Early treatment with N-acetylcysteine reduces hepatotoxicity in acute acetaminophen poisoning.

During the outbreak of COVID19 measures taken to contain the spread of the virus have influenced the mental well-being of adults and adolescents. Acetaminophen overdose is the major cause of drug intoxication among children and adolescents. We reported a case of a 15-year- old girl referred to our Emergency Department 3 hours after ingestion of 10 g of paracetamol for suicidal purposes. She promptly started the administration of intravenous N-acetylcysteine (NAC) and the patient was discharged after 5 days of hospitalization in good clinical condition and with neuropsychiatric follow-up. Our case shows that the timing of the intravenous NAC administration is considered the most important factor in the prevention of acetaminophen-induced hepatic failure, despite high serum levels after acetaminophen ingestion.

Boesenbergia stenophylla-Derived Stenophyllol B Exerts Antiproliferative and Oxidative Stress Responses in Triple-Negative Breast Cancer Cells with Few Side Effects in Normal Cells.

Triple-negative breast cancer (TNBC) is insensitive to target therapy for non-TNBC and needs novel drug discovery. Extracts of the traditional herb Boesenbergia plant in Southern Asia exhibit anticancer effects and contain novel bioactive compounds but merely show cytotoxicity. We recently isolated a new compound from B. stenophylla, stenophyllol B (StenB), but the impact and mechanism of its proliferation-modulating function on TNBC cells remain uninvestigated. This study aimed to assess the antiproliferative responses of StenB in TNBC cells and examine the drug safety in normal cells. StenB effectively suppressed the proliferation of TNBC cells rather than normal cells in terms of an ATP assay. This preferential antiproliferative function was alleviated by pretreating inhibitors for oxidative stress (N-acetylcysteine (NAC)) and apoptosis (Z-VAD-FMK). Accordingly, the oxidative-stress-related mechanisms were further assessed. StenB caused subG1 and G2/M accumulation but reduced the G1 phase in TNBC cells, while normal cells remained unchanged between the control and StenB treatments. The apoptosis behavior of TNBC cells was suppressed by StenB, whereas that of normal cells was not suppressed according to an annexin V assay. StenB-modulated apoptosis signaling, such as for caspases 3, 8, and 9, was more significantly activated in TNBC than in normal cells. StenB also caused oxidative stress in TNBC cells but not in normal cells according to a flow cytometry assay monitoring reactive oxygen species, mitochondrial superoxide, and their membrane potential. StenB induced greater DNA damage responses (γH2AX and 8-hydroxy-2-deoxyguanosine) in TNBC than in normal cells. All these StenB responses were alleviated by NAC pretreatment. Collectively, StenB modulated oxidative stress responses, leading to the antiproliferation of TNBC cells with little cytotoxicity in normal cells.

Response to Intravenous N-Acetylcysteine Supplementation in Critically Ill Patients with COVID-19.

Administering N-acetylcysteine (NAC) could counteract the effect of free radicals, improving the clinical evolution of patients admitted to the Intensive Care Unit (ICU). This study aimed to investigate the clinical and biochemical effects of administering NAC to critically ill patients with COVID-19. A randomized controlled clinical trial was conducted on ICU patients (n = 140) with COVID-19 and divided into two groups: patients treated with NAC (NAC-treated group) and patients without NAC treatment (control group). NAC was administered as a continuous infusion with a loading dose and a maintenance dose during the study period (from admission until the third day of ICU stay). NAC-treated patients showed higher PaO2/FiO2 (p ≤ 0.014) after 3 days in ICU than their control group counterparts. Moreover, C-reactive protein (p ≤ 0.001), D-dimer (p ≤ 0.042), and lactate dehydrogenase (p ≤ 0.001) levels decreased on the third day in NAC-treated patients. Glutathione concentrations decreased in both NAC-treated (p ≤ 0.004) and control (p ≤ 0.047) groups after 3 days in ICU; whereas glutathione peroxidase did not change during the ICU stay. The administration of NAC manages to improve the clinical and analytical response of seriously ill patients with COVID-19 compared to the control group. NAC is able to stop the decrease in glutathione concentrations.

NEUROPROTECTIVE AND ANTIOXIDANT POTENTIAL OF MONTELUKAST-ACETYLCYSTEINE COMBINATION THERAPY FOR BRAIN PROTECTION IN PATIENTS WITH COVID-19 INDUCED PNEUMONIA.

