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Miao S, Yang M, Li W, Yang Z, Yan J. Efficacy and safety of calcineurin inhibitors (CNIs) for septic patients in ICU: a cohort study from MIMIC database. Front Pharmacol 2024; 15:1394553. [PMID: 39359246 PMCID: PMC11445137 DOI: 10.3389/fphar.2024.1394553] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Accepted: 09/09/2024] [Indexed: 10/04/2024] Open
Abstract
Background Sepsis is marked by a dysregulated immune response to infection. Calcineurin inhibitors (CNIs), commonly used as immunosuppressants, have unique properties that may help mitigate the overactive immune response in sepsis, potentially leading to better patient outcomes. This study aims to assess whether CNIs improve prognosis in septic patients and to evaluate any associated adverse reactions. Methods We utilized the Medical Information Mart for Intensive Care IV 2.2 (MIMIC-IV 2.2) database to identify septic patients who were treated with CNIs and those who were not. Propensity score matching (PSM) was employed to balance baseline characteristics between the CNI user group and the non-user group. The primary outcome was 28-day mortality, analyzed using the Kaplan-Meier method and Cox proportional hazard regression models to examine the relationship between CNI use and patient survival. Results From the MIMIC-IV database, 22,517 septic patients were identified. After propensity score matching, a sample of 874 patients was analyzed. The CNI group exhibited a significantly lower 28-day mortality risk compared to the non-user group (HR: 0.26; 95% CI: 0.17, 0.41) in the univariate Cox hazard analysis. Kaplan-Meier survival curves also demonstrated a significantly higher 28- and 365-day survival rate for CNI users compared to non-users (log-rank test p-value = 0.001). No significant association was found between CNI use and an increased risk of new-onset infection (p = 0.144), but an association with mild hypertension (P < 0.001) and liver injury (P < 0.001) was observed. Conclusion The use of calcineurin inhibitors was associated with reduced short- and long-term mortality in septic patients without an increased incidence of new-onset infections, hyperkalemia, severe hypertension, or acute kidney injury (AKI). However, CNI use may lead to adverse effects, such as liver injury and mild hypertension.
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Affiliation(s)
- ShengHui Miao
- The Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu, China
| | - Mingkun Yang
- Department of Second Clinical Medical College, Zhejiang Chinese Medicine University, Hangzhou, Zhejiang, China
| | - Wen Li
- Department of Second Clinical Medical College, Zhejiang Chinese Medicine University, Hangzhou, Zhejiang, China
| | - Zhouxin Yang
- Department of Critical Care Medicine, Zhejiang Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Jing Yan
- Department of Critical Care Medicine, Zhejiang Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
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Inayat F, Patel P, Ali H, Afzal A, Tahir H, Chaudhry A, Ishtiaq R, Rehman AU, Darji K, Afzal MS, Nawaz G, Giammarino A, Satapathy SK. Impact of COVID-19 on liver transplant recipients: A nationwide cohort study evaluating hospitalization, transplant rejection, and inpatient mortality. World J Transplant 2024; 14:90866. [PMID: 38947960 PMCID: PMC11212588 DOI: 10.5500/wjt.v14.i2.90866] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 03/22/2024] [Accepted: 04/23/2024] [Indexed: 06/13/2024] Open
Abstract
BACKGROUND The coronavirus disease 2019 (COVID-19) pandemic has posed a major public health concern worldwide. Patients with comorbid conditions are at risk of adverse outcomes following COVID-19. Solid organ transplant recipients with concurrent immunosuppression and comorbidities are more susceptible to a severe COVID-19 infection. It could lead to higher rates of inpatient complications and mortality in this patient population. However, studies on COVID-19 outcomes in liver transplant (LT) recipients have yielded inconsistent findings. AIM To evaluate the impact of the COVID-19 pandemic on hospital-related outcomes among LT recipients in the United States. METHODS We conducted a retrospective cohort study using the 2019-2020 National Inpatient Sample database. Patients with primary LT hospitalizations and a secondary COVID-19 diagnosis were identified using the International Classification of Diseases, Tenth Revision coding system. The primary outcomes included trends in LT hospitalizations before and during the COVID-19 pandemic. Secondary outcomes included comparative trends in inpatient mortality and transplant rejection in LT recipients. RESULTS A total of 15720 hospitalized LT recipients were included. Approximately 0.8% of patients had a secondary diagnosis of COVID-19 infection. In both cohorts, the median admission age was 57 years. The linear trends for LT hospitalizations did not differ significantly before and during the pandemic (P = 0.84). The frequency of in-hospital mortality for LT recipients increased from 1.7% to 4.4% between January 2019 and December 2020. Compared to the pre-pandemic period, a higher association was noted between LT recipients and in-hospital mortality during the pandemic, with an odds ratio (OR) of 1.69 [95% confidence interval (CI): 1.55-1.84), P < 0.001]. The frequency of transplant rejections among hospitalized LT recipients increased from 0.2% to 3.6% between January 2019 and December 2020. LT hospitalizations during the COVID-19 pandemic had a higher association with transplant rejection than before the pandemic [OR: 1.53 (95%CI: 1.26-1.85), P < 0.001]. CONCLUSION The hospitalization rates for LT recipients were comparable before and during the pandemic. Inpatient mortality and transplant rejection rates for hospitalized LT recipients were increased during the COVID-19 pandemic.
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Affiliation(s)
- Faisal Inayat
- Department of Internal Medicine, Allama Iqbal Medical College, Lahore, Punjab 54550, Pakistan
| | - Pratik Patel
- Division of Gastroenterology, Mather Hospital and Zucker School of Medicine at Hofstra University, Port Jefferson, NY 11777, United States
| | - Hassam Ali
- Division of Gastroenterology and Hepatology, East Carolina University Brody School of Medicine, Greenville, NC 27834, United States
| | - Arslan Afzal
- Division of Gastroenterology and Hepatology, East Carolina University Brody School of Medicine, Greenville, NC 27834, United States
| | - Hamza Tahir
- Department of Internal Medicine, Jefferson Einstein Hospital, Philadelphia, PA 19141, United States
| | - Ahtshamullah Chaudhry
- Department of Internal Medicine, St. Dominic's Hospital, Jackson, MS 39216, United States
| | - Rizwan Ishtiaq
- Department of Internal Medicine, Saint Francis Hospital and Medical Center, Hartford, CT 06105, United States
| | - Attiq Ur Rehman
- Division of Hepatology, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA 18711, United States
| | - Kishan Darji
- Department of Internal Medicine, Campbell University and Cape Fear Valley Medical Center, Fayetteville, NC 28301, United States
| | - Muhammad Sohaib Afzal
- Department of Internal Medicine, Louisiana State University Health, Shreveport, LA 71103, United States
| | - Gul Nawaz
- Department of Internal Medicine, Allama Iqbal Medical College, Lahore, Punjab 54550, Pakistan
| | - Alexa Giammarino
- Department of Internal Medicine, North Shore University Hospital and Zucker School of Medicine at Hofstra University, Manhasset, NY 11030, United States
| | - Sanjaya K Satapathy
- Division of Hepatology, North Shore University Hospital and Zucker School of Medicine at Hofstra University, Manhasset, NY 11030, United States
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Cobo-Ibáñez T, Mora Ortega G, Sánchez-Piedra C, Serralta-San Martín G, Thuissard-Vasallo IJ, Lores Gutiérrez V, Soler Rangel L, García Yubero C, Esteban-Vázquez A, López-Aspiroz E, Andreu Vázquez C, Toboso I, Martínez Alonso de Armiño BM, Olivares Alviso RA, Calderón Nieto R, Yañez C, Zakhour González MA, Sainz Sánchez T, Arroyo de la Torre S, Del Amo Del Arco N, Gómez-Cerezo JF, Ramírez Prieto T, Martínez Hernández A, Muñoz-Fernández S. Cyclosporine A in hospitalized COVID-19 pneumonia patients to prevent the development of interstitial lung disease: a pilot randomized clinical trial. Sci Rep 2024; 14:3789. [PMID: 38360855 PMCID: PMC10869838 DOI: 10.1038/s41598-024-54196-5] [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: 06/26/2023] [Accepted: 02/09/2024] [Indexed: 02/17/2024] Open
Abstract
Post-COVID-19 interstitial lung disease (ILD) is a new entity that frequently causes pulmonary fibrosis and can become chronic. We performed a single-center parallel-group open-label pilot randomized clinical trial to investigate the efficacy and safety of cyclosporine A (CsA) in the development of ILD in the medium term among patients hospitalized with COVID-19 pneumonia. Patients were randomized 1:1 to receive CsA plus standard of care or standard of care alone. The primary composite outcome was the percentage of patients without ILD 3 months after diagnosis of pneumonia and not requiring invasive mechanical ventilation (IMV) (response without requiring IMV). The key secondary composite outcomes were the percentage of patients who achieve a response requiring IMV or irrespective of the need for IMV, and adverse events. A total of 33 patients received at least one dose of CsA plus standard of care (n = 17) or standard of care alone (n = 16). No differences were found between the groups in the percentage of patients who achieved a response without requiring IMV or a response requiring IMV. A higher percentage of patients achieved a response irrespective of the need for IMV in the CsA plus standard of care group although the RR was almost significant 2.833 (95% CI, 0.908-8.840; p = 0.057). No differences were found between the groups for adverse events. In hospitalized patients with COVID-19 pneumonia, we were unable to demonstrate that CsA achieved a significant effect in preventing the development of ILD. (EU Clinical Trials Register; EudraCT Number: 2020-002123-11; registration date: 08/05/2020).
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Affiliation(s)
- Tatiana Cobo-Ibáñez
- Department of Rheumatology, Hospital Universitario Infanta Sofía, Universidad Europea de Madrid, 28702, Madrid, Spain.
