health and Hospitals: Queens), New York, NY 11373, United States
| | - Raheel S Siddiqui
- Department of Medicine, Icahn School of Medicine at Mount Sinai (NYC Health and Hospitals: Queens), New York, NY 11373, United States
| | - Matthew Li
- Clinical pharmacy department, Icahn School of Medicine at Mount Sinai (NYC Health and Hospitals: Queens), New York, NY 11373, United States
| | - Howard Chung
- Department of Medicine, Icahn School of Medicine at Mount Sinai (NYC Health and Hospitals: Queens), New York, NY 11373, United States
| | - Amira Al Balakosy
- Tropical Medicine Department, Ain Shams University, Cairo 11517, Egypt
| | - Ahmed Alqassieh
- Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, United States
| | - Tibor Fülöp
- Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, United States
| | - Vincent Rizzo
- Department of Medicine, Icahn School of Medicine at Mount Sinai (NYC Health and Hospitals: Queens), New York, NY 11373, United States
| | - Ahmed Daoud
- Department of Medicine, Kasr Alainy Medical School, Cairo University, Cairo 11562, Egypt
| | - Karim M Soliman
- Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, United States
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20
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Alattar RA, Shaar SH, Othman M, Abu Jarir SH, Hashim SM, Iqbal F, Rustom F, Almaslamani MA, Omrani AS. Coronavirus disease 2019 in solid organ transplant recipients in the setting of proactive screening and contact tracing of Qatar. Qatar Med J 2021; 2021:23. [PMID: 34604011 PMCID: PMC8474076 DOI: 10.5339/qmj.2021.23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Accepted: 03/07/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Clinical data on Coronavirus Disease 2019 (COVID-19) in solid organ transplant (SOT) recipients are limited. We herein report the initial clinical experience with COVID-19 in SOT recipients in Qatar. METHODS All SOT recipients with laboratory-confirmed COVID-19 up to May 23, 2020 were included. Demographic and clinical data were extracted retrospectively from the hospital's electronic health records. Categorical data are presented as frequency and percentages, while continuous variables are summarized as medians and ranges. RESULTS Twenty-four SOT recipients with COVID-19 were identified (kidney 16, liver 6, heart 1, and liver and kidney 1). Organ transplantation preceded COVID-19 by a median of 60 months (range 1.7-184). The median age was 57 years (range 24-72), and 9 (37.5%) transplant recipients were females. Five (21%) asymptomatic patients were diagnosed through proactive screening. For the rest, fever (15/19) and cough (13/19) were the most frequent presenting symptoms. Five (20.8%) patients required invasive mechanical ventilation in the intensive care unit (ICU). Eleven (46%) patients developed acute kidney injury, including three in association with drug-drug interactions involving investigational COVID-19 therapies. Maintenance immunosuppressive therapy was modified in 18 (75%) patients, but systemic corticosteroids were not discontinued in any. After a median follow-up of 226 days (26-272), 20 (83.3%) patients had been discharged home, 2 (8.3%) were still hospitalized, 1 (4.2%) was still in the ICU, and 1 (4.2%) had died. CONCLUSIONS Our results suggest that asymptomatic COVID-19 is possible in SOT recipients and that overall outcomes are not uniformly worse than those in the general population. The results require confirmation in large, international cohorts.
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Affiliation(s)
- Rand A Alattar
- Communicable Diseases Center, Hamad Medical Corporation, Doha, Qatar
| | - Shahd H Shaar
- Communicable Diseases Center, Hamad Medical Corporation, Doha, Qatar
| | - Muftah Othman
- Division of Nephrology, Hamad Medical Corporation, Doha, Qatar
| | - Sulieman H Abu Jarir
- Communicable Diseases Center, Hamad Medical Corporation, Doha, Qatar
- Division of Infectious Diseases, Hamad Medical Corporation, Doha, Qatar
| | - Samar M Hashim
- Communicable Diseases Center, Hamad Medical Corporation, Doha, Qatar
- Division of Infectious Diseases, Hamad Medical Corporation, Doha, Qatar
| | - Fatima Iqbal
- Communicable Diseases Center, Hamad Medical Corporation, Doha, Qatar
| | - Fatima Rustom
- Communicable Diseases Center, Hamad Medical Corporation, Doha, Qatar
| | - Muna A Almaslamani
- Communicable Diseases Center, Hamad Medical Corporation, Doha, Qatar
- Division of Infectious Diseases, Hamad Medical Corporation, Doha, Qatar
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21
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Cajamarca-Baron J, Guavita-Navarro D, Buitrago-Bohorquez J, Gallego-Cardona L, Navas A, Cubides H, Arredondo AM, Escobar A, Rojas-Villarraga A. SARS-CoV-2 (COVID-19) in patients with some degree of immunosuppression. REUMATOLOGIA CLINICA 2021; 17:408-419. [PMID: 34301385 PMCID: PMC7566826 DOI: 10.1016/j.reumae.2020.08.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Accepted: 08/06/2020] [Indexed: 01/08/2023]
Abstract
BACKGROUND It is not clear whether patients with some degree of immunosuppression have worse outcomes in SARS-CoV-2 infection, compared to healthy people. OBJECTIVE To carry out a narrative review of the information available on infection by SARS-CoV-2 in immunosuppressed patients, especially patients with cancer, transplanted, neurological diseases, primary and secondary immunodeficiencies. RESULTS Patients with cancer and recent cancer treatment (chemotherapy or surgery) and SARS-CoV-2 infection have a higher risk of worse outcomes. In transplant patients (renal, cardiac and hepatic), with neurological pathologies (multiple sclerosis (MS), neuromyelitis optica (NMODS), myasthenia gravis (MG)), primary immunodeficiencies and infection with human immunodeficiency virus (HIV) in association with immunosuppressants, studies have shown no tendency for worse outcomes. CONCLUSION Given the little evidence we have so far, the behaviour of SARS-CoV-2 infection in immunosuppressed patients is unclear, but current studies have not shown worse outcomes, except for patients with cancer.
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Affiliation(s)
- Jairo Cajamarca-Baron
- Fundación Universitaria de Ciencias de la Salud (FUCS), Hospital San José, Bogotá, Colombia.
| | - Diana Guavita-Navarro
- Fundación Universitaria de Ciencias de la Salud (FUCS), Hospital San José, Bogotá, Colombia
| | | | - Laura Gallego-Cardona
- Fundación Universitaria de Ciencias de la Salud (FUCS), Hospital San José, Bogotá, Colombia
| | - Angela Navas
- Servicio de Neurología, Fundación Universitaria de Ciencias de la Salud (FUCS), Hospital San José, Bogotá, Colombia
| | - Hector Cubides
- Servicio de Reumatología, Hospital San José, Bogotá, Colombia
| | | | | | - Adriana Rojas-Villarraga
- Servicio de Reumatología, Instituto de Investigaciones, Fundación Universitaria de Ciencias de la Salud (FUCS), Bogotá, Colombia
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22
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Dumortier J, Duvoux C, Roux O, Altieri M, Barraud H, Besch C, Caillard S, Coilly A, Conti F, Dharancy S, Durand F, Francoz C, Garaix F, Houssel-Debry P, Kounis I, Lassailly G, Laverdure N, Leroy V, Mallet M, Mazzola A, Meunier L, Radenne S, Richardet JP, Vanlemmens C, Hazzan M, Saliba F, for the French Solid Organ Transplant COVID Registry, the Groupe de Recherche Français en Greffe de Foie (GReF²). Covid-19 in liver transplant recipients: the French SOT COVID registry. Clin Res Hepatol Gastroenterol 2021; 45:101639. [PMID: 33636654 PMCID: PMC7843027 DOI: 10.1016/j.clinre.2021.101639] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Accepted: 01/14/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND Notwithstanding the ongoing coronavirus disease-2019 (Covid-19) pandemic, information on its clinical presentation and prognosis in organ transplant recipients remains limited. The aim of this registry-based observational study was to report the characteristics and clinical outcomes of liver transplant (LT) recipients included in the French nationwide Registry of Solid Organ Transplant Recipients with Covid-19. METHODS COVID-19 was diagnosed in patients who had a positive PCR assay for SARS-CoV-2 or in presence of typical lung lesions on imaging or specific SARS-CoV-2 antibodies. Clinical and laboratory characteristics, management of immunosuppression, treatment for Covid-19, and clinical outcomes (hospitalization, admission to intensive care unit, mechanical ventilation, or death) were recorded. RESULTS Of the 104 patients, 67 were admitted to hospital and 37 were managed at home (including all 13 children). Hospitalized patients had a median age of 65.2 years (IQR: 58.1 - 73.2 years) and two thirds were men. Most common comorbidities included overweight (67.3%), hypertension (61.2%), diabetes (50.7%), cardiovascular disease (20.9%) and respiratory disease (16.4%). SARS-CoV-2 infection was identified after a median of 92.8 months (IQR: 40.1 - 194.7 months) from LT. During hospitalization, antimetabolites, mTOR inhibitor, and CNIs were withdrawn in 41.9%, 30.0% and 12.5% of patients, respectively. The composite endpoint of severe Covid-19 within 30 days after diagnosis was reached by 33.0% of the adult patients. The 30-day mortality rate was 20.0%, and 28.1% for hospitalized patients. Multivariate analysis identified that age was independently associated with mortality. CONCLUSION In our large nationwide study, Covid-19 in LT recipients was associated with a high mortality rate.
