Front Mol Biosci. Sharafkhah M, Abdolrazaghnejad A, Zarinfar N, Mohammadbeigi A, Massoudifar A, Abaszadeh S. Safety and efficacy of N-acetyl-cysteine for prophylaxis of ventilator-associated pneumonia: a randomized, double blind, placebo-controlled clinical trial. -, Huang C, Wang Y, Li X, et al. Adults aged 18 years or older with documented COVID-19 infection. The repurposing of a known drug such as N-acetylcysteine may significantly hasten the deployment of a novel approach for COVID-19. Infection by SARS-CoV-2 causing coronavirus disease 2019 (COVID-19) can be associated with serious and life-threatening conditions, including acute respiratory distress syndrome (ARDS). ClinicalTrials.gov Identifier: Multicenter, randomized, parallel-group, double-blinded, placebo-controlled trial, Phase 3. As a drug, it's used by healthcare providers to treat acetaminophen ( Tylenol) poisoning. No patient experienced any adverse drug reactions. Angioedema and respiratory symptoms require the administration of antihistamine, corticosteroid, or symptomatic management.100 In such cases, N-acetylcysteine should be discontinued, and if necessary, it can be re-started 1 hour after the administration of antihistamine in the absence of signs and symptoms of anaphylaxis.101,102 Patients with a history of atopy (asthma and allergy) are recommended to receive prophylactic antihistamine 15 minutes prior to N-acetylcysteine administration to eliminate the excess risk of adverse reactions.102,103. N-acetylcysteine, a drug that treats lung conditions as well as acetaminophen overdoses, is being studied as a potential COVID-19 treatment by Melisa Lai-Becker, MD, site chief of emergency. doi:10.1002/jmv.20255 Following thrombolysis and heparinization, his clinical condition continued a positive trend until discharge. N-acetylcysteine for prevention and treatment of COVID-19: Current state of evidence and future directions. Gencer S, Lacy M, Atzler D, van der Vorst EPC, Dring Y, Weber C. Immunoinflammatory, Thrombohaemostatic, and Cardiovascular Mechanisms in COVID-19. No adverse event was noted in patients who received N-acetylcysteine. Adults aged 18 to 75 years with COVID-19 infection confirmed 2 days before randomization, currently hospitalized and requiring medical care and had a peripheral capillary oxygen saturation (SpO2) <94% on room air at screening. In mice following intranasal infection with a lethal dose of influenza A virus A/PR/8, the use of N-acetylcysteine increased survival rate from 58% (ribavirin monotherapy) to 92% (N-acetylcysteine and ribavirin), suggesting the antioxidants role in improving host defense mechanism and preventing pathogenesis of lung inflammation.61,62 Further experiment depicted that survival rates of mice were 20% in the N-acetylcysteine group, 60% in the oseltamivir group, and 100% in combination treatment of N-acetylcysteine and oseltamivir.63 In these three models, the mice were infected with 23 LD50 of influenza virus and N-acetylcysteine was administered as a single daily dose of 1,000 mg/kg.6163 N-acetylcysteine increased survival by contributing to host defense mechanisms or by direct antioxidant effect against oxidative stress associated with viral infection.63 On the contrary, mice infected intranasally with a deadly dose of porcine A/swine/Iowa/4 (H1N1) influenza strain showed no significant difference in percent survival and mean survival time between N-acetylcysteine and control groups, showing that different virus strains resulted in different susceptibilities to N-acetylcysteine.58 The porcine A/swine/Iowa/4 (H1N1) strain was found to be more resistant to N-acetylcysteine than the human strain A/PR/8 (H1N1) deployed in other animal models.6163 The lack of treatment effect was possibly due to the virus phenotypic susceptibility to N-acetylcysteine and the viral pathotype.64, Findings from H9N2 swine influenza virus-infected murine model indicated that N-acetylcysteine ameliorated pulmonary edema and inflammatory response, reduced myeloperoxidase activity in the lungs, decreased total and differential cell counts, neutrophils, macrophages, IL-6, IL-1, TNF-, and CXCL-10 in the bronchoalveolar lavage fluid, and inhibited protein expression of TLR4 and its mRNA in the lungs.65, In an experiment of H3N2-infected mice, N-acetylcysteine decreased pulmonary responsiveness and increased immune cytokine expression of IFN- in comparison to saline controls, with no effect on virus titers and expression of IL-4, IL-13, and IL-12p40.66, Currently, there have been several clinical studies to measure the effects of N-acetylcysteine on