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Huo R, Wei C, Yang Y, Lin J, Huang X. Hydroxychloroquine: A double‑edged sword (Review). Mol Med Rep 2025; 31:102. [PMID: 39981928 PMCID: PMC11868775 DOI: 10.3892/mmr.2025.13467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Accepted: 01/14/2025] [Indexed: 02/22/2025] Open
Abstract
Hydroxychloroquine (HCQ) is an antimalarial drug that has historically been used to treat and prevent malaria. However, its mechanism of action has not yet been fully elucidated. HCQ affects various cellular and molecular pathways through different mechanisms. HCQ has also been shown to be a disease‑improving agent for the treatment of rheumatic diseases, including systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis and primary Sjögren's syndrome. Although generally considered safe, adverse reactions have been reported with the use of HCQ and clinicians should carefully monitor patients with rheumatism when prescribing these drugs. The purpose of the present review is to strengthen the clinical use of HCQ for autoimmune diseases while highlighting the adverse effects that may occur during treatment.
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Affiliation(s)
- Rongxiu Huo
- Department of Rheumatology and Immunology, Guangxi Academy of Medical Sciences, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Autonomous Region 530016, P.R. China
| | - Chengcheng Wei
- Department of Rheumatology and Immunology, Guangxi Academy of Medical Sciences, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Autonomous Region 530016, P.R. China
| | - Yanting Yang
- Department of Rheumatology and Immunology, Guangxi Academy of Medical Sciences, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Autonomous Region 530016, P.R. China
| | - Jinying Lin
- Department of Rheumatology and Immunology, Guangxi Academy of Medical Sciences, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Autonomous Region 530016, P.R. China
| | - Xinxiang Huang
- Department of Rheumatology and Immunology, Guangxi Academy of Medical Sciences, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Autonomous Region 530016, P.R. China
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Alwakeel M, Abi Fadel F, Nanah A, Wang Y, Awad MKA, Abdeljaleel F, Obeidat M, Saleem T, Afzal S, Alayan D, Harnegie MP, Wang X, Duggal A, Zhang P. Efficacy of COVID-19 Treatments in Intensive Care Unit: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Crit Care Res Pract 2024; 2024:2973795. [PMID: 39633779 PMCID: PMC11617054 DOI: 10.1155/ccrp/2973795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 10/23/2024] [Accepted: 11/16/2024] [Indexed: 12/07/2024] Open
Abstract
Objectives: Examining the cumulative evidence from randomized controlled trials (RCTs), evaluating the use of pharmacological agents for the treatment of COVID-19 infections in patients with critical illness. Data Sources: Databases Medline, Embase, Web of Science, Scopus, CINAHL, and Cochrane. Study Selection: Inclusion criteria were RCTs that enrolled patients with confirmed or suspected COVID-19 infection who are critically ill. Only RCTs that examined therapeutic agents against one another or no intervention, placebo, or standard of care, were included. Data Extraction: Pairs of reviewers extracted data independently. Outcomes of interest included the overall reported mortality defined as either the ICU mortality, hospital mortality, mortality within 28 days or mortality within 90 days. Data Synthesis: A total of 40 studies (11,613 patients) evaluated 50 therapeutic intervention arms divided into five main therapy categories; steroids, antiviral medications, immunomodulators, plasma therapies [intravenous immunoglobulins (IVIG), convalescent plasma and/or, therapeutic plasma exchange], and therapeutic anticoagulation. Immunomodulators was the only group with possible mortality benefit, risk ratio (RR) 0.83 (95% CI 0.73; 0.95), with nonsignificant heterogeneity (I 2 = 8%, p=0.36). In contrast, the other therapy groups showed no significant impact on mortality, as indicated by their respective pooled RRs: steroids [RR 0.91 (95% CI 0.82; 1.01), I 2 = 31%], antiviral medications [RR 1.11 (95% CI 0.82; 1.49), I 2 = 57%], plasma therapies [RR 0.77 (95% CI 0.58; 1.01), I 2 = 36%], and anticoagulation [RR 1.06 (95% CI 0.95; 1.18), I 2 = 0%]. Conclusions: This meta-analysis highlights both the heterogeneity and a lack of benefit from therapies evaluated during the COVID-19 pandemic. Many of the RCTs were developed based on limited observational data. Future RCTs investigating pharmaceutical interventions in critically ill patients during pandemics need to be designed based on better evidence.
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Affiliation(s)
- Mahmoud Alwakeel
- Department of Pulmonary and Critical Care Medicine, Respiratory Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Francois Abi Fadel
- Department of Pulmonary and Critical Care Medicine, Respiratory Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Abdelrahman Nanah
- Department of Medicine, Cleveland Clinic Fairview Hospital, Cleveland, Ohio, USA
| | - Yan Wang
- Department of Anesthesiology, Boston Medical Center, Boston, Massachusetts, USA
| | - Mohamed K. A. Awad
- Department of Pulmonary, Critical Care and Allergy, University of Alabama, Birmingham, Alabama, USA
| | - Fatima Abdeljaleel
- Department of Medicine, Cleveland Clinic Fairview Hospital, Cleveland, Ohio, USA
| | - Mohammed Obeidat
- Department of Medicine, Cleveland Clinic Fairview Hospital, Cleveland, Ohio, USA
| | - Talha Saleem
- Department of Pulmonary and Critical Care Medicine, Respiratory Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Saira Afzal
- Department of Neurology, Cleveland Clinic Florida, Weston, Florida, USA
- Department of Internal Medicine, Cleveland Clinic Florida, Cleveland, USA
| | - Dina Alayan
- Department of Medicine, Cleveland Clinic Fairview Hospital, Cleveland, Ohio, USA
| | - Mary Pat Harnegie
- Floyd D. Loop Alumni Library, Cleveland Clinic, Cleveland, Ohio, USA
| | - Xiaofeng Wang
- Department of Qualitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, USA
| | - Abhijit Duggal
- Department of Pulmonary and Critical Care Medicine, Respiratory Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Peng Zhang
- Department of Pulmonary and Critical Care Medicine, Respiratory Institute, Cleveland Clinic, Cleveland, Ohio, USA
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Al-Mistarehi AHW, El-Akawi S, Kheirallah KA, Bani Ata EM, Zaitoun KJ, Khassawneh AB, Jarrah A, Alzoubi HM, Al-Azzam S, Karasneh RA, Altawalbeh RB, Khassawneh B. Enhanced Treatment in Severe-Critical COVID-19 With Tocilizumab, Remdesivir, Dexamethasone: A Jordanian Cohort Study. Cureus 2024; 16:e67467. [PMID: 39314607 PMCID: PMC11417280 DOI: 10.7759/cureus.67467] [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] [Accepted: 08/21/2024] [Indexed: 09/25/2024] Open
Abstract
BACKGROUND Several medications have been proposed to manage COVID-19, with controversial data regarding their clinical benefits. We aimed to investigate the clinical efficacy of using remdesivir (RDV) with and without tocilizumab (TCZ) and standard therapy in treating severe COVID-19. METHODS This retrospective cohort study was conducted in a Jordanian tertiary hospital (September 26th, 2020 - August 28th, 2021) and included adult COVID-19 patients requiring oxygen support. Patients were categorized into three groups based on treatment: TCZ+RDV and standard therapy; RDV and standard therapy; and standard therapy alone, which included dexamethasone, vitamins, anticoagulants, and ceftriaxone. RESULTS Of 1,556 screened, 1,244 patients (mean age 62.33, 60.8% men) were included. Distribution was 106 in TCZ+RDV, 520 in RDV, and 618 in standard therapy. No significant differences were observed in age, gender, or BMI. Mortality was lowest in TCZ+RDV (32.1%), followed by RDV (40.6%) and standard therapy (47.1%) (p=0.005). Among ICU patients, TCZ+RDV showed significantly lower mortality (51.1%) compared to RDV (75%) and standard therapy (85.8%) (p<0.001). The ICU stays and invasive mandatory ventilation (IMV) durations were significantly shorter with TCZ+RDV (4.30 and 2.69 days, respectively) compared to RDV (7.61 and 4.52 days) and standard therapy (7.98 and 5.32 days) (p<0.001 for ICU stays, p=0.025 for IMV durations). CONCLUSIONS Combining TCZ, RDV, and dexamethasone shows promise in reducing mortality and ICU/IMV duration for severe COVID-19.