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Affiliation(s)
- Jérôme Dumortier
- Hospices Civils de Lyon, Hôpital Edouard Herriot, Unité de Transplantation Hépatique et Université Claude Bernard Lyon 1, Lyon, France,Corresponding author
| | | | - Olivier Roux
- APHP, Hôpital Beaujon, Service d'Hépatologie et Transplantation Hépatique - Université Paris Diderot - INSERM U1149, Clichy, France
| | - Mario Altieri
- Hôpital Côte de Nacre, Service d'Hépato-Gastroentérologie, Nutrition et Oncologie Digestive, Caen, France
| | - Hélène Barraud
- CHU Tours, Hôpital Trousseau Service de Chirurgie Digestive, Oncologique et Endocrinienne, Transplantation Hépatique, Tours, France
| | - Camille Besch
- CHRU Hautepierre, Service de Chirurgie Hépato-Bilio-Pancréatique et Transplantation Hépatique, Strasbourg, France
| | - Sophie Caillard
- CHRU Hautepierre, Service de Néphrologie et Transplantation et INSERM, IRM UMR-S 1109, Strasbourg, France
| | - Audrey Coilly
- AP-HP, Hôpital Paul Brousse, Centre Hépato-Biliaire, INSERM, Unité 1193, Villejuif, France
| | - Filomena Conti
- APHP – Hôpital de la Pitié Salpétrière, Service d’Hépatologie et Transplantation Hépatique, Paris, France
| | - Sébastien Dharancy
- CHRU Lille, Hôpital Claude Huriez, Service des Maladies de l’appareil Digestif et Université de Lille, Lille, France
| | - François Durand
- APHP, Hôpital Beaujon, Service d'Hépatologie et Transplantation Hépatique - Université Paris Diderot - INSERM U1149, Clichy, France
| | - Claire Francoz
- APHP, Hôpital Beaujon, Service d'Hépatologie et Transplantation Hépatique - Université Paris Diderot - INSERM U1149, Clichy, France
| | - Florentine Garaix
- APHM, Hôpital La Timone, Service de Pédiatrie Multidisciplinaire, Marseille, France
| | - Pauline Houssel-Debry
- Hôpital Universitaire de Pontchaillou, Service d’Hépatologie et Transplantation Hépatique, Rennes, France
| | - Ilias Kounis
- AP-HP, Hôpital Paul Brousse, Centre Hépato-Biliaire, INSERM, Unité 1193, Villejuif, France
| | - Guillaume Lassailly
- CHRU Lille, Hôpital Claude Huriez, Service des Maladies de l’appareil Digestif et Université de Lille, Lille, France
| | - Noémie Laverdure
- Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Unité d’Hépato-gastroentérologie et Nutrition Pédiatriques, Lyon, France
| | - Vincent Leroy
- APHP, Hôpital Henri Mondor, Service d’Hépatologie, Créteil, France
| | - Maxime Mallet
- APHP – Hôpital de la Pitié Salpétrière, Service d’Hépatologie et Transplantation Hépatique, Paris, France
| | - Alessandra Mazzola
- APHP – Hôpital de la Pitié Salpétrière, Service d’Hépatologie et Transplantation Hépatique, Paris, France
| | - Lucy Meunier
- CHU Saint Eloi, Département d’Hépatologie et Transplantation Hépatique, Montpellier, France
| | - Sylvie Radenne
- Hospices Civils de Lyon, Hôpital de la Croix-Rousse, Service d'Hépato-Gastroentérologie, Lyon, France
| | | | - Claire Vanlemmens
- Hôpital Jean Minjoz, Service d'Hépatologie et Soins Intensifs Digestifs, Besançon, France
| | - Marc Hazzan
- CHRU Lille, Hôpital Claude Huriez, Service de Néphrologie et Transplantation et Université de Lille, Lille, France
| | - Faouzi Saliba
- AP-HP, Hôpital Paul Brousse, Centre Hépato-Biliaire, INSERM, Unité 1193, Villejuif, France
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23
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Abstract
Recent literature suggests that severe COVID-19 is associated with an exaggerated immune response during viral infection, resulting in cytokine storm. Although elevated plasma interleukin 6 (IL-6) has been reported in severe COVID-19 infections, and treatment with anti–IL-6 (tocilizumab) has demonstrated promising outcomes both domestically and abroad, reports remain limited and therapeutic regimens vary considerably. Furthermore, research pertaining to transplant recipients, COVID-19 infection, and anti–IL-6 therapy remains underdeveloped. Herein, we report the successful treatment of the only reported facial vascularized composite allograft (VCA) recipient who contracted severe COVID-19 and the first reported VCA recipient with COVID-19 infection that received anti–IL-6 immunotherapy resulting in an excellent recovery despite his multiple preexisting and COVID-19–related comorbidities—adult respiratory distress syndrome, acute renal failure requiring hemodialysis, and concomitant sepsis due to extensive drug-resistant bacterial pneumonia upon presentation. To date, he has not demonstrated any anti-IL-6 drug-related adverse effects. This preliminary report also suggests that our immunosuppressed VCA patients can indeed demonstrate a robust cytokine response during COVID-19 infection and may also respond favorably to emerging anticytokine immune therapies. We hope that our experience proves helpful to other centers that might encounter critically ill VCA recipients in the ongoing COVID-19 pandemic and in the years to follow.
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24
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Coll E, Fernández-Ruiz M, Sánchez-Álvarez JE, Martínez-Fernández JR, Crespo M, Gayoso J, Bada-Bosch T, Oppenheimer F, Moreso F, López-Oliva MO, Melilli E, Rodríguez-Ferrero ML, Bravo C, Burgos E, Facundo C, Lorenzo I, Yañez Í, Galeano C, Roca A, Cabello M, Gómez-Bueno M, García-Cosío M, Graus J, Lladó L, de Pablo A, Loinaz C, Aguado B, Hernández D, Domínguez-Gil B, the Spanish Group for the Study of COVID-19 in Transplant Recipients. COVID-19 in transplant recipients: The Spanish experience. Am J Transplant 2021; 21:1825-1837. [PMID: 33098200 PMCID: PMC9906239 DOI: 10.1111/ajt.16369] [Citation(s) in RCA: 135] [Impact Index Per Article: 33.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 10/06/2020] [Accepted: 10/09/2020] [Indexed: 02/06/2023]
Abstract
We report the nationwide experience with solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients diagnosed with coronavirus disease 2019 (COVID-19) in Spain until 13 July 2020. We compiled information for 778 (423 kidney, 113 HSCT, 110 liver, 69 heart, 54 lung, 8 pancreas, 1 multivisceral) recipients. Median age at diagnosis was 61 years (interquartile range [IQR]: 52-70), and 66% were male. The incidence of COVID-19 in SOT recipients was two-fold higher compared to the Spanish general population. The median interval from transplantation was 59 months (IQR: 18-131). Infection was hospital-acquired in 13% of cases. No donor-derived COVID-19 was suspected. Most patients (89%) were admitted to the hospital. Therapies included hydroxychloroquine (84%), azithromycin (53%), protease inhibitors (37%), and interferon-β (5%), whereas immunomodulation was based on corticosteroids (41%) and tocilizumab (21%). Adjustment of immunosuppression was performed in 85% of patients. At the time of analysis, complete follow-up was available from 652 patients. Acute respiratory distress syndrome occurred in 35% of patients. Ultimately, 174 (27%) patients died. In univariate analysis, risk factors for death were lung transplantation (odds ratio [OR]: 2.5; 95% CI: 1.4-4.6), age >60 years (OR: 3.7; 95% CI: 2.5-5.5), and hospital-acquired COVID-19 (OR: 3.0; 95% CI: 1.9-4.9).
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Affiliation(s)
- Elisabeth Coll
- Organización Nacional de Trasplantes (Spanish National Transplant Organization), Madrid, Spain
| | - Mario Fernández-Ruiz
- Unit of Infectious Diseases, Hospital Universitario 12 de Octubre. Instituto de Investigación Sanitaria, Hospital Universitario 12 de Octubre (imas12), President of the Group for the Study of Infection in Transplantation and the Immunocompromised Host (GESITRA-IC) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), Madrid, Spain
- Group for the Study of Infection in Transplantation and the Immunocompromised Host (GESITRA-IC) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), Madrid, Spain
| | - J. Emilio Sánchez-Álvarez
- Department of Nephrology, Hospital Universitario de Cabueñes, Gijón, Spain
- Spanish Society of Nephrology (SEN), Gijón, Spain
| | | | - Marta Crespo
- Department of Nephrology, Hospital del Mar, Barcelona, Spain
- Transplant Working Group of the Spanish Society of Nephrology (SEN), Barcelona, Spain
- REDinREN (RD16/0009/0013), Barcelona, Spain
| | - Jorge Gayoso
- Organización Nacional de Trasplantes (Spanish National Transplant Organization), Madrid, Spain
| | - Teresa Bada-Bosch
- Department of Nephrology, Hospital Universitario 12 de Octubre, Madrid, Spain
| | | | - Francesc Moreso
- Kidney Transplant Unit, Department of Nephrology, Hospital Universitario Vall d´Hebrón, Barcelona, Spain
| | | | - Edoardo Melilli
- Kidney Transplant Unit, Department of Nephrology, Hospital Universitario de Bellvitge, Barcelona, Spain
| | | | - Carlos Bravo
- Department of Pulmonology, Lung transplant Unit, Hospital Universitario Vall d´Hebrón, Barcelona, Spain
| | - Elena Burgos
- Department of Nephrology, Hospital Germans Trias i Pujol, Badalona, Spain
| | - Carme Facundo
- Kidney Transplant Unit, Fundación Puigvert, Barcelona, Spain
| | - Inmaculada Lorenzo
- Department of Nephrology, Complejo Hospitalario Universitario de Albacete, Albacete, Spain
| | - Íñigo Yañez
- Department of Nephrology, Hospital Universitario de Cruces, Barakaldo, Spain
| | - Cristina Galeano
- Kidney Transplant Unit, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Ana Roca
- Department of Nephrology, Complejo Hospitalario Universitario de Toledo, Toledo, Spain
| | - Mercedes Cabello
- Department of Nephrology, Hospital Regional Universitario de Málaga, Málaga, Spain
| | - Manuel Gómez-Bueno
- Department of Cardiology, Hospital Universitario Puerta de Hierro, Madrid, Spain
| | - MaDolores García-Cosío
- Cardiology Service, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain
- Centro de Investigación Biomédica en Red Cardiovascular (CIBERCV), Madrid, Spain
| | - Javier Graus
- Department of Gastroenterology, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Laura Lladó
- Liver Transplant Unit, Hospital Universitario de Bellvitge, Barcelona, Spain
| | - Alicia de Pablo
- Lung Transplant Unit, Department of Pneumology, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Carmelo Loinaz
- Transplant Unit, Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Beatriz Aguado
- Transplant Unit. Department of Hematology, Hospital Universitario La Princesa, Madrid, Spain
| | - Domingo Hernández
- Department of Nephrology, Hospital Regional Universitario, Málaga, Spain
- Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain
- Spanish Society of Transplantation (SET), Málaga, Spain
| | - Beatriz Domínguez-Gil
- Organización Nacional de Trasplantes (Spanish National Transplant Organization), Madrid, Spain
| | - the Spanish Group for the Study of COVID-19 in Transplant Recipients
- Organización Nacional de Trasplantes (Spanish National Transplant Organization), Madrid, Spain
- Unit of Infectious Diseases, Hospital Universitario 12 de Octubre. Instituto de Investigación Sanitaria, Hospital Universitario 12 de Octubre (imas12), President of the Group for the Study of Infection in Transplantation and the Immunocompromised Host (GESITRA-IC) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), Madrid, Spain