- Fundación para la Investigación e Innovación Biomédica del Hospital Universitario Infanta Sofía y Hospital Universitario del Henares (FIIB HUIS HHEN), 28702, Madrid, Spain.
| | - Gemma Mora Ortega
- Department of Pneumology, Hospital Universitario Infanta Sofía, Universidad Europea de Madrid, 28702, Madrid, Spain
| | | | - Gonzalo Serralta-San Martín
- Department of Internal Medicine, Hospital Universitario Infanta Sofía, Universidad Europea de Madrid, 28702, Madrid, Spain
| | - Israel J Thuissard-Vasallo
- Department of Medicine, Faculty of Biomedical and Health Sciences, Universidad Europea de Madrid, 28670, Madrid, Spain
| | - Vanesa Lores Gutiérrez
- Department of Pneumology, Hospital Universitario Infanta Sofía, Universidad Europea de Madrid, 28702, Madrid, Spain
| | - Llanos Soler Rangel
- Department of Internal Medicine, Hospital Universitario Infanta Sofía, Universidad Europea de Madrid, 28702, Madrid, Spain
| | | | - Ana Esteban-Vázquez
- Department of Rheumatology, Hospital Universitario Infanta Sofía, Universidad Europea de Madrid, 28702, Madrid, Spain
| | - Elena López-Aspiroz
- Deparment of Pharmacy, Hospital Universitario Infanta Sofía, 28702, Madrid, Spain
| | - Cristina Andreu Vázquez
- Department of Medicine, Faculty of Biomedical and Health Sciences, Universidad Europea de Madrid, 28670, Madrid, Spain
| | - Inmaculada Toboso
- Deparment of Immunology, Hospital Universitario Infanta Sofía, 28702, Madrid, Spain
| | | | | | - Rocío Calderón Nieto
- Department of Emergency, Hospital Universitario Infanta Sofía, 28702, Madrid, Spain
| | - Cecilia Yañez
- Department of Emergency, Hospital Universitario Infanta Sofía, 28702, Madrid, Spain
| | | | - Tatiana Sainz Sánchez
- Department of Pneumology, Hospital Universitario Infanta Sofía, Universidad Europea de Madrid, 28702, Madrid, Spain
| | - Silvia Arroyo de la Torre
- Department of Pneumology, Hospital Universitario Infanta Sofía, Universidad Europea de Madrid, 28702, Madrid, Spain
| | | | - Jorge Francisco Gómez-Cerezo
- Department of Internal Medicine, Hospital Universitario Infanta Sofía, Universidad Europea de Madrid, 28702, Madrid, Spain
| | - Teresa Ramírez Prieto
- Department of Pneumology, Hospital Universitario Infanta Sofía, Universidad Europea de Madrid, 28702, Madrid, Spain
| | | | - Santiago Muñoz-Fernández
- Department of Rheumatology, Hospital Universitario Infanta Sofía, Universidad Europea de Madrid, 28702, Madrid, Spain
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Migliorini F, Maffulli N, Shukla T, D'Ambrosi R, Singla M, Vaish A, Vaishya R. The pandemic is gone but its consequences are here to stay: avascular necrosis following corticosteroids administration for severe COVID-19. J Orthop Surg Res 2024; 19:135. [PMID: 38347592 PMCID: PMC10860242 DOI: 10.1186/s13018-024-04556-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Accepted: 01/11/2024] [Indexed: 02/15/2024] Open
Abstract
BACKGROUND In patients with COVID-19 infection and respiratory insufficiency, corticosteroid (CCS) administration is recommended. Among the wide range of complications and interactions, time-limited high-dose CCS administration might promote avascular necrosis (AVN) in a cumulative dose. This systematic review updated the current evidence and characterises the trend of AVN following time-limited high-dose CCS administration in patients who had severe COVID-19, discussing management strategies and outcomes. METHODS This systematic review was conducted according to the 2020 PRISMA statement. In October 2023, the following databases were accessed: PubMed, Web of Science, Google Scholar, and Scopus restricting the search to the years 2019 to 2023. All the clinical studies which investigated the association between time-limited high-dose CCS administration in patients with severe COVID-19 infection and AVN were accessed. RESULTS A total of 245 patients (9 studies) who experienced AVN following COVID-19 were included in the present investigation. 26% (63 of 245 included patients) were women. The mean age of the patients was 42.9 ± 17.7 years. Four studies focused on AVN of the hip and two on the knee, and the other studies included patients with AVN from mixed areas of the body (spine, pelvis, and shoulder). The mean time elapsed from COVID-19 infection to the development of symptomatic AVN was 79.4 ± 59.2 days (range, 14 to 166 days). CONCLUSION It is possible that even time-limited high-dose CCS administration in patients with severe COVID-19 infection increased the incidence of AVN. The mean time elapsed from COVID-19 infection to the development of symptomatic AVN was approximately 80 days. Given the high risk of bias in all the included studies, the quality of recommendations of the present investigation is low, and no reliable conclusion can be inferred.
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Affiliation(s)
- Filippo Migliorini
- Department of Orthopaedic, Trauma, and Reconstructive Surgery, RWTH University Hospital, Pauwelsstraße 30, 52074, Aachen, Germany.
- Department of Orthopedics and Trauma Surgery, Academic Hospital of Bolzano (SABES-ASDAA), Teaching Hospital of the Paracelsus Medical University, 39100, Bolzano, Italy.
| | - Nicola Maffulli
- Department of Medicine and Psychology, University of Rome "La Sapienza", Rome, Italy
- Faculty of Medicine, School of Pharmacy and Bioengineering, Keele University, Stoke on Trent, ST4 7QB, England
- Barts and the London School of Medicine and Dentistry, Centre for Sports and Exercise Medicine, Mile End Hospital, Queen Mary University of London, London, E1 4DG, England
| | - Tapish Shukla
- Department of Orthopaedics and Joint Replacement Surgery, Indraprastha Apollo Hospitals Institutes of Orthopaedics, New Delhi, 110076, India
| | - Riccardo D'Ambrosi
- Department of Orthopaedics, IRCCS Istituto Ortopedico Galeazzi, 20161, Milan, Italy
| | - Mohit Singla
- Department of Orthopedics, PGIMS, Rohtak, Haryana, 124001, India
| | - Abhishek Vaish
- Department of Orthopaedics and Joint Replacement Surgery, Indraprastha Apollo Hospitals Institutes of Orthopaedics, New Delhi, 110076, India
| | - Raju Vaishya
- Department of Orthopaedics and Joint Replacement Surgery, Indraprastha Apollo Hospitals Institutes of Orthopaedics, New Delhi, 110076, India
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Heydari B, Sahebnasagh A, Omrani MA, Azimi S, Dehghani MH, Salehi-Abargouei A, Farman F, Saghafi F. Promises and Pitfalls of Calcineurin Inhibitors in COVID-19: A Systematic Review and Meta-analysis of Controlled Trials. Curr Med Chem 2024; 31:4745-4755. [PMID: 38099537 DOI: 10.2174/0109298673264362231022150520] [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: 05/27/2023] [Revised: 06/24/2023] [Accepted: 07/31/2023] [Indexed: 01/23/2025]
Abstract
OBJECTIVE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a violent attack on the body that leads to multi-organ failure and death in COVID-19 patients. The aim of this study was to systematically review the existing literature on the potential benefits of calcineurin inhibitors (CIs) as anti-vascular endothelial growth factor (VEGF) agents in improving the clinical outcomes of COVID-19 patients. METHODS We searched various databases, including PubMed, Scopus, ISI Web of Science, Google Scholar, Cochrane databases, and ClinicalTrials.gov from 31st December, 2019, to 3rd February, 2023, for relevant controlled trials. The quality of the evidence was assessed using the Cochrane Collaboration tool. Comprehensive Meta-Analysis Software was used for the statistical analyses using a random-effects model. RESULTS Three trials enrolling 293 participants were reviewed in the present systematic review and meta-analysis. The results showed CIs to lead to a significant reduction in mortality rate [risk ratio (RR): 0.598, 95% CI: 0.404-0.885, P-value = 0.010] with a low between-study heterogeneity (Cochrane Q test: I2 = 0.000%, P-value = 0.371). Pooled analysis of two studies (84 patients) illustrated that CIs could not significantly increase the rate of hospital discharge (RR: 1.161, 95% CI: 0.764-1.764, P-value = 0.485) and heterogeneity was not significant (Cochrane Q test: I2 = 26.798%, P-value = 0.242). CONCLUSION CIs are able to inhibit the virus nucleocapsid protein so that they can prevent replication and respiratory tract tissue damage caused by SARS-CoV-2. Based on the characteristics mentioned in detail, CIs can play a potential therapeutic role for COVID-19 patients.
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Affiliation(s)
- Behrooz Heydari
- Department of Clinical Pharmacy, School of Pharmacy, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran
| | - Adeleh Sahebnasagh
- Department of Internal Medicine, Clinical Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Mohammad Ali Omrani
- Pharmaceutical Sciences Research Center, School of Pharmacy, Student Research Committee, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Saeed Azimi
- Student Research Committee, Department of Clinical Pharmacy, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Hossein Dehghani
- Department of Anesthesiology and Critical Care, Shahid Rahnemoun Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Amin Salehi-Abargouei
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Farnoosh Farman
- Pharmaceutical Sciences Research Center, School of Pharmacy, Student Research Committee, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Fatemeh Saghafi
- Department of Clinical Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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Lan Q, Yan Y, Zhang G, Xia S, Zhou J, Lu L, Jiang S. Clinical development of antivirals against SARS-CoV-2 and its variants. CURRENT RESEARCH IN MICROBIAL SCIENCES 2023; 6:100208. [PMID: 38149085 PMCID: PMC10750039 DOI: 10.1016/j.crmicr.2023.100208] [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] [Indexed: 12/28/2023] Open
Abstract
The unceasing global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) calls for the development of novel therapeutics. Although many newly developed antivirals and repurposed antivirals have been applied to the treatment of coronavirus disease 2019 (COVID-19), antivirals showing satisfactory clinical efficacy are few in number. In addition, the loss of sensitivity to variants of concern (VOCs) and lack of oral bioavailability have also limited the clinical application of some antivirals. These facts remind us to develop more potent and broad-spectrum antivirals with better pharmacokinetic/pharmacodynamic properties to fight against infections from SARS-CoV-2, its variants, and other human coronaviruses (HCoVs). In this review, we summarize the latest advancements in the clinical development of antivirals against infections by SARS-CoV-2 and its variants.
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Affiliation(s)
- Qiaoshuai Lan
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China
- Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong, China
| | - Yan Yan
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China
| | - Guangxu Zhang
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China
| | - Shuai Xia
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China
| | - Jie Zhou
- Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong, China
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China
| | - Lu Lu
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China
| | - Shibo Jiang
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China
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Arends EJ, Meziyerh S, Moes DJA, Kamerling SW, van der Kooy S, Ogando NS, Snijder EJ, van Hemert M, Visser LG, Feltkamp MC, Claas EC, Rabelink TJ, van Kooten C, de Vries AP, Teng YO. Voclosporin and the Antiviral Effect Against SARS-CoV-2 in Immunocompromised Kidney Patients. Kidney Int Rep 2023; 8:2654-2664. [PMID: 38106593 PMCID: PMC10719564 DOI: 10.1016/j.ekir.2023.09.003] [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: 06/16/2023] [Revised: 08/17/2023] [Accepted: 09/04/2023] [Indexed: 12/19/2023] Open
Abstract
Introduction Immunocompromised kidney patients are at increased risk of prolonged SARS-CoV-2 infection and related complications. Preclinical evidence demonstrates a more potent inhibitory effect of voclosporin on SARS-CoV-2 replication than tacrolimus in vitro. We investigated the potential antiviral effects of voclosporin on SARS-CoV-2 in immunocompromised patients. Methods First, we conducted a prospective, randomized, open-label, proof-of-concept study in 20 kidney transplant recipients (KTRs) on tacrolimus-based immunosuppression who contracted mild to moderate SARS-CoV-2 infection. Patients were randomized to continue tacrolimus or switch to voclosporin. Second, we performed a post hoc analysis on SARS-CoV-2 infections in 216 patients with lupus nephritis (LN) on standard immunosuppression who were randomly exposed to voclosporin or placebo as part of a clinical trial that was conducted during the worldwide COVID-19 pandemic. Results The primary end point was clearance of SARS-CoV-2 viral load and that did not differ between voclosporin-treated KTRs (median 12 days, interquartile range [IQR] 8-28) and tacrolimus-treated KTRs (median 12 days, IQR 4-16) nor was there a difference in clinical recovery. Pharmacokinetic analyses demonstrated that, when voclosporin trough levels were on-target, SARS-CoV-2 viral load dropped significantly more (ΔCt 7.7 [3.4-10.7]) compared to tacrolimus-treated KTRs (ΔCt 2.7 [2.0-4.3]; P = 0.035). In voclosporin-exposed patients with LN, SARS-CoV-2 infection was detected in 6% (7/116) compared to 12% (12/100) in placebo-exposed patients (relative risk [RR] 1.4 [0.97-2.06]). Notably, no voclosporin-exposed patients with LN died from severe SARS-CoV-2 infection compared to 3% (3/100) in placebo-exposed patients (RR 2.2 [1.90-2.54]). Conclusion This proof-of-concept study shows a potential positive risk-benefit profile for voclosporin in immunocompromised patients with SARS-CoV-2 infection. These results warrant further investigations on voclosporin to establish an equipoise between infection and maintenance immunosuppression.