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Affiliation(s)
| | - Shadi El-Akawi
- Internal Medicine, MedStar Washington Hospital Center-Georgetown University, Washington, DC, USA
| | - Khalid A Kheirallah
- Faculty of Medicine, Jordan University of Science and Technology, Irbid, JOR
| | - Ehab M Bani Ata
- Faculty of Medicine, Jordan University of Science and Technology, Irbid, JOR
| | - Khaled J Zaitoun
- Faculty of Medicine, Jordan University of Science and Technology, Amman, JOR
| | - Ahmad B Khassawneh
- Faculty of Medicine, Jordan University of Science and Technology, Irbid, JOR
| | - Abdullah Jarrah
- Internal Medicine, Detroit Medical Center/Sinai Grace Hospital/Wayne State University, Detroit, USA
| | - Hamed M Alzoubi
- Faculty of Medicine, Jordan University of Science and Technology, Irbid, JOR
| | - Sayer Al-Azzam
- Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, JOR
| | | | - Rana B Altawalbeh
- Faculty of Medicine, Jordan University of Science and Technology, Irbid, JOR
| | - Basheer Khassawneh
- Faculty of Medicine, Jordan University of Science and Technology, Irbid, JOR
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Calderón-Ochoa C, Plamenov-Donchev N, Hernández-Quiñones F, Mendoza-López O, Hinojos-Gallardo LC, Longino-Gómez AJ, Hernádez-Saldaña R, Duque-Rodríguez J, Ishida-Gutiérrez MC. Tocilizumab demonstrates superiority in decreasing C-reactive protein levels in hospitalized COVID-19 patients, compared to standard care treatment alone. Microbiol Spectr 2024; 12:e0249823. [PMID: 38687065 PMCID: PMC11237561 DOI: 10.1128/spectrum.02498-23] [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: 07/21/2023] [Accepted: 03/21/2024] [Indexed: 05/02/2024] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 has caused a global pandemic, leading to health, economic, and political crisis. The virus triggers the activation of inflammatory reactants including interleukin-6 (IL-6), ferritin, and C-reactive protein (CRP), causing multiorgan damage, particularly affecting the lungs. Tocilizumab, an IL-6 receptor blocker, has the potential to diminish the progression of the disease and reduce organ damage and long-term complications. The aim of this observational retrospective cohort study was to evaluate the efficacy of tocilizumab in decreasing CRP levels in hospitalized coronavirus disease 2019 (COVID-19) patients compared to standard care without the drug. The study included 141 patients during their Hospital Stay (HS), with 100 in the Tocilizumab group and 41 in the non-Tocilizumab group. Clinical information was collected from the electronic clinical record, analyzed using statistical software, and homogenized the CRP levels from the severe group to the levels of the less complicated group at 48 h of hospitalization. The results showed a statistically significant greater decrease in CRP levels in the Tocilizumab group at 48 h after the use of the treatment, with no differences in mortality or length of stay between the groups. In conclusion, tocilizumab accelerates the diminishing of CRP levels compared to standard treatment alone, and its use may have potential benefits in the management of severe COVID-19 patients when used alongside with follow-up quantification of CRP levels reduction.IMPORTANCESevere acute respiratory syndrome coronavirus 2 has caused a global pandemic, leading to health, economic, and political crises. International guidelines for managing coronavirus disease 2019 (COVID-19) give recommendations according to the severity of the disease and the level of oxygen therapy needed. Tocilizumab is an option for the therapeutic management of hospitalized patients with any level of oxygen therapy; IL-6 serum level is the parameter for the follow-up on the efficacy, but it is not available at many hospitals. In this study, we demonstrate that C-reactive protein determination can predict the response to tocilizumab in severe COVID-19, the target patients for treatment with this drug. The use of this affordable and extensively available biomarker supports clinical decisions for the early escalation of the therapy and for the rational use of this drug on those prone to improve with the use of it.
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Affiliation(s)
- Carolina Calderón-Ochoa
- Autonomous University of Chihuahua, Faculty of Medicine and Biomedical Sciences, Laboratory of Pharmacoepidemiology, Chihuahua, Mexico
| | - Narek Plamenov-Donchev
- Autonomous University of Chihuahua, Faculty of Medicine and Biomedical Sciences, Laboratory of Pharmacoepidemiology, Chihuahua, Mexico
| | - Fernando Hernández-Quiñones
- Autonomous University of Chihuahua, Faculty of Medicine and Biomedical Sciences, Laboratory of Pharmacoepidemiology, Chihuahua, Mexico
| | - Olga Mendoza-López
- Autonomous University of Chihuahua, Faculty of Medicine and Biomedical Sciences, Laboratory of Pharmacoepidemiology, Chihuahua, Mexico
| | - Luis Carlos Hinojos-Gallardo
- Autonomous University of Chihuahua, Faculty of Medicine and Biomedical Sciences, Laboratory of Pharmacoepidemiology, Chihuahua, Mexico
| | | | | | - Jorge Duque-Rodríguez
- Autonomous University of Chihuahua, Faculty of Medicine and Biomedical Sciences, Laboratory of Pharmacoepidemiology, Chihuahua, Mexico
| | - María Cecilia Ishida-Gutiérrez
- Autonomous University of Chihuahua, Faculty of Medicine and Biomedical Sciences, Laboratory of Pharmacoepidemiology, Chihuahua, Mexico
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Tseng PT, Zeng BS, Thompson T, Stubbs B, Hsueh PR, Su KP, Chen YW, Chen TY, Wu YC, Lin PY, Carvalho AF, Hsu CW, Li DJ, Yeh TC, Sun CK, Cheng YS, Shiue YL, Liang CS, Tu YK. Placebo effects on all-cause mortality of patients with COVID-19 in randomized controlled trials of interleukin 6 antagonists: A systematic review and network meta-analysis. Psychiatry Clin Neurosci 2023; 77:638-645. [PMID: 37646204 DOI: 10.1111/pcn.13592] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 08/14/2023] [Accepted: 08/23/2023] [Indexed: 09/01/2023]
Abstract
AIM Many randomized controlled trials (RCTs) have investigated the use of interleukin 6 antagonists for the treatment of coronavirus disease 2019 (COVID-19), yielding inconsistent results. This network meta-analysis (NMA) aimed to identify the source of these inconsistent results by reassessing whether participants treated with standard of care (SoC) plus placebo have different all-cause mortality from those treated with SoC alone and to reevaluate the efficacy of interleukin 6 antagonists in the treatment of COVID-19. METHODS We conducted a systematic search for relevant RCTs from the inception of electronic databases through 1 September 2022. The primary outcome was all-cause mortality. The secondary outcomes were the incidences of major medical events, secondary infections, all-cause discontinuation, and serious adverse events. RESULTS The results of NMA of 33 RCTs showed that patients with COVID-19 treated with SoC plus placebo had lower odds of all-cause mortality than those who received SoC alone (OR, 0.75 [95% confidence interval, 0.58-0.97]). This finding remained consistent after excluding studies with no incident deaths. In addition, when we consider the impact of the widely promoted COVID-19 vaccination and newly developed antiviral treatment strategy, the results from the analysis of the RCT published in 2021 and 2022 remained similar. CONCLUSION These findings suggest the potential influence of placebo effects on the treatment outcomes of COVID-19 in RCTs. When evaluating the efficacy of treatment strategies for COVID-19, it is crucial to consider the use of placebo in the design of clinical trials.