- Group for the Study of Infection in Transplantation and the Immunocompromised Host (GESITRA-IC) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), Madrid, Spain
- Department of Nephrology, Hospital Universitario de Cabueñes, Gijón, Spain
- Spanish Society of Nephrology (SEN), Gijón, Spain
- Department of Nephrology, Hospital del Mar, Barcelona, Spain
- Transplant Working Group of the Spanish Society of Nephrology (SEN), Barcelona, Spain
- REDinREN (RD16/0009/0013), Barcelona, Spain
- Department of Nephrology, Hospital Universitario 12 de Octubre, Madrid, Spain
- Department of Nephrology, Hospital Clinic, Barcelona, Spain
- Kidney Transplant Unit, Department of Nephrology, Hospital Universitario Vall d´Hebrón, Barcelona, Spain
- Department oof Nephrology, Hospital Universitario La Paz, Madrid, Spain
- Kidney Transplant Unit, Department of Nephrology, Hospital Universitario de Bellvitge, Barcelona, Spain
- Department of Nephrology, Hospital General Universitario Gregorio Marañón, Madrid, Spain
- Department of Pulmonology, Lung transplant Unit, Hospital Universitario Vall d´Hebrón, Barcelona, Spain
- Department of Nephrology, Hospital Germans Trias i Pujol, Badalona, Spain
- Kidney Transplant Unit, Fundación Puigvert, Barcelona, Spain
- Department of Nephrology, Complejo Hospitalario Universitario de Albacete, Albacete, Spain
- Department of Nephrology, Hospital Universitario de Cruces, Barakaldo, Spain
- Kidney Transplant Unit, Hospital Universitario Ramón y Cajal, Madrid, Spain
- Department of Nephrology, Complejo Hospitalario Universitario de Toledo, Toledo, Spain
- Department of Nephrology, Hospital Regional Universitario de Málaga, Málaga, Spain
- Department of Cardiology, Hospital Universitario Puerta de Hierro, Madrid, Spain
- Cardiology Service, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain
- Centro de Investigación Biomédica en Red Cardiovascular (CIBERCV), Madrid, Spain
- Department of Gastroenterology, Hospital Universitario Ramón y Cajal, Madrid, Spain
- Liver Transplant Unit, Hospital Universitario de Bellvitge, Barcelona, Spain
- Lung Transplant Unit, Department of Pneumology, Hospital Universitario 12 de Octubre, Madrid, Spain
- Transplant Unit, Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario 12 de Octubre, Madrid, Spain
- Transplant Unit. Department of Hematology, Hospital Universitario La Princesa, Madrid, Spain
- Department of Nephrology, Hospital Regional Universitario, Málaga, Spain
- Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain
- Spanish Society of Transplantation (SET), Málaga, Spain
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Angelico R, Blasi F, Manzia TM, Toti L, Tisone G, Cacciola R. The Management of Immunosuppression in Kidney Transplant Recipients with COVID-19 Disease: An Update and Systematic Review of the Literature. MEDICINA (KAUNAS, LITHUANIA) 2021; 57:435. [PMID: 33946462 PMCID: PMC8147172 DOI: 10.3390/medicina57050435] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Revised: 04/22/2021] [Accepted: 04/28/2021] [Indexed: 02/05/2023]
Abstract
Background and Objectives: In the era of the coronavirus disease 2019 (COVID-19) pandemic, the management of immunosuppressive (IS) therapy in kidney transplant (KT) recipients affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires attention. It is not yet understood whether IS therapy may protect from the cytokine storm induced by SARS-CoV-2 infection or a temporary adjustment/withdrawal of IS therapy to restore the immune system may be necessary. We performed a systematic literature review to investigate the current management of IS therapy in KT recipients with COVID-1. Materials and Methods: Out of 71 articles published from 1 February 2020 until 30 October 2020, 554 KT recipients with SARS-CoV-2 infection were identified. Results: Modifications of IS therapy were based on the clinical conditions. For asymptomatic patients or those with mild COVID-19 symptoms, a "wait and see approach" was mostly used; a suspension of antimetabolites drugs (347/461, 75.27%) or mTOR inhibitors (38/48, 79.2%) was adopted in the majority of patients with symptomatic COVID-19 infections. For CNIs, the most frequent attitude was their maintenance (243/502, 48.4%) or dose-reduction (99/502, 19.72%) in patients asymptomatic or with mild COVID-19 symptoms, while drug withdrawal was the preferred choice in severely symptomatic patients (160/450, 31.87%). A discontinuation of all IS drugs was used only in severely symptomatic COVID-19 patients on invasive mechanical ventilation. Renal function remained stable in 422(76.17%) recipients, while 49(8.84%) patients experienced graft loss. Eight (1.44%) patients experienced a worsening of renal function. The overall mortality was 21.84%, and 53(9.56%) patients died with functioning grafts. Conclusion: A tailored approach to the patient has been the preferred strategy for the management of IS therapy in KT recipients, taking into account the clinical conditions of patients and the potential interactions between IS and antiviral drugs, in the attempt to balance the risks of COVID-19-related complications and those due to rejection or graft loss.
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Affiliation(s)
- Roberta Angelico
- Department of Surgery Sciences, Transplant and HPB Unit, University of Rome Tor Vergata, 00133 Rome, Italy; (R.A.); (F.B.); (L.T.); (G.T.); (R.C.)
| | - Francesca Blasi
- Department of Surgery Sciences, Transplant and HPB Unit, University of Rome Tor Vergata, 00133 Rome, Italy; (R.A.); (F.B.); (L.T.); (G.T.); (R.C.)
| | - Tommaso Maria Manzia
- Department of Surgery Sciences, Transplant and HPB Unit, University of Rome Tor Vergata, 00133 Rome, Italy; (R.A.); (F.B.); (L.T.); (G.T.); (R.C.)
| | - Luca Toti
- Department of Surgery Sciences, Transplant and HPB Unit, University of Rome Tor Vergata, 00133 Rome, Italy; (R.A.); (F.B.); (L.T.); (G.T.); (R.C.)
| | - Giuseppe Tisone
- Department of Surgery Sciences, Transplant and HPB Unit, University of Rome Tor Vergata, 00133 Rome, Italy; (R.A.); (F.B.); (L.T.); (G.T.); (R.C.)
| | - Roberto Cacciola
- Department of Surgery Sciences, Transplant and HPB Unit, University of Rome Tor Vergata, 00133 Rome, Italy; (R.A.); (F.B.); (L.T.); (G.T.); (R.C.)
- Department of Surgery, King Salman Armed Forces Hospital, Tabuk 47512, Saudi Arabia
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Predictors of disease severity and outcome of hospitalized renal transplant recipients with COVID-19 infection: a systematic review of a globally representative sample. ACTA ACUST UNITED AC 2021; 59:10-42. [PMID: 33155999 DOI: 10.2478/rjim-2020-0034] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Indexed: 02/07/2023]
Abstract
Introduction. COVID-19 presents a special challenge to the kidney transplant population.Methods. A systematic review of articles that examined COVID-19 in kidney transplant recipients was performed. Patients' demographics, clinical, laboratory and radiological presentations, immunosuppression modification, and COVID-19 specific management were abstracted and analyzed. COVID-19 severity was classified into mild, moderate, and severe. Disease outcome was classified by whether the patient was discharged, still hospitalized, or died.Results. 44 articles reporting individual data and 13 articles reporting aggregated data on 149 and 561 kidney transplant recipients respectively with COVID-19 from Asia, Europe and America fulfilled all inclusion and exclusion criteria. Among studies reporting case specific data, 76% of cases had severe disease. Compared to patients with mild/moderate disease, patients with severe disease had higher CRP, LDH, Ferritin, D-dimer and were more likely to have bilateral lung involvement at presentation and longer time since transplantation (P < 0.05 for all). Recipients' age, gender and comorbidities did not impact disease severity. Patients with severe disease had a more aggressive CNI reduction and more antiviral medications utilization. Outcome was reported on 145 cases, of those 34 (23%) died all with severe disease. Longer duration from transplant to disease diagnosis, hypoxia and higher LDH were associated with mortality (P < 0.05). Different immunosuppression reduction strategies, high dose parenteral corticosteroids use and various antiviral combinations did not demonstrate survival advantage. Similar finding was observed for studies reporting aggregated data.Conclusion. COVID-19 in kidney transplant patients is associated with high rate of disease severity and fatality. Higher LDH and longer time since transplantation predicted both disease severity and mortality. None of the COVID-19 specific treatment correlated with, or improved disease outcome in kidney transplant recipients.
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27
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Deb S, Arrighi S. Potential Effects of COVID-19 on Cytochrome P450-Mediated Drug Metabolism and Disposition in Infected Patients. Eur J Drug Metab Pharmacokinet 2021; 46:185-203. [PMID: 33538960 PMCID: PMC7859725 DOI: 10.1007/s13318-020-00668-8] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Coronavirus Disease 2019 (COVID-19) has been a global health crisis since it was first identified in December 2019. In addition to fever, cough, headache, and shortness of breath, an intense increase in immune response-based inflammation has been the hallmark of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) virus infection. This narrative review summarizes and critiques pathophysiology of COVID-19 and its plausible effects on drug metabolism and disposition. The release of inflammatory cytokines (e.g., interleukins, tumor necrosis factor α), also known as 'cytokine storm', leads to altered molecular pathophysiology and eventually organ damage in the lung, heart, and liver. The laboratory values for various liver function tests (e.g., alanine aminotransferase, aspartate aminotransferase, total bilirubin, albumin) have indicated potential hepatocellular injury in COVID-19 patients. Since the liver is the powerhouse of protein synthesis and the primary site of cytochrome P450 (CYP)-mediated drug metabolism, even a minor change in the liver function status has the potential to affect the hepatic clearance of xenobiotics. It has now been well established that extreme increases in cytokine levels are common in COVID-19 patients, and previous studies with patients infected with non-SARS-CoV-2 virus have shown that CYP enzymes can be suppressed by an infection-related cytokine increase and inflammation. Alongside the investigational COVID-19 drugs, the patients may also be on therapeutics for comorbidities; especially epidemiological studies have indicated that individuals with hypertension, hyperglycemia, and obesity are more vulnerable to COVID-19 than the average population. This complicates the drug-disease interaction profile of the patients as both the investigational drugs (e.g., remdesivir, dexamethasone) and the agents for comorbidities can be affected by compromised CYP-mediated hepatic metabolism. Overall, it is imperative that healthcare professionals pay attention to the COVID-19 and CYP-driven drug metabolism interactions with the goal to adjust the dose or discontinue the affected drugs as appropriate.