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Affiliation(s)
- Eline J. Arends
- Department of Internal Medicine section Nephrology, Center of Expertise for Lupus-, Vasculitis and Complement- mediated Systemic Autoimmune Diseases, Leiden University Medical Center, Leiden, the Netherlands
| | - Soufian Meziyerh
- Department of Internal Medicine section Nephrology, Leiden Transplant Center, Leiden University Medical Center, Leiden, the Netherlands
| | - Dirk Jan A.R. Moes
- Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, the Netherlands
| | - Sylvia W.A. Kamerling
- Department of Internal Medicine section Nephrology, Center of Expertise for Lupus-, Vasculitis and Complement- mediated Systemic Autoimmune Diseases, Leiden University Medical Center, Leiden, the Netherlands
| | - Sandra van der Kooy
- Department of Internal Medicine section Nephrology, Center of Expertise for Lupus-, Vasculitis and Complement- mediated Systemic Autoimmune Diseases, Leiden University Medical Center, Leiden, the Netherlands
| | - Natacha S. Ogando
- Department of Medical Microbiology, Leiden University Medical Center, Leiden, the Netherlands
| | - Eric J. Snijder
- Department of Medical Microbiology, Leiden University Medical Center, Leiden, the Netherlands
| | - Martijn van Hemert
- Department of Medical Microbiology, Leiden University Medical Center, Leiden, the Netherlands
| | - Leo G. Visser
- Department of Internal Medicine section Infectious diseases, Leiden University Medical Center, Leiden, the Netherlands
| | - Mariet C.W. Feltkamp
- Department of Medical Microbiology, Leiden University Medical Center, Leiden, the Netherlands
| | - Eric C.J. Claas
- Department of Medical Microbiology, Leiden University Medical Center, Leiden, the Netherlands
| | - Ton J. Rabelink
- Department of Internal Medicine section Nephrology, Center of Expertise for Lupus-, Vasculitis and Complement- mediated Systemic Autoimmune Diseases, Leiden University Medical Center, Leiden, the Netherlands
| | - Cees van Kooten
- Department of Internal Medicine section Nephrology, Center of Expertise for Lupus-, Vasculitis and Complement- mediated Systemic Autoimmune Diseases, Leiden University Medical Center, Leiden, the Netherlands
| | - Aiko P.J. de Vries
- Department of Internal Medicine section Nephrology, Leiden Transplant Center, Leiden University Medical Center, Leiden, the Netherlands
| | - Y.K. Onno Teng
- Department of Internal Medicine section Nephrology, Center of Expertise for Lupus-, Vasculitis and Complement- mediated Systemic Autoimmune Diseases, Leiden University Medical Center, Leiden, the Netherlands
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Song Y, Yao L, Li S, Zhou J. Psoriasis comorbidity management in the COVID era: a pressing challenge. Front Microbiol 2023; 14:1294056. [PMID: 38029150 PMCID: PMC10667470 DOI: 10.3389/fmicb.2023.1294056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Accepted: 10/26/2023] [Indexed: 12/01/2023] Open
Abstract
The global COVID-19 pandemic has presented a significant, ongoing challenge since its emergence in late 2019. Today, the Omicron strain, which is less lethal but more contagious than the original outbreak strain, continues to pose substantial health risks. In this background, the management of psoriatic comorbidities has become even more complex, particularly for patients with underlying inflammatory, metabolic, or cardiovascular diseases. This review aims to summarize current research on comorbid COVID-19 and psoriasis, and provide insights into the development of evidence-based management strategies. By providing appropriate patient instruction, implementing protective measures, and re-evaluating medication prescriptions based on each patient's unique situation, healthcare professionals can effectively address the challenges faced by patients with comorbid psoriasis in the COVID-19 era.
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Affiliation(s)
| | | | | | - Junfeng Zhou
- Department of Dermatology, First Hospital of Jilin University, Changchun, China
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Kaneko S, Inoue T, Tarumoto N, Haga Y, Yokota K, Yamaguchi H, Okada H. A case of hemophagocytic lymphohistiocytosis in a hemodialysis patient with coronavirus disease 2019. CEN Case Rep 2023; 12:390-396. [PMID: 36864233 PMCID: PMC9982797 DOI: 10.1007/s13730-023-00776-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 02/06/2023] [Indexed: 03/04/2023] Open
Abstract
During the treatment of a patient on hemodialysis with severe coronavirus disease 2019 (COVID-19), the patient was weaned from extracorporeal membrane oxygenation, which was used to treat severe COVID-19 pneumonia. However, the patient's condition worsened after the peak infection phase of COVID-19 because of acute respiratory distress syndrome with suspected hemophagocytic lymphohistiocytosis (HLH). After a bone marrow biopsy confirmed the diagnosis, methylprednisolone pulse therapy, followed by combination therapy (including oral prednisolone and cyclosporine) was immediately administered, and the patient survived. Because HLH can occur a month or more after the onset of COVID-19, even if the viral load is reduced to the point of being undetectable by reverse transcriptase-polymerase chain reaction, it can be considered to correspond to the "post-acute COVID-19 syndrome," which has recently been proposed. Early intervention is necessary, because HLH can be fatal. Therefore, it is important to know that HLH can occur at any stage of COVID-19 and to pay attention to the patient's progress over time, including checking the HScore.
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Affiliation(s)
- Satoru Kaneko
- Department of Nephrology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama, 350-0451, Japan
| | - Tsutomu Inoue
- Department of Nephrology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama, 350-0451, Japan
| | - Norihito Tarumoto
- Department of Infectious Disease and Infection Control, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama, 350-0451, Japan
| | - Yoshiyuki Haga
- Department of Intensive Care Medicine, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama, 350-0451, Japan
| | - Kazuhiro Yokota
- Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama, 350-0451, Japan
| | - Hiroshi Yamaguchi
- Department of Pathology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-Machi, Iruma-gun, Saitama, 350-0451, Japan
| | - Hirokazu Okada
- Department of Nephrology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama, 350-0451, Japan.
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10
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Arai T, Kurahara Y, Moda M, Kobayashi T, Matsuda Y, Kagawa T, Sugawara R, Tsuyuguchi K, Inoue Y. COVID-19 in Patients with Pre-Existing Interstitial Lung Disease: Potential Value of a Steroid-Based Treatment Strategy. J Clin Med 2023; 12:4940. [PMID: 37568341 PMCID: PMC10419957 DOI: 10.3390/jcm12154940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 07/23/2023] [Accepted: 07/25/2023] [Indexed: 08/13/2023] Open
Abstract
The prognosis of patients with coronavirus disease 2019 (COVID-19) and pre-existing interstitial lung disease (preILD) is poor, and no effective treatment strategy has been determined. The aim of this study was to assess the effectiveness of a steroid-based treatment strategy for patients with COVID-19 and preILD. We retrospectively reviewed the medical records of 610 consecutive patients with COVID-19 treated at our institution between 1 March 2020 and 30 October 2021 and identified 7 patients with preILD, all of whom were treated with corticosteroids and remdesivir. All the patients were men with a median age of 63 years. Three of four patients with severe disease required invasive positive-pressure ventilation (n = 2) or nasal high-flow therapy (n = 1). All three patients could be weaned from respiratory support; however, one died in hospital. The remaining patient with severe COVID-19 had a do-not-resuscitate order in place and died while hospitalized. All three patients with moderate COVID-19 were discharged. The 30-day mortality was 0%, and the mortality rate during the entire observation period was 28.5%. The prognosis of our patients with COVID-19 and preILD has been better than in previous reports. Our management strategy using corticosteroids may have improved these patients' prognosis.
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Affiliation(s)
- Toru Arai
- Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai City 591-8555, Osaka Prefecture, Japan; (Y.K.); (T.K.); (Y.M.); (T.K.); (K.T.); (Y.I.)
| | - Yu Kurahara
- Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai City 591-8555, Osaka Prefecture, Japan; (Y.K.); (T.K.); (Y.M.); (T.K.); (K.T.); (Y.I.)
- Department of Infectious Diseases, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai City 591-8555, Osaka Prefecture, Japan
| | - Mitsuhiro Moda
- Department of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai City 591-8555, Osaka Prefecture, Japan; (M.M.); (R.S.)
| | - Takehiko Kobayashi
- Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai City 591-8555, Osaka Prefecture, Japan; (Y.K.); (T.K.); (Y.M.); (T.K.); (K.T.); (Y.I.)
| | - Yoshinobu Matsuda
- Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai City 591-8555, Osaka Prefecture, Japan; (Y.K.); (T.K.); (Y.M.); (T.K.); (K.T.); (Y.I.)
- Department of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai City 591-8555, Osaka Prefecture, Japan; (M.M.); (R.S.)
| | - Tomoko Kagawa
- Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai City 591-8555, Osaka Prefecture, Japan; (Y.K.); (T.K.); (Y.M.); (T.K.); (K.T.); (Y.I.)
- Department of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai City 591-8555, Osaka Prefecture, Japan; (M.M.); (R.S.)
| | - Reiko Sugawara
- Department of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai City 591-8555, Osaka Prefecture, Japan; (M.M.); (R.S.)
| | - Kazunari Tsuyuguchi
- Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai City 591-8555, Osaka Prefecture, Japan; (Y.K.); (T.K.); (Y.M.); (T.K.); (K.T.); (Y.I.)
- Department of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai City 591-8555, Osaka Prefecture, Japan; (M.M.); (R.S.)
| | - Yoshikazu Inoue
- Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai City 591-8555, Osaka Prefecture, Japan; (Y.K.); (T.K.); (Y.M.); (T.K.); (K.T.); (Y.I.)