Direct critical attack of the coronavirus on the alveoli and the excessive release of a large number of cytokines (IL-6, IL-1, TNF-α, etc.) provides suitable conditions for the further development of acute respiratory distress syndrome (ARDS) and severe acute respiratory failure. Serious decrease in blood oxygenation often lead to the deterioration of macro- and microcirculation, irreversible brain damage and hence, persistent neurological and mental disorders despite background intensive therapy and adequate respiratory support. Therefore, the aim of our open prospective observational study was to investigate the neuroprotective and antioxidant effectiveness of montelukast-acetylcysteine combination therapy for brain protection in patients with COVID-19 viral pneumonia. A study was performed for five hundred seventy-eight (n=578) outpatients who were tested positive for novel coronavirus (SARS-CoV-2) by nasopharyngeal swap. The median age of patients was 62±17.45 years. In addition to clinical features and RT-PCR results, chest CT and chest X-ray (CXR) with high sensitivity were also very helpful for the early identification of viral pneumonia and COVID-19 disease assessment. Considering the severity of Covid-19 pneumonia and the level of arterial oxygen saturation (transcutaneous hemoglobin oxygen saturation) on room air, all patients were divided into three major groups. Group 1 (n=288) consisted of patients with a mild shift in oxygen saturation (SpO2 ≥ 95%) and well-defined pulmonary lesions (within 1-2 segments) without concomitant diseases; the second group (Group 2, n=250) included patients with clinical manifestations of moderate severity associated with a current saturation of 90-95% (SpO2) and small pulmonary lesions on chest X-ray in the presence of concomitant diseases: arterial hypertension (stage III) or CHF (FC/NYHA-2), coronary heart disease or type 2 diabetes, cancer, tuberculosis, etc. Most of the patients in third group (Group 3, n=48), during imaging studies, showed bilateral lung affection with low and peripheral distribution (with both - either ground glass opacities or multiple pulmonary nodules) and cardiomegaly. The respiratory failure of stage II-III (current oxygen saturation SpO2 75-90%), high respiratory rate (≥25 per minute), hemodynamic impairment (BP≤100/60 mm Hg. Art., heart rate ≥125/min) were the most common objective clinical findings seen in this subset of patients. Laboratory changes included leukopenia less than 4.0x109/L or leukocytosis (≥10.0X109/L). Background respiratory support with low-flow oxygen therapy and combined pharmacotherapy, where, along with montelukast and acetylcysteine, patients were prescribed a cephalosporin, a fluoroquinolone, an antifungal drug, a histamine blocker, an antiplatelet agent, a complex of B vitamins, led to a significant improvement in symptoms and laboratory parameters during the course of the disease. The mean values of the blood biomarkers (CRP - 21.46±4.43 mg/l, LDH - 410.71±40.63 U/l, procalcitonin - 1.08±0.31 ng/ml, and ferritin - 270.43±27.23 ng/ml) return to normal by the 20th day after the fever subsides. Laboratory parameters before and after treatment course showed statistically significant differences between variables (p<0.05). No patient in Group 3 received JAK inhibitors (tofacitinib and baricitinib), IL-6 (olokizumab), IL-17A (netakimab) and glucocorticosteroids, however, recovery rates were completely good. Assessment of the patient's neurological status (based on the NIHSS scores) revealed no signs of neurological changes. Thus, based on the data given, it can be concluded that the high efficacy of the acetylcysteine/montelukast combination (as neuroprotectors) in pneumonia caused by COVID-19 is due to the effect of drugs on key mechanisms of pathogenesis: reduction of oxidative stress as drugs (combination) ensuring the free radical scavenging; stimulation of glutathione synthesis; suppression of cytokine storm; reduction of bronchospasm, mucus secretion and airway edema; lowering of BBB permeability and the ability to improve cerebral microcirculatory perfusion in the presence of antiplatelet agents. In conclusion, the combination of montelukast and acetylcysteine may provide an effective, safe, multicomponent approach to the prevention of hypoxic brain injury in patients with COVID-19 pneumonia.

Effect of Nebulized BromAc on Rheology of Artificial Sputum: Relevance to Muco-Obstructive Respiratory Diseases.