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Affiliation(s)
- Subrata Deb
- Department of Pharmaceutical Sciences, College of Pharmacy, Larkin University, Miami, FL, 33169, USA.
| | - Scott Arrighi
- Department of Pharmaceutical Sciences, College of Pharmacy, Larkin University, Miami, FL, 33169, USA
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28
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Karruli A, Spiezia S, Boccia F, Gagliardi M, Patauner F, Salemme A, Maiello C, Zampino R, Durante-Mangoni E. Effect of immunosuppression maintenance in solid organ transplant recipients with COVID-19: Systematic review and meta-analysis. Transpl Infect Dis 2021; 23:e13595. [PMID: 33641202 PMCID: PMC7995235 DOI: 10.1111/tid.13595] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2020] [Revised: 12/30/2020] [Accepted: 02/14/2021] [Indexed: 12/21/2022]
Abstract
Background The aim of this study was to assess the effect of continuing immune suppressive therapy in solid organ transplant recipients (SOTR) with coronavirus disease 2019 (COVID‐19). Methods Systematic review and meta‐analysis of data on 202 SOTR with COVID‐19, published as case reports or case series. We extracted clinical, hemato‐chemical, imaging, treatment, and outcome data. Results Most patients were kidney recipients (61.9%), males (68.8%), with median age of 57 years. The majority was on tacrolimus (73.5%) and mycophenolate (65.8%). Mortality was 18.8%, but an equal proportion was still hospitalized at last follow up. Immune suppressive therapy was withheld in 77.2% of patients, either partially or completely. Tacrolimus was continued in 50%. One third of survivors that continued immunosuppressants were on dual therapy plus steroids. None of those who continued immunosuppressants developed critical COVID‐19 disease. Age (OR 1.07, 95% CI 1‐1.11, P = .001) and lopinavir/ritonavir use (OR 3.3, 95%CI 1.2‐8.5, P = .013) were independent predictors of mortality while immunosuppression maintenance (OR 0.067, 95% CI 0.008‐0.558, P = .012) and tacrolimus continuation (OR 0.3, 95% CI 0.1‐0.7, P = .013) were independent predictors of survival. Conclusions Our data suggest that maintaining immune suppression might be safe in SOTR with moderate and severe COVID‐19. Specifically, receiving tacrolimus could be beneficial for COVID‐19 SOTR. Because of the quality of the available evidence, no definitive guidance on how to manage SOTR with COVID‐19 can be derived from our data.
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Affiliation(s)
- Arta Karruli
- Division of Internal Medicine, University of Campania 'L. Vanvitelli', Naples, Italy
| | - Serenella Spiezia
- Division of Internal Medicine, University of Campania 'L. Vanvitelli', Naples, Italy
| | - Filomena Boccia
- Division of Internal Medicine, University of Campania 'L. Vanvitelli', Naples, Italy
| | - Massimo Gagliardi
- Division of Internal Medicine, University of Campania 'L. Vanvitelli', Naples, Italy
| | - Fabian Patauner
- Division of Internal Medicine, University of Campania 'L. Vanvitelli', Naples, Italy
| | - Anna Salemme
- Division of Internal Medicine, University of Campania 'L. Vanvitelli', Naples, Italy
| | - Ciro Maiello
- Unit of Cardiac Surgery and Transplants, AORN Ospedali dei Colli-Monaldi Hospital, Naples, Italy
| | - Rosa Zampino
- Division of Internal Medicine, University of Campania 'L. Vanvitelli', Naples, Italy.,Unit of Infectious and Transplant Medicine, AORN Ospedali dei Colli-Monaldi Hospital, Naples, Italy
| | - Emanuele Durante-Mangoni
- Division of Internal Medicine, University of Campania 'L. Vanvitelli', Naples, Italy.,Unit of Infectious and Transplant Medicine, AORN Ospedali dei Colli-Monaldi Hospital, Naples, Italy
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Fung M, Babik JM. COVID-19 in Immunocompromised Hosts: What We Know So Far. Clin Infect Dis 2021; 72:340-350. [PMID: 33501974 PMCID: PMC7337668 DOI: 10.1093/cid/ciaa863] [Citation(s) in RCA: 365] [Impact Index Per Article: 91.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 06/23/2020] [Indexed: 01/08/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused significant morbidity and mortality for patients and stressed healthcare systems worldwide. The clinical features and outcomes of COVID-19 among immunosuppressed patients, who are at presumed risk of more severe disease but who may also have decreased detrimental inflammatory responses, are not well characterized. We review the existing literature on COVID-19 among immunocompromised populations ranging from patients with cancer and solid-organ transplant recipients to patients with HIV and those receiving immunomodulatory therapy for autoimmune disease. Patients with malignancy and solid-organ transplant recipients may be at increased risk of severe COVID-19 disease and death, whereas for those with other types of immunocompromise, current evidence is less clear. Overall, further prospective controlled studies are needed to determine the attributable risk of immunocompromising conditions and therapies on COVID-19 disease prognosis.
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Affiliation(s)
- Monica Fung
- Division of Infectious Disease, Department of Medicine, University of California, San Francisco, San Francisco, California, USA
| | - Jennifer M Babik
- Division of Infectious Disease, Department of Medicine, University of California, San Francisco, San Francisco, California, USA
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30
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NasrAllah MM, Osman NA, Elalfy M, Malvezzi P, Rostaing L. Transplantation in the era of the Covid-19 pandemic: How should transplant patients and programs be handled? Rev Med Virol 2021; 31:1-9. [PMID: 32954602 PMCID: PMC7537021 DOI: 10.1002/rmv.2149] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 07/06/2020] [Accepted: 07/07/2020] [Indexed: 01/08/2023]
Abstract
Due to the Covid-19 pandemic caused by SARS-CoV-2, transplant programs worldwide have been severely impacted with dwindling numbers of transplantations performed and a complete halt in several areas. In this review we examine whether SARS-CoV-2 infection presents differently in transplant recipients, whom and how we should test, how susceptible the transplant population is to overt infection and describe the range of outcomes. From retrieved published reports on SARS-CoV-2infections in 389solid organ transplant recipients reported in the literature, the overall mortality rate was 16.7% (n = 65); however for those with mild or moderate Covid-19 disease this was 2.9% and 2.3% respectively; conversely, for those with severe infection the mortality rate was 52.2%.We then address questions regarding halting transplantation programs during this pandemic, whether all human tissues being considered for transplantation are capable of transmitting the infection, and if we should alter immunosuppressive medications during the pandemic.
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Affiliation(s)
- Mohamed M. NasrAllah
- Department of NephrologyKasr Al Ainy School of Medicine, Cairo UniversityCairoEgypt
- Misr International HospitalCairoEgypt
| | - Noha A. Osman
- Department of NephrologyKasr Al Ainy School of Medicine, Cairo UniversityCairoEgypt
- Misr International HospitalCairoEgypt
| | - Mahmoud Elalfy
- Misr International HospitalCairoEgypt
- Cairo University Student's HospitalCairoEgypt
| | - Paolo Malvezzi
- Service de Néphrologie, Hémodialyse, Aphérèseset Transplantation Rénale, CHU Grenoble‐AlpesGrenobleFrance
| | - Lionel Rostaing
- Service de Néphrologie, Hémodialyse, Aphérèseset Transplantation Rénale, CHU Grenoble‐AlpesGrenobleFrance
- Université Grenoble AlpesGrenobleFrance
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31
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Mohamed IH, Chowdary PB, Shetty S, Sammartino C, Sivaprakasam R, Lindsey B, Thuraisingham R, Yaqoob MM, Khurram MA. Outcomes of Renal Transplant Recipients With SARS-CoV-2 Infection in the Eye of the Storm: A Comparative Study With Waitlisted Patients. Transplantation 2021; 105:115-120. [PMID: 33350626 DOI: 10.1097/tp.0000000000003406] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
BACKGROUND Patients with chronic kidney disease stage 5 and those on immunosuppression are particularly vulnerable and are shielded as per public health strategy. We present our experience of coronavirus disease 2019 (COVID-19) transplant patients in one of the most affected parts of the UK with direct comparison to waitlisted patients. METHODS A single-center prospective study of symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive waitlisted and transplant patients was undertaken to compare these groups and assess clinical outcomes. RESULTS A total of 60 consecutive symptomatic SARS-CoV-2 positive patients were identified with 32 active waitlisted patients and 28 functioning renal transplants. Demographics were similar. The incidence of symptomatic COVID-19 in the waitlisted group was 9.9% compared to 1.9% in renal transplant patients (P < 0.001). Immunosuppression did not influence initial symptomology. Fifteen percent of patients in the waitlisted and 32% in the transplant groups died (P = 0.726). Mortality as proportion of total waitlisted (321 patients) and transplant population (1434 patients) of our centre was 1.5% and 0.6% (P < 0.001), respectively. C-reactive protein (CRP) at 48 h and peak CRP were associated with mortality in both groups while quick sequential organ failure assessment score at 48 h (P = 0.036) was associated with mortality for transplant patients. CONCLUSIONS Incidence of COVID-19 is higher in the waitlisted population but transplant patients have more severe disease, reflected by higher mortality. CRP at 48 h can be used as a predictive tool. In the absence of effective treatments, the current strategy of shielding is arguably the most important factor in protecting patients while resuming transplantation.