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Perreault G, Ching C, Nobel YR. COVID-19 in patients with liver disease and liver transplant: clinical implications, prevention, and management. Therap Adv Gastroenterol 2023; 16:17562848231188586. [PMID: 37521085 PMCID: PMC10372508 DOI: 10.1177/17562848231188586] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Accepted: 07/02/2023] [Indexed: 08/01/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has had enormous implications for the care of patients with chronic liver disease (CLD), cirrhosis, and liver transplant (LT). Clinical outcomes of COVID-19 vary in patients with CLD and cirrhosis compared to healthy controls, and in patients with LT compared to patients without LT. Several special considerations apply to the approach to vaccination and treatment in patients with CLD and LT. The practice of liver transplantation has also been heavily impacted by the pandemic, including persistent reductions in living donor LT and increases in LT for an indication of alcohol-related liver disease. Recent medical society guidelines strive to standardize severe acute respiratory syndrome coronavirus 2 testing in donors and recipients and the approach to transplantation after recovered from COVID-19 infection, but certain controversies remain.
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Affiliation(s)
- Gabriel Perreault
- Division of Digestive and Liver Diseases, Columbia University Irving Medical Center, New York, NY, USA
| | - Charlotte Ching
- Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA
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Gupta Y, Savytskyi OV, Coban M, Venugopal A, Pleqi V, Weber CA, Chitale R, Durvasula R, Hopkins C, Kempaiah P, Caulfield TR. Protein structure-based in-silico approaches to drug discovery: Guide to COVID-19 therapeutics. Mol Aspects Med 2023; 91:101151. [PMID: 36371228 PMCID: PMC9613808 DOI: 10.1016/j.mam.2022.101151] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Revised: 10/19/2022] [Accepted: 10/21/2022] [Indexed: 11/06/2022]
Abstract
With more than 5 million fatalities and close to 300 million reported cases, COVID-19 is the first documented pandemic due to a coronavirus that continues to be a major health challenge. Despite being rapid, uncontrollable, and highly infectious in its spread, it also created incentives for technology development and redefined public health needs and research agendas to fast-track innovations to be translated. Breakthroughs in computational biology peaked during the pandemic with renewed attention to making all cutting-edge technology deliver agents to combat the disease. The demand to develop effective treatments yielded surprising collaborations from previously segregated fields of science and technology. The long-standing pharmaceutical industry's aversion to repurposing existing drugs due to a lack of exponential financial gain was overrun by the health crisis and pressures created by front-line researchers and providers. Effective vaccine development even at an unprecedented pace took more than a year to develop and commence trials. Now the emergence of variants and waning protections during the booster shots is resulting in breakthrough infections that continue to strain health care systems. As of now, every protein of SARS-CoV-2 has been structurally characterized and related host pathways have been extensively mapped out. The research community has addressed the druggability of a multitude of possible targets. This has been made possible due to existing technology for virtual computer-assisted drug development as well as new tools and technologies such as artificial intelligence to deliver new leads. Here in this article, we are discussing advances in the drug discovery field related to target-based drug discovery and exploring the implications of known target-specific agents on COVID-19 therapeutic management. The current scenario calls for more personalized medicine efforts and stratifying patient populations early on for their need for different combinations of prognosis-specific therapeutics. We intend to highlight target hotspots and their potential agents, with the ultimate goal of using rational design of new therapeutics to not only end this pandemic but also uncover a generalizable platform for use in future pandemics.
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Affiliation(s)
- Yash Gupta
- Department of Medicine, Infectious Diseases, Mayo Clinic, Jacksonville, FL, USA
| | - Oleksandr V Savytskyi
- Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA; In Vivo Biosystems, Eugene, OR, USA
| | - Matt Coban
- Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA; Department of Cancer Biology, Mayo Clinic, Jacksonville, FL, USA
| | | | - Vasili Pleqi
- Department of Medicine, Infectious Diseases, Mayo Clinic, Jacksonville, FL, USA
| | - Caleb A Weber
- Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA
| | - Rohit Chitale
- Department of Medicine, Infectious Diseases, Mayo Clinic, Jacksonville, FL, USA; The Council on Strategic Risks, 1025 Connecticut Ave NW, Washington, DC, USA
| | - Ravi Durvasula
- Department of Medicine, Infectious Diseases, Mayo Clinic, Jacksonville, FL, USA
| | | | - Prakasha Kempaiah
- Department of Medicine, Infectious Diseases, Mayo Clinic, Jacksonville, FL, USA
| | - Thomas R Caulfield
- Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA; Department of QHS Computational Biology, Mayo Clinic, Jacksonville, FL, USA; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA; Department of Clinical Genomics, Mayo Clinic, Rochester, MN, USA; Department of Neurosurgery, Mayo Clinic, Jacksonville, FL, USA.
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13
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Maynard N, Armstrong AW. The Impact of Immune-Modulating Treatments for Dermatological Diseases on the Risk of Infection with SARS-CoV-2 and Outcomes Associated with COVID-19 Illness. CURRENT DERMATOLOGY REPORTS 2023; 12:45-55. [PMID: 37304177 PMCID: PMC10068706 DOI: 10.1007/s13671-023-00385-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/13/2023] [Indexed: 04/05/2023]
Abstract
Purpose of Review Immune-modulating treatments are used in dermatology for a variety of conditions. The authors aim to review the data regarding the safety of these treatments during the COVID-19 pandemic, namely the risk of infection with SARS-CoV-2 and the outcomes associated with COVID-19-related illness. Recent Findings Several large-scale studies found no increased risk of COVID-19 infection for patients on TNF-α inhibitors, IL-17 inhibitors, IL-12/23 inhibitors, IL-23 inhibitors, dupilumab, and methotrexate. They also found that these patients did not have worse outcomes when infected with COVID-19. The data regarding JAK inhibitors, rituximab, prednisone, cyclosporine, mycophenolate mofetil, and azathioprine are more mixed. Summary Based on current research and guidelines from the American Academy of Dermatology and the National Psoriasis Foundation, dermatology patients on immune-modulating therapies can continue treatment during the COVID-19 pandemic when they are not infected with SARS-CoV-2. For patients who have COVID-19, guidelines encourage individualized assessment of the benefits and risks of continuing or temporarily withholding treatment.
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Affiliation(s)
- Nicole Maynard
- Keck School of Medicine of USC, 1975 Zonal Avenue, KAM 510, MC 9034, Los Angeles, CA 90089 USA
| | - April W. Armstrong
- Keck School of Medicine of USC, 1975 Zonal Avenue, KAM 510, MC 9034, Los Angeles, CA 90089 USA
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Tacke F, Cornberg M, Sterneck M, Trebicka J, Settmacher U, Bechstein WO, Berg T. S1-Leitlinie zur Versorgung von Lebertransplantierten während der COVID-19-Pandemie – AWMF-Registernummer: 021-031 – Stand 15. Juni 2022. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:1678-1698. [PMID: 36368659 DOI: 10.1055/a-1934-1989] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Affiliation(s)
- Frank Tacke
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Charité Mitte/Campus Virchow-Klinikum, 13353 Berlin
| | - Markus Cornberg
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, 30625 Hannover; Centre for individualised infection Medicine (CiiM), Hannover; Deutsches Zentrum für Infektionsforschung (DZIF)
| | - Martina Sterneck
- Universitätsklinikum Hamburg-Eppendorf, I. Medizinische Klinik und Poliklinik, 20246 Hamburg
| | - Jonel Trebicka
- Universitätsklinikum Münster, Medizinische Klinik B, 48149 Münster
| | - Utz Settmacher
- Universitätsklinikum Jena, Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, 07747 Jena
| | - Wolf Otto Bechstein
- Universitätsklinikum Frankfurt, Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, 60590 Frankfurt
| | - Thomas Berg
- Universitätsklinikum Leipzig AöR, Bereich Hepatologie, Klinik und Poliklinik für Onkologie, Gastroenterologie, Hepatologie, Pneumologie und Infektiologie, 04103 Leipzig
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15
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Impact of COVID-19 on the liver and on the care of patients with chronic liver disease, hepatobiliary cancer, and liver transplantation: An updated EASL position paper. J Hepatol 2022; 77:1161-1197. [PMID: 35868584 PMCID: PMC9296253 DOI: 10.1016/j.jhep.2022.07.008] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 07/06/2022] [Accepted: 07/06/2022] [Indexed: 02/06/2023]
Abstract
The COVID-19 pandemic has presented a serious challenge to the hepatology community, particularly healthcare professionals and patients. While the rapid development of safe and effective vaccines and treatments has improved the clinical landscape, the emergence of the omicron variant has presented new challenges. Thus, it is timely that the European Association for the Study of the Liver provides a summary of the latest data on the impact of COVID-19 on the liver and issues guidance on the care of patients with chronic liver disease, hepatobiliary cancer, and previous liver transplantation, as the world continues to deal with the consequences of the COVID-19 pandemic.
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16
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Schiene‐Fischer C, Fischer G, Braun M. Non-Immunosuppressive Cyclophilin Inhibitors. Angew Chem Int Ed Engl 2022; 61:e202201597. [PMID: 35290695 PMCID: PMC9804594 DOI: 10.1002/anie.202201597] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Indexed: 01/05/2023]
Abstract
Cyclophilins, enzymes with peptidyl-prolyl cis/trans isomerase activity, are relevant to a large variety of biological processes. The most abundant member of this enzyme family, cyclophilin A, is the cellular receptor of the immunosuppressive drug cyclosporine A (CsA). As a consequence of the pathophysiological role of cyclophilins, particularly in viral infections, there is a broad interest in cyclophilin inhibition devoid of immunosuppressive activity. This Review first gives an introduction into the physiological and pathophysiological roles of cyclophilins. The presentation of non-immunosuppressive cyclophilin inhibitors will commence with drugs based on chemical modifications of CsA. The naturally occurring macrocyclic sanglifehrins have become other lead structures for cyclophilin-inhibiting drugs. Finally, de novo designed compounds, whose structures are not derived from or inspired by natural products, will be presented. Relevant synthetic concepts will be discussed, but the focus will also be on biochemical studies, structure-activity relationships, and clinical studies.
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Affiliation(s)
- Cordelia Schiene‐Fischer
- Institute of Biochemistry and BiotechnologyMartin-Luther-University Halle-Wittenberg06099Halle (Saale)Germany
| | - Gunter Fischer
- Max Planck Institute for Biophysical Chemistry37077GöttingenGermany
| | - Manfred Braun
- Institute of Organic and Macromolecular ChemistryHeinrich-Heine-University Düsseldorf40225DüsseldorfGermany
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Hernandez-Hernandez ME, Zee RYL, Pulido-Perez P, Torres-Rasgado E, Romero JR. The Effects of Biological Sex and Cardiovascular Disease on COVID-19 Mortality. Am J Physiol Heart Circ Physiol 2022; 323:H397-H402. [PMID: 35867708 PMCID: PMC9359635 DOI: 10.1152/ajpheart.00295.2022] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Cardiovascular disease (CVD) is a common comorbidity observed in patients with COVID-19 that is associated with increased severity and mortality. However, the effects of biological sex on CVD associated mortality in COVID-19 patients is poorly established particularly among Hispanic/Latin Americans. We examined the association of preexisting CVD with COVID-19 mortality in hospitalized Latin American men and women. This multicenter study included hospitalized Mexican patients with a positive diagnosis of COVID-19. The main outcome was in-hospital mortality. Multivariable regression analyses were used to calculate the adjusted odd ratios with 95% confidence interval for mortality in women and men. Of 81,400 patients with a positive diagnosis for SARS-CoV-2 infection, 28,929 (35.54%) hospitalized patients were evaluated. Of these, the 35.41% (10,243) were women. In-hospital death was higher in men than in women. In relation to CVD between the sexes, women had a higher incidence of CVD than men (4.69% vs 3.93%. P=0.0023). The adjusted logistic regression analyses showed that CVD was significantly associated with COVID-19 mortality in women but not men. We then stratified by sex according to age <52 and ≥52 years old. Similar significant association was also found in pre-specified analysis in women ≥52 years old but not in men of similar age. We conclude that CVD's effect on mortality among COVID-19 hospitalized patients is dependent on biological sex and age in this Latin American cohort. These results suggest that therapeutic strategies for Latin American women with CVD and COVID-19 should include particular attention to their cardiovascular health.