Respiratory diseases such as cystic fibrosis, COPD, and COVID-19 are difficult to treat owing to viscous secretions in the airways that evade mucocilliary clearance. Earlier studies have shown success with BromAc as a mucolytic agent. Hence, we tested the formulation on two gelatinous airway representative sputa models, to determine whether similar efficacy exist. Sputum lodged in an endotracheal tube was treated to aerosol N-acetylcysteine, bromelain, or their combination (BromAc). After measuring the particle size of aerosolized BromAc, the apparent viscosity was measured using a capillary tube method, whilst the sputum flow was assessed using a 0.5 mL pipette. Further, the concentration of the agents in the sputa after treatment were quantified using chromogenic assays. The interaction index of the different formulations was also determined. Results indicated that the mean particle size of BromAc was suitable for aerosol delivery. Bromelain and N-acetylcysteine affected both the viscosities and pipette flow in the two sputa models. BromAc showed a greater rheological effect on both the sputa models compared to individual agents. Further, a correlation was found between the rheological effects and the concentration of agents in the sputa. The combination index using viscosity measurements showed synergy only with 250 µg/mL bromelain + 20 mg/mL NAC whilst flow speed showed synergy for both combinations of bromelain (125 and 250 µg/mL) with 20 mg/mL NAC. Hence, this study indicates that BromAc may be used as a successful mucolytic for clearing airway congestion caused by thick mucinous immobile secretions.

Optimizing Respiratory Therapy Resources by De-Implementing Low-Value Care.

BACKGROUND: Our institution was experiencing a respiratory therapy staffing crisis during the COVID-19 pandemic, in part due to excessive workload. We identified an opportunity to reduce burden by limiting use of 3% hypertonic saline and/or N-acetylcysteine nebulizer therapies (3%HTS/NAC). METHODS: Leveraging the science of de-implementation, we established a policy empowering respiratory therapists to discontinue 3%HTS/NAC not meeting the American Association for Respiratory Care (AARC) Clinical Practice Guideline: Effectiveness of Pharmacologic Airway Clearance Therapies in Hospitalized Patients. After a 3-month period of educating physicians and advanced practice practitioners the policy went to into effect. Outcomes measured included monthly number of treatments, orders, and full-time employees associated with administering nebulized 3%HTS/NAC. RESULTS: Post policy activation, the monthly mean 3%HTS/NAC treatments were significantly reduced to 547.5 ± 284.3 from 3,565.2 ± 596.4 (P < .001) as were the associated monthly mean of full-time employees, 0.8 ± 0.41 from 5.1 ± 0.86 (P < .001). The monthly mean 3%HTS/NAC orders also fell to 93.8 ± 31.5 from 370.0 ± 46.9 (P < .001). Monthly mean non-3%HTS/NAC treatments remained stable; post policy was 3,089.4 ± 611.4 and baseline 3,279.6 ± 695.0 (P = 1.0). CONCLUSIONS: Implementing a policy that empowers respiratory therapists to promote adherence to AARC Clinical Guidelines reduced low-value therapies, costs, and staffing needs.

Use of N-Acetylcysteine at high doses as an oral treatment for patients hospitalized with 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). Severity and mortality have been related to a cytokine storm, an imbalance of oxidative stress, and a pro-thrombotic state.We conducted an observational retrospective cohort study from a community-based large population of hospitalized COVID-19 PCR + patients admitted from March 01, 2020, to January 24, 2021, with integrated primary to tertiary care information in Castilla la Mancha, Spain. We explored the potential benefits of the antioxidant, anti-inflammatory and anti-thrombotic drug N-acetylcysteine (NAC) administered orally in high doses (600 mg every 8 h), added to standard of care in COVID-19 patients by using the free text information contained in their electronic health records (EHRs).Out of 19,208 patients with a diagnosis of COVID-19 hospitalized, we studied 2071 (10.8%) users of oral NAC at high doses. COVID-19 patients treated with NAC were older, predominantly male, and with more comorbidities such as hypertension, dyslipidemia, diabetes, and COPD when compared with those not on NAC (all p < 0.05). Despite greater baseline risk, use of NAC in COVID-19 patients was associated with significantly lower mortality (OR 0.56; 95%CI 0.47-0.67), a finding that remained significant in a multivariate analysis adjusting by baseline characteristics and concomitant use of corticosteroids. There were no significant differences with the use of NAC on the mean duration of hospitalization, admission to the intensive care unit or use of invasive mechanical ventilation. The observed association signaling to better relevant outcomes in COVID-19 patients treated with NAC at high doses should be further explored in other settings and populations and in randomized controlled trials.