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Affiliation(s)
- Ismail H Mohamed
- Department of Renal Transplantation, Bart's Health NHS Trust, London, United Kingdom
| | - Prashanth B Chowdary
- Department of Renal Transplantation, Bart's Health NHS Trust, London, United Kingdom
| | - Shraddha Shetty
- Department of Renal Transplantation, Bart's Health NHS Trust, London, United Kingdom
| | - Cinzia Sammartino
- Department of Renal Transplantation, Bart's Health NHS Trust, London, United Kingdom
| | - Rajesh Sivaprakasam
- Department of Renal Transplantation, Bart's Health NHS Trust, London, United Kingdom
| | - Ben Lindsey
- Department of Renal Transplantation, Bart's Health NHS Trust, London, United Kingdom
| | - Raj Thuraisingham
- Department of Renal Transplantation, Bart's Health NHS Trust, London, United Kingdom
| | - Muhammad M Yaqoob
- Department of Renal Transplantation, Bart's Health NHS Trust, London, United Kingdom
- William Harvey Research Institute, Bart's Health NHS Trust, London, United Kingdom
| | - Muhammad A Khurram
- Department of Renal Transplantation, Bart's Health NHS Trust, London, United Kingdom
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32
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Lai Q, Spoletini G, Bianco G, Graceffa D, Agnes S, Rossi M, Lerut J. SARS-CoV2 and immunosuppression: A double-edged sword. Transpl Infect Dis 2020; 22:e13404. [PMID: 32639598 PMCID: PMC7361075 DOI: 10.1111/tid.13404] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2020] [Accepted: 06/29/2020] [Indexed: 12/15/2022]
Abstract
Severe acute respiratory syndrome Coronavirus 2 (SARS-Cov2) outbreak has caused a pandemic rapidly impacting on the way of life of the entire world. This impact in the specific setting of transplantation and immunosuppression has been poorly explored to date. Discordant data exist on the impact of previous coronavirus outbreaks on immunosuppressed patients. Overall, only a very limited number of cases have been reported in literature, suggesting that transplanted patients not necessarily present an increased risk of severe SARS-Cov2-related disease compared to the general population. We conducted a literature review related to the impact of immunosuppression on coronavirus infections including case reports and series describing immunosuppression management in transplant recipients. The role of steroids, calcineurin inhibitors, and mycophenolic acid has been explored more in detail. A point-in-time snapshot of the yet released literature and some considerations in relation to the use of immunosuppression in SARS-Cov2 infected transplant recipients are provided here for the physicians dealing with immunocompromised patients.
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Affiliation(s)
- Quirino Lai
- Hepatobiliary and Organ Transplantation UnitSapienza University of RomeUmberto I Polyclinic of RomeRomeItaly
| | - Gabriele Spoletini
- General Surgery and Liver TransplantationFondazione Policlinico Universitario A. Gemelli IRCCSRomeItaly
| | - Giuseppe Bianco
- General Surgery and Liver TransplantationFondazione Policlinico Universitario A. Gemelli IRCCSRomeItaly
| | - Dario Graceffa
- Centre for the Study and Treatment of PsoriasisDepartment of Clinical DermatologySan Gallicano Dermatological InstituteIRCCSRomeItaly
| | - Salvatore Agnes
- General Surgery and Liver TransplantationFondazione Policlinico Universitario A. Gemelli IRCCSRomeItaly
| | - Massimo Rossi
- General Surgery and Liver TransplantationFondazione Policlinico Universitario A. Gemelli IRCCSRomeItaly
| | - Jan Lerut
- Institute for Experimental and Clinical Research *IREC ‐ Université catholique de Louvain – UCLBrusselsBelgium
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33
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Moris D, Kesseli SJ, Barbas AS. Kidney transplant recipients infected by COVID-19: Review of the initial published experience. Transpl Infect Dis 2020; 22:e13426. [PMID: 32702150 PMCID: PMC7404372 DOI: 10.1111/tid.13426] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Revised: 07/12/2020] [Accepted: 07/16/2020] [Indexed: 12/19/2022]
Abstract
There is an accumulating body of literature surrounding the impact of COVID-19 infection in solid organ transplant recipients. The aim of this review was to summarize the existing literature specifically in kidney transplant (KTx) recipients, with an emphasis on the epidemiology, clinical presentation, laboratory findings, post-operative outcomes, and therapeutic strategies currently employed. We identified thirty-seven studies published between January 1, 2020, and June 10, 2020, that were included in our analysis. As is reported in the general population, there is a wide variation in COVID-19 presentation among KTx patients, ranging from asymptomatic to life-threatening end-organ failure. The most common symptoms are predominantly respiratory and associated with fever. On laboratory evaluation, many patients present with lymphopenia and increased CRP, which are both associated with inferior outcomes. The majority of patients with severe symptoms have been managed with reduction of immunosuppression, including decreased doses of CNIs and withdrawal of MMF. Lastly, although there are no high-level data supporting the use of immunomodulatory drugs, such as IL-6 inhibitors, early experiences have suggested these drugs may improve outcomes in KTx patients with severe COVID-19.
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Affiliation(s)
- Dimitrios Moris
- Department of SurgeryDuke University School of MedicineDurhamNCUSA
| | | | - Andrew S. Barbas
- Department of SurgeryDuke University School of MedicineDurhamNCUSA
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34
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Chavant A, Gautier-Veyret E, Chhun S, Guilhaumou R, Stanke-Labesque F. [Pharmacokinetic changes related to acute infection. Examples from the SARS-CoV-2 pandemic]. Therapie 2020; 76:319-333. [PMID: 33129512 PMCID: PMC7833468 DOI: 10.1016/j.therap.2020.10.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Revised: 09/18/2020] [Accepted: 10/12/2020] [Indexed: 01/08/2023]
Abstract
The knowledge of factors of pharmacokinetic variability is important in order to personalize pharmacological treatment, particularly for drugs with a narrow therapeutic range for which pharmacological therapeutic monitoring is recommended. Inflammation is a protective response against acute infections and injuries that contributes to intra- and inter-individual variability in drug exposure by modulating the activity of enzymes involved in drug metabolism, and by altering the binding of drugs to plasma proteins. The understanding of the impact of inflammation on drug metabolism and the related clinical consequences allow to better take into consideration the effect of inflammation on the variability of drug exposure. We first summarized the molecular mechanisms by which inflammation contributes to the inhibition of drug metabolism enzymes. We then presented an updated overview of the consequences of the outcome of acute infectious event on pharmacokinetic exposure of drugs with a narrow therapeutic range and that are substrates of cytochrome P450, and the related clinical consequences. Finally, in the context of the COVID-19 pandemic, we reported examples of drug overexposures in COVID- 19 infected patients.
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Affiliation(s)
- Anaëlle Chavant
- Laboratoire de pharmacologie-pharmacogénétique-toxicologie, pôle de biologie et pathologie, CHU Grenoble Alpes, 38700 La Tronche, France
| | - Elodie Gautier-Veyret
- Laboratoire de pharmacologie-pharmacogénétique-toxicologie, pôle de biologie et pathologie, CHU Grenoble Alpes, 38700 La Tronche, France; University Grenoble Alpes, Inserm, CHU Grenoble Alpes, HP2, 38043 Grenoble, France
| | - Stéphanie Chhun
- UFR de médecine Paris centre, 75015 Paris, France; Institut Necker-Enfants Malades (INEM), Inserm U1151-CNRS UMR 8253, 75015 Paris, France; Laboratoire d'immunologie biologique, département médico universitaire BioPhyGen, hôpital universitaire Necker-enfants malades, AP-HP, 75015 Paris, France
| | - Romain Guilhaumou
- Unité de pharmacologie clinique et pharmacovigilance AP-HM, 13354 Marseille, France; Aix Marseille Univ, Inserm, INS Inst Neurosci Syst, 13354 Marseille, France
| | - Françoise Stanke-Labesque
- Laboratoire de pharmacologie-pharmacogénétique-toxicologie, pôle de biologie et pathologie, CHU Grenoble Alpes, 38700 La Tronche, France; University Grenoble Alpes, Inserm, CHU Grenoble Alpes, HP2, 38043 Grenoble, France.
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35
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Corse T, Dayan L, Kersten S, Battaglia F, Terlecky SR, Han Z. Clinical Outcomes of COVID-19 Patients with Pre-existing, Compromised Immune Systems: A Review of Case Reports. Int J Med Sci 2020; 17:2974-2986. [PMID: 33173418 PMCID: PMC7646123 DOI: 10.7150/ijms.50537] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Accepted: 10/08/2020] [Indexed: 12/17/2022] Open
Abstract
In the ongoing COVID-19 pandemic, all COVID-19 patients are naïve patients as it is the first-time humans have been exposed to the SARS-CoV-2 virus. As with exposure to many viruses, individuals with pre-existing, compromised immune systems may be at increased risk of developing severe symptoms and/or dying because of (SARS-CoV-2) infection. To learn more about such individuals, we conducted a search and review of published reports on the clinical characteristics and outcomes of COVID-19 patients with pre-existing, compromised immune systems. Here we present our review of patients who possess pre-existing primary antibody deficiency (PAD) and those who are organ transplant recipients on maintenance immunosuppressants. Our review indicates different clinical outcomes for the patients with pre-existing PAD, depending on the underlying causes. For organ transplant recipients, drug-induced immune suppression alone does not appear to enhance COVID-19 mortality risk - rather, advanced age, comorbidities, and the development of secondary complications appears required.
