Randomized Clinical Trial of Antioxidant Therapy Patients with Septic Shock and Organ Dysfunction in the ICU: SOFA Score Reduction by Improvement of the Enzymatic and Non-Enzymatic Antioxidant System.

BACKGROUND AND AIM: Here, we assess the effect of adjuvant antioxidant therapies in septic shock patients with organ dysfunction and their effect on the enzymatic and non-enzymatic antioxidant systems. METHODS: Randomized clinical trial run between 2018 and 2022. One hundred and thirty-one patients with septic shock were included in five groups with 25, 27, 24, 26 and 29 patients each. Group 1 received vitamin C (Vit C), Group 2 vitamin E (Vit E), Group 3 n-acetylcysteine (NAC), Group 4 melatonin (MT) and group 5 no treatment. All antioxidants were administered orally or through a nasogastric tube for 5 days as an adjuvant to standard therapy. RESULTS: All patients had multiple organ failure (MOF) and low Vit C levels. Vit C therapy decreased CRP, PCT and NO3-/NO2- but increased Vit C levels. The SOFA score decreased with MT in 75%, Vit C 63% and NAC 50% vs. controls 33% (p = 0.0001, p = 0.03 and p = 0.001 respectively). MT diminished lipid peroxidation (LPO) (p = 0.01) and improved total antioxidant capacity (TAC) (p = 0.04). Vit E increased thiol levels (p = 0.02) and tended to decrease LPO (p = 0.06). Selenium levels were decreased in the control group (p = 0.04). CONCLUSIONS: Antioxidants used as an adjuvant therapy in the standard treatment of septic shock decrease MOF and oxidative stress markers. They increase the TAC and thiols, and maintain selenium levels.

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.

Efficacy of N-acetyl Cysteine in Severe COVID-19 Patients: A Randomized Controlled Phase III Clinical Trial

Background: Today, various drugs have been investigated as the primary or complementary treatment for coronavirus disease 2019 (COVID-19). N-acetylcysteine (NAC) has been used as a mucolytic in pulmonary diseases. This drug apparently contributes to the retrieval of the intracellular antioxidant system. Objective(s): This study aimed to determine the efficacy of NAC in severe COVID-19 patients admitted to the intensive care unit (ICU). Method(s): This single-blinded randomized controlled phase III clinical trial included 40 patients with confirmed COVID-19 (based on polymerase chain reaction) admitted to the Shahid Mohammadi Hospital's ICU, Bandar Abbas, Iran, in 2020. All cases had severe COVID-19. They were allocated randomly to two equal groups. Patients in the control group received standard drug therapy based on the treatment protocol of the national COVID-19 committee, while those in the NAC group received a single dose of intravenous NAC (300 mg/kg) upon admission to the ICU in addition to standard drug treatment. Clinical status and laboratory tests were done on admission to the ICU and then 14 days later or at discharge without knowing the patient grouping. Result(s): The two groups were comparable regarding age, gender, and other baseline laboratory and clinical parameters. At the final evaluation, respiratory rate (21.25 +/- 4.67 vs. 27.37 +/- 6.99 /min) and D-dimer (186.37 +/- 410.23 vs. 1339.04 +/- 2183.87 ng/mL) were significantly lower in the NAC group (P = 0.004 and P = 0.030, respectively). Also, a lower percentage of patients in the NAC group had lactate dehydrogenase (LDH) <= 245 U/L (0% vs. 25%, P = 0.047). Although the length of ward and ICU stay was shorter in the NAC group than in controls, the difference was statistically insignificant (P = 0.598 and P = 0.629, respectively). Mortality, on the other hand, was 75% in the control group and 50% in the NAC group, with no statistically significant difference (P = 0.102). Concerning the change in the study parameters, only the decrease in diastolic blood pressure (DBP) was significantly higher with NAC (P = 0.042). The intubation and mechanical ventilation rates were higher, while oxygen with mask and nasal oxygen rates were lower with NAC, but the difference was statistically insignificant. Conclusion(s): Based on the current research, NAC is related to a significant decrease in RR, D-dimer, and DBP in severe COVID-19. Also, LDH was significantly lower in the NAC group than in the controls. More research with larger sample sizes is needed to validate the current study results.Copyright © 2023, Author(s).