Is N -acetylcysteine effective in treating patients with coronavirus disease 2019? A meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). It has brought tremendous challenges to public health and medical systems around the world. The current strategy for drug repurposing has accumulated some evidence on the use of N -acetylcysteine (NAC) in treating patients with COVID-19. However, the evidence remains debated. METHODS: We performed the systematic review and meta-analysis that complies with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Five databases and reference lists were searched from inception to May 14, 2022. Studies evaluating the efficacy of NAC in treating patients with COVID-19 were regarded as eligible. The review was registered prospectively on PROSPERO (CRD42022332791). RESULTS: Of 778 records identified from the preliminary search, four studies were enrolled in the final qualitative review and quantitative meta-analysis. A total of 355 patients were allocated into the NAC group and the control group. The evaluated outcomes included intubation rate, improvement, duration of intensive unit stay and hospital stay and mortality. The pooled results showed nonsignificant differences in intubation rate (OR, 0.55; 95% CI, 0.16-1.89; p = 0.34; I2 = 75%), improvement of oxygenation ([MD], 80.84; 95% CI, -38.16 to 199.84; p = 0.18; I2 = 98%), ICU stay (MD, -0.74; 95% CI, -3.19 to 1.71; p = 0.55; I2 = 95%), hospital stay (MD, -1.05; 95% CI, -3.02 to 0.92; p = 0.30; I2 = 90%), and mortality (OR, 0.58; 95% CI, 0.23-1.45; p = 0.24; I2 = 54%). Subsequent trial sequential analysis (TSA) showed conclusive nonsignificant results for mortality, while the TSA for the other outcomes suggested that a larger sample size is essential. CONCLUSIONS: The current evidence reveals NAC is not beneficial for treating patients with COVID- 19 with regard to respiratory outcome, mortality, duration of ICU stay and hospital stay.

Oral high-dose acetylcysteine: Effective against the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)?

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a high rate of transmission and it exhibits immune escape characteristics. N-acetyl-L-cysteine (NAC) is a precursor of reduced glutathione (GSH), which can enter cells to play an antioxidant role, so it is better than glutathione. Patients tolerate NAC well, and adverse reactions are rare and mild, so this type of drug with multiple actions is considered to be a mucolytic agent as well as a drug for the prevention/treatment of various diseases, including COVID-19. Previous studies indicated that the clinical effectiveness of NAC is dose-dependent. Low-dose NAC (0.2 g tid for adults) is a mucolytic expectorant, high-dose NAC (0.6 g bid or tid) has expectorant action as well as antioxidant action, and extreme-dose NAC (300 mg/kg.d) is used for detoxification in cases of an acetaminophen overdose. Presumably, orally administered high-dose NAC (0.6 g tid for adults and 10 mg/kg tid for children) could be used as an adjuvant to treat an Omicron infection. It should reduce the time to negative conversion and prevent severe COVID-19, reducing the duration of hospitalization and increasing the bed turnover rate.

Antipsychotic Augmentation With N-Acetylcysteine for Patients With Schizophrenia.

N-acetylcysteine (NAC) augmentation of antipsychotic medication is one of very many antipsychotic augmentation strategies that have been studied in schizophrenia. A recent systematic review and meta-analysis of 6 randomized controlled trials (RCTs) found that NAC (median dose, 2,000 mg/d) improved several clinical outcomes at different time points with medium to large effect sizes; however, many of the significant findings in this meta-analysis are suspect because they appeared to be influenced by 2 short-term (8-week) RCTs with outlying characteristics. Important findings not influenced by the 2 outlying RCTs were significant attenuation by NAC of negative symptom (3 RCTs) and total psychopathology (2 RCTs) ratings at ≥ 24 weeks and improvement in working memory but not processing speed (3 RCTs). Of these findings, reduction in psychopathology ratings, though statistically significant, appeared too small to be clinically meaningful. Finally, a newly published, moderately large RCT of NAC (2,000 mg/d) in schizophrenia patients refractory to clozapine found that 1 year of treatment with NAC did not outperform placebo for any clinical, cognitive, or quality of life outcome. The take-home message is that it is premature to recommend the use of NAC to treat schizophrenia for any target domain in routine clinical practice and that there does not appear to be a role for NAC for any indication in clozapine-refractory schizophrenia. However, it may be worth studying whether NAC, dosed at 2,000 mg/d or higher for 6 months or longer, improves functional outcomes in schizophrenia.