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Affiliation(s)
- Tanner Corse
- Hackensack Meridian School of Medicine, Nutley, NJ 07110, USA
| | - Linda Dayan
- Hackensack Meridian School of Medicine, Nutley, NJ 07110, USA
| | - Sydney Kersten
- Hackensack Meridian School of Medicine, Nutley, NJ 07110, USA
| | - Fortunato Battaglia
- Department of Medical Sciences, Hackensack Meridian School of Medicine, Nutley, NJ 07110, USA
| | - Stanley R Terlecky
- Department of Medical Sciences, Hackensack Meridian School of Medicine, Nutley, NJ 07110, USA
| | - Zhiyong Han
- Department of Medical Sciences, Hackensack Meridian School of Medicine, Nutley, NJ 07110, USA
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36
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Maritati F, Cerutti E, Zuccatosta L, Fiorentini A, Finale C, Ficosecco M, Cristiano F, Capestro A, Balestra E, Taruscia D, Vivarelli M, Donati A, Perna GP, Giacometti A, Tavio M, Onesta M, Di Sante L, Ranghino A. SARS-CoV-2 infection in kidney transplant recipients: Experience of the italian marche region. Transpl Infect Dis 2020; 22:e13377. [PMID: 32573895 PMCID: PMC7361066 DOI: 10.1111/tid.13377] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2020] [Revised: 05/30/2020] [Accepted: 06/14/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Infection related to Coronavirus-19 (CoV-2) is pandemic affecting more than 4 million people in 187 countries worldwide. By May 10, 2020, it caused more than 280 000 deaths all over the world. Preliminary data reported a high prevalence of CoV-2 infection and mortality due to severe acute respiratory syndrome related CoV-2 (SARS-CoV-2) in kidney-transplanted patients (KTRs). Nevertheless, the outcomes and the best treatments for SARS-CoV-2-affected KTRs remain unclear. METHODS In this report, we describe the clinical data, the treatments, and the outcomes of 5 KTRs with SARS-CoV-2 admitted to our hospital in Ancona, Marche region, Italy, from March 17 to present. Due to the severity of SARS-CoV-2, immunosuppression with calcineurin inhibitors, antimetabolites, and mTOR-inhibitors were stopped at the admission. All KTRs were treated with low-dose steroids. 4/5 KTRs were treated with hydroxychloroquine. All KTRs received tocilizumab up to one dose. RESULTS Overall, the incidence of SARS-CoV-2 in KTRs in the Marche region was 0.85%. 3/5 were admitted in ICU and intubated. One developed AKI with the need of CRRT with Cytosorb. At present, two patients died, two patients were discharged, and one is still inpatient in ICU. CONCLUSIONS The critical evaluation of all cases suggests that the timing of the administration of tocilizumab, an interleukin-6 receptor antagonist, could be associated with a better efficacy when administered in concomitance to the drop of the oxygen saturation. Thus, in SARS-CoV-2-affected KTRs, a close biochemical and clinical monitoring should be set up to allow physicians to hit the virus in the right moment such as a sudden reduction of the oxygen saturation and/or a significant increase in the laboratory values such as D-dimer.
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Affiliation(s)
- Federica Maritati
- Nephrology, Dialysis and Renal Transplantation UnitAzienda Ospedaliera Universitaria Ospedali Riuniti Umberto ILancisiSalesi of AnconaAnconaItaly
| | - Elisabetta Cerutti
- Anesthesia and Transplant Surgical Intensive Care UnitAzienda Ospedaliero Universitaria Ospedali RiunitiAnconaItaly
| | - Lina Zuccatosta
- Operative Unit of PneumologyOspedali Riuniti University HospitalAnconaItaly
| | - Alessandro Fiorentini
- Infectious Diseases ClinicDepartment of Biological Sciences and Public HealthMarche Polytechnic UniversityAnconaItaly
| | - Carolina Finale
- Nephrology, Dialysis and Renal Transplantation UnitAzienda Ospedaliera Universitaria Ospedali Riuniti Umberto ILancisiSalesi of AnconaAnconaItaly
| | - Marta Ficosecco
- Anesthesia and Intensive Care UnitAzienda Ospedaliero Universitaria Ospedali RiunitiAnconaItaly
- Department of Biomedical Sciences and Public HealthUniversità Politecnica delle MarcheAnconaItaly
| | - Fabrizio Cristiano
- Italian Civil Protection Department for Covid‐19 EmergencyNephrology and Dialysis UnitOspedale "San Pio da Pietrelcina"Vasto ChietiItaly
| | - Alessandro Capestro
- Department of Paediatric and Congenital Cardiac Surgery and CardiologyOspedali RiunitiAnconaItaly
| | - Emilio Balestra
- Nephrology, Dialysis and Renal Transplantation UnitAzienda Ospedaliera Universitaria Ospedali Riuniti Umberto ILancisiSalesi of AnconaAnconaItaly
| | - Domenica Taruscia
- Nephrology, Dialysis and Renal Transplantation UnitAzienda Ospedaliera Universitaria Ospedali Riuniti Umberto ILancisiSalesi of AnconaAnconaItaly
| | - Marco Vivarelli
- Hepatobiliary and Abdominal Transplantation SurgeryDepartment of Experimental and Clinical MedicinePolytechnic University of MarcheAnconaItaly
| | - Abele Donati
- Anesthesia and Intensive Care UnitAzienda Ospedaliero Universitaria Ospedali RiunitiAnconaItaly
- Department of Biomedical Sciences and Public HealthUniversità Politecnica delle MarcheAnconaItaly
| | - Gian Piero Perna
- Cardiovascular Science Department, Cardiology and Coronary Care UnitOspedali Riuniti di AnconaAnconaItaly
| | - Andrea Giacometti
- Infectious Diseases ClinicDepartment of Biological Sciences and Public HealthMarche Polytechnic UniversityAnconaItaly
| | - Marcello Tavio
- Unit of Emerging and Immunosuppressed Infectious DiseasesDepartment of Gastroenterology and TransplantationPolytechnic University of MarcheAnconaItaly
| | - Maicol Onesta
- Internal Medicine UnitOspedale di FabrianoFabriano AnconaItaly
| | - Laura Di Sante
- Unit of VirologyDepartment of Biomedical Sciences and Public HealthPolytechnic University of MarcheAnconaItaly
| | - Andrea Ranghino
- Nephrology, Dialysis and Renal Transplantation UnitAzienda Ospedaliera Universitaria Ospedali Riuniti Umberto ILancisiSalesi of AnconaAnconaItaly
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Cravedi P, Schold JD, Safa K, Kates OS, Elfadawy N, Mannon RB, Shah MB, Hammond SP, Avery R, Guerrero Miranda C, Riella LV, Jowsey-Gregoire S, Akalin E, Camirand G, Alegre ML, Azzi J. The COVID-19 pandemic: A community approach. Clin Transplant 2020; 34:e14059. [PMID: 32762055 PMCID: PMC7435543 DOI: 10.1111/ctr.14059] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Accepted: 07/29/2020] [Indexed: 12/23/2022]
Abstract
An unprecedented global pandemic caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) has quickly overwhelmed the health care systems worldwide. While there is an absence of consensus among the community in how to manage solid organ transplant recipients and donors, a platform provided by the American Society of Transplantation online community “Outstanding Questions in Transplantation,” hosted a collaborative multicenter, multinational discussions to share knowledge in a rapidly evolving global situation. Here, we present a summary of the discussion in addition to the latest published literature.
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Affiliation(s)
- Paolo Cravedi
- Department of Medicine, Translational Transplant Research Center, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
| | - Jesse D Schold
- Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA
| | - Kassem Safa
- Transplant Center and Division of Nephrology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Olivia S Kates
- Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA
| | - Nissreen Elfadawy
- Division of Nephrology, Hypertension and Kidney Transplant, Department of Medicine, Case Western Reserve University and University Hospitals, Cleveland, OH, USA
| | - Roslyn B Mannon
- Division of Nephrology, Department of Medicine, University of Nebraska Medical Center, Omaha, NE, USA
| | - Malay B Shah
- Division of Transplantation, Department of Surgery, University of Kentucky Medical Center, Lexington, KY, USA
| | - Sarah P Hammond
- Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Robin Avery
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | | | - Leonardo V Riella
- Transplanation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | | | - Enver Akalin
- Albert Einstein College of Medicine, Montefiore Medical Center, New York City, NY, USA
| | - Geoffrey Camirand
- The Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical, Pittsburgh, PA, USA
| | | | - Jamil Azzi
- Transplanation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
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38
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Rammohan A. Post-transplant immunosuppression and COVID-19: From a double whammy to a mixed blessing. World J Transplant 2020; 10:267-276. [PMID: 32995321 PMCID: PMC7504191 DOI: 10.5500/wjt.v10.i9.267] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 07/21/2020] [Accepted: 08/15/2020] [Indexed: 02/05/2023] Open
Abstract
The coronavirus pandemic (COVID-19) has had an unprecedented effect on various disease processes and their management. COVID-19 is likely to have a complex pathophysiological interplay with the post-transplant patients; one affecting the clinical course and outcome of the other. In the absence of validated data from trials, there is strong dependence on experience based on previous similar epidemics (SARS/MERS), and from consensus based on expert opinions. Despite the fact that our knowledge is rapidly evolving with time, there still is relatively limited objective data on the effect of COVID-19 on the human body. Numerous questions remain unanswered, one of which involves the management of immunosuppression in the post-transplant recipient during this contagion. The core tenet of which continues to be that of establishing an equipoise between infection and rejection. This review summarises the current knowledge on immune interactions of the virus, the immunomodulatory effects that may be at play, and its relation to the art of immunosuppression.
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Affiliation(s)
- Ashwin Rammohan
- The Institute of Liver Disease and Transplantation, Dr. Rela Institute and Medical Centre, Chennai 600044, India
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39
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Marinaki S, Tsiakas S, Korogiannou M, Grigorakos K, Papalois V, Boletis I. A Systematic Review of COVID-19 Infection in Kidney Transplant Recipients: A Universal Effort to Preserve Patients' Lives and Allografts. J Clin Med 2020; 9:2986. [PMID: 32947798 PMCID: PMC7563559 DOI: 10.3390/jcm9092986] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 09/08/2020] [Accepted: 09/10/2020] [Indexed: 02/06/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has posed a significant challenge to physicians and healthcare systems worldwide. Evidence about kidney transplant (KTx) recipients is still limited. A systematic literature review was performed. We included 63 articles published from 1 January until 7 July 2020, reporting on 420 adult KTx recipients with confirmed COVID-19. The mean age of patients was 55 ± 15 years. There was a male predominance (67%). The majority (74%) were deceased donor recipients, and 23% were recently transplanted (<1 year). Most patients (88%) had at least one comorbidity, 29% had two, and 18% three. Ninety-three percent of cases were hospitalized. Among them, 30% were admitted to the intensive care unit, 45% developed acute respiratory distress syndrome, and 44% had acute kidney injury with 23% needing renal replacement therapy. From the hospitalized patients a total of 22% died, 59% were discharged, and 19% were still in hospital at the time of publication. Immunosuppression was reduced in 27%, discontinued in 31%, and remained unchanged in 5%. Hydroxychloroquine was administered to 78% of patients, antibiotics to 73%, and antivirals to 30% while 25% received corticosteroid boluses, 28% received anti-interleukin agents, and 8% were given immunoglobulin. The main finding of our analysis was that the incidence of COVID-19 among kidney transplant patients is not particularly high, but when they do get infected, this is related to significant morbidity and mortality.