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Affiliation(s)
- Ping-Tao Tseng
- Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan
- Department of Psychology, College of Medical and Health Science, Asia University, Taichung, Taiwan
- Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung, Taiwan
- Institute of Precision Medicine, National Sun Yat-sen University, Kaohsiung City, Taiwan
| | - Bing-Syuan Zeng
- Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan
- Department of Internal Medicine, E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Trevor Thompson
- Centre for Chronic Illness and Ageing, University of Greenwich, London, UK
| | - Brendon Stubbs
- Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
- Physiotherapy Department, South London and Maudsley NHS Foundation Trust, London, UK
- Faculty of Health, Social Care Medicine and Education, Anglia Ruskin University, Chelmsford, UK
| | - Po-Ren Hsueh
- Departments of Laboratory Medicine and Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Kuan-Pin Su
- College of Medicine, China Medical University, Taichung, Taiwan
- Mind-Body Interface Laboratory (MBI-Lab), China Medical University and Hospital, Taichung, Taiwan
- An-Nan Hospital, China Medical University, Tainan, Taiwan
| | - Yen-Wen Chen
- Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung, Taiwan
| | - Tien-Yu Chen
- Department of Psychiatry, Tri-Service General Hospital; School of Medicine, National Defense Medical Center, Taipei, Taiwan
- Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yi-Cheng Wu
- Department of Sports Medicine, Landseed International Hospital, Taoyuan, Taiwan
| | - Pao-Yen Lin
- Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
- Institute for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Andre F Carvalho
- Innovation in Mental and Physical Health and Clinical Treatment (IMPACT) Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, Geelong, Victoria, Australia
| | - Chih-Wei Hsu
- Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Dian-Jeng Li
- Department of Addiction Science, Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Kaohsiung City, Taiwan
| | - Ta-Chuan Yeh
- Department of Psychiatry, Tri-Service General Hospital; School of Medicine, National Defense Medical Center, Taipei, Taiwan
| | - Cheuk-Kwan Sun
- Department of Emergency Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
- School of Medicine for International Students, College of Medicine, I-Shou University Kaohsiung, Kaohsiung, Taiwan
| | - Yu-Shian Cheng
- Department of Psychology, College of Medical and Health Science, Asia University, Taichung, Taiwan
- Department of Psychiatry, Tsyr-Huey Mental Hospital, Kaohsiung Jen-Ai's Home, Kaohsiung, Taiwan
| | - Yow-Ling Shiue
- Department of Internal Medicine, E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan
- Institute for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chih-Sung Liang
- Department of Psychiatry, Beitou Branch, Tri-Service General Hospital; School of Medicine, National Defense Medical Center, Taipei, Taiwan
- Department of Psychiatry, National Defense Medical Center, Taipei, Taiwan
| | - Yu-Kang Tu
- Institute of Health Data Analytics & Statistics, College of Public Health, National Taiwan University, Taipei, Taiwan
- Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan
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Libra A, Ciancio N, Sambataro G, Sciacca E, Muscato G, Marino A, Vancheri C, Spicuzza L. Use of Remdesivir in Patients Hospitalized for COVID-19 Pneumonia: Effect on the Hypoxic and Inflammatory State. Viruses 2023; 15:2101. [PMID: 37896877 PMCID: PMC10612076 DOI: 10.3390/v15102101] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Revised: 10/13/2023] [Accepted: 10/14/2023] [Indexed: 10/29/2023] Open
Abstract
Remdesivir is one of the most attractive options for patients with hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19). The aim of our study was to evaluate the effect of remdesivir on the hypoxic and inflammatory state in patients with moderate to severe COVID-19. We retrospectively enrolled 112 patients admitted for COVID-19 pneumonia, requiring low-flow oxygen, 57 treated with remdesivir plus standard of care (SoC) and 55 treated only with SoC that were similar for demographic and clinical data. We evaluated changes in hypoxemia and inflammatory markers at admission (Day 0) and after 5 days of treatment (Day 5) and the clinical course of the disease. From Day 0 to Day 5, the ratio of arterial oxygen partial pressure to fractional inspired oxygen (P/F) increased from 222 ± 62 to 274 ± 97 (p < 0.0001) in the remdesivir group and decreased from 223 ± 62 to 183 ± 76 (p < 0.05) in the SoC group. Interleukine-6 levels decreased in the remdesivir (45.9 to 17.5 pg/mL, p < 0.05) but not in the SoC group. Remdesivir reduced the need for ventilatory support and the length of hospitalization. In conclusion, compared to standard care, remdesivir rapidly improves hypoxia and inflammation, causing a better course of the disease in moderate to severe COVID-19.
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Affiliation(s)
- Alessandro Libra
- Regional Referral Centre for Rare Lung Disease, University Hospital “Policlinico-San Marco”, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy; (N.C.); (G.S.); (E.S.); (G.M.); (C.V.); (L.S.)
| | - Nicola Ciancio
- Regional Referral Centre for Rare Lung Disease, University Hospital “Policlinico-San Marco”, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy; (N.C.); (G.S.); (E.S.); (G.M.); (C.V.); (L.S.)
| | - Gianluca Sambataro
- Regional Referral Centre for Rare Lung Disease, University Hospital “Policlinico-San Marco”, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy; (N.C.); (G.S.); (E.S.); (G.M.); (C.V.); (L.S.)
| | - Enrico Sciacca
- Regional Referral Centre for Rare Lung Disease, University Hospital “Policlinico-San Marco”, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy; (N.C.); (G.S.); (E.S.); (G.M.); (C.V.); (L.S.)
| | - Giuseppe Muscato
- Regional Referral Centre for Rare Lung Disease, University Hospital “Policlinico-San Marco”, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy; (N.C.); (G.S.); (E.S.); (G.M.); (C.V.); (L.S.)
| | - Andrea Marino
- Department of Biomedical and Biotechnological Sciences, Unit of Infectious Diseases, University of Catania, 95123 Catania, Italy;
| | - Carlo Vancheri
- Regional Referral Centre for Rare Lung Disease, University Hospital “Policlinico-San Marco”, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy; (N.C.); (G.S.); (E.S.); (G.M.); (C.V.); (L.S.)
| | - Lucia Spicuzza
- Regional Referral Centre for Rare Lung Disease, University Hospital “Policlinico-San Marco”, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy; (N.C.); (G.S.); (E.S.); (G.M.); (C.V.); (L.S.)
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7
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Flisiak R, Flisiak-Jackiewicz M, Rzymski P, Zarębska-Michaluk D. Tocilizumab for the treatment of COVID-19. Expert Rev Anti Infect Ther 2023; 21:791-797. [PMID: 37326214 DOI: 10.1080/14787210.2023.2226867] [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: 03/26/2023] [Accepted: 06/14/2023] [Indexed: 06/17/2023]
Abstract
INTRODUCTION Since the beginning of the COVID-19 pandemic, the repurposing of medicines has been pursued to find interventions effective in preventing fatal outcome of the disease. One of these drugs was tocilizumab, an interleukin-6 inhibiting monoclonal antibody, previously used to treat several immune-related disorders. AREAS COVERED In this article, we present the results of the initial observational studies and subsequent randomized clinical trials on the efficacy and safety of tocilizumab in the treatment of COVID-19. Despite conflicting results, possibly due to the heterogeneity of the studied populations, large studies have ultimately proven that preventing IL-6 from attaching to its receptors can effectively reverse the fatal course of the disease. We also discuss the meta-analyses, which mostly supported the validity of tocilizumab therapy. We show how tocilizumab found its place in the most important recommendations on COVID-19 treatment and obtained authorization from the major regulatory authorities. EXPERT OPINION The criteria for optimizing tocilizumab therapy in COVID-19 still need to be established. They are also important considering the existing risks of future zoonotic spillovers and epidemics that may trigger hyperinflammation that could be efficiently blocked. The experience gained with tocilizumab shall be perceived as preparedness for future challenges.
