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      Therapeutic Potential Of Induced Iron Depletion Using Iron Chelators In Covid-19

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          Abstract

          Ferritin, which includes twenty-four light and heavy chains in varying proportions in different tissues, is primarily responsible for maintaining the body's iron metabolism. Its normal value is between 10 and 200 ngmL -1 in men and between 30-300 ngmL -1 in women. Iron is delivered to the tissue via them, and they act as immunomodulators, signaling molecules, and inflammatory markers. When ferritin level exceeds 1000 µgL -1, the patient is categorized as having hyperferritinemia. Iron chelators such as deferiprone, deferirox, and deferoxamine are currently FDA approved to treat iron overload. The inflammation cascade and poor prognosis of COVID-19 may be attributed to high ferritin levels. Critically ill patients can benefit from deferasirox, an iron chelator administered orally at 20-40 mgkg -1 once daily, as well as intravenous deferoxamine at 1000 mg initially followed by 500 mg every 4 to 12 hours. It can be combined with monoclonal antibodies, antioxidants, corticosteroids, and lactoferrin to make iron chelation therapy effective for COVID-19 victims. In this article, we analyze the antiviral and antifibrotic activity of iron chelators, thereby promoting iron depletion therapy as a potentially innovative treatment strategy for COVID-19.

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          Clinical and immunologic features in severe and moderate Coronavirus Disease 2019

          Journal of Clinical Investigation
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            Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China

            Dear Editor, The rapid emergence of COVID-19 in Wuhan city, Hubei Province, China, has resulted in thousands of deaths [1]. Many infected patients, however, presented mild flu-like symptoms and quickly recover [2]. To effectively prioritize resources for patients with the highest risk, we identified clinical predictors of mild and severe patient outcomes. Using the database of Jin Yin-tan Hospital and Tongji Hospital, we conducted a retrospective multicenter study of 68 death cases (68/150, 45%) and 82 discharged cases (82/150, 55%) with laboratory-confirmed infection of SARS-CoV-2. Patients met the discharge criteria if they had no fever for at least 3 days, significantly improved respiratory function, and had negative SARS-CoV-2 laboratory test results twice in succession. Case data included demographics, clinical characteristics, laboratory results, treatment options and outcomes. For statistical analysis, we represented continuous measurements as means (SDs) or as medians (IQRs) which compared with Student’s t test or the Mann–Whitney–Wilcoxon test. Categorical variables were expressed as numbers (%) and compared by the χ 2 test or Fisher’s exact test. The distribution of the enrolled patients’ age is shown in Fig. 1a. There was a significant difference in age between the death group and the discharge group (p < 0.001) but no difference in the sex ratio (p = 0.43). A total of 63% (43/68) of patients in the death group and 41% (34/82) in the discharge group had underlying diseases (p = 0.0069). It should be noted that patients with cardiovascular diseases have a significantly increased risk of death when they are infected with SARS-CoV-2 (p < 0.001). A total of 16% (11/68) of the patients in the death group had secondary infections, and 1% (1/82) of the patients in the discharge group had secondary infections (p = 0.0018). Laboratory results showed that there were significant differences in white blood cell counts, absolute values of lymphocytes, platelets, albumin, total bilirubin, blood urea nitrogen, blood creatinine, myoglobin, cardiac troponin, C-reactive protein (CRP) and interleukin-6 (IL-6) between the two groups (Fig. 1b and Supplementary Table 1). Fig. 1 a Age distribution of patients with confirmed COVID-19; b key laboratory parameters for the outcomes of patients with confirmed COVID-19; c interval from onset of symptom to death of patients with confirmed COVID-19; d summary of the cause of death of 68 died patients with confirmed COVID-19 The survival times of the enrolled patients in the death group were analyzed. The distribution of survival time from disease onset to death showed two peaks, with the first one at approximately 14 days (22 cases) and the second one at approximately 22 days (17 cases) (Fig. 1c). An analysis of the cause of death was performed. Among the 68 fatal cases, 36 patients (53%) died of respiratory failure, five patients (7%) with myocardial damage died of circulatory failure, 22 patients (33%) died of both, and five remaining died of an unknown cause (Fig. 1d). Based on the analysis of the clinical data, we confirmed that some patients died of fulminant myocarditis. In this study, we first reported that the infection of SARS-CoV-2 may cause fulminant myocarditis. Given that fulminant myocarditis is characterized by a rapid progress and a severe state of illness [3], our results should alert physicians to pay attention not only to the symptoms of respiratory dysfunction but also the symptoms of cardiac injury. Further, large-scale studies and the studies on autopsy are needed to confirm our analysis. In conclusion, predictors of a fatal outcome in COVID-19 cases included age, the presence of underlying diseases, the presence of secondary infection and elevated inflammatory indicators in the blood. The results obtained from this study also suggest that COVID-19 mortality might be due to virus-activated “cytokine storm syndrome” or fulminant myocarditis. Electronic supplementary material Below is the link to the electronic supplementary material. Supplementary material 1 (DOCX 38 kb)
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              Detection of SARS-CoV-2 in Different Types of Clinical Specimens

              This study describes results of PCR and viral RNA testing for SARS-CoV-2 in bronchoalveolar fluid, sputum, feces, blood, and urine specimens from patients with COVID-19 infection in China to identify possible means of non-respiratory transmission.
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                Author and article information

                Journal
                Saudi J Biol Sci
                Saudi J Biol Sci
                Saudi Journal of Biological Sciences
                The Author(s). Published by Elsevier B.V. on behalf of King Saud University.
                1319-562X
                2213-7106
                13 December 2021
                13 December 2021
                Affiliations
                [a ]Department of Pharmaceutics, Moulana College of Pharmacy, Perinthalmanna 679321, Kerala, India
                [b ]Department of Animal Breeding and Genetics, College of Veterinary and Animal Sciences,Kerala Veterinary and Animal Sciences University,Pookode, Wayanad, Kerala, India
                [c ]Department of Pharmacy Practice, Al Shifa College of Pharmacy, Kerala, India
                [d ]Department of Pharmacy Prac tice, KTN College of Pharmacy, Chalavara, Kerala, India
                [e ]Department of Dental Technology, College of Applied Medical Sciences, King Khalid University, Abha 61421, Saudi Arabia
                Author notes
                [* ]Corresponding author.
                Article
                S1319-562X(21)01027-5
                10.1016/j.sjbs.2021.11.061
                8666385
                34924800
                1bfef72f-b504-4c6f-a8a0-4221fdedb8b0
                © 2021 The Author(s)

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 14 October 2021
                : 24 October 2021
                : 28 November 2021
                Categories
                Review

                covid 19,hyperferritinemia,pathogenesis,genomics,proteomic interaction,iron chelator,ferritin,clinical use

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