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Affiliation(s)
- Smaragdi Marinaki
- Clinic of Nephrology and Renal Transplantation, National and Kapodistrian University of Athens Medical School, Laiko Hospital, 11527 Athens, Greece; (S.M.); (M.K.); (I.B.)
| | - Stathis Tsiakas
- Clinic of Nephrology and Renal Transplantation, National and Kapodistrian University of Athens Medical School, Laiko Hospital, 11527 Athens, Greece; (S.M.); (M.K.); (I.B.)
| | - Maria Korogiannou
- Clinic of Nephrology and Renal Transplantation, National and Kapodistrian University of Athens Medical School, Laiko Hospital, 11527 Athens, Greece; (S.M.); (M.K.); (I.B.)
| | | | - Vassilios Papalois
- Renal and Transplant Directorate, Imperial College Healthcare NHS Trust, London W12 0HS, UK;
- Department of Surgery and Cancer, Imperial College London, London SW7 2AZ, UK
| | - Ioannis Boletis
- Clinic of Nephrology and Renal Transplantation, National and Kapodistrian University of Athens Medical School, Laiko Hospital, 11527 Athens, Greece; (S.M.); (M.K.); (I.B.)
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40
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Abu Jawdeh BG. COVID-19 in Kidney Transplantation: Outcomes, Immunosuppression Management, and Operational Challenges. Adv Chronic Kidney Dis 2020; 27:383-389. [PMID: 33308503 PMCID: PMC7366980 DOI: 10.1053/j.ackd.2020.07.004] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 06/29/2020] [Accepted: 07/14/2020] [Indexed: 12/15/2022]
Abstract
The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2, has led to the death of hundreds of thousands of people worldwide. If infected, older individuals and those with diabetes, hypertension, cardiovascular disease, and compromised immune systems are at higher risk for unfavorable outcomes. These comorbidities are prevalent in patients with kidney disease, hence the significant burden of COVID-19 on kidney transplant programs. Multiple case series of kidney transplant recipients with COVID-19 have shown increased mortality compared to nontransplant patients. To date, we do not have high-level evidence to inform immunosuppression minimization strategies in infected transplant recipients. Most centers however have adopted early antimetabolite withdrawal in addition to other interventions. This review summarizes the published COVID-19 literature as it relates to outcomes and immunosuppression management in kidney transplant recipients. It also discusses challenges pertaining to pretransplant evaluation and wait-listed patients.
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Affiliation(s)
- Bassam G Abu Jawdeh
- Division of Nephrology & Hypertension, University of Cincinnati, Kidney C.A.R.E. Program, Cincinnati, OH.
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41
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Moosavi SA, Mashhadiagha A, Motazedian N, Hashemazar A, Hoveidaei AH, Bolignano D. COVID-19 clinical manifestations and treatment strategies among solid-organ recipients: A systematic review of cases. Transpl Infect Dis 2020; 22:e13427. [PMID: 32779820 PMCID: PMC7404594 DOI: 10.1111/tid.13427] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Revised: 07/15/2020] [Accepted: 07/16/2020] [Indexed: 01/08/2023]
Abstract
BACKGROUND COVID-19 has been spreading worldwide with a significant death toll. Solid-organ transplantation (SOT) recipients are at higher risk due to their suppressed immune system. In this study, we aimed to conduct a systematic review on COVID-19 clinical manifestations and treatment strategies in SOT recipients. METHODS We searched three databases for relevant terms related to COVID-19 and transplantation. 50 studies, including 337 patients, were reviewed. RESULTS Two hundred thirty six patients were male, with a mean age of 49.9 years. The most prevalent group was the kidney 57.0%, followed by 17.2% heart and 13.6% liver. Fever and cough were the most reported clinical presentations. Infiltration (55.4%) in chest x-ray and ground-glass opacity (67.1%) in CT scans were the most radiological findings. It was found that 96.8% and 72.4% of patients present with CRP level and lymphocytopenia, respectively, and 70.6% of kidney recipients patients presented with high creatinine levels. The most common baseline immunosuppressants were calcineurin inhibitors (88.9%) and antimetabolites (73.2%). Antimetabolites (84.3%) and calcineurin inhibitors (54.3%) were discontinued/decreased 84.3% whereas glucocorticoids dosage almost has no change (77.9%) or even increased. 18.4% of cases had died, and 65.9% were discharged. CONCLUSIONS Patients' demographics, signs, symptoms, and radiographic findings in SOT recipients are almost similar to the general population. However, gastrointestinal symptoms appear to be more common. There are different treatment strategies, but in most of them, antimetabolite and calcineurin inhibitors were decreased or discontinued, while corticosteroids were increased. Finally, COVID-19 seems to be more severe and has higher mortality in SOT recipients compared to the general population.
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Affiliation(s)
- Seyed Ali Moosavi
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.,Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Amirali Mashhadiagha
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.,Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Nasrin Motazedian
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Alireza Hashemazar
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Amir Human Hoveidaei
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran.,Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Davide Bolignano
- Department of Surgical and Medical Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy
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42
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Raëth J, Tomio A, Eugene A, Mouffak A, Durand M, Hamidfar R, Pison C, Pluchart H, Mounayar AL. Immunosuppression in a lung transplant recipient with COVID-19? Lessons from an early case. Respir Med Res 2020; 78:100782. [PMID: 32801101 PMCID: PMC7833068 DOI: 10.1016/j.resmer.2020.100782] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 07/09/2020] [Accepted: 07/23/2020] [Indexed: 11/03/2022]
Affiliation(s)
- J Raëth
- Pôle thorax et vaisseaux, service hospitalier universitaire pneumologie, CHU Grenoble Alpes, Grenoble, France; Université Grenoble Alpes, Grenoble, France
| | - A Tomio
- Pôle thorax et vaisseaux, service hospitalier universitaire pneumologie, CHU Grenoble Alpes, Grenoble, France; Université Grenoble Alpes, Grenoble, France
| | - A Eugene
- Université Grenoble Alpes, Grenoble, France; Pôle pharmacie, CHU Grenoble Alpes, Grenoble, France
| | - A Mouffak
- Université Grenoble Alpes, Grenoble, France; Centre régional de pharmacovigilance, centre hospitalier universitaire Grenoble-Alpes, 38000 Grenoble, France
| | - M Durand
- Pôle anesthésie réanimation, CHU Grenoble Alpes, Grenoble, France
| | - R Hamidfar
- Pôle thorax et vaisseaux, service hospitalier universitaire pneumologie, CHU Grenoble Alpes, Grenoble, France
| | - C Pison
- Pôle thorax et vaisseaux, service hospitalier universitaire pneumologie, CHU Grenoble Alpes, Grenoble, France; Université Grenoble Alpes, Grenoble, France.
| | - H Pluchart
- Université Grenoble Alpes, Grenoble, France; Pôle pharmacie, CHU Grenoble Alpes, Grenoble, France; TIMC-IMAG UMR5525/ThEMAS, CNRS, université Grenoble Alpes, Grenoble, France
| | - A L Mounayar
- Pôle urgence médecine aiguë, service des maladies infectieuses et tropicales, CHU Grenoble Alpes, Grenoble, France
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43
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Kataria A, Yakubu I, Winstead R, Gowda M, Gupta G. COVID-19 in Kidney Transplantation: Epidemiology, Management Considerations, and the Impact on Kidney Transplant Practice. Transplant Direct 2020; 6:e582. [PMID: 33134506 PMCID: PMC7581117 DOI: 10.1097/txd.0000000000001031] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 06/12/2020] [Accepted: 06/14/2020] [Indexed: 12/13/2022] Open
Abstract
The novel severe acute respiratory syndrome coronavirus 2 was identified in the late 2019 as the cause of coronavirus disease 2019 (COVID-19), an acute respiratory viral illness. Patients with chronic underlying conditions may have an increased risk of morbidity and mortality from COVID-19. Kidney transplant recipients may be at a uniquely increased risk of serious complications from COVID-19 as compared to the general population because of a chronically immunosuppressed state and a high prevalence of comorbidities like diabetes, heart disease, and lung disease. Early data suggest that the mortality of patients on dialysis may be comparable to those with kidney transplants, although more research is needed. This concise review aims to describe the epidemiology of COVID-19 in kidney transplant recipients, manifestations, appropriate management, and clinical outcomes based on the available literature. Current evidence on many of the specific antiviral measures against COVID-19 has not shown a clear-cut benefit in smaller studies and the results of several ongoing larger clinical trials are awaited. In addition, we also highlight the impact of COVID-19 on kidney transplant center practice and volumes; potential living or deceased donors, recipients; and induction immunosuppression and surgical strategies.
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Affiliation(s)
| | - Idris Yakubu
- Virginia Commonwealth University Health System, Richmond, VA
| | - Ryan Winstead
- Virginia Commonwealth University Health System, Richmond, VA
| | | | - Gaurav Gupta
- Virginia Commonwealth University Health System, Richmond, VA
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44
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de Vries APJ, Alwayn IPJ, Hoek RAS, van den Berg AP, Ultee FCW, Vogelaar SM, Haase-Kromwijk BJJM, Heemskerk MBA, Hemke AC, Nijboer WN, Schaefer BS, Kuiper MA, de Jonge J, van der Kaaij NP, Reinders MEJ. Immediate impact of COVID-19 on transplant activity in the Netherlands. Transpl Immunol 2020; 61:101304. [PMID: 32371150 PMCID: PMC7194049 DOI: 10.1016/j.trim.2020.101304] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Accepted: 04/28/2020] [Indexed: 01/08/2023]
Abstract
The rapid emergence of the COVID-19 pandemic is unprecedented and poses an unparalleled obstacle in the sixty-five year history of organ transplantation. Worldwide, the delivery of transplant care is severely challenged by matters concerning - but not limited to - organ procurement, risk of SARS-CoV-2 transmission, screening strategies of donors and recipients, decisions to postpone or proceed with transplantation, the attributable risk of immunosuppression for COVID-19 and entrenched health care resources and capacity. The transplant community is faced with choosing a lesser of two evils: initiating immunosuppression and potentially accepting detrimental outcome when transplant recipients develop COVID-19 versus postponing transplantation and accepting associated waitlist mortality. Notably, prioritization of health care services for COVID-19 care raises concerns about allocation of resources to deliver care for transplant patients who might otherwise have excellent 1-year and 10-year survival rates. Children and young adults with end-stage organ disease in particular seem more disadvantaged by withholding transplantation because of capacity issues than from medical consequences of SARS-CoV-2. This report details the nationwide response of the Dutch transplant community to these issues and the immediate consequences for transplant activity. Worrisome, there was a significant decrease in organ donation numbers affecting all organ transplant services. In addition, there was a detrimental effect on transplantation numbers in children with end-organ failure. Ongoing efforts focus on mitigation of not only primary but also secondary harm of the pandemic and to find right definitions and momentum to restore the transplant programs.