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Affiliation(s)
- Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok, Poland
| | - Marta Flisiak-Jackiewicz
- Department of Pediatrics, Gastroenterology, Hepatology, Nutrition and Allergology, Medical University of Bialystok, Bialystok, Poland
| | - Piotr Rzymski
- Department of Environmental Medicine, Poznan University of Medical Sciences, Poznań, Poland
- Integrated Science Association (ISA), Universal Scientific Education and Research Network (USERN), Poznań, Poland
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Sarhan RM, E Altyar A, Essam Abou Warda A, Saied YM, Ibrahim HSG, Schaalan MF, Fathy S, Sarhan N, Boshra MS. Pentoxifylline Effects on Hospitalized COVID-19 Patients with Cytokine Storm Syndrome: A Randomized Clinical Trial. Pharmaceuticals (Basel) 2023; 16:ph16040631. [PMID: 37111389 PMCID: PMC10142327 DOI: 10.3390/ph16040631] [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: 02/13/2023] [Revised: 04/14/2023] [Accepted: 04/17/2023] [Indexed: 04/29/2023] Open
Abstract
COVID-19 is a fatal, fast-spreading pandemic, and numerous attempts are being made around the world to understand and manage the disease. COVID-19 patients may develop a cytokine-release syndrome, which causes serious respiratory diseases and, in many cases, death. The study examined the feasibility of employing legally available anti-inflammatory pentoxifylline (PTX), a low toxicity and cost medication, to mitigate the hyper-inflammation caused by COVID-19. Thirty adult patients who tested positive for SARS-CoV2 were hospitalized owing to the cytokine storm syndrome. They were given 400 mg of pentoxifylline orally TID according to the standard COVID-19 protocol of the Egyptian Ministry of Health. Besides this, a group of thirty-eight hospitalized COVID-19 patients who received the standard COVID-19 protocol was included in the study as a control group. The outcomes included laboratory test parameters, clinical improvements, and number of deaths in both groups. After receiving PTX, all patients showed a significant improvement in C reactive protein (CRP), and interleukin-6 (IL-6) levels at p < 0.01 and p = 0.004, respectively, while there was an increase in total leukocyte count (TLC) and neutrophil-to-leucocyte ratio (NLR) at p < 0.01 compared to their baseline levels. The D-dimer level showed a significant increase in the treatment group at p < 0.01, while showing no statistically significant difference in the control group. The median initial ALT (42 U/L) in the treatment group showed a decrease compared to the control group (51 U/L). No statistical significance was reported regarding clinical improvement, length of stay, and death percentages between the two groups. Our results showed no significant improvement of PTX over controls in clinical outcomes of hospitalized COVID-19 patients. Nevertheless, PTX displayed a positive effect on certain inflammatory biomarkers.
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Affiliation(s)
- Rania M Sarhan
- Clinical Pharmacy Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62511, Egypt
| | - Ahmed E Altyar
- Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, P.O. Box 80260, Jeddah 21589, Saudi Arabia
- Pharmacy Program, Batterjee Medical College, P.O. Box 6231, Jeddah 21442, Saudi Arabia
| | - Ahmed Essam Abou Warda
- Clinical Pharmacy Department, Faculty of Pharmacy, October 6 University, Giza 12585, Egypt
| | - Yasmine Mohamed Saied
- Microbiology and Immunology Postgraduate Program, Faculty of Pharmacy, Cairo University, Cairo 11828, Egypt
| | | | - Mona F Schaalan
- Clinical Pharmacy Department, Faculty of Pharmacy, Misr International University, Cairo 11828, Egypt
| | - Shaimaa Fathy
- Clinical Pharmacy Department, Faculty of Pharmacy, Misr International University, Cairo 11828, Egypt
| | - Neven Sarhan
- Clinical Pharmacy Department, Faculty of Pharmacy, Misr International University, Cairo 11828, Egypt
| | - Marian S Boshra
- Clinical Pharmacy Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62511, Egypt
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9
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Al Kharusi M, Al Sheikh N, Alhajri M, Al Mandhri SA, Khafagy ES, Moglad EH, Alotaibi HF, Hegazy WAH. A Prospective Cohort Study of COVID-19: Evaluation of the Early Role of IL-1 and IL-6 Antagonists in Improving the Outcome of the Illness and Reduction in the Risk of Death. Healthcare (Basel) 2023; 11:healthcare11071025. [PMID: 37046952 PMCID: PMC10094110 DOI: 10.3390/healthcare11071025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 03/29/2023] [Accepted: 03/30/2023] [Indexed: 04/14/2023] Open
Abstract
The COVID-19 pandemic had a profound impact on global health, economies, and social systems. The crucial factor that determines the success of COVID-19 treatments is preventing the need for mechanical ventilation and intensive care admission. In the context of COVID-19, several treatments have been found to play a role in the disease's progression and severity. Interleukins (ILs) have been identified as key mediators of the cytokine storm that can occur in severe cases of COVID-19, leading to respiratory failure and other complications. For instance, IL-1 antagonist (anakinra) and IL-6 antagonist (tocilizumab) are supposed to be promising treatments as well as cortisones for COVID-19. This prospective study aims to evaluate the effectiveness of anakinra or tocilizumab in addition to cortisone in preventing the progression of mild to moderate COVID-19 cases to severe intensive care admission. Biochemical and hematological parameters, such as D-dimer, ferritin, LDH, CRP, and white blood cells (WBCs), were measured after treatment with either anakinra or tocilizumab in addition to cortisone or cortisone alone. The study also recorded the number of deaths and patients admitted to intensive care. The results indicate that anakinra significantly improved outcomes and decreased the number of intensive care admissions compared to tocilizumab or cortisone alone. Therefore, anakinra may play a vital role in controlling the progression of COVID-19, and its use in mild to moderate cases may prevent the worsening of the disease to severe stages.
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Affiliation(s)
| | | | - Maiya Alhajri
- Pharmacy Department, Field Hospital, Muscat 111, Oman
| | | | - El-Sayed Khafagy
- Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-kharj 11942, Saudi Arabia
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt
| | - Ehssan H Moglad
- Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-kharj 11942, Saudi Arabia
- Department of Microbiology and Parasitology, Medicinal and Aromatic Plants Research Institute, National Center for Research, Khartoum 2404, Sudan
| | - Hadil Faris Alotaibi
- Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia
| | - Wael A H Hegazy
- Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt
- Pharmacy Program, Department of Pharmaceutical Sciences, Oman College of Health Sciences, Muscat 113, Oman
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10
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Panahi Y, Gorabi AM, Talaei S, Beiraghdar F, Akbarzadeh A, Tarhriz V, Mellatyar H. An overview on the treatments and prevention against COVID-19. Virol J 2023; 20:23. [PMID: 36755327 PMCID: PMC9906607 DOI: 10.1186/s12985-023-01973-9] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Accepted: 01/14/2023] [Indexed: 02/10/2023] Open
Abstract
BACKGROUND The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to plague the world. While COVID-19 is asymptomatic in most individuals, it can cause symptoms like pneumonia, ARDS (acute respiratory distress syndrome), and death in others. Although humans are currently being vaccinated with several COVID-19 candidate vaccines in many countries, however, the world still is relying on hygiene measures, social distancing, and approved drugs. RESULT There are many potential therapeutic agents to pharmacologically fight COVID-19: antiviral molecules, recombinant soluble angiotensin-converting enzyme 2 (ACE2), monoclonal antibodies, vaccines, corticosteroids, interferon therapies, and herbal agents. By an understanding of the SARS-CoV-2 structure and its infection mechanisms, several vaccine candidates are under development and some are currently in various phases of clinical trials. CONCLUSION This review describes potential therapeutic agents, including antiviral agents, biologic agents, anti-inflammatory agents, and herbal agents in the treatment of COVID-19 patients. In addition to reviewing the vaccine candidates that entered phases 4, 3, and 2/3 clinical trials, this review also discusses the various platforms that are used to develop the vaccine COVID-19.
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Affiliation(s)
- Yunes Panahi
- Pharmacotherapy Department, Faculty of Pharmacy, Bagyattallah University of Medical Sciences, Tehran, Iran
| | - Armita Mahdavi Gorabi
- Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Sona Talaei
- Department of Basic Sciences, Maragheh University of Medical Sciences, Maragheh, Iran
| | - Fatemeh Beiraghdar
- Nephrology and Urology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Abolfazl Akbarzadeh
- Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Vahideh Tarhriz
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hassan Mellatyar
- Pharmacotherapy Department, Faculty of Pharmacy, Bagyattallah University of Medical Sciences, Tehran, Iran
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11
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Ferrarini A, Vacca A, Solimando AG, Tavio M, Acquaviva R, Rocchi M, Nitti C, Salvi A, Menditto V, Luchetti Gentiloni MM, Russo A, Moretti M, Pavani M, Giacometti A, Bonifazi M, Zuccatosta L, Romani L, Racanelli V, Moroncini G, Gabrielli A, Pomponio G. Early administration of tofacitinib in COVID-19 pneumonitis: An open randomised controlled trial. Eur J Clin Invest 2023; 53:e13898. [PMID: 36380693 DOI: 10.1111/eci.13898] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 10/03/2022] [Accepted: 10/04/2022] [Indexed: 11/17/2022]
Abstract
BACKGROUND Controversies on sub-populations most sensitive to therapy and the best timing of starting the treatment still surround the use of immunomodulatory drugs in COVID-19. OBJECTIVES We designed a multicentre open-label randomised controlled trial to test the effect of prompt adding of tofacitinib to standard therapy for hospitalised patients affected by mild/moderate COVID-19 pneumonitis. METHODS Patients admitted to three Italian hospitals affected by COVID-19 pneumonitis not requiring mechanical ventilation were randomised to receive standard treatment alone or tofacitinib (10 mg/bid) for 2 weeks, starting within the first 24 h from admission. RESULTS A total of 116 patients were randomised; 49 in the experimental arm completed the 14-day treatment period, 9 discontinued tofacitinib as the disease worsened and were included in the analysis, and 1 died of respiratory failure. All 58 control patients completed the study. Clinical and demographic characteristics were similar between the study groups. In the tofacitinib group, 9/58 (15.5%) patients progressed to noninvasive ventilation (CPAP) to maintain SO2 > 93%, invasive mechanical ventilation or death by day 14 was 15.5%, significantly less than in the control group (20/58, 34.4%, RR 0,45, RRR -55%, NNT 5; p = .018). No differences in severe adverse effect incidence had been observed across the groups. CONCLUSION High-dose tofacitinib therapy in patients with COVID pneumonitis is safe and may prevent deterioration to respiratory failure.
