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N-Acetylcysteine as Adjuvant Therapy for COVID-19 - A Perspective on the Current State of the Evidence.

ABSTRACT: The looming severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a long-lasting pandemic of coronavirus disease 2019 (COVID-19) around the globe with substantial morbidity and mortality. N-acetylcysteine, being a nutraceutical precursor of an important antioxidant glutathione, can perform several biological functions in mammals and microbes. It has consequently garnered a growing interest as a potential adjunctive therapy for coronavirus disease. Here, we review evidence concerning the effects of N-acetylcysteine in respiratory viral infections based on currently available in vitro, in vivo, and human clinical investigations. The repurposing of a known drug such as N-acetylcysteine may significantly hasten the deployment of a novel approach for COVID-19. Since the drug candidate has already been translated into the clinic for several decades, its established pharmacological properties and safety and side-effect profiles expedite preclinical and clinical assessment for the treatment of COVID-19. In vitro data have depicted that N-acetylcysteine increases antioxidant capacity, interferes with virus replication, and suppresses expression of pro-inflammatory cytokines in cells infected with influenza viruses or respiratory syncytial virus. Furthermore, findings from in vivo studies have displayed that, by virtue of immune modulation and anti-inflammatory mechanism, N-acetylcysteine reduces the mortality rate in influenza-infected mice animal models. The promising in vitro and in vivo results have prompted the initiation of human subject research for the treatment of COVID-19, including severe pneumonia and acute respiratory distress syndrome. Albeit some evidence of benefits has been observed in clinical outcomes of patients, precision nanoparticle design of N-acetylcysteine may allow for greater therapeutic efficacy.

SUBMITTER: Wong KK

PROVIDER: S-EPMC8274825 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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:IntroductionAlthough the consequences of testicular torsion (TT) have been recognized for centuries, little progress has been made to improve outcomes beyond those seen with timely scrotal exploration. Even with testicular salvage, ischemia/reperfusion injury cause significant atrophy and functional impairment. Recent efforts have sought to identify adjuvant pharmacological or surgical interventions that may attenuate these consequences. In this review, we assess the evidence supporting clinical use of these nascent interventions.MethodsWe conducted a review of the literature published from 2000 to 2020, using the search terms "torsion", "testicular", "reperfusion", "ischemia", and "injury". Clinical and laboratory research focused on adjuvant pharmacological and surgical techniques mitigating torsion-associated injury in animal models and humans were identified. We recorded intervention timing/dose/route, and outcome timing/category through biomarkers of reperfusion injury, histology, and hormonal/reproductive function.ResultsFifty-four FDA-approved agents, plus 52 herbal/investigational drugs, were reported in animal TT models. In every study, the investigated agents showed beneficial effects on measured endpoints compared to controls. Despite these universally promising animal findings, no pharmacological trials in humans were reported. Surgical techniques studied in animal models included decompression (tunica albuginea incision, TAI), "ischemic conditioning", and hypothermia. Only three human studies on surgical adjuvant maneuvers have been reported, all involving TAI; these showed potential benefit, but the level of evidence is low.ConclusionThere is preliminary evidence that adjuvant treatments may mitigate the effects of ischemia/reperfusion injury. However, the pool of investigated pharmacological agents is wide, yet remarkably shallow; most compounds have been reported in a single animal study. To advance this field, a mechanism-based approach should be used to select promising agents that can be tested systematically. This will determine treatment parameters that maximize safety, efficacy, and tolerability. Only then is it possible to move toward human trials. Adjuvant surgical methods such as TAI show promise in humans but require more robust clinical evaluation.

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N-Acetylcysteine as Adjuvant Therapy for COVID-19 - A Perspective on the Current State of the Evidence.

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