viral respiratory tract infections. Is IL-6 a key cytokine target for therapy in COVID-19? All severe COVID-19 patients with at least one of the following five conditions: (respiration rate > 30 per minute), hypoxemia (O2 saturation, arterial oxygen partial pressure ratio <300), pulmonary infiltration (> 50% of lung area during 24 48 h), Lactate dehydrogenase (LDH) > 245 U / l, Progressive lymphopenia, and admitted to the intensive . Further studies are warranted to design a formulation with increased bioavailability or target-oriented delivery, ascertain optimal dosage and route of administration, and conduct well-controlled, adequately powered, randomized clinical trials to determine the safety and efficacy of N-acetylcysteine in patients with COVID-19. ClinicalTrials.gov Identifier: Multicenter, randomized, open-label, parallel-group, controlled trial, Phase 4. Hypothesis and Theory, N-acetyl-L-cysteine (NAC) inhibits virus replication and expression of pro-inflammatory molecules in A549 cells infected with highly pathogenic H5N1 influenza A virus. Kircik LH, Del Rosso JQ, Layton AM, Schauber J. doi:10.1016/j.cell.2020.08.001 Directly Acting Antivirals for COVID-19: where Do We Stand? Furthermore the SARS-CoV-2 virus is, like the influenza virus, an RNA virus with a lipid double membrane envelope. Moreover, an oxidative stress imbalance has been demonstrated . National Library of Medicine N-acetylcysteine (NAC) was introduced in the 1960s as a mucolytic drug for chronic respiratory diseases. J Med Virol. Clinical application of methylene blue for treatment of COVID-19 patients (COVID-19). 90.0% of patients receiving ImmunoFormulation recovered compared to 47.4% in the control group (, Single center, non-randomized, open-label, parallel-group trial, Phase 2. The Potential Mechanism of N-acetylcysteine in Treating COVID-19. Bethesda, MD 20894, Web Policies "Looking for advice on supplements to add to my stack. Kalra RS, Tomar D, Meena AS, Kandimalla R. SARS-CoV-2, ACE2, and Hydroxychloroquine: cardiovascular Complications, Therapeutics, and Clinical Readouts in the Current Settings, ACTIVating Resources for the COVID-19 Pandemic: in Vivo Models for Vaccines and Therapeutics. N-acetylcysteine has recently been suggested as an adjunctive therapy to the standard care for SARS-CoV-2 infection considering the favorable risk and benefit ratio and its effects on synthesizing glutathione, improving immune function, and modulating inflammatory response.3234 It achieves the therapeutic effects through two main activities: 1) mucolytic action conferred by the free sulfhydryl group which reduces disulfide bonds in the cross-linked mucus glycoproteins matrix, thus decreasing the viscosity of mucus; 2) antioxidative action attributable to a direct interaction with free radicals, an indirect effect as a precursor to cysteine which is required for glutathione biosynthesis, and a replenishment of thiol pools that is central to redox regulation and control.35 In light of these properties, we hypothesize that N-acetylcysteine plays a role in the treatment of COVID-19 infection by the following postulated mechanisms of action (Figure 1): Schematic representation of the possible effects of N-acetylcysteine on SARS-CoV-2 infection. 1Department of Microbiology and Immunology, Hospital Canselor Tuanku Muhriz UKM, Cheras, Kuala Lumpur, Malaysia, 2Faculty of Medicine, The National University of Malaysia, Cheras, Kuala Lumpur, Malaysia, 3School of Pharmacy, Monash University, Bandar Sunway, Selangor, Malaysia, 4Asian Centre for Evidence Synthesis in Population, Implementation, and Clinical Outcomes (PICO), Health and Well-being Cluster, Global Asia in the 21st Century (GA21) Platform, Monash University, Bandar Sunway, Selangor, Malaysia, 5Gerontechnology Laboratory, Global Asia in the 21st Century (GA21) Platform, Monash University, Bandar Sunway, Selangor, Malaysia, 6Faculty of Health and Medical Sciences, Taylors University, Bandar Sunway, Selangor, Malaysia, 7Puchong Health Clinic, Petaling District Health Office, Ministry of Health Malaysia, Petaling, Selangor, Malaysia. Indeed, intrinsic Gclc expression in T-cells is necessary for antigen-specific immunity to virus infections. An old drug repurposed? Over 25 Years of Clinical Experience With Ivermectin: an Overview of Safety for an Increasing Number of Indications, Dual anti-inflammatory and anti-parasitic action of topical ivermectin 1% in papulopustular rosacea. [Updated 2016 Nov 7]. Federal government websites often end in .gov or .mil. Oka S, Kamata H, Kamata K, Yagisawa H, Hirata H. N-Acetylcysteine suppresses