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Affiliation(s)
- Alessia Ferrarini
- Clinica Medica, Ospedali Riuniti di Ancona, Ancona, Italy.,Gastroenterologia ed Endoscopia Digestiva, Ospedali Riuniti Marche Nord, Fano, Italy
| | - Angelo Vacca
- Dipartimento di Scienze Biomediche e Oncologia Umana U.O.C, Medicina Interna Universitaria "G. Baccelli" A.O.U.C, Policlinico di Bari, Bari, Italy
| | - Antonio Giovanni Solimando
- Dipartimento di Scienze Biomediche e Oncologia Umana U.O.C, Medicina Interna Universitaria "G. Baccelli" A.O.U.C, Policlinico di Bari, Bari, Italy.,IRCCS Istituto Tumori "Giovanni Paolo II" Bari, Bari, Italy
| | - Marcello Tavio
- Malattie Infettive, Ospedali Riuniti di Ancona, Ancona, Italy
| | - Rossella Acquaviva
- Dipartimento di Scienze Biomediche e Oncologia Umana U.O.C, Medicina Interna Universitaria "G. Baccelli" A.O.U.C, Policlinico di Bari, Bari, Italy
| | - Marco Rocchi
- Statistica Medica, Dipartimento di Scienze Biomolecolari, Università di Urbino, Urbino, Italy
| | - Cinzia Nitti
- Medicina Interna e Sub Intensiva, Ospedali Riuniti di Ancona, Ancona, Italy
| | - Aldo Salvi
- Medicina Interna e Sub Intensiva, Ospedali Riuniti di Ancona, Ancona, Italy
| | - Vincenzo Menditto
- Medicina Interna e Sub Intensiva, Ospedali Riuniti di Ancona, Ancona, Italy
| | | | - Alessandro Russo
- Clinica di Malattie Infettive e Tropicali Dipartimento di Scienze Mediche e Chirurgiche Università "Magna Graecia" di Catanzaro, Catanzaro, Italy
| | - Marco Moretti
- SOD Medicina di Laboratorio Ospedali Riuniti di Ancona, Ancona, Italy
| | - Marianna Pavani
- SOD Medicina di Laboratorio Ospedali Riuniti di Ancona, Ancona, Italy
| | - Andrea Giacometti
- Clinica di Malattie Infettive, Ospedali Riuniti di Ancona, Ancona, Italy
| | | | | | - Laura Romani
- Clinica Medica, Ospedali Riuniti di Ancona, Ancona, Italy
| | - Vito Racanelli
- Dipartimento di Scienze Biomediche e Oncologia Umana U.O.C, Medicina Interna Universitaria "G. Baccelli" A.O.U.C, Policlinico di Bari, Bari, Italy
| | - Gianluca Moroncini
- Clinica Medica, Ospedali Riuniti di Ancona, Ancona, Italy.,Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy
| | - Armando Gabrielli
- Clinica Medica, Ospedali Riuniti di Ancona, Ancona, Italy.,Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy
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12
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Zhao SW, Li YM, Li YL, Su C. Liver injury in COVID-19: Clinical features, potential mechanisms, risk factors and clinical treatments. World J Gastroenterol 2023; 29:241-256. [PMID: 36687127 PMCID: PMC9846943 DOI: 10.3748/wjg.v29.i2.241] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 11/11/2022] [Accepted: 12/08/2022] [Indexed: 01/06/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has been a serious threat to global health for nearly 3 years. In addition to pulmonary complications, liver injury is not uncommon in patients with novel COVID-19. Although the prevalence of liver injury varies widely among COVID-19 patients, its incidence is significantly increased in severe cases. Hence, there is an urgent need to understand liver injury caused by COVID-19. Clinical features of liver injury include detectable liver function abnormalities and liver imaging changes. Liver function tests, computed tomography scans, and ultrasound can help evaluate liver injury. Risk factors for liver injury in patients with COVID-19 include male sex, preexisting liver disease including liver transplantation and chronic liver disease, diabetes, obesity, and hypertension. To date, the mechanism of COVID-19-related liver injury is not fully understood. Its pathophysiological basis can generally be explained by systemic inflammatory response, hypoxic damage, ischemia-reperfusion injury, and drug side effects. In this review, we systematically summarize the existing literature on liver injury caused by COVID-19, including clinical features, underlying mechanisms, and potential risk factors. Finally, we discuss clinical management and provide recommendations for the care of patients with liver injury.
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Affiliation(s)
- Shu-Wu Zhao
- Department of Anesthesiology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha 410013, Hunan Province, China
| | - Yi-Ming Li
- School of Basic Medical Science, Naval Medical University/Second Military University, Shanghai 200433, China
| | - Yi-Lin Li
- Department of Pathology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha 410013, Hunan Province, China
| | - Chen Su
- Department of Anesthesiology and Pain, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha 410013, Hunan Province, China
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13
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Kokulnathan T, Wang TJ, Murugesan T, Anthuvan AJ, Kumar RR, Ahmed F, Arshi N. Structural growth of zinc oxide nanograins on carbon cloth as flexible electrochemical platform for hydroxychloroquine detection. CHEMOSPHERE 2023; 312:137186. [PMID: 36368534 DOI: 10.1016/j.chemosphere.2022.137186] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 10/25/2022] [Accepted: 11/05/2022] [Indexed: 06/16/2023]
Abstract
Pharmaceutical pollution that imposes a health threat worldwide is making accurate and rapid detection crucial to prevent adverse effects. Herein, binder-free zinc oxide nanograins on carbon cloth (ZnO NGs@CC) have been synthesized hydrothermally and employed to fabricate a flexible electrochemical sensor for the quantification of hydroxychloroquine (HCQ) that is typical pharmaceutical pollution. The characteristics of ZnO NGs@CC were investigated by various in-depth electron microscopic, spectroscopic and electroanalytical approaches. Compared with the pristine CC platform, the ZnO NGs@CC platform exhibits superior electrochemical performance in detecting HCQ with a large oxidation current at a low over-potential of +0.92 V with respect to the Ag/AgCl (Sat. KCl) reference electrode. With the support of desirable characteristics, the fabricated ZnO NGs@CC-based electrochemical sensor for HCQ detection displays good performances in terms of wide sensing range (0.5-116 μM), low detection limit (0.09 μM), high sensitivity (0.279 μA μM-1 cm-2), and strong selectivity. By the resulting 3D hierarchical nanoarchitecture, ZnO NGs@CC has progressive structural advantages that led to its excellent electrochemical performance in sensing applications. Furthermore, the electrochemical sensor is employed to detect HCQ in biological and environmental samples and also achieves good recovery rates. Thus, the designed ZnO NGs@CC demonstrates admirable electrochemical activity toward HCQ real-time monitoring and would be an excellent electrochemical platform for HCQ sensing.