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Affiliation(s)
- Maria Elena Hernandez-Hernandez
- Doctorate in Biological Science, Autonomous University of Tlaxcala, Puebla, Mexico.,Faculty of Medicine, Autonomous University of Puebla, Puebla, Puebla, Mexico
| | - Robert Y L Zee
- Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, United States.,Department of Pediatric Dentistry, Tufts University School of Dental Medicine, Boston, MA, United States
| | | | | | - Jose R Romero
- Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, United States
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18
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Langford BJ, So M, Leung V, Raybardhan S, Lo J, Kan T, Leung F, Westwood D, Daneman N, MacFadden DR, Soucy JPR. Predictors and microbiology of respiratory and bloodstream bacterial infection in patients with COVID-19: living rapid review update and meta-regression. Clin Microbiol Infect 2022; 28:491-501. [PMID: 34843962 PMCID: PMC8619885 DOI: 10.1016/j.cmi.2021.11.008] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 10/27/2021] [Accepted: 11/05/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND The prevalence of bacterial infection in patients with COVID-19 is low, however, empiric antibiotic use is high. Risk stratification may be needed to minimize unnecessary empiric antibiotic use. OBJECTIVE To identify risk factors and microbiology associated with respiratory and bloodstream bacterial infection in patients with COVID-19. DATA SOURCES We searched MEDLINE, OVID Epub and EMBASE for published literature up to 5 February 2021. STUDY ELIGIBILITY CRITERIA Studies including at least 50 patients with COVID-19 in any healthcare setting. METHODS We used a validated ten-item risk of bias tool for disease prevalence. The main outcome of interest was the proportion of COVID-19 patients with bloodstream and/or respiratory bacterial co-infection and secondary infection. We performed meta-regression to identify study population factors associated with bacterial infection including healthcare setting, age, comorbidities and COVID-19 medication. RESULTS Out of 33 345 studies screened, 171 were included in the final analysis. Bacterial infection data were available from 171 262 patients. The prevalence of co-infection was 5.1% (95% CI 3.6-7.1%) and secondary infection was 13.1% (95% CI 9.8-17.2%). There was a higher odds of bacterial infection in studies with a higher proportion of patients in the intensive care unit (ICU) (adjusted OR 18.8, 95% CI 6.5-54.8). Female sex was associated with a lower odds of secondary infection (adjusted OR 0.73, 95% CI 0.55-0.97) but not co-infection (adjusted OR 1.05, 95% CI 0.80-1.37). The most common organisms isolated included Staphylococcus aureus, coagulase-negative staphylococci and Klebsiella species. CONCLUSIONS While the odds of respiratory and bloodstream bacterial infection are low in patients with COVID-19, meta-regression revealed potential risk factors for infection, including ICU setting and mechanical ventilation. The risk for secondary infection is substantially greater than the risk for co-infection in patients with COVID-19. Understanding predictors of co-infection and secondary infection may help to support improved antibiotic stewardship in patients with COVID-19.
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Affiliation(s)
- Bradley J Langford
- Public Health Ontario, ON, Canada; Hotel Dieu Shaver Health and Rehabilitation Centre, ON, Canada.
| | - Miranda So
- Sinai Health-University Health Network Antimicrobial Stewardship Program, University Health Network, Toronto, Canada; University of Toronto, ON, Canada; Toronto General Hospital Research Institute, Toronto, ON, Canada
| | - Valerie Leung
- Public Health Ontario, ON, Canada; Toronto East Health Network, Michael Garron Hospital, ON Canada
| | | | - Jennifer Lo
- Sunnybrook Health Sciences Centre, ON, Canada
| | - Tiffany Kan
- Toronto East Health Network, Michael Garron Hospital, ON Canada
| | | | | | - Nick Daneman
- Public Health Ontario, ON, Canada; University of Toronto, ON, Canada; Sunnybrook Health Sciences Centre, ON, Canada; Sunnybrook Research Institute, ON, Canada; ICES (formerly Institute for Clinical Evaluative Sciences), ON Canada
| | | | - Jean-Paul R Soucy
- Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, ON, Canada
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19
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Wu H, Cheng K, Tong L, Wang Y, Yang W, Sun Z. Knowledge structure and emerging trends on osteonecrosis of the femoral head: a bibliometric and visualized study. J Orthop Surg Res 2022; 17:194. [PMID: 35346273 PMCID: PMC8960091 DOI: 10.1186/s13018-022-03068-7] [Citation(s) in RCA: 46] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Accepted: 03/15/2022] [Indexed: 11/15/2022] Open
Abstract
Background Osteonecrosis of the femoral head (ONFH) is a common disabling disease with considerable social and economic impacts. Although extensive studies related to ONFH have been conducted in recent years, a specific bibliometric analysis on this topic has not yet been performed. Our study attempted to summarize the comprehensive knowledge map, development landscape, and future directions of ONFH research with the bibliometric approach. Methods All publications concerning ONFH published from 2001 to 2020 were identified from Web of Science Core Collection. Key bibliometric indicators were calculated and evaluated using CiteSpace, VOSviewer, and the online bibliometric analysis platform. Results A total of 2594 publications were included. Our analysis revealed a significant exponential growth trend in the annual number of publications over the past 20 years (R2 = 0.9663). China, the USA, and Japan were the major contributors both from the quality and quantity points of view. Correlation analysis indicated that there was a high positive correlation between the number of publications and gross domestic product (r = 0.774), and a moderate positive correlation between publications and demographic factor (r = 0.673). All keywords were categorized into four clusters including Cluster 1 (etiology and risk factors study); Cluster 2 (basic research and stem cell therapy); cluster 3 (hip-preserving study); and Cluster 4 (hip replacement study). Stem cell therapy-related research has been recognized as an important research hotspot in this field. Several topics including exosomes, autophagy, biomarkers, osteogenic differentiation, microRNAs, steroid-induced osteonecrosis, mesenchymal stem cells, double-blind, early-stage osteonecrosis, and asymptomatic osteonecrosis were considered as research focuses in the near future. Conclusion Over the past two decades, increasing attention has been paid to global ONFH-related research. Our bibliometric findings provide valuable information for researchers to understand the basic knowledge structure, identify the current research hotspots, potential collaborators, and future research frontiers in this field.
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20
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Braun M, Schiene-Fischer C, Fischer G. Non‐Immunosuppressive Cyclophilin Inhibitors. Angew Chem Int Ed Engl 2022. [DOI: 10.1002/ange.202201597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Affiliation(s)
- Manfred Braun
- Heinrich-Heine-Universität Düsseldorf: Heinrich-Heine-Universitat Dusseldorf Organic CHemistry Universitätsstr. 1 40225 Düsseldorf GERMANY
| | - Cordelia Schiene-Fischer
- Martin-Luther-Universität Halle-Wittenberg: Martin-Luther-Universitat Halle-Wittenberg Institute of Biochemistry and Biotechnology, GERMANY
| | - Gunter Fischer
- Max-Planck-Institut für Biophysikalische Chemie Abteilung Meiosis: Max-Planck-Institut fur Multidisziplinare Naturwissenschaften Abteilung Meiosis Max Planck Institute for Biophysical Chemistry GERMANY
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21
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Schaffrath J, Brummer C, Wolff D, Holtick U, Kröger N, Bornhäuser M, Kraus S, Hilgendorf I, Blau IW, Penack O, Wittke C, Steiner N, Nachbaur D, Thurner L, Hindah H, Zeiser R, Maier CP, Bethge W, Müller LP. High mortality of COVID-19 early after allogeneic stem cell transplantation – a retrospective multicenter analysis on behalf of the German Cooperative Transplant Study Group. Transplant Cell Ther 2022; 28:337.e1-337.e10. [PMID: 35296445 PMCID: PMC8918088 DOI: 10.1016/j.jtct.2022.03.010] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2021] [Revised: 03/08/2022] [Accepted: 03/09/2022] [Indexed: 11/29/2022]
Abstract
Recipients of allogeneic stem cell transplantation (alloSCT) are at high risk for contracting infectious diseases with high morbidity and mortality. Coronavirus disease 2019 (COVID-19) is a viral respiratory disease that can lead to severe pneumonia and acute respiratory distress syndrome, with a potentially fatal outcome. In this retrospective study conducted on behalf of the German Cooperative Transplant Study Group, we aimed to analyze risk factors, disease course, and outcomes of COVID-19 in patients who underwent alloSCT. AlloSCT recipients who became infected with SARS-CoV-2 at German and Austrian transplant centers between February 2020 and July 2021 were included. Classification of COVID-19 severity into mild, moderate-severe, or critical disease and division of the course of the pandemic into 4 phases were done according to the German Robert Koch Institute. The main endpoint was overall mortality at the end of follow-up. We further analyzed the need for treatment in an intensive care unit (ICU) and the severity of disease. Risk factors were evaluated using univariate and multivariate analyses, and survival analysis was performed using Kaplan-Meier method. The study cohort comprised 130 patients from 14 transplant centers, with a median age at diagnosis of COVID-19 of 59 years (range, 20 to 81 years) and a median interval between alloSCT and COVID-19 of 787 days (range, 19 to 8138 days). The most common underlying diseases were acute myeloid leukemia (45.4%) and lymphoma (10.8%). The majority of patients (84.9%) were infected in the later phases of the pandemic; 20.8% had moderate-severe disease, 12.3% had critical disease, and 19.2% were treated in an ICU. After a median follow-up of 127 days, overall mortality was 16.2%, 52.0% among patients treated in an ICU. Risk factors for mortality in multivariate analysis were active disease (odds ratio [OR], 4.46), infection with SARS-CoV-2 ≤365 days after alloSCT (OR, 5.60), age >60 years (OR, 5.39), and ongoing immunosuppression with cyclosporine (OR, 8.55). Risk factors for developing moderate-severe or critical disease were concurrent immunosuppression (OR, 4.06) and age >40 years (OR, 4.08). Patients after alloSCT exhibit a substantially increased mortality risk after COVID-19 infection compared with the normal population, without considerable improvement over the course of the pandemic. Risk factors include age, early infection post-alloSCT, and active immunosuppression. Further studies are needed to improve prevention and treatment in this high-risk patient group.