TNF-induced NF-B activation through inhibition of IB kinases. the contents by NLM or the National Institutes of Health. NAC: A Natural Product So Powerful It Is Used in Hospitals. Patients received both standard care and ImmunoFormulation consisting of transfer factors (oligo- and polypeptides from porcine spleen. The study is scheduled to complete in August 2021. As the most commonly approved nanomedicines by the US FDA,128 lipid-based nanoparticles afford many advantages such as relatively simple formulation, self-assembled structure, biocompatibility, drug load capacity, and adjustable physicochemical properties to suit biological characteristics.129 However, the lipid nanoparticle system is limited by low physicochemical stability and low-to-moderate encapsulation efficiency for N-acetylcysteine.130 A liposomal formulation of co-encapsulated azithromycin and N-acetylcysteine has been demonstrated to have a synergistic effect against bacterial strains.131 The high cellular membrane permeability and targeting accuracy associated with such a delivery system illuminates a potential implication for the co-formulation strategy of N-acetylcysteine with antiviral drug. Correspondence: Kok Pim Kua Email kokpimkua@gmail.com. Hadzic T, Li L, Cheng N, Walsh SA, Spitz DR, Knudson CM. The full terms of this license are available at, Envelope (E) and spike (S) proteins have a triple cysteine structural motif located directly after the E proteins transmembrane domain (NH, N-acetylcysteine is a chemical reducer of disulfide bonds via its free sulfhydryl groups may interact with the extracellular disulfide bridges of angiotensin II receptor, alter its tertiary structure, and inhibit the binding of angiotensin II to its surface receptors (AT. N-Acetylcysteine Selectively Antagonizes the Activity of Imipenem in Pseudomonas aeruginosa by an OprD-Mediated Mechanism, Acetylcysteine-Mediated Modulation of Bacterial Antibiotic Susceptibility, N-Acetyl-L-Cysteine and Cysteamine as New Strategies against Mixed Biofilms of Nonencapsulated Streptococcus pneumoniae and Nontypeable Haemophilus influenzae. The US Food and Drug Administration (FDA) has approved N-acetylcysteine to treat the liver side effects resulting from an overdose of the anti-inflammatory medication Tylenol (acetaminophen). However, more trials are underway to determine its safety and effectiveness. N-Acetyl Cysteine Restores the Diminished Activity of the Antioxidant Enzymatic System Caused by SARS-CoV-2 Infection: Preliminary Findings. High dose N-acetyl cysteine improves inflammatory response and outcome in patients with COPD exacerbations. Similarly, infection of alveolar pneumocytes cells by SARS-CoV-2 virus triggers the initiation of systemic inflammation and elevated immunoreactivity that potentiate T-cell and macrophage activation infiltrating infected myocardial tissues, leading to cardiovascular damage and myocarditis. It is noteworthy that molecular attraction forces between chitin found on the exoskeleton of mites on human skin (Demodecidae or Pyemotidae species) and lipids present on the viral envelope cause interactions between arthropod and coronavirus which play a major role in the transmission of SARS-CoV-2.106 Natural small molecules, namely cyclodextrins and phytosterols, may hinder viral lipiddependent attachment to host cells and thus reduce infectivity of the virus.107 Nowadays, these natural compounds exist in various forms of dietary supplements.107 Their potential to exhibit antiviral effects invigorates additional research to create novel biomedical applications for the treatment and prevention of COVID-19. Interleukin-6: designing specific therapeutics for a complex cytokine, Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer, Interleukin-6 receptor blockade in patients with COVID-19: placing clinical trials into context. Daoud A, Dalhoff KP, Christensen MB, Bgevig S, Petersen TS. HHS Vulnerability Disclosure, Help In the intervention group, serum alanine aminotransferase (P=0.032), lactate dehydrogenase (P<0.0001), and creatinine levels (P<0.0001) were significantly lower on Day 14 compared to Day 0. A549 cells were, The effect of 30 min incubation of neutrophils with different NAC concentrations on. Acetylcysteine is a derivative of the natural amino acid cysteine, which serves as a substrate for the synthesis of glutathione in the body. The patient tolerated hydroxychloroquine and N-acetylcysteine well. 2023 Apr 28;11(5):1308. doi: 10.3390/biomedicines11051308. Adults aged 18 years or older with known or suspect COVID-19 disease. As a pharmacist, I am very impressed by a natural product called NAC, short for N-acetylcysteine. and transmitted securely. de Alencar JCG, Moreira CDL, Mller AD, et al. NAC has antioxidant, anti-inflammatory and immune-modulating characteristics that may prove beneficial in the treatment and prevention of SARS-Cov-2. Several . 