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Rationale for the use of N-acetylcysteine in both prevention and adjuvant therapy of COVID-19.

ABSTRACT: COVID-19 may cause pneumonia, acute respiratory distress syndrome, cardiovascular alterations, and multiple organ failure, which have been ascribed to a cytokine storm, a systemic inflammatory response, and an attack by the immune system. Moreover, an oxidative stress imbalance has been demonstrated to occur in COVID-19 patients. N- Acetyl-L-cysteine (NAC) is a precursor of reduced glutathione (GSH). Due to its tolerability, this pleiotropic drug has been proposed not only as a mucolytic agent, but also as a preventive/therapeutic agent in a variety of disorders involving GSH depletion and oxidative stress. At very high doses, NAC is also used as an antidote against paracetamol intoxication. Thiols block the angiotensin-converting enzyme 2 thereby hampering penetration of SARS-CoV-2 into cells. Based on a broad range of antioxidant and anti-inflammatory mechanisms, which are herein reviewed, the oral administration of NAC is likely to attenuate the risk of developing COVID-19, as it was previously demonstrated for influenza and influenza-like illnesses. Moreover, high-dose intravenous NAC may be expected to play an adjuvant role in the treatment of severe COVID-19 cases and in the control of its lethal complications, also including pulmonary and cardiovascular adverse events.

SUBMITTER: De Flora S

PROVIDER: S-EPMC7436914 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Rationale for the use of N-acetylcysteine in both prevention and adjuvant therapy of COVID-19.

De Flora Silvio S Balansky Roumen R La Maestra Sebastiano S

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20200811 10

COVID-19 may cause pneumonia, acute respiratory distress syndrome, cardiovascular alterations, and multiple organ failure, which have been ascribed to a cytokine storm, a systemic inflammatory response, and an attack by the immune system. Moreover, an oxidative stress imbalance has been demonstrated to occur in COVID-19 patients. N- Acetyl-L-cysteine (NAC) is a precursor of reduced glutathione (GSH). Due to its tolerability, this pleiotropic drug has been proposed not only as a mucolytic agent, ...[more]

PMID: 32780893

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Project description:Background:Current recommendations for the self-management of SARS-Cov-2 disease (COVID-19) include self-isolation, rest, hydration, and the use of NSAID in case of high fever only. It is expected that many patients will add other symptomatic/adjuvant treatments, such as herbal medicines. Aims:To provide a benefits/risks assessment of selected herbal medicines traditionally indicated for "respiratory diseases" within the current frame of the COVID-19 pandemic as an adjuvant treatment. Method:The plant selection was primarily based on species listed by the WHO and EMA, but some other herbal remedies were considered due to their widespread use in respiratory conditions. Preclinical and clinical data on their efficacy and safety were collected from authoritative sources. The target population were adults with early and mild flu symptoms without underlying conditions. These were evaluated according to a modified PrOACT-URL method with paracetamol, ibuprofen, and codeine as reference drugs. The benefits/risks balance of the treatments was classified as positive, promising, negative, and unknown. Results:A total of 39 herbal medicines were identified as very likely to appeal to the COVID-19 patient. According to our method, the benefits/risks assessment of the herbal medicines was found to be positive in 5 cases (Althaea officinalis, Commiphora molmol, Glycyrrhiza glabra, Hedera helix, and Sambucus nigra), promising in 12 cases (Allium sativum, Andrographis paniculata, Echinacea angustifolia, Echinacea purpurea, Eucalyptus globulus essential oil, Justicia pectoralis, Magnolia officinalis, Mikania glomerata, Pelargonium sidoides, Pimpinella anisum, Salix sp, Zingiber officinale), and unknown for the rest. On the same grounds, only ibuprofen resulted promising, but we could not find compelling evidence to endorse the use of paracetamol and/or codeine. Conclusions:Our work suggests that several herbal medicines have safety margins superior to those of reference drugs and enough levels of evidence to start a clinical discussion about their potential use as adjuvants in the treatment of early/mild common flu in otherwise healthy adults within the context of COVID-19. While these herbal medicines will not cure or prevent the flu, they may both improve general patient well-being and offer them an opportunity to personalize the therapeutic approaches.