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22
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Zetina-Tun HJ, Careaga-Reyna G. Infección por SARS-CoV-2 en pacientes trasplantados de corazón. Experiencia en México. CIRUGIA CARDIOVASCULAR 2022. [PMCID: PMC8226102 DOI: 10.1016/j.circv.2021.06.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
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23
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Calderón-Parra J, Cuervas-Mons V, Moreno-Torres V, Rubio-Rivas M, Blas PAD, Pinilla-Llorente B, Helguera-Amezua C, Jiménez-García N, Pesqueira-Fontan PM, Méndez-Bailón M, Artero A, Gilabert N, Ibánez-Estéllez F, Freire-Castro SJ, Lumbreras-Bermejo C, Antón-Santos JM. Influence of chronic corticosteroids and calcineurin inhibitors on COVID-19 clinical outcomes: Analysis of a nationwide registry. Int J Infect Dis 2021; 116:51-58. [PMID: 34971824 PMCID: PMC8713429 DOI: 10.1016/j.ijid.2021.12.327] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 12/07/2021] [Accepted: 12/08/2021] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVES To analyze whether subgroups of immunosuppressive (IS) medications confer different outcomes in COVID-19. METHODS Multicenter retrospective cohort of consecutive immunosuppressed patients (ISP) hospitalized with COVID-19 from March to July 2020. The primary outcome was in-hospital mortality. A propensity score-matched (PSM) model comparing ISP and non-ISP was planned, as well as specific PSM models comparing individual IS medications associated with mortality. RESULTS Out of 16,647 patients, 868 (5.2%) were on chronic IS therapy prior to admission and were considered ISP. In the PSM model, ISP had greater in-hospital mortality (OR 1.25, 95%CI 0.99-1.62), which was related to a worse outcome associated with chronic corticoids (OR 1.89, 95%CI 1.43-2.49). Other IS drugs had no repercussion on mortality risk (including calcineurin inhibitors (CNI), OR 1.19, 95% CI 0.65-2.20). In the pre-planned specific PSM model within patients on chronic IS treatment before admission, corticosteroids were associated with an increased risk of mortality (OR 2.34, 95%CI 1.43-3.82). CONCLUSIONS Chronic IS therapies pose a heterogeneous group of drugs with different risk profiles for severe COVID-19 and death. Chronic systemic corticosteroid is associated with increased mortality. On the contrary, CNI and other IS treatments prior to admission do not seem to convey different outcomes.
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Affiliation(s)
- Jorge Calderón-Parra
- Department of Internal Medicine, Hospital Universitario Puerta de Hierro Majadahonda (Madrid).
| | - Valentín Cuervas-Mons
- Department of Internal Medicine, Hospital Universitario Puerta de Hierro Majadahonda (Madrid); Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain. IDIPHISA-(Madrid).
| | - Victor Moreno-Torres
- Department of Internal Medicine, Hospital Universitario Puerta de Hierro Majadahonda (Madrid).
| | - Manuel Rubio-Rivas
- Department of Internal Medicine, H. Univ. de Bellvitge. L'Hospitalet de Llobregat (Barcelona).
| | | | | | | | | | | | | | - Arturo Artero
- Department of Internal Medicine, H. Universitario Dr. Peset (Valencia).
| | - Noemí Gilabert
- Department of Internal Medicine, H. U. La Princesa (Madrid).
| | - Fátima Ibánez-Estéllez
- Department of Internal Medicine, Hospital Universitario Puerta de Hierro Majadahonda (Madrid).
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24
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Arora H, Boothby-Shoemaker W, Braunberger T, Lim HW, Veenstra J. Safety of conventional immunosuppressive therapies for patients with dermatological conditions and coronavirus disease 2019: A review of current evidence. J Dermatol 2021; 49:317-329. [PMID: 34962304 DOI: 10.1111/1346-8138.16182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 09/16/2021] [Accepted: 09/21/2021] [Indexed: 12/15/2022]
Abstract
The effect of coronavirus disease 2019 (COVID-19) on patients receiving conventional immunosuppressive (IS) therapy has yet to be fully determined; however, research on using IS therapy for treating COVID-19 in acutely ill patients is increasing. While some believe that IS therapy may be protective, others argue that these agents may make patients more susceptible to COVID-19 infection and morbidity and advocate for a more cautious, individualized approach to determining continuation, reduction, or discontinuation of therapy. In this review, we aim to provide an overview of COVID-19 risk in dermatological patients who are receiving conventional IS therapies, including mycophenolate mofetil, methotrexate, cyclosporine, azathioprine, apremilast, JAK inhibitors, and systemic steroids. Additionally, we provide recommendations for management of these medications for dermatological patients during the COVID-19 pandemic. Treatment of dermatological disease during the COVID-19 pandemic should involve shared decision-making between the patient and provider, with consideration of each patient's comorbidities and the severity of the patient's dermatological disease.
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Affiliation(s)
- Harleen Arora
- Department of Dermatology, Henry Ford Hospital, Detroit, Michigan, USA
| | - Wyatt Boothby-Shoemaker
- Department of Dermatology, Henry Ford Hospital, Detroit, Michigan, USA.,College of Human Medicine, Michigan State University, East Lansing, Michigan, USA
| | | | - Henry W Lim
- Department of Dermatology, Henry Ford Hospital, Detroit, Michigan, USA
| | - Jesse Veenstra
- Department of Dermatology, Henry Ford Hospital, Detroit, Michigan, USA
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25
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Kawazoe M, Kihara M, Nanki T. Antirheumatic Drugs against COVID-19 from the Perspective of Rheumatologists. Pharmaceuticals (Basel) 2021; 14:ph14121256. [PMID: 34959657 PMCID: PMC8705607 DOI: 10.3390/ph14121256] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Revised: 11/27/2021] [Accepted: 11/28/2021] [Indexed: 12/15/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) remains a global threat to humanity. Its pathogenesis and different phases of disease progression are being elucidated under the pandemic. Active viral replication activates various immune cells and produces large amounts of inflammatory cytokines, which leads to the cytokine storm, a major cause of patient death. Therefore, viral inhibition is expected to be the most effective early in the course of the disease, while immunosuppressive treatment may be useful in the later stages to prevent disease progression. Based on the pathophysiology of rheumatic diseases, various immunomodulatory and immunosuppressive drugs are used for the diseases. Due to their mechanism of action, the antirheumatic drugs, including hydroxychloroquine, chloroquine, colchicine, calcineurin inhibitors (e.g., cyclosporine A and tacrolimus), glucocorticoids, cytokines inhibitors, such as anti-tumor necrosis factor-α (e.g., infliximab), anti-interleukin (IL)-6 (e.g., tocilizumab, sarilumab, and siltuximab), anti-IL-1 (e.g., anakinra and canakinumab) and Janus kinase inhibitors (e.g., baricitinib and tofacitinib), cytotoxic T lymphocyte-associated antigen 4 blockade agents (e.g., abatacept), and phosphodiesterase 4 inhibitors (e.g., apremilast), have been tried as a treatment for COVID-19. In this review, we discuss the mechanisms of action and clinical impact of these agents in the management of COVID-19.
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Affiliation(s)
- Mai Kawazoe
- Division of Rheumatology, Department of Internal Medicine, School of Medicine, Faculty of Medicine, Toho University, Tokyo 143-8541, Japan;
| | - Mari Kihara
- Department of Rheumatology, Tokyo Medical and Dental University, Tokyo 113-8519, Japan;
| | - Toshihiro Nanki
- Division of Rheumatology, Department of Internal Medicine, School of Medicine, Faculty of Medicine, Toho University, Tokyo 143-8541, Japan;
- Correspondence: ; Tel.: +81-3-3762-4151 (ext. 2762)
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Dominguez-Nicolas SM, Manjarrez E. Low-field thoracic magnetic stimulation increases peripheral oxygen saturation levels in coronavirus disease (COVID-19) patients: A single-blind, sham-controlled, crossover study. Medicine (Baltimore) 2021; 100:e27444. [PMID: 34622862 PMCID: PMC8500560 DOI: 10.1097/md.0000000000027444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 09/17/2021] [Indexed: 01/05/2023] Open
Abstract
ABSTRACT Severe acute respiratory syndrome coronavirus-2 may cause low oxygen saturation (SpO2) and respiratory failure in patients with coronavirus disease (COVID-19). Hence, increased SpO2 levels in COVID-19 patients could be crucial for their quality of life and recovery. This study aimed to demonstrate that a 30-minute single session of dorsal low-field thoracic magnetic stimulation (LF-ThMS) can be employed to increase SpO2 levels in COVID-19 patients significantly. Furthermore, we hypothesized that the variables associated with LF-ThMS, such as frequency, magnetic flux density, and temperature in the dorsal thorax, might be correlated to SpO2 levels in these patients.Here we employed an LF-ThMS device to noninvasively deliver a pulsed magnetic field from 100 to 118 Hz and 10.5 to 13.1 milliTesla (i.e., 105 to 131 Gauss) to the dorsal thorax. These values are within the intensity range of several pulsed electromagnetic field devices employed in physical therapy worldwide. We designed a single-blind, sham-controlled, crossover study on 5 COVID-19 patients who underwent 2 sessions of the study (real and sham LF-ThMS) and 12 patients who underwent only the real LF-ThMS.We found a statistically significant positive correlation between magnetic flux density, frequency, or temperature, associated with the real LF-ThMS and SpO2 levels in all COVID-19 patients. However, the 5 patients in the sham-controlled study did not exhibit a significant change in their SpO2 levels during sham stimulation. The employed frequencies and magnetic flux densities were safe for the patients. We did not observe adverse events after the LF-ThMS intervention.This study is a proof-of-concept that a single session of LF-ThMS applied for 30 minutes to the dorsal thorax of 17 COVID-19 patients significantly increased their SpO2 levels. However, future research will be needed to understand the physiological mechanisms behind this finding.The study was registered at ClinicalTrials.gov (Identifier: NCT04895267, registered on May 20, 2021) retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT04895267.