2020;182(6):14191440. As a library, NLM provides access to scientific literature. The formulation delivers N-acetylcysteine directly to the lungs with increased pulmonary deposition and higher pulmonary concentrations with a lower dose of N-acetylcysteine.132 Polymer-based nanoparticle enhances pharmacokinetic and pharmacodynamics properties of encapsulated drug via prolonged drug release and particle retention.133,134 While poly(lactic-co-glycolic acid) is one of the most commonly used biodegradable polymers, its poor drug loading requires higher polymer load to facilitate dose delivery.135 Polymer-based nanoparticles are biodegradable, water soluble, biocompatible, biomimetic, and stable during storage. The use of ImmunoFormulation was associated with resolution of all clinical symptoms within 25 days, except for the loss of taste or smell (19.73 days) that was recognized as a long-term complication of COVID-19. Hydroxychloroquine 400 mg was given as a single oral dose and N-acetylcysteine was administered intravenously at 75 mg/kg over 4 hours, then 35 mg/kg over 16 hours, followed by 17 mg/kg over 24 hours on Day 2. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). The product code (s) for this leaflet is: 44490/0006. N-acetyl cysteine is an antioxidant that might play a role in preventing cancer. Pincemail J, Rousseau AF, Kaux JF, Cheramy-Bien JP, Bruyre C, Prick J, Stern D, Kaci MM, Maertens De Noordhout B, Albert A, Eubelen C, Goff CL, Misset B, Cavalier E, Charlier C, Meziane S. Biomedicines. The role of low molecular weight thiols in T lymphocyte proliferation and IL-2 secretion, Glutathione Primes T Cell Metabolism for Inflammation, High-Dose Acetylcysteine in Idiopathic Pulmonary Fibrosis, N-acetylcysteine reduces disease activity by blocking mammalian target of rapamycin in T cells from systemic lupus erythematosus patients: a randomized, double-blind, placebo-controlled trial, Pulmonary fibrosis and COVID-19: the potential role for antifibrotic therapy, In Vitro and Animal Models for SARS-CoV-2 research, Interleukin-6 Receptor Inhibition in Covid-19 cooling the Inflammatory Soup. Predisposing factors such as age, diabetes, cardiovascular disease, and lowered immune function increase the risk of disease severity. A Pilot Study on Oxidative Stress during the Recovery Phase in Critical COVID-19 Patients in a Rehabilitation Facility: Potential Utility of the PAOT. The patients hypercapnia was significantly improved and disengaged from mechanical ventilation intermittently. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012. The study is scheduled to complete in August 2021. Currently, there are some clinical trials assessing the potential use of NAC against COVID-19; for example, the 'Efficacy and Safety of Nebulized Heparin-N-acetylcysteine in COVID-19 Patients by Evaluation of Pulmonary Function Improvement (HOPE)' clinical trial is aimed at determining the efficacy of nebulized NAC and heparin in ventilated . N-acetylcysteine (NAC) has been used in clinical practice to treat critically ill septic patients, and more recently for COVID-19 patients. None of the patients on ImmunoFormulation experienced an adverse drug reaction. 144 patients were discharged with a mean hospital stay of 12 days. Physico-chemical stability of colloidal lipid particles. N-Acetylcysteine in the Prevention of Contrast-Induced Nephropathy, ACEIs and ARBs and Their Correlation with COVID-19: a Review. Ullian ME, Gelasco AK, Fitzgibbon WR, Beck CN. An official website of the United States government. Detailed Description: After being informed of the study and potential risks and benefits, patients meeting eligibility requirements will be randomized to receive oral N-acetylcysteine (NAC) as follows: Inpatients: N-acetylcystine (NAC) 25 mg/kg PO (rounded up to the nearest 600 mg) q4hrs until discharge Epub 2022 Nov 12. The median C-reactive protein level during IV N-acetylcysteine administration was 55 mg/dL which was considerably lower compared to the time before administration (143 mg/dL) or after N-acetylcysteine discontinuation (69 mg/dL). Current therapeutic strategies for COVID-19 have failed to effectively reduce mortality rate, especially for elderly patients. Elevated D-dimer levels concomitant with high levels of fibrin degradation products and low antithrombin activity render COVID-19 patients to be at risk of hypercoagulability and thrombotic complications. Patients will not receive N-acetylcysteine. Landini G, Di Maggio T, Sergio F, Docquier J-D, Rossolini GM, Pallecchi L. Effect of High N-Acetylcysteine Concentrations on Antibiotic Activity against a Large Collection of Respiratory Pathogens, The chemistry and biological activities of N-acetylcysteine. Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment. sharing sensitive information, make sure youre on a federal Lai KY, Ng WY, Osburga Chan PK, Wong KF, Cheng F. High-dose N-acetylcysteine therapy for novel H1N1 influenza pneumonia. Izquierdo-Alonso JL, Prez-Rial S, Rivera CG, Peces-Barba G. J Infect Public Health. Mahmoud Abd El Hafiz A, Mohammed El Wakeel L, Mohammed El Hady H, Mourad AER. Rabi FA, Al Zoubi MS, Kasasbeh GA, Salameh DM. Siemieniuk RA, Bartoszko JJ, Ge L, et al. N-acetylcysteine was well tolerated: 146 (29%) of 495 patients who received at least one dose of N-acetylcysteine had adverse events (48 serious), as did 130 (26%) of 495 patients who received at least . Apart from the fact that acetylcysteine is able to normalise a state of glutathione depletion, it is able to conjugate with various toxic compounds. Reduction of adverse effects from intravenous acetylcysteine treatment for paracetamol poisoning: a randomised controlled trial. Der Kinderen DJ, Koten JW. Karimi Zarchi AA, Faramarzi MA, Gilani K, Ghazi-Khansari M, Ghamami G, Amani A. N-acetylcysteine-loaded PLGA nanoparticles outperform conventional N-acetylcysteine in acute lung injuries in vivo, Nanoparticle formulations in pulmonary drug delivery, Nanoparticle-mediated pulmonary drug delivery: a review. Further studies with cautious approach are needed to establish the benefits and risks before considering NAC as an adjuvant treatment for COVID-19. Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19: a Randomized Clinical Trial, COVID-19 and its implications for thrombosis and anticoagulation, Coagulation abnormalities and thrombosis in patients with COVID-19, The Impact of COVID-19 Disease on Platelets and Coagulation, D-dimer level in COVID-19 infection: a systematic review, D-dimer tests detect both plasmin and neutrophil elastase derived split products, Neutrophil elastase contributes to acute lung injury induced by bilateral nephrectomy, Disseminated intravascular coagulation: a devastating systemic disorder of special concern with COVID-19. The https:// ensures that you are connecting to the A549 cells were infected with A/Vietnam/1203/04 (VN1203) at a MOI of 0.01. In a G6PD deficient patient, N-acetylcysteine elicited improvements in hemolysis indices (direct bilirubin), liver enzymes (ALT and AST), and inflammatory markers (C-reactive protein and ferritin), decreased dependence on respirator and veno-venous extracorporeal membrane oxygenator, and reduced neutrophil to lymphocyte ratio. FOIA Influenza A strain-dependent pathogenesis in fatal H1N1 and H5N1 subtype infections of mice, N-acetyl-l-cystine (NAC) protects against H9N2 swine influenza virus-induced acute lung injury, Role of oxidative stress on diesel-enhanced influenza infection in mice, Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment, N-acetylcysteine improves oxidative stress and inflammatory response in patients with community acquired pneumonia: a randomized controlled trial. 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. 2021;22(12):1584-1590. doi: 10.2174/1389201021999201228212043. Yilmaz B, Trk G, engl E, Gl A, zkurt FE, Akda M. Efficacy of N-Acetylcysteine on Wound Healing of Nasal Mucosa. Viruses. In vitro effect of bioactive compounds on influenza virus specific B- and T-cell responses, N-acetyl-L-cysteine (NAC) inhibit mucin synthesis and pro-inflammatory mediators in alveolar type II epithelial cells infected with influenza virus A and B and with respiratory syncytial virus (RSV), Proteomics study of N-acetylcysteine response in H1N1-infected cells by using mass spectrometry, N-acetylcysteine lacks universal inhibitory activity against influenza A viruses, Respiratory syncytial virus inhibits ciliagenesis in differentiated normal human bronchial epithelial cells: effectiveness of N-acetylcysteine, Respiratory syncytial virus and TNFalpha induction of chemokine gene expression involves differential activation of Rel A and NF-kappaB1, Synergistic combination of N-acetylcysteine and ribavirin to protect from lethal influenza viral infection in a mouse model, Protective effect of n-acetylcysteine in a model of influenza infection in mice. Glutathione