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Affiliation(s)
- Thangavelu Kokulnathan
- Department of Electro-Optical Engineering, National Taipei University of Technology, Taipei 10608, Taiwan
| | - Tzyy-Jiann Wang
- Department of Electro-Optical Engineering, National Taipei University of Technology, Taipei 10608, Taiwan.
| | - Thangapandian Murugesan
- Department of Materials Science and Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan
| | - Allen Joseph Anthuvan
- Department of Electro-Optical Engineering, National Taipei University of Technology, Taipei 10608, Taiwan; Nanotech Division, Accubits Invent Pvt. Ltd, Trivandrum 695 592, Kerala, India
| | - Rishi Ranjan Kumar
- Department of Materials Science and Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan
| | - Faheem Ahmed
- Department of Physics, College of Science, King Faisal University, P.O Box 400, Hofuf, Al-Ahsa 31982, Saudi Arabia
| | - Nishat Arshi
- Department of Basic Sciences, Preparatory Year Deanship, King Faisal University, P.O. Box-400, Al-Ahsa 31982, Saudi Arabia
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14
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Efficacy of Tocilizumab in Management of COVID-19 Patients Admitted to Intensive Care Units: A Multicenter Retrospective Cohort Study. Medicina (B Aires) 2022; 59:medicina59010053. [PMID: 36676678 PMCID: PMC9864835 DOI: 10.3390/medicina59010053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 12/11/2022] [Accepted: 12/16/2022] [Indexed: 12/29/2022] Open
Abstract
Background and Objectives: Mortality and illness due to COVID-19 have been linked to a condition known as cytokine release syndrome (CRS) that is characterized by excessive production of inflammatory cytokines, particularly interleukin-6 (IL-6). Tocilizumab (TCZ), a recent IL-6 antagonist, has been redeployed as adjunctive treatment for CRS remission in COVID-19 patients. This study aimed to determine the efficacy of Tocilizumab on patients' survival and the length of stay in hospitalized COVID-19 patients admitted to the intensive care unit. Methods: Between January 2021 and June 2021, a multicenter retrospective cohort study was carried out in six tertiary care hospitals in Egypt's governorate of Giza. Based on the use of TCZ during ICU stay, eligible patients were divided into two groups (control vs. TCZ). In-hospital mortality was the main outcome. Results: A total of 740 patient data records were included in the analysis, where 630 patients followed the routine COVID-19 protocol, while 110 patients received TCZ, need to different respiratory support after hospitalization, and inflammatory mediators such as C-reactive protein (CRP), ferritin, and Lactate dehydrogenase (LDH) showed a statistically significant difference between the TCZ group and the control group. Regarding the primary outcome (discharged alive or death) and neither the secondary outcome (length of hospital stay), there is no statistically significant difference between patients treated with TCZ and the control group. Conclusions: Our cohort of patients with moderate to severe COVID-19 did not assert a reduction in the risk of mortality or the length of stay (LOS) after TCZ administration.
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15
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Charles J, Ploplis VA. COVID-19 Induces Cytokine Storm and Dysfunctional Hemostasis. Curr Drug Targets 2022; 23:1603-1610. [PMID: 36284376 DOI: 10.2174/1389450124666221025102929] [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: 06/23/2022] [Revised: 10/05/2022] [Accepted: 10/12/2022] [Indexed: 01/25/2023]
Abstract
BACKGROUND Infection with SARS-CoV-2 leads to COVID-19 which can manifest in various ways from asymptomatic or mild disease to acute respiratory distress syndrome. The occurrence of dysregulated inflammatory responses in the form of a cytokine storm has been reported in patients with severe COVID-19. Infection can also lead to dysfunctional hemostasis reflected in elevated circulating D-dimer and fibrin degradation products. Components of hemostasis and the immune system during infection can result in a procoagulation and/or proinflammatory state. The interplay between coagulation and inflammation has been elucidated in a number of diseases. OBJECTIVE In this article, we discuss the occurrence of cytokine storms and dysfunctional hemostasis induced in COVID-19. METHODS This review was written using literature from the past two to three years investigating coagulation and inflammation in COVID-19. Additional literature, both clinical and basic research, related to pathogen infection and host responses were also considered in this review. RESULTS/CONCLUSIONS Infection with SARS-CoV-2 can lead to dysregulated inflammatory responses that may be detrimental to the host. The increased expression of various inflammatory factors can ultimately create an environment that promotes thrombosis.
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Affiliation(s)
- Jermilia Charles
- W.M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN 46556, USA
| | - Victoria A Ploplis
- W.M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN 46556, USA
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16
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Molina-Ramos AI, Gómez-Moyano E, Rodríguez-Capitán J, Angullo-Gómez M, Gallardo-Jiménez P, Pérez de Pedro I, Valiente de Santis L, Pérez-Villardón B, Piñero-Uribe I, Mora-Robles J, Becerra-Muñoz VM, Jiménez-Navarro M. Myocarditis Related to COVID-19 and SARS-CoV-2 Vaccination. J Clin Med 2022; 11:6999. [PMID: 36498573 PMCID: PMC9738968 DOI: 10.3390/jcm11236999] [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: 09/30/2022] [Revised: 11/21/2022] [Accepted: 11/24/2022] [Indexed: 11/29/2022] Open
Abstract
The coronavirus disease of 2019 (COVID-19) has been a cause of significant morbidity and mortality worldwide. Among the short- and long-term consequences of COVID-19, myocarditis is a disease to be taken into consideration. Myocarditis, in general, is related to a poor prognosis. However, the epidemiology and prognosis of myocarditis related to COVID-19 are currently unknown. While vaccination against COVID-19 is of great benefit at a public health level, the risk of myocarditis should be considered in the context of the global benefits of vaccination. In this narrative review, we will summarize the etiopathogenic bases, the epidemiology, the clinical manifestations, the course, diagnosis, prognosis, and the treatment of myocarditis related to SARS-CoV-2, as well as myocarditis secondary to mRNA vaccines.
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Affiliation(s)
- Ana I. Molina-Ramos
- Centro de Investigación en Red de Enfermedades Cardiovasculares (CIBERCV), Cardiology Department, Hospital Universitario Virgen de la Victoria, 29010 Málaga, Spain
- IBIMA-Plataforma BIONAND, Universidad de Málaga, 29590 Málaga, Spain
| | | | - Jorge Rodríguez-Capitán
- Centro de Investigación en Red de Enfermedades Cardiovasculares (CIBERCV), Cardiology Department, Hospital Universitario Virgen de la Victoria, 29010 Málaga, Spain
- IBIMA-Plataforma BIONAND, Universidad de Málaga, 29590 Málaga, Spain
| | - María Angullo-Gómez
- Centro de Investigación en Red de Enfermedades Cardiovasculares (CIBERCV), Cardiology Department, Hospital Universitario Virgen de la Victoria, 29010 Málaga, Spain
- IBIMA-Plataforma BIONAND, Universidad de Málaga, 29590 Málaga, Spain
| | | | - Iván Pérez de Pedro
- Internal Medicine Department, Hospital Regional Universitario de Málaga, 29010 Málaga, Spain
| | | | | | - Isabel Piñero-Uribe
- Cardiology Department, Hospital Regional Universitario de Málaga, 29010 Málaga, Spain
| | - Javier Mora-Robles
- Cardiology Department, Hospital Regional Universitario de Málaga, 29010 Málaga, Spain
| | - Víctor Manuel Becerra-Muñoz
- Centro de Investigación en Red de Enfermedades Cardiovasculares (CIBERCV), Cardiology Department, Hospital Universitario Virgen de la Victoria, 29010 Málaga, Spain
- IBIMA-Plataforma BIONAND, Universidad de Málaga, 29590 Málaga, Spain
| | - Manuel Jiménez-Navarro
- Centro de Investigación en Red de Enfermedades Cardiovasculares (CIBERCV), Cardiology Department, Hospital Universitario Virgen de la Victoria, 29010 Málaga, Spain
- IBIMA-Plataforma BIONAND, Universidad de Málaga, 29590 Málaga, Spain
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17
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Wu Z, Han Z, Liu B, Shen N. Remdesivir in treating hospitalized patients with COVID-19: A renewed review of clinical trials. Front Pharmacol 2022; 13:971890. [PMID: 36160434 PMCID: PMC9493488 DOI: 10.3389/fphar.2022.971890] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Accepted: 08/17/2022] [Indexed: 01/18/2023] Open
Abstract
Since December 2019, COVID-19 has spread across the world almost through 2.5 years. As of 16 June 2022, the cumulative number of confirmed cases of COVID-19 worldwide has reached 542.62 million, and the death toll has risen to 6.33 million. With the increasing number of deaths, it is urgent to find effective treatment drugs. Remdesivir, an investigational broad-spectrum antiviral drug produced by Gilead has been shown to inhibit SARS-CoV-2, in vitro and in vivo. This review is aimed to analyze the feasibility of remdesivir in COVID-19 and put forward the shortcomings of present clinical studies. We systematically searched PubMed and Web of Science up until 24 May 2022, using several specific terms such as “remdesivir” or “GS-5734” and “COVID-19” or “SARS-CoV-2” and retrieved basic researches and clinical studies of remdesivir in COVID-19. In this review, we summarized and reviewed the mechanism of remdesivir in SARS-COV-2, clinical trials of using remdesivir in COVID-19, analyzed the efficacy and safety of remdesivir, and judged whether the drug was effective for the treatment of COVID-19. In different clinical trials, remdesivir showed a mixed result in the treatment of COVID-19. It seemed that remdesivir shortened the time to recovery and had an acceptable safety profile. However, more clinical trials are needed to test the efficacy and safety of remdesivir.