Role of oxidative stress and therapeutic options in SARS-COV-2 infection [Version 1, Peer Review - In Progress]

Introduction: elevated levels of oxidative stress in patients with SARS-CoV-2 infection generate tissue damage, causing organ dysfunction and generating a suitable environment for viral replication. Aim: to describe the mechanisms by which oxidative stress is generated in patients with Sars-Cov-2 and its therapeutic options. Methodology: a non-experimental and narrative study of bibliographic review type was carried out, data will be collected from original articles in indexed journals using the PubMed database. Results: patients with SARS-CoV-2 infection present elevated levels of oxidative stress, on the contrary, the levels of antioxidant agents are depleted, increasing the degree of oxidative stress to a greater extent. The use of N-acetylcysteine in a COVID-19 positive patient is a subject under discussion since, although there are inconsistencies in its degree of efficacy, no adverse effects of any kind have been observed. Conclusions: there are antioxidant therapeutic options under study, however, despite having a high safety profile, their efficacy in the treatment of COVID-19 is still unproven. © Este es un artículo en acceso abierto, distribuido bajo los términos de una licencia Creative Commons.

Role of Supplements in the Management of COVID-19 - A Comprehensive Review.

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) and patients with COVID-19 may be treated primarily with SARS CoV-2-targeting drugs and the therapeutic agents assisting in the management of COVID-19 complications. This review focuses on the supplements like vitamins, minerals, herbal constituents, and others that help prevent or manage negative outcomes among COVID-19 patients. The literature was searched in databases such as Medline/PubMed Central/PubMed, Google Scholar, Science Direct, EBSCO, Scopus, EMBASE, the Directory of Open Access Journals (DOAJ), and reference lists to identify relevant articles. The vitamins, including vitamin C, and vitamin D, minerals such as zinc, selenium, and copper, herbal constituents like thymoquinone, curcumin, naringenin, quercetin, and glycyrrhizin, and other supplements, including N-acetylcysteine and melatonin. Melatonin have been identified as having the potential to manage patients with COVID-19 along with standard care. Some of the ongoing clinical trials are investigating the effectiveness of different supplements among COVID-19 patients.

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.

Efficacy and safety of inhalation 6% N-acetylcysteine in 3% NaCl solution in clinical practice (literature review)

The article summarizes the literature on the use of N-acetylcysteine and its combination with 3% NaCl solution (FLU-ACYL broncho) in clinical practice. Studies show that N-acetylcysteine is currently effective in the treatment of respiratory diseases due to its multicomponent effects on the respiratory system and the immune system. Hypertonic (3%) NaCl solution potentiates the action of N-acetylcysteine by inhalation and allows to achieve good results in the treatment of acute and chronic respiratory diseases in the optimal time. One of the well-known in Ukraine products for fast and effective evacuation of viscous sputum is FLU-ACIL broncho, sterile solution for nebulizer and instillation. One 5 ml ampoule contains 300 mg of NAC, which has a mucolytic effect in direct contact with mucus, and 150 mg of hypertonic NaCl solution, which draws water from the intracellular space into the extracellular space by osmosis and increases the proportion of water in the bronchial secretion, dilutes it and thus facilitates its removal. The combination of NAC with hypertonic NaCl solution creates synergy and allows to obtain optimal treatment results with minimal side effects. This combination has mucolytic, anti-film, antiviral, antioxidant, anti-inflammatory and immunomodulatory effects, making it promising in a pandemic SARS-CoV-2. © 2022 by the Author(s).