N-acetylcysteine efficacy in patients hospitalized with COVID-19 pneumonia: a systematic review and meta-analysis.

BACKGROUND: N-acetylcysteine (NAC) is a mucolytic agents with anti-inflammatory properties that has been suggested as an adjunctive therapy in patients with COVID-19 pneumonia. OBJECTIVES: We conducted a systematic review and meta-analysis to evaluate available evidence on the possible beneficial effects of NAC on SARS-CoV-2 infection. METHODS: In September 2022, we conducted a comprehensive search on Pubmed/Medline and Embase on randomized controlled trials (RCTs) and observational studies on NAC in patients with COVID-19 pneumonia. Study selection, data extraction and risk of bias assessment was performed by two independent authors. RCTs and observational studies were analyzed separately. RESULTS: We included 3 RCTs and 5 non-randomized studies on the efficacy of NAC in patients with COVID-19, enrolling 315 and 20826 patients respectively. Regarding in-hospital mortality, the summary effect of all RCTs was OR: 0.85 (95% CI: 0.43 to 1.67, I2=0%) and for non-randomized studies OR: 1.02 (95% CI: 0.47 to 2.23, I2=91%). Need for ICU admission was only reported by 1 RCT (OR: 0.86, 95% CI:0.44-1.69, p=0.66), while all included RCTs reported need for invasive ventilation (OR:0.91, 95% CI:0.54 to 1.53, I2=0). Risk of bias was low for all included RCTs, but certainty of evidence was very low for all outcomes due to serious imprecision and indirectness. CONCLUSION: The certainty of evidence in the included studies was very low, thus recommendations for clinical practice cannot be yet made. For all hard clinical outcomes point estimates in RCTs are close to the line of no effect, while observational studies have a high degree of heterogeneity with some of them suggesting favorable results in patients receiving NAC. More research is warranted to insure that NAC is both effective and safe in patients with COVID-19 pneumonia.

Oxidative stress and viral Infections: rationale, experiences, and perspectives on N-acetylcysteine.

This article explores current evidence on the role of oxidative stress in viral infections, and on the use of antioxidant drugs as adjunctive treatment. MEDLINE/PubMed was searched for appropriate keywords, and preclinical and clinical studies with reviews were retrieved and examined by authors. Old and current evidence shows that GSH content reduction is the main mechanism of redox imbalance in viral-infected cells. Clinical studies found that GSH levels are depleted in patients with viral infections such as HIV and SARS-CoV. Viral infections activate inflammation through different pathways, and several of these mechanisms are related to oxidative stress. NAC is a precursor of GSH, and many of its intracellular effects are mediated by GSH replenishment, but it also activates some anti-inflammatory mechanisms. NAC has an excellent safety profile and better oral and topical bioavailability than GSH. These characteristics make NAC a suitable option as a repurposed drug. Adjunctive antioxidant treatment may improve the outcomes of antiviral therapies. Current evidence supports the rationale for this practice and some clinical experience showed encouraging results.

Evaluation the efficacy and safety of N-acetylcysteine inhalation spray in controlling the symptoms of patients with COVID-19: An open-label randomized controlled clinical trial.