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Affiliation(s)
- Zhenchao Wu
- Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, China
- Center for Infectious Diseases, Peking University Third Hospital, Beijing, China
| | - Zhifei Han
- Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, China
- School of Basic and Clinical Medicine, Shandong First Medical University, Jinan, China
| | - Beibei Liu
- Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, China
- Center for Infectious Diseases, Peking University Third Hospital, Beijing, China
- *Correspondence: Beibei Liu, ; Ning Shen,
| | - Ning Shen
- Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, China
- Center for Infectious Diseases, Peking University Third Hospital, Beijing, China
- *Correspondence: Beibei Liu, ; Ning Shen,
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18
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Battaglini D, Cruz F, Robba C, Pelosi P, Rocco PRM. Failed clinical trials on COVID-19 acute respiratory distress syndrome in hospitalized patients: common oversights and streamlining the development of clinically effective therapeutics. Expert Opin Investig Drugs 2022; 31:995-1015. [PMID: 36047644 DOI: 10.1080/13543784.2022.2120801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
INTRODUCTION The coronavirus disease 2019 (COVID-19) pandemic has put a strain on global healthcare systems. Despite admirable efforts to develop rapidly new pharmacotherapies, supportive treatments remain the standard of care. Multiple clinical trials have failed due to design issues, biased patient enrollment, small sample sizes, inadequate control groups, and lack of long-term outcomes monitoring. AREAS COVERED This narrative review depicts the current situation around failed and success COVID-19 clinical trials and recommendations in hospitalized patients with COVID-19, oversights and streamlining of clinically effective therapeutics. PubMed, EBSCO, Cochrane Library, and WHO and NIH guidelines were searched for relevant literature up to 5 August 2022. EXPERT OPINION The WHO, NIH, and IDSA have issued recommendations to better clarify which drugs should be used during the different phases of the disease. Given the biases and high heterogeneity of published studies, interpretation of the current literature is difficult. Future clinical trials should be designed to standardize clinical approaches, with appropriate organization, patient selection, addition of control groups, and careful identification of disease phase to reduce heterogeneity and bias and should rely on the integration of scientific societies to promote a consensus on interpretation of the data and recommendations for optimal COVID-19 therapies.
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Affiliation(s)
- Denise Battaglini
- Dipartimento di Anestesia e Rianimazione, Policlinico San Martino, IRCCS per l'Oncologia e le Neuroscienze, Genoa, Italy
| | - Fernanda Cruz
- Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Chiara Robba
- Policlinico San Martino, IRCCS per l'Oncologia e Neuroscienze, Dipartimento di Scienze Chirurgiche e Diagnostiche Integrate, Università degli Studi di Genova, Genoa, Italy
| | - Paolo Pelosi
- Dipartimento di Anestesia e Rianimazione, Policlinico San Martino, IRCCS per l'Oncologia e le Neuroscienze, Genoa, Italy.,Policlinico San Martino, IRCCS per l'Oncologia e Neuroscienze, Dipartimento di Scienze Chirurgiche e Diagnostiche Integrate, Università degli Studi di Genova, Genoa, Italy
| | - Patricia R M Rocco
- Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.,COVID-19 Virus Network from Ministry of Science, Technology, and Innovation, Brazilian Council for Scientific and Technological Development, and Foundation Carlos Chagas Filho Research Support of the State of Rio de Janeiro, Rio de Janeiro, Brazil
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19
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Terkes V, Lisica K, Marusic M, Verunica N, Tolic A, Morovic M. Remdesivir Treatment in Moderately Ill COVID-19 Patients: A Retrospective Single Center Study. J Clin Med 2022; 11:jcm11175066. [PMID: 36078997 PMCID: PMC9457067 DOI: 10.3390/jcm11175066] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 08/24/2022] [Accepted: 08/25/2022] [Indexed: 11/29/2022] Open
Abstract
Almost two years after remdesivir was approved and extensively used in numerous clinical studies for the treatment of COVID-19 patients, there is still no clear recommendation for the time and phase of the disease of remdesivir administration. This retrospective observational study included adults (≥18 years) with severe COVID-19, radiologically confirmed pneumonia, a need for supplemental oxygen and an interval from symptom onset to enrolment of 10 days or less. All patients were treated with remdesivir for 5 to 10 days, or with clinical improvement within that period. The primary goal was the outcome in patients treated with remdesivir during the early stage of the disease considering the different disease severity. The median time from symptom onset to treatment was 8.4 days (3−10). Clinical improvements and good outcomes were observed in 104 of 137 patients (75.9%); 33 (24.1%) of 137 patients died. Subgroup analyses showed that the mortality rate was significantly lower in moderately ill patients (3 out of 51 patients; 5.9%) than in the group of severely/critically ill patients (30 out of 86 patients; 34.8%; p < 0.005). Older age, rise of CRP and CT score were shown to be significant predictors of disease outcome. Overall, remdesivir was well tolerated, and the treatment was discontinued in only four patients. The results of this observational study in 137 patients with different disease severity contribute to the attitude concerning remdesivir administration in the early stage of COVID-19, at least in moderately ill patients with a high risk of progression, before the transition to a more severe stage.
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Affiliation(s)
- Vedrana Terkes
- Department of Infectious Diseases, Zadar General Hospital, 23000 Zadar, Croatia
| | - Karla Lisica
- Department of Infectious Diseases, Zadar General Hospital, 23000 Zadar, Croatia
| | - Martina Marusic
- Emergency Department, Zadar General Hospital, 23000 Zadar, Croatia
| | - Nikola Verunica
- Department of Cardiology, Zadar General Hospital, 23000 Zadar, Croatia
| | - Anela Tolic
- Department of Radiology, Zadar General Hospital, 23000 Zadar, Croatia
| | - Miro Morovic
- Department of Infectious Diseases, Zadar General Hospital, 23000 Zadar, Croatia
- Correspondence:
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20
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Ogunsakin RE, Ebenezer O, Jordaan MA, Shapi M, Ginindza TG. Mapping Scientific Productivity Trends and Hotspots in Remdesivir Research Publications: A Bibliometric Study from 2016 to 2021. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19148845. [PMID: 35886696 PMCID: PMC9318242 DOI: 10.3390/ijerph19148845] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Revised: 07/16/2022] [Accepted: 07/18/2022] [Indexed: 01/18/2023]
Abstract
In response to global efforts to control and exterminate infectious diseases, this study aims to provide insight into the productivity of remdesivir research and highlight future directions. To achieve this, there is a need to summarize and curate evidence from the literature. As a result, this study carried out comprehensive scientific research to detect trends in published articles related to remdesivir using a bibliometric analysis. Keywords associated with remdesivir were used to access pertinent published articles using the Scopus database. A total of 5321 research documents were retrieved, primarily as novel research articles (n = 2440; 46%). The number of publications increased exponentially from 2020 up to the present. The papers published by the top 12 institutions focusing on remdesivir accounted for 25.69% of the overall number of articles. The USA ranked as the most productive country, with 906 documents (37.1%), equivalent to one-third of the global publications in this field. The most productive institution was Icahn School of Medicine, Mount Sinai, in the USA (103 publications). The New England Journal of Medicine was the most cited, with an h-index of 13. The publication of research on remdesivir has gained momentum in the past year. The importance of remdesivir suggests that it needs continued research to help global health organizations detect areas requiring instant action to implement suitable measures. Furthermore, this study offers evolving hotspots and valuable insights into the scientific advances in this field and provides scaling-up analysis and evidence diffusion on remdesivir.