precursors such as N-acetylcysteine are suggested as a potential therapeutic approach for blocking NF-B activation and addressing cytokine storm syndrome and respiratory distress in patients suffering from COVID-19 pneumonia.84 In plasma, N-acetylcysteine reacts with cystine, reducing it to cysteine and yielding diacetylcystine and N-acetylcysteine-cysteine via redox exchange reactions, and subsequently enters human erythrocytes and sustains glutathione synthesis.85 Additional research has illuminated the action of N-acetylcysteine on T-cell proliferation and IL-2 secretion which implies intracellular thiols regulate selective signaling pathways for a novel target of immunoregulation.86 Furthermore, in vitro treatment of murine T-cells with N-acetylcysteine induces reactive oxygen species scavenging and initiates NFAT expression and nuclear translocation. eCollection 2021. However, the beneficial effects of NAC in early-stage COPD are . It is well tolerated without any serious side effects . Epub 2022 Dec 12. Vitamins & Supplements N-Acetyl Cysteine (Nac) Reviews User Reviews for n-acetyl cysteine (nac) Comments & ratings on the side effects, benefits, and effectiveness of n-acetyl cysteine (nac).. Severity and mortality have been related to a cytokine storm, an imbalance of oxidative stress, and a pro-thrombot Accelerated Preclinical Paths to Support Rapid Development of COVID-19 Therapeutics, Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results. Rapid response: N-acetylcysteine as a possible adjuvant in the treatment of SARS-CoV-2. However, the vaccine has shown limited benefit in the elderly, suggesting an age-dependent immune response. doi: 10.1128/mbio.02370-22. It has a well-established safety profile and is still commonly used orally at doses of 600mg/day as a mucolytic. Repeated bedside bronchoscopy with 1015 g/time of N-acetylcysteine nebulized inhalation solution lavage was given in combination with routine nebulization and sputum suction airway management. Bookshelf Herpes Simplex Virus 1-Induced Ferroptosis Contributes to Viral Encephalitis. This condition is accompanied by a massive release of cytokines, also denominated cytokin Possible uses range from improving athletic performance to managing blood sugar levels and treating chronic lung. Intravenous N-acetylcysteine was re-started at 600 mg every 12 hours for 1 week and was subsequently withheld for 10 days. Dextrose 5% in water was administered intravenously (n=70). Primary outcome measures include mortality rate, improvement in Pa0, Multicenter, randomized, parallel-group, controlled trial, Phase 4. N-acetylcysteine may inhibit envelope (E) protein and spike (S) protein of the virus, decrease angiotensin II receptor binding (AT2R), inhibit angiotensin converting enzyme (ACE), induce endogenous glutathione (GSH) synthesis which is associated with increased antioxidant effect and decreased glycation of intracellular proteins, and prevent nuclear translocation of NF-B which suppresses the production of pro-inflammatory mediators and cytokines. The plasma levels of cytokines associated with inflammatory reactions (CSF-1, IL-15RA, IL18, MCP-1, and TNF) were significantly downregulated in the intervention group compared to the placebo group on Day 14. 2022 Dec;15(12):1477-1483. doi: 10.1016/j.jiph.2022.11.009. Cell. A brief overview of a NAC therapeutic strategy to combat COVID-19. Both patients experienced a mild rash on the upper body and they completed. King Saud University. Grobler JA, Anderson AS, Fernandes P, et al. The authors received no specific funding for this work. At present, there are six registered clinical trials evaluating the potential therapeutic value of N-acetylcysteine against COVID-19.7883 The findings will build on in vitro and early in vivo evidence for the use of N-acetylcysteine as an adjuvant therapy for COVID-19. sharing sensitive information, make sure youre on a federal If anyone with #MECFS and #LongCovid have spoons. ClinicalTrials.gov Identifier: Single center, randomized, open-label, parallel-group, controlled trial, Phase 1. N-acetylcysteine is a mucolytic drug which exhibits antioxidant and anti-inflammatory effects.26 The compound has been available in clinical practice for several decades to treat various medical conditions, including bronchitis, acute respiratory distress syndrome, paracetamol intoxication, chemotherapy-related toxicity, doxorubicin cardiotoxicity, heavy metal intoxication, ischemia-reperfusion cardiac injury, human immunodeficiency virus infection or acquired immunodeficiency syndrome, and neuropsychiatric disorders.