The aim of this study was to evaluate the effect and safety of N-acetylcysteine (NAC) inhalation spray in the treatment of patients with coronavirus disease 2019 (COVID-19). This randomized controlled clinical trial study was conducted on patients with COVID-19. Eligible patients (n = 250) were randomly allocated into the intervention group (routine treatment + NAC inhaler spray one puff per 12 h, for 7 days) or the control group who received routine treatment alone. Clinical features, hemodynamic, hematological, biochemical parameters and patient outcomes were assessed and compared before and after treatment. The mortality rate was significantly higher in the control group than in the intervention group (39.2% vs. 3.2%, p < 0.001). Significant differences were found between the two groups (intervention and control, respectively) for white blood cell count (6.2 vs. 7.8, p < 0.001), hemoglobin (12.3 vs. 13.3, p = 0.002), C-reactive protein (CRP: 6 vs. 11.5, p < 0.0001) and aspartate aminotransferase (AST: 32 vs. 25.5, p < 0.0001). No differences were seen for hospital length of stay (11.98 ± 3.61 vs. 11.81 ± 3.52, p = 0.814) or the requirement for intensive care unit (ICU) admission (7.2% vs. 11.2%, p = 0.274). NAC was beneficial in reducing the mortality rate in patients with COVID-19 and inflammatory parameters, and a reduction in the development of severe respiratory failure; however, it did not affect the length of hospital stay or the need for ICU admission. Data on the effectiveness of NAC for Severe Acute Respiratory Syndrome Coronavirus-2 is limited and further research is required.

N-acetylcysteine Reduces Inflammasome Activation Induced by SARS-CoV-2 Proteins In Vitro.

Inflammasome activation is one of the first steps in initiating innate immune responses. In this work, we studied the activation of inflammasomes in the airways of critically ill COVID-19 patients and the effects of N-acetylcysteine (NAC) on inflammasomes. Tracheal biopsies were obtained from critically ill patients without COVID-19 and no respiratory disease (control, n = 32), SARS-CoV-2 B.1 variant (n = 31), and B.1.1.7 VOC alpha variant (n = 20) patients. Gene expression and protein expression were measured by RT-qPCR and immunohistochemistry. Macrophages and bronchial epithelial cells were stimulated with different S, E, M, and N SARS-CoV-2 recombinant proteins in the presence or absence of NAC. NLRP3 inflammasome complex was over-expressed and activated in the COVID-19 B.1.1.7 VOC variant and associated with systemic inflammation and 28-day mortality. TLR2/MyD88 and redox NOX4/Nrf2 ratio were also over-expressed in the COVID-19 B.1.1.7 VOC variant. The combination of S-E-M SARS-CoV-2 recombinant proteins increased cytokine release in macrophages and bronchial epithelial cells through the activation of TLR2. NAC inhibited SARS-CoV-2 mosaic (S-E-M)-induced cytokine release and inflammasome activation. In summary, inflammasome is over-activated in severe COVID-19 and increased in B.1.1.7 VOC variant. In addition, NAC can reduce inflammasome activation induced by SARS-CoV-2 in vitro, which may be of potential translational value in COVID-19 patients.

N-acetylcysteine for prevention and treatment of COVID-19: Current state of evidence and future directions.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (COVID-19) and can be associated with serious complications, including acute respiratory distress syndrome. This condition is accompanied by a massive release of cytokines, also denominated cytokine storm, development of systemic oxidative stress and a prothrombotic state. In this context, it has been proposed a role for acetylcysteine (NAC) in the management of patients with COVID-19. NAC is a molecule classically known for its mucolytic effect, but it also has direct and indirect antioxidant activity as a precursor of reduced glutathione. Other effects of NAC have also been described, such as modulating the immune and inflammatory response, counteracting the thrombotic state, and having an antiviral effect. The pharmacological activities of NAC and its effects on the mechanisms of disease progression make it a potential therapeutic agent for COVID-19. NAC is safe, tolerable, affordable, and easily available. Moreover, the antioxidant effects of the molecule may even prevent infection and play an important role as a complement to vaccination. Although the clinical efficacy and dosing regimens of NAC have been evaluated in the clinical setting with small series of patients, the results are promising. In this article, we review the pathogenesis of SARS-CoV-2 infection and the current knowledge of the mechanisms of action of NAC across disease stages. We also propose NAC posology strategies to manage COVID-19 patients in different clinical scenarios.

Inhibition of the Cell Uptake of Delta and Omicron SARS-CoV-2 Pseudoviruses by N-Acetylcysteine Irrespective of the Oxidoreductive Environment.