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Affiliation(s)
- Ropo E. Ogunsakin
- Discipline of Public Health Medicine, School of Nursing & Public Health, College of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa;
- Correspondence:
| | - Oluwakemi Ebenezer
- Department of Chemistry, Faculty of Natural Sciences, Mangosuthu University of Technology, Umlazi 4031, South Africa; (O.E.); (M.A.J.); (M.S.)
| | - Maryam A. Jordaan
- Department of Chemistry, Faculty of Natural Sciences, Mangosuthu University of Technology, Umlazi 4031, South Africa; (O.E.); (M.A.J.); (M.S.)
| | - Michael Shapi
- Department of Chemistry, Faculty of Natural Sciences, Mangosuthu University of Technology, Umlazi 4031, South Africa; (O.E.); (M.A.J.); (M.S.)
| | - Themba G. Ginindza
- Discipline of Public Health Medicine, School of Nursing & Public Health, College of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa;
- Cancer & Infectious Diseases Epidemiology Research Unit (CIDERU), College of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa
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21
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Moeinafshar A, Yazdanpanah N, Rezaei N. Immune-based therapeutic approaches in COVID-19. Biomed Pharmacother 2022; 151:113107. [PMID: 35594701 PMCID: PMC9108029 DOI: 10.1016/j.biopha.2022.113107] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 05/02/2022] [Accepted: 05/10/2022] [Indexed: 02/01/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) is a viral disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a member of the Coronaviridae family. On March 11, 2020 the World Health Organization (WHO) has named the newly emerged rapidly-spreading epidemic as a pandemic. Besides the risk-reduction measures such as physical and social distancing and vaccination, a wide range of treatment modalities have been developed; aiming to fight the disease. The immune system is known as a double-edged sword in COVID-19 pathogenesis, with respect to its role in eliminating the pathogen and in inducing complications such as cytokine storm syndrome. Hence, immune-based therapeutic approaches have become an interesting field of COVID-19 research, including corticosteroids, intravenous immunoglobulins (IVIG), interferon therapy, and more COVID-19-specific approaches such as anti-SARS-CoV-2-monoclonal antibodies. Herein, we did a comprehensive review on immune-based therapeutic approaches for COVID-19. DATA AVAILABILITY STATEMENT: Not applicable.
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Affiliation(s)
- Aysan Moeinafshar
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran,Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Niloufar Yazdanpanah
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran,Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran,Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Nima Rezaei
- Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran,Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran,Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran,Correspondence to: Children's Medical Center Hospital, Dr. Qarib St, Keshavarz Blvd, Tehran 14194, Iran
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22
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Calvo-Alvarez E, Dolci M, Perego F, Signorini L, Parapini S, D’Alessandro S, Denti L, Basilico N, Taramelli D, Ferrante P, Delbue S. Antiparasitic Drugs against SARS-CoV-2: A Comprehensive Literature Survey. Microorganisms 2022; 10:1284. [PMID: 35889004 PMCID: PMC9320270 DOI: 10.3390/microorganisms10071284] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 06/10/2022] [Accepted: 06/13/2022] [Indexed: 01/09/2023] Open
Abstract
More than two years have passed since the viral outbreak that led to the novel infectious respiratory disease COVID-19, caused by the SARS-CoV-2 coronavirus. Since then, the urgency for effective treatments resulted in unprecedented efforts to develop new vaccines and to accelerate the drug discovery pipeline, mainly through the repurposing of well-known compounds with broad antiviral effects. In particular, antiparasitic drugs historically used against human infections due to protozoa or helminth parasites have entered the main stage as a miracle cure in the fight against SARS-CoV-2. Despite having demonstrated promising anti-SARS-CoV-2 activities in vitro, conflicting results have made their translation into clinical practice more difficult than expected. Since many studies involving antiparasitic drugs are currently under investigation, the window of opportunity might be not closed yet. Here, we will review the (controversial) journey of these old antiparasitic drugs to combat the human infection caused by the novel coronavirus SARS-CoV-2.
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Affiliation(s)
- Estefanía Calvo-Alvarez
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy; (M.D.); (F.P.); (L.S.); (L.D.); (N.B.); (P.F.); (S.D.)
| | - Maria Dolci
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy; (M.D.); (F.P.); (L.S.); (L.D.); (N.B.); (P.F.); (S.D.)
| | - Federica Perego
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy; (M.D.); (F.P.); (L.S.); (L.D.); (N.B.); (P.F.); (S.D.)
| | - Lucia Signorini
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy; (M.D.); (F.P.); (L.S.); (L.D.); (N.B.); (P.F.); (S.D.)
| | - Silvia Parapini
- Department of Biomedical Sciences for Health, University of Milan, 20133 Milan, Italy;
| | - Sarah D’Alessandro
- Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy; (S.D.); (D.T.)
| | - Luca Denti
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy; (M.D.); (F.P.); (L.S.); (L.D.); (N.B.); (P.F.); (S.D.)
| | - Nicoletta Basilico
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy; (M.D.); (F.P.); (L.S.); (L.D.); (N.B.); (P.F.); (S.D.)
| | - Donatella Taramelli
- Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy; (S.D.); (D.T.)
| | - Pasquale Ferrante
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy; (M.D.); (F.P.); (L.S.); (L.D.); (N.B.); (P.F.); (S.D.)
| | - Serena Delbue
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy; (M.D.); (F.P.); (L.S.); (L.D.); (N.B.); (P.F.); (S.D.)
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23
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Ruscitti P, Di Cola I, Di Muzio C, Italiano N, Ursini F, Giacomelli R, Cipriani P. Expanding the spectrum of the hyperferritinemic syndrome, from pathogenic mechanisms to clinical observations, and therapeutic implications. Autoimmun Rev 2022; 21:103114. [PMID: 35595050 DOI: 10.1016/j.autrev.2022.103114] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Accepted: 05/15/2022] [Indexed: 01/19/2023]
Abstract
From the introduction of hyperferritinemic syndrome concept, a growing body of evidence has suggested the role of ferritin as a pathogenic mediator and a relevant clinical feature in the management of patients with inflammatory diseases. From a pathogenic point of view, ferritin may directly stimulate the aberrant immune response by triggering the production of pro-inflammatory mediators in inducing a vicious pathogenic loop and contributing to the occurrence of cytokine storm syndrome. The latter has been recently defined as a clinical picture characterised by elevated circulating cytokine levels, acute systemic inflammatory symptoms, and secondary organ dysfunction beyond that which could be attributed to a normal response to a pathogen It is noteworthy that the occurrence of hyperferritinemia may be correlated with the development of the cytokine storm syndrome in the context of an inflammatory disease. In addition to adult onset Still's disease, macrophage activation syndrome, catastrophic anti-phospholipids syndrome, and septic shock, recent evidence has suggested this association between ferritin and life-threatening evolution in patients with systemic lupus erythematosus, with anti-MDA5 antibodies in the context of poly-dermatomyositis, with severe COVID-19, and with multisystem inflammatory syndrome. The possible underlying common inflammatory mechanisms, associated with hyperferritinemia, may led to the similar clinical picture observed in these patients. Furthermore, similar therapeutic strategies could be suggested inhibiting pro-inflammatory cytokines and improving long-term outcomes in these disorders. Thus, it could be possible to expand the spectrum of the hyperferritinemic syndrome to those diseases burdened by a dreadful clinical picture correlated with hyperferritinemia and the occurrence of the cytokine storm syndrome. In addition, the assessment of ferritin may provide useful information to the physicians in clinical practice to manage these patients. Therefore, ferritin may be considered a relevant clinical feature to be used as biomarker in dissecting the unmet needs in the management of these disorders. Novel evidence may thus support an expansion of the spectrum of the hyperferritinemic syndrome to these diseases burdened by a life-threatening clinical picture correlated with hyperferritinemia and the occurrence of the cytokine storm syndrome.
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Affiliation(s)
- Piero Ruscitti
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
| | - Ilenia Di Cola
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Claudia Di Muzio
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Noemi Italiano
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Francesco Ursini
- Rheumatology Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy; Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Roberto Giacomelli
- Rheumatology and Immunology Unit, Department of Medicine, University of Rome Campus Biomedico, Rome, Italy
| | - Paola Cipriani
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
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