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Affiliation(s)
- Saul M Dominguez-Nicolas
- Centro de Investigación de Micro y Nanotecnología, Universidad Veracruzana, Calzada Ruiz Cortines 455 Boca del Rio, Veracruz, México
- Facultad de Ingeniería Eléctrica y Electrónica, Universidad Veracruzana, Calzada Ruiz Cortines 455, Boca del Rio, Veracruz, México
| | - Elias Manjarrez
- Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, 14 Sur 6301, Colonia San Manuel, Apartado Postal 406, Puebla, Puebla, México
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27
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Barati S, MohammadReza Hashemian S, Tabarsi P, Abedini A, Ashrafzadeh M, Haseli S, Abtahian Z, Yousefian S, Dastan A, Sobhanian A, Dastan F. Combined Therapy of Ciclosporin Plus Favipiravir in the Management of Patients with Severe COVID-19, not Responding to Dexamethasone: A non-Controlled Prospective Trial. Int Immunopharmacol 2021; 99:108043. [PMID: 34426105 PMCID: PMC8332739 DOI: 10.1016/j.intimp.2021.108043] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Revised: 07/31/2021] [Accepted: 07/31/2021] [Indexed: 11/24/2022]
Abstract
BACKGROUND Regarding the COVID-19 pandemic, potential therapeutic agents are being evaluated almost every day. Ciclosporin, a calcineurin inhibitor, is characterized by beneficial antiviral and immunomodulatory effects. The present study aimed to evaluate the efficacy of ciclosporin in managing COVID-19. METHODS This study was a prospective non-controlled clinical trial carried out on 20 patients. Confirmed COVID-19 patients received two doses of ciclosporin (10 mg/kg and 5 mg/kg injections) 24 h apart. Mortality rate and the lengths of intensive care unit (ICU) and hospital stays were assessed for all 20 patients. RESULTS The mortality rate and the need for mechanical ventilation were calculated as 50%. The percentage of ICU admission was 70%. The lengths of ICU and hospital stays were 8.13 ± 6.81 and 14.25 ± 8.55 days, respectively. The levels of ferritin and white blood cells were significantly higher after injecting the second dose of ciclosporin. Seven patients (35%) had radiologically improved lungs after ciclosporin therapy. CONCLUSION It seems that the protocol of two doses of ciclosporin in combination with favipiravir does not have favorable effects among COVID-19 patients that do not respond to dexamethasone. Controlled trials are needed to confirm the results.
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Affiliation(s)
- Saghar Barati
- Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyed MohammadReza Hashemian
- Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Payam Tabarsi
- Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Atefeh Abedini
- Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahshid Ashrafzadeh
- Critical Care Quality Improvement Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sara Haseli
- Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zahra Abtahian
- Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sahar Yousefian
- Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Alireza Dastan
- Ernest and Julio Gallo Management Program, School of Engineering, University of California, Merced, United States
| | - Ali Sobhanian
- Faculty member of Islamic Azad University of Medical Sciences, Tehran, Iran
| | - Farzaneh Dastan
- Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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28
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Qiu L, Zhang J, Huang Y, Chen G, Chen Z, Ming C, Lu X, Gong N. Long-Term Clinical and Immunological Impact of Severe COVID-19 on a Living Kidney Transplant Recipient - A Case Report. Front Immunol 2021; 12:741765. [PMID: 34567007 PMCID: PMC8456079 DOI: 10.3389/fimmu.2021.741765] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 08/24/2021] [Indexed: 12/24/2022] Open
Abstract
The long-term impact of COVID-19 on transplant recipients remains unknown. We describe the case of a 30-year-old male kidney transplant recipient from Wuhan, China that was treated for severe COVID-19 in February 2020. He suffered an acute lung and renal injury and required systemic treatment including adjustment of his immunosuppressant regime. He was followed up to 1-year after discharge. No chronic lung fibrosis or deterioration of his pulmonary function was observed. Despite COVID-19 mediated damage to his renal tubular cells, no transplant rejection occurred. His immunological profile demonstrated both cellular anti-SARS-CoV-2 reactivity and specific humoral immunity, indicating that it is beneficial for the transplanted patients to be immunized with SARS-CoV-2 virus vaccine. This case will help guide clinical decision making for immunocompromised individuals that become infected with SARS-CoV-2.
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Affiliation(s)
- Liru Qiu
- Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ji Zhang
- Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.,Institute of Urology, Anhui Medical University, Hefei, China.,Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, China.,Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation of Ministry of Education, National Health Commission and Chinese Academy of Medical Sciences, Wuhan, China
| | - Yafei Huang
- Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Gen Chen
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhishui Chen
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation of Ministry of Education, National Health Commission and Chinese Academy of Medical Sciences, Wuhan, China
| | - Changsheng Ming
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation of Ministry of Education, National Health Commission and Chinese Academy of Medical Sciences, Wuhan, China
| | - Xia Lu
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation of Ministry of Education, National Health Commission and Chinese Academy of Medical Sciences, Wuhan, China
| | - Nianqiao Gong
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation of Ministry of Education, National Health Commission and Chinese Academy of Medical Sciences, Wuhan, China
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29
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Devaux CA, Melenotte C, Piercecchi-Marti MD, Delteil C, Raoult D. Cyclosporin A: A Repurposable Drug in the Treatment of COVID-19? Front Med (Lausanne) 2021; 8:663708. [PMID: 34552938 PMCID: PMC8450353 DOI: 10.3389/fmed.2021.663708] [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: 02/03/2021] [Accepted: 08/04/2021] [Indexed: 12/22/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) is now at the forefront of major health challenge faced globally, creating an urgent need for safe and efficient therapeutic strategies. Given the high attrition rates, high costs, and quite slow development of drug discovery, repurposing of known FDA-approved molecules is increasingly becoming an attractive issue in order to quickly find molecules capable of preventing and/or curing COVID-19 patients. Cyclosporin A (CsA), a common anti-rejection drug widely used in transplantation, has recently been shown to exhibit substantial anti-SARS-CoV-2 antiviral activity and anti-COVID-19 effect. Here, we review the molecular mechanisms of action of CsA in order to highlight why this molecule seems to be an interesting candidate for the therapeutic management of COVID-19 patients. We conclude that CsA could have at least three major targets in COVID-19 patients: (i) an anti-inflammatory effect reducing the production of proinflammatory cytokines, (ii) an antiviral effect preventing the formation of the viral RNA synthesis complex, and (iii) an effect on tissue damage and thrombosis by acting against the deleterious action of angiotensin II. Several preliminary CsA clinical trials performed on COVID-19 patients report lower incidence of death and suggest that this strategy should be investigated further in order to assess in which context the benefit/risk ratio of repurposing CsA as first-line therapy in COVID-19 is the most favorable.
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Affiliation(s)
- Christian A. Devaux
- Aix-Marseille Univ, IRD, APHM, MEPHI, IHU-Méditerranée Infection, Marseille, France
- CNRS, Marseille, France
| | - Cléa Melenotte
- Aix-Marseille Univ, IRD, APHM, MEPHI, IHU-Méditerranée Infection, Marseille, France
| | - Marie-Dominique Piercecchi-Marti
- Department of Legal Medicine, Hôpital de la Timone, Marseille University Hospital Center, Marseille, France
- Aix Marseille Univ, CNRS, EFS, ADES, Marseille, France
| | - Clémence Delteil
- Department of Legal Medicine, Hôpital de la Timone, Marseille University Hospital Center, Marseille, France
- Aix Marseille Univ, CNRS, EFS, ADES, Marseille, France
| | - Didier Raoult
- Aix-Marseille Univ, IRD, APHM, MEPHI, IHU-Méditerranée Infection, Marseille, France
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30
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Habibi M, Taheri G. Topological network based drug repurposing for coronavirus 2019. PLoS One 2021; 16:e0255270. [PMID: 34324563 PMCID: PMC8320924 DOI: 10.1371/journal.pone.0255270] [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: 04/22/2021] [Accepted: 07/13/2021] [Indexed: 12/14/2022] Open
Abstract
The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has become the current health concern and threat to the entire world. Thus, the world needs the fast recognition of appropriate drugs to restrict the spread of this disease. The global effort started to identify the best drug compounds to treat COVID-19, but going through a series of clinical trials and our lack of information about the details of the virus's performance has slowed down the time to reach this goal. In this work, we try to select the subset of human proteins as candidate sets that can bind to approved drugs. Our method is based on the information on human-virus protein interaction and their effect on the biological processes of the host cells. We also define some informative topological and statistical features for proteins in the protein-protein interaction network. We evaluate our selected sets with two groups of drugs. The first group contains the experimental unapproved treatments for COVID-19, and we show that from 17 drugs in this group, 15 drugs are approved by our selected sets. The second group contains the external clinical trials for COVID-19, and we show that 85% of drugs in this group, target at least one protein of our selected sets. We also study COVID-19 associated protein sets and identify proteins that are essential to disease pathology. For this analysis, we use DAVID tools to show and compare disease-associated genes that are contributed between the COVID-19 comorbidities. Our results for shared genes show significant enrichment for cardiovascular-related, hypertension, diabetes type 2, kidney-related and lung-related diseases. In the last part of this work, we recommend 56 potential effective drugs for further research and investigation for COVID-19 treatment. Materials and implementations are available at: https://github.com/MahnazHabibi/Drug-repurposing.
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Affiliation(s)
- Mahnaz Habibi
- Department of Mathematics, Qazvin Branch, Islamic Azad University, Qazvin, Iran
- * E-mail:
| | - Golnaz Taheri
- Department of Electrical Engineering and Computer Science, KTH Royal Institute of Technology, Stockholm, Sweden
- Science for Life Laboratory, Stockholm, Sweden
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31
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Solanich X, Antolí A, Rocamora-Blanch G, Padullés N, Fanlo-Maresma M, Iriarte A, Mitjavila F, Capdevila O, Riera-Mestre A, Bas J, Vicens-Zygmunt V, Niubó J, Calvo N, Bolivar S, Rigo-Bonnin R, Mensa-Vilaró A, Arregui L, Tebe C, Videla S, Hereu P, Corbella X. Methylprednisolone Pulses Plus Tacrolimus in Addition to Standard of Care vs. Standard of Care Alone in Patients With Severe COVID-19. A Randomized Controlled Trial. Front Med (Lausanne) 2021; 8:691712. [PMID: 34195214 PMCID: PMC8236585 DOI: 10.3389/fmed.2021.691712] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Accepted: 05/25/2021] [Indexed: 12/15/2022] Open
Abstract
Introduction: Severe lung injury is triggered by both the SARS-CoV-2 infection and the subsequent host-immune response in some COVID-19 patients. Methods: We conducted a randomized, single-center, open-label, phase II trial with the aim to evaluate the efficacy and safety of methylprednisolone pulses and tacrolimus plus standard of care (SoC) vs. SoC alone, in hospitalized patients with severe COVID-19. The primary outcome was time to clinical stability within 56 days after randomization. Results: From April 1 to May 2, 2020, 55 patients were prospectively included for subsequent randomization; 27 were assigned to the experimental group and 28 to the control group. The experimental treatment was not associated with a difference in time to clinical stability (hazard ratio 0.73 [95% CI 0.39–1.37]) nor most secondary outcomes. Median methylprednisolone cumulative doses were significantly lower (360 mg [IQR 360–842] vs. 870 mg [IQR 364–1451]; p = 0.007), and administered for a shorter time (median of 4.00 days [3.00–17.5] vs. 18.5 days [3.00–53.2]; p = 0.011) in the experimental group than in the control group. Although not statistically significant, those receiving the experimental therapy showed a numerically lower all-cause mortality than those receiving SoC, especially at day 10 [2 (7.41%) vs. 5 (17.9%); OR 0.39 (95% CI 0.05–2.1); p = 0.282]. The total number of non-serious adverse events was 42 in each the two groups. Those receiving experimental treatment had a numerically higher rate of non-serious infectious adverse events [16 (38%) vs. 10 (24%)] and serious infectious adverse events [7 (35%) vs. 3 (23%)] than those receiving SoC. Conclusions: The combined use of methylprednisolone pulses plus tacrolimus, in addition to the SoC, did not significantly improve the time to clinical stability or other secondary outcomes compared with the SoC alone in severe COVID-19. Although not statistically significant, patients receiving the experimental therapy had numerically lower all-cause mortality than those receiving SoC, supporting recent non-randomized studies with calcineurin inhibitors. It is noteworthy that the present trial had a limited sample size and several other limitations. Therefore, further RCTs should be done to assess the efficacy and safety of tacrolimus to tackle the inflammatory stages of COVID-19. Clinical Trial Registration: Identifier [NCT04341038/EudraCT: 2020-001445-39].