The binding of SARS-CoV-2 spikes to the cell receptor angiotensin-converting enzyme 2 (ACE2) is a crucial target both in the prevention and in the therapy of COVID-19. We explored the involvement of oxidoreductive mechanisms by investigating the effects of oxidants and antioxidants on virus uptake by ACE2-expressing cells of human origin (ACE2-HEK293). The cell uptake of pseudoviruses carrying the envelope of either Delta or Omicron variants of SARS-CoV-2 was evaluated by means of a cytofluorimetric approach. The thiol N-acetyl-L-cysteine (NAC) inhibited the uptake of both variants in a reproducible and dose-dependent fashion. Ascorbic acid showed modest effects. In contrast, neither hydrogen peroxide (H2O2) nor a system-generating reactive oxygen species (ROS), which play an important role in the intracellular alterations produced by SARS-CoV-2, were able to affect the ability of either Delta or Omicron SARS-CoV-2 pseudoviruses to be internalized into ACE2-expressing cells. In addition, neither H2O2 nor the ROS generating system interfered with the ability of NAC to inhibit that mechanism. Moreover, based on previous studies, a preventive pharmacological approach with NAC would have the advantage of decreasing the risk of developing COVID-19, irrespective of its variants, and at the same time other respiratory viral infections and associated comorbidities.

EFFICIENT COMPREHENSIVE TREATMENT OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE EXACERBATION AND POSTCOVIDAL SYNDROME IN ELDERLY PATIENTS.

OBJECTIVE: The aim: The purpose of the study is to increase the efficacy of сomprehensive treatment in elderly patients with COPD , who have suffered of coronavirus disease-COVID-19 in the last 3-6 months, by using nebulizer therapy with N-acetylcysteine and 3% hypertonic sodium chloride solution (Flu-Acyl broncho) and the drug glycine, to correct psychosomatic disorders. PATIENTS AND METHODS: Materials and methods: Under our supervision there were 60 elderly patients with COPD gr D, who underwent Covid 19 in the last 3-6 months, were under observation. The average age was 66.3±2.1 years. Рatients of the main and control groups were prescribed complex basic therapy. However, mucolytic therapy was administered to patients in the main group using combined drug - N-acetylcysteine and 3% hypertonic sodium chloride solution through a 5.0 №10 nebulizer. For the treatment of astheno-neurotic disorders of postcovidal syndrome was prescribed glycine 100 mg 2 times a day for 10 days. Subsequently, Flu-Acyl broncho through a nebulizer at 5.0 No.10, and glycised was used in courses once a day for 10 days per month. Patients in the control group were prescribed acetylcysteine 200 mg 3 times a day N10. RESULTS: Results: The results of observation for 6 months showed that in patients of the main group, recurrence of the disease was not observed. whereas in patients of the control group in 6 patients (20%). CONCLUSION: Conclusions: Comprehensive treatment of elderly patients with comorbid pathology - COPD group D and postcovidal syndrome, with the additional use of nebulizer delivery of the combined drug - N-acetylcysteine and 3% hypertonic sodium chloride solution in combination with the sedative drug glycine, promotes improving the quality of life in patients, reducing the duration of treatment, prevents recurrence and progression of COPD.

N-acetylcysteine as a therapeutic approach to post-COVID-19 pulmonary fibrosis adjunctive treatment.

OBJECTIVE: Growing interest is directed to the outcomes of COVID-19 in survivors, both in the convalescent period and in the long-term, which are responsible for morbidity and quality of life deterioration. This article aims to describe the mechanisms supporting the possible use of NAC as an adjuvant treatment for post-COVID-19 pulmonary fibrosis. MATERIALS AND METHODS: A search was performed in PubMed/MEDLINE. RESULTS: Interstitial changes have been observed in the CT scan of COVID-19 pneumonia. In patients with respiratory outcomes in the post-COVID-19 stage, glutathione (GSH) deficiency was found and interpreted as a reaction to the inflammatory cascade caused by the viral infection, while the pathophysiological process of pulmonary fibrosis involves numerous cytokines, such as TGF-ß, TNF-α, IL-1, PDGF and VEGF. NAC has a good tolerability profile, is easily administered orally and inexpensively, and has antioxidant and anti-inflammatory effects that may target the pathophysiologic mechanisms involved in pulmonary fibrosis. It may revert GSH deficiency, exerts direct and indirect antioxidant activity, anti-inflammatory activity and improves immune T-cell response. CONCLUSIONS: The mechanism of action of NAC suggests a role in the treatment of pulmonary fibrosis induced by COVID-19.