Project description:The coronavirus disease-2019 (COVID-19) pandemic has affected millions of people worldwide. As our understanding of the disease is evolving, our approach to the patient management is also changing swiftly. Available new evidence is helping us take radical decisions in COVID-19 management. We searched for inclusion of the published literature on treatment of COVID-19 from around the globe. All relevant evidences available till the time of submission of this article were briefly discussed. Once advised as blanket therapy for all patients, recent reports of hydroxychloroquine with or without azithromycin indicated no potential benefit and use of such combination may increase the risk of arrhythmias. Clinical evidence with newer antivirals such as remdesivir and favipiravir is promising that can hasten the patient recovery and reduce the mortality. With steroids, evidence is much clear in that it should be used in low dose and for short period not extending beyond 7 days in moderate to severe hospitalized patients. Low-molecular-weight heparin should be initiated in all hospitalized COVID-19 patients and dose should be based on the coagulation profile and risk of thromboembolism. Immunomodulatory drugs such tocilizumab may be considered for severe and critically ill patients to improve the outcomes. Though ulinastatin can be a potential alternative immunomodulator, there is lack of clinical evidence on its usage in COVID-19. Convalescent plasma therapy can be potentially lifesaving in critically ill patients. However, there is need to generate further evidence with various such therapies. Though availability of a potent vaccine is awaited, current treatment of COVID-19 is based on available therapies, which is guided by the evidence. In this review, we discuss the potential treatments available around the globe with current evidence on each of such treatments. How to cite this article: Dixit SB, Zirpe KG, Kulkarni AP, Chaudhry D, Govil D, Mehta Y, et al. Current Approaches to COVID-19: Therapy and Prevention. Indian J Crit Care Med 2020;24(9):838-846.

Project description:BACKGROUND:Based on current evidence, recent guidelines of the National Institute of Health, USA indicated the use of remdesivir and dexamethasone for the treatment of COVID-19 patients with mild-moderate disease, not requiring high-flow oxygen. No therapeutic agent directed against the immunologic pathogenic mechanisms related to the cytokine release syndrome complicating the disease was indicated. OBJECTIVES:The purpose of this review was to assess the clinical impact of different therapies for COVID-19; thus, helping to identify the optimal management of the disease. To explain the rationale for the different therapeutic approaches, the characteristics of SARS-CoV-2, the pathogenesis of COVID-19, and the immune response triggered by SARS-CoV-2 infection were reported. METHODS:The efficacy assessment of the different treatments was performed by a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Available English language published articles including randomised controlled trials, open-label trials of antivirals and immune therapies extracted from Medline, Google Scholar, and MedRxiv databases were analysed. For inclusion, the primary end point of the trials had to be the efficacy as measured by the improvement of clinical features, or mortality, or the Intensive Care Unit Admission rate, or the discharge number. Case reports, paediatric studies, and studies without control group were excluded. The literature search was extended up to August 15, 2020. RESULTS:After the removal of duplicate articles, and the exclusion of studies not meeting the eligibility criteria, 2 trials of lopinavir/ritonavir, 1 of favipiravir, 3 of remdesivir, 1 of dexamethasone, 3 of hydroxychloroquine, 2 of colchicine, 6 of tocilizumab, 1 of sarilumab, 1 of siltuximab, 2 of anakinra, 3 of baricitinib, 1 of ruxolitinib, 1 of mavrilimumab, and 1 of itolizumab were suitable for the review. Among antivirals, only remdesivir significantly reduced the time to recovery, and mortality. Data for chloroquine and hydroxychloroquine were largely inconclusive. In a large trial, dexamethasone 6 mg/day reduced mortality by one-third. Trials of tocilizumab and sarilumab did not definitively demonstrate efficacy. Anakinra significantly reduced the mortality in 2 trials. Three retrospective trials on a cumulative number of 145 patients, reported the efficacy of baricitinib, with significant reduction of intensive care unit admission, and deaths. These results were recently confirmed by the ACTT-2 trial. Due to paucity of studies and to the small size clinical series, the results of other immune therapies were not conclusive. CONCLUSIONS:Beyond the supportive therapy, up to now the best therapeutic approach for COVID-19 may be a three-step combination therapy, including remdesivir 100 mg/day (200 mg loading dose on first day) in the first stage of the disease, and combined dexamethasone 6 mg/day plus baricitinib 4 mg/day to target the immune dysregulation triggered by the SARS-CoV-2 infection. The promising results of anakinra should be confirmed by the ongoing RCTs.

Dataset Information

Rationale for the use of N-acetylcysteine in both prevention and adjuvant therapy of COVID-19.

Publications

Rationale for the use of N-acetylcysteine in both prevention and adjuvant therapy of COVID-19.

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