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Affiliation(s)
- Xavier Solanich
- Department of Internal Medicine, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
| | - Arnau Antolí
- Department of Internal Medicine, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
| | - Gemma Rocamora-Blanch
- Department of Internal Medicine, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
| | - Núria Padullés
- Department of Pharmacy, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.,Faculty of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain
| | - Marta Fanlo-Maresma
- Department of Internal Medicine, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
| | - Adriana Iriarte
- Department of Internal Medicine, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
| | - Francesca Mitjavila
- Department of Internal Medicine, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.,Faculty of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain
| | - Olga Capdevila
- Department of Internal Medicine, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.,Faculty of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain
| | - Antoni Riera-Mestre
- Department of Internal Medicine, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.,Faculty of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain
| | - Jordi Bas
- Faculty of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain.,Department of Immunology, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
| | - Vanesa Vicens-Zygmunt
- Department of Pneumology, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
| | - Jordi Niubó
- Department of Microbiology, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
| | - Nahum Calvo
- Department of Diagnostic Imaging, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
| | - Santiago Bolivar
- Department of Diagnostic Imaging, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
| | - Raúl Rigo-Bonnin
- Department of Clinical Laboratory, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
| | - Anna Mensa-Vilaró
- Department of Immunology, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
| | - Laura Arregui
- HUB-ICO-IDIBELL Biobank, Spanish Clinical Research Network, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
| | - Cristian Tebe
- Faculty of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain.,Department of Biostatistics, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
| | - Sebastià Videla
- Faculty of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain.,Department of Clinical Pharmacology, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.,Clinical Research and Clinical Trial Unit (UICEC-IDIBELL), Spanish Clinical Research Network, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
| | - Pilar Hereu
- Faculty of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain.,Department of Clinical Pharmacology, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.,Clinical Research and Clinical Trial Unit (UICEC-IDIBELL), Spanish Clinical Research Network, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
| | - Xavier Corbella
- Department of Internal Medicine, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.,School of Medicine, Universitat Internacional de Catalunya, Barcelona, Spain
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32
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Gálvez-Romero JL, Deveaux-Homs J, Real-Ramírez FA, Palmeros-Rojas O, Pedraza-Sánchez S. Reply letter to: Inhibition of SARS-CoV-2 replication using calcineurin inhibitors: Are concentrations required clinically achievable? J Intern Med 2021; 289:928-929. [PMID: 33822418 PMCID: PMC8250789 DOI: 10.1111/joim.13278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Accepted: 02/24/2021] [Indexed: 11/27/2022]
Affiliation(s)
- J L Gálvez-Romero
- From the, Departamento de Investigación, Hospital Regional Puebla del ISSSTE, Puebla, México
| | - J Deveaux-Homs
- Dirección Médica, Hospital Regional Puebla del ISSSTE, Puebla, México
| | - F A Real-Ramírez
- Departamento de Medicina Interna, Hospital Regional Puebla del ISSSTE, Puebla, México
| | - O Palmeros-Rojas
- Área de Matemáticas, Universidad Autónoma de Chapingo, Texcoco, México
| | - S Pedraza-Sánchez
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Tlalpan, México.,Facultad de Ciencias, Universidad Nacional Autónoma de México (UNAM), Coyoacan, México
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33
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Alunno A, Najm A, Mariette X, De Marco G, Emmel J, Mason L, McGonagle DG, Machado PM. Immunomodulatory therapies for SARS-CoV-2 infection: a systematic literature review to inform EULAR points to consider. Ann Rheum Dis 2021; 80:803-815. [PMID: 33589438 PMCID: PMC8142448 DOI: 10.1136/annrheumdis-2020-219725] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 01/24/2021] [Accepted: 01/27/2021] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To summarise the available information on efficacy and safety of immunomodulatory agents in SARS-CoV-2 infection. METHODS As part of a European League Against Rheumatism (EULAR) taskforce, a systematic literature search was conducted from January 2019 to 11 December 2020. Two reviewers independently identified eligible studies according to the Population, Intervention, Comparator and Outcome framework and extracted data on efficacy and safety of immunomodulatory agents used therapeutically in SARS-CoV-2 infection at any stage. The risk of bias was assessed with validated tools. RESULTS Of the 60 372 records, 401 articles were eligible for inclusion. Studies were at variable risk of bias. Randomised controlled trials (RCTs) were available for the following drugs: hydroxychloroquine (n=12), glucocorticoids (n=6), tocilizumab (n=4), convalescent plasma (n=4), interferon beta (n=2), intravenous immunoglobulins (IVIg) (n=2) and n=1 each for anakinra, baricitinib, colchicine, leflunomide, ruxolitinib, interferon kappa and vilobelimab. Glucocorticoids were able to reduce mortality in specific subsets of patients, while conflicting data were available about tocilizumab. Hydroxychloroquine was not beneficial at any disease stage, one RCT with anakinra was negative, one RCT with baricitinib+remdesivir was positive, and individual trials on some other compounds provided interesting, although preliminary, results. CONCLUSION Although there is emerging evidence about immunomodulatory therapies for the management of COVID-19, conclusive data are scarce with some conflicting data. Since glucocorticoids seem to improve survival in some subsets of patients, RCTs comparing glucocorticoids alone versus glucocorticoids plus anticytokine/immunomodulatory treatment are warranted. This systematic literature review informed the initiative to formulate EULAR 'points to consider' on COVID-19 pathophysiology and immunomodulatory treatment from the rheumatology perspective.
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Affiliation(s)
- Alessia Alunno
- Rheumatology Unit, Department of Medicine, University of Perugia, Perugia, Italy
| | - Aurélie Najm
- Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
| | - Xavier Mariette
- Department of Rheumatology, Université Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, INSERM UMR1184, Le Kremlin Bicêtre, France
| | - Gabriele De Marco
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, Leeds, UK
- The NIHR Leeds Biomedical Research Centre, Chapel Allerton Hospital, Leeds, UK
| | - Jenny Emmel
- Library & Evidence Research Centre, Medical Education, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Laura Mason
- Library & Evidence Research Centre, Medical Education, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Dennis G McGonagle
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, Leeds, UK
- The NIHR Leeds Biomedical Research Centre, Chapel Allerton Hospital, Leeds, UK
| | - Pedro M Machado
- Department of Rheumatology, Northwick Park Hospital, London North West University Healthcare NHS Trust, London, UK
- Centre for Rheumatology & Department of Neuromuscular Diseases, University College London, London, UK
- National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre (BRC), University College London Hospitals (UCLH) NHS Foundation Trust, London, UK
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34
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Zhang S, Wang C, Shi L, Xue Q. Beware of Steroid-Induced Avascular Necrosis of the Femoral Head in the Treatment of COVID-19-Experience and Lessons from the SARS Epidemic. DRUG DESIGN DEVELOPMENT AND THERAPY 2021; 15:983-995. [PMID: 33692615 PMCID: PMC7939498 DOI: 10.2147/dddt.s298691] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 02/19/2021] [Indexed: 01/08/2023]
Abstract
Summary The recent outbreak of coronavirus disease 2019 (COVID-19) has become a global epidemic. Corticosteroids have been widely used in the treatment of severe acute respiratory syndrome (SARS), and the pathological findings seen in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are very similar to those observed in severe acute respiratory syndrome-related coronavirus (SARS-CoV) infection. However, the long-term use of corticosteroids (especially at high doses) is associated with potentially serious adverse events, particularly steroid-induced avascular necrosis of the femoral head (SANFH). In today’s global outbreak, whether corticosteroid therapy should be used, the dosage and duration of treatment, and ways for the prevention, early detection, and timely intervention of SANFH are some important issues that need to be addressed. This review aims to provide a reference for health care providers in COVID-19 endemic countries and regions. Article Focus Hormones are a double-edged sword. This review aims to provide a reference for health care providers in coronavirus disease 2019 (COVID-19) endemic countries and regions, especially with respect to the pros and cons of corticosteroid use in the treatment of patients with COVID-19. Key Messages In today’s global outbreak, whether corticosteroid therapy should be used, the dosage and duration of treatment, and ways for the prevention, early detection, and timely intervention of SANFH are some important issues that need to be addressed. Strengths and Limitations Since SARS was mainly prevalent in China at that time, many evidences in this paper came from the reports of Chinese scholars. There is a bias in the selection of data, which may ignore the differences in environment, race, living habits, medical level and so on. SANFH may be the result of multiple factors. Whether the virus itself is an independent risk factor for SANFH has not been confirmed. In this paper, through literature retrieval, some reference opinions on glucocorticoid usage, diagnosis and treatment of SANFH are given. However, due to the lack of large-scale research data support, it can not be used as the gold standard for the above problems.
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Affiliation(s)
- Shenqi Zhang
- Department of Orthopedics, Beijing Hospital, National Center of Gerontology, Beijing, People's Republic of China.,Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.,Department of Joint and Sports Medicine, Zaozhuang Municipal Hospital Affiliated to Jining Medical University, Shandong, People's Republic of China
| | - Chengbin Wang
- Department of Joint and Sports Medicine, Zaozhuang Municipal Hospital Affiliated to Jining Medical University, Shandong, People's Republic of China
| | - Lei Shi
- Department of Orthopedics, Beijing Hospital, National Center of Gerontology, Beijing, People's Republic of China
| | - Qingyun Xue
- Department of Orthopedics, Beijing Hospital, National Center of Gerontology, Beijing, People's Republic of China.,Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
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35
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Pearson MM, Limaye AP, Biggins SW. Tacrolimus: Unlikely Harmful and Perhaps Helpful in Liver Transplant Recipients with COVID-19. Gastroenterology 2021; 160:1012-1013. [PMID: 33387518 PMCID: PMC7836612 DOI: 10.1053/j.gastro.2020.12.050] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Accepted: 12/29/2020] [Indexed: 01/08/2023]
Affiliation(s)
- Meredith M Pearson
- Division of Gastroenterology and HepatologyLiver Care Line, University of Washington Medical Center and, Center for Liver Investigation Fostering discovEry (C-LIFE), University of Washington, Seattle, Washington
| | - Ajit P Limaye
- Division of Infectious Disease, Department of Surgery, Division of Transplantation, University of Washington, Seattle, Washington
| | - Scott W Biggins
- Division of Gastroenterology and Hepatology, Liver Care Line, University of Washington Medical Center and, Center for Liver Investigation Fostering discovEry (C-LIFE), University of Washington, Seattle, Washington.
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