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Affiliation(s)
- A P J de Vries
- Department of Internal Medicine, Division of Nephrology and Transplant Center, Leiden University Medical Center, Leiden, the Netherlands
| | - I P J Alwayn
- Department of Surgery, Division of Transplant Surgery and Transplant Center, Leiden University Medical Center, Leiden, the Netherlands
| | - R A S Hoek
- Department of Pulmonary Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - A P van den Berg
- Department of Gastroenterology and Hepatology, University Hospital Groningen, Groningen, the Netherlands
| | - F C W Ultee
- Department of Nephrology and surgery/transplant coordination, Academic Medical Center, Amsterdam, the Netherlands
| | - S M Vogelaar
- Eurotransplant International, Leiden, the Netherlands
| | | | - M B A Heemskerk
- Dutch Transplant Foundation (DTF/NTS), Leiden, the Netherlands
| | - A C Hemke
- Dutch Transplant Foundation (DTF/NTS), Leiden, the Netherlands
| | - W N Nijboer
- Department of Surgery, Division of Transplant Surgery and Transplant Center, Leiden University Medical Center, Leiden, the Netherlands
| | - B S Schaefer
- Dutch Transplant Foundation (DTF/NTS), Leiden, the Netherlands
| | - M A Kuiper
- Dutch Transplant Foundation (DTF/NTS), Leiden, the Netherlands.; Medical Center Leeuwarden, Department of Intensive care, Leeuwarden, the Netherlands
| | - J de Jonge
- Department of Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands; Dutch Transplant Society (DTS/NTV), the Netherlands
| | - N P van der Kaaij
- Department of Cardiothoracic Surgery, University Medical Center Utrecht, Utrecht, the Netherlands; Dutch Transplant Society (DTS/NTV), the Netherlands
| | - M E J Reinders
- Department of Internal Medicine, Division of Nephrology and Transplant Center, Leiden University Medical Center, Leiden, the Netherlands; Dutch Transplant Society (DTS/NTV), the Netherlands.
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45
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Mirjalili M, Shafiekhani M, Vazin A. Coronavirus Disease 2019 (COVID-19) and Transplantation: Pharmacotherapeutic Management of Immunosuppression Regimen. Ther Clin Risk Manag 2020; 16:617-629. [PMID: 32694915 PMCID: PMC7340365 DOI: 10.2147/tcrm.s256246] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Accepted: 06/13/2020] [Indexed: 12/15/2022] Open
Abstract
The 2019 novel coronavirus disease (COVID-19) was first detected in Wuhan, Hubei Province, China, in late 2019. Since then, COVID-19 has spread to more than 200 countries in the world, and a global pandemic has been declared by the World Health Organization (WHO). At present, no vaccines or therapeutic regimens with proven efficacy are available for the management of COVID-19. Hydroxychloroquine/chloroquine, lopinavir/ritonavir, ribavirin, interferons, umifenovir, remdesivir, and interleukin antagonists, such as tocilizumab, have been recommended as potential treatment options in COVID-19. Transplant patients receiving immunosuppressant medications are at the highest risk of severe illness from COVID-19. At the same time, with regard to receiving polypharmacy and immunosuppressants, treatment options should be chosen with more attention in this population. Considering drug-drug interactions and adverse effects of medications used for the treatment of COVID-19, such as QT prolongation, the dose reduction of some immunosuppressants or avoidance is recommended in transplant recipients with COVID-19. Thus, this narrative review describes clinically important considerations about the treatment of COVID-19 and immunosuppressive regimens regarding modifications, side effects, and interactions in adult kidney or liver allograft recipients.
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Affiliation(s)
- Mahtabalsadat Mirjalili
- Department of Clinical Pharmacy, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mojtaba Shafiekhani
- Department of Clinical Pharmacy, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
- Shiraz Organ Transplant Center, Abu-Ali Sina Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Afsaneh Vazin
- Department of Clinical Pharmacy, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
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46
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Meziyerh S, Zwart TC, van Etten RW, Janson JA, van Gelder T, Alwayn IP, de Fijter JW, Reinders ME, Moes DJ, de Vries AP. Severe COVID-19 in a renal transplant recipient: A focus on pharmacokinetics. Am J Transplant 2020; 20:1896-1901. [PMID: 32337790 PMCID: PMC7267503 DOI: 10.1111/ajt.15943] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Revised: 04/05/2020] [Accepted: 04/16/2020] [Indexed: 01/25/2023]
Abstract
The current coronavirus disease 2019 (COVID-19) pandemic requires extra attention for immunocompromised patients, including solid organ transplant recipients. We report on a case of a 35-year-old renal transplant recipient who suffered from a severe COVID-19 pneumonia. The clinical course was complicated by extreme overexposure to the mammalian target of rapamycin inhibitor everolimus, following coadministration of chloroquine and lopinavir/ritonavir therapy. The case is illustrative for dilemmas that transplant professionals may face in the absence of evidence-based COVID-19 therapy and concurrent pressure for exploration of experimental pharmacological treatment options. However, the risk-benefit balance of experimental or off-label therapy may be weighed differently in organ transplant recipients than in otherwise healthy COVID-19 patients, owing to their immunocompromised status and potential drug interactions with immunosuppressive therapy. With this case report, we aimed to achieve increased awareness and improved management of drug-drug interactions associated with the various treatment options for COVID-19 in renal transplant patients.
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Affiliation(s)
- Soufian Meziyerh
- Department of Internal Medicine, Division of Nephrology, Leiden University Medical Center, Leiden, The Netherlands,LUMC Transplant Center, Leiden University Medical Center, Leiden, The Netherlands,Correspondence Soufian Meziyerh
| | - Tom C. Zwart
- Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands
| | - Ronald W. van Etten
- Department of Internal Medicine, Division of Nephrology, Amphia Hospital, Breda, The Netherlands
| | - Jeroen A. Janson
- Department of Intensive Care, Leiden University Medical Center, Leiden, The Netherlands
| | - Teun van Gelder
- Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands
| | - Ian P.J. Alwayn
- LUMC Transplant Center, Leiden University Medical Center, Leiden, The Netherlands,Department of Surgery, Division of Transplantation Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Johan W. de Fijter
- Department of Internal Medicine, Division of Nephrology, Leiden University Medical Center, Leiden, The Netherlands,LUMC Transplant Center, Leiden University Medical Center, Leiden, The Netherlands
| | - Marlies E.J. Reinders
- Department of Internal Medicine, Division of Nephrology, Leiden University Medical Center, Leiden, The Netherlands,LUMC Transplant Center, Leiden University Medical Center, Leiden, The Netherlands
| | - Dirk J.A.R. Moes
- Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands
| | - Aiko P.J. de Vries
- Department of Internal Medicine, Division of Nephrology, Leiden University Medical Center, Leiden, The Netherlands,LUMC Transplant Center, Leiden University Medical Center, Leiden, The Netherlands
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47
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Multiple drugs. REACTIONS WEEKLY 2020. [PMCID: PMC7378983 DOI: 10.1007/s40278-020-81246-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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48
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Alfishawy M, Elbendary A, Mohamed M, Nassar M. COVID-19 Mortality in Transplant Recipients. Int J Organ Transplant Med 2020; 11:145-162. [PMID: 33335696 PMCID: PMC7726838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/12/2023] Open
Abstract
BACKGROUND Organ transplant recipients are vulnerable to multiple infectious agents and in a world with a circulating SARS-CoV-2 virus, it would be expected that patients who are immunosuppressed would have higher mortality. OBJECTIVE To determine the COVID-19 mortality in transplant recipients. METHODS We conducted a search in PubMed and Google scholar databases using the keywords for COVID-19 and transplantation. All related studies between January 1, 2020 and May 7, 2020 were reviewed. All relevant published articles related to COVID-19 in transplant recipients were included. RESULTS 46 articles were included; they studied a total of 320 transplant patients-220 kidney transplant recipients, 42 liver, 19 heart, 22 lung, 8 HSCT, and 9 dual organ transplant recipients. The overall mortality rate was 20% and was variable among different organs and different countries. 65 transplant recipients died of complications attributable to COVID-19; 33 were males (15% of males in this cohort), 8 females (8% of females in this cohort), and 24 whose sex was not determined. They had a median age of 66 (range: 32-87) years. The median transplantation duration was 8 years (range: 30 days to 20 years). The most frequent comorbidity reported was hypertensions followed by diabetes mellitus, obesity, malignancy, ischemic heart disease, and chronic obstructive pulmonary disease. The most frequent cause of death reported was acute respiratory distress syndrome. CONCLUSION Transplant recipients in our cohort had a high mortality rate. However, outcomes were not the same in different countries based on outbreak settings. Mortality was noted in elder patients with comorbidities.
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Affiliation(s)
- M. Alfishawy
- Infectious Diseases Consultants and Academic Researchers of Egypt (IDCARE), Cairo, Egypt
- Aswan Heart Centre, Aswan, Egypt
| | - A. Elbendary
- Dermatology Department, Kasr Alainy Faculty of Medicine, Cairo University, Cairo, Egypt
| | - M. Mohamed
- Nephrology Division, University of Tennessee Health Science Center, Memphis, TN, USA
| | - M. Nassar
- Internal Medicine Department, Beni Suef University, Beni Suef, Egypt
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