N-Acetylcysteine for COVID-19: A Potential Adjuvant Therapy

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) infection or known as coronavirus disease 2019 (COVID-19) is a highly infectious disease that has been declared as a world pandemic by WHO. Although the majority of patients only experience mild symptoms, older patients and those with comorbidities are in the risk of falling into critically ill and even death. This is thought to correlate with systemic inflammatory response and oxidative stress imbalance. N-acetylcysteine (NAC) is recognized as a potent mucolytic, yet its lesser-known function as an antioxidant is a precursor of glutathione. Basic aspects and either in vivo or in vitro studies showed various mechanisms of NAC acting as a counterbalance in viral infections and its role in decreasing inflammation and oxidative stress. High-dose NAC is reported to be effective as an antioxidant in pneumonia, influenza, sepsis, and acute respiratory distress syndrome. Early evidence in COVID-19 patients showed that NAC could be beneficial. This review gives the scientific background in considering NAC as an adjuvant treatment for COVID-19.

Multifaceted Effects and Mechanisms of N-Acetylcysteine on Intestinal Injury in a Porcine Epidemic Diarrhea Virus-Infected Porcine Model.

SCOPE: This study investigates the potential effects of N-acetylcysteine (NAC) on intestinal injury in a porcine epidemic diarrhea virus (PEDV)-infected porcine model. METHODS AND RESULTS: Thirty-two piglets are randomly assigned to one of four groups: the control, PEDV, NAC, and NAC+PEDV. Piglets in the NAC+PEDV group are orally administrated with NAC (100 mg (kg·BW)-1  day-1 ) for 4 consecutive days after 2 days of PEDV infection. The results show that NAC administration decreases the diarrhea rate and improves intestinal morphology. The concentration of diamine oxidase and intestinal fatty-acid binding protein, as well as IL-1ß, IL-8, and TNF-α in the plasma, is decreased by NAC. Intriguingly, NAC administration significantly increases the viral load in the jejunum and ileum and down-regulates the expression of interferon-related genes. Microarray and proteomic analyses show that the differentially expressed genes/proteins between NAC+PEDV and PEDV groups are highly enriched in substance transport. Furthermore, aquaporin 8/10 expression is significantly increased by NAC upon PEDV infection. CONCLUSION: NAC administration alleviates PEDV-induced intestinal injury by inhibiting inflammatory responses and improving substance transport, but promotes viral replication by inhibiting interferon signaling. These results suggest NAC exhibits multifaceted effects upon PEDV infection, and thus caution is required when using NAC as a dietary supplement to prevent viral infection.

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.

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.

COVID-19: Opportunities to Improve Prognosis.

COVID-19 is characterized by a severe course in approximately 5‒10% of patients, who require admittance to the intensive care unit and mechanical ventilation, which is associated with a very high risk of a poor prognosis. At present, in real clinical practice, in managing severe patients with COVID-19, noninvasive ventilation (NIV) is widely used (in some countries, up to 60% of all methods of respiratory support). In most studies on the effectiveness of NIV in hypoxemic acute respiratory failure in patients with COVID-19, the need for tracheal intubation and hospital mortality with the use of NIV averaged 20-30%, which suggests the rather high efficiency of this method. The COVID-19 pandemic has given a powerful impetus to the widespread use of prone positioning among nonintubated patients with acute respiratory failure caused by COVID-19. Several studies have shown that prone positioning can reduce the need for mechanical ventilation and hospital mortality. Medications that have proven effective in severe forms of COVID-19 include remdesivir, systemic glucocorticoids, tocilizumab, baricitinib, and anticoagulants. Among the new promising areas of drug therapy, noteworthy is the use of thiol-containing drugs (N-acetylcysteine), inhaled surfactant, and inhaled prostacyclin analogues.

Molecular Mechanisms Related to Responses to Oxidative Stress and Antioxidative Therapies in COVID-19: A Systematic Review.

The coronavirus disease (COVID-19) pandemic is a leading global health and economic challenge. What defines the disease's progression is not entirely understood, but there are strong indications that oxidative stress and the defense against reactive oxygen species are crucial players. A big influx of immune cells to the site of infection is marked by the increase in reactive oxygen and nitrogen species. Our article aims to highlight the critical role of oxidative stress in the emergence and severity of COVID-19 and, more importantly, to shed light on the underlying molecular and genetic mechanisms. We have reviewed the available literature and clinical trials to extract the relevant genetic variants within the oxidative stress pathway associated with COVID-19 and the anti-oxidative therapies currently evaluated in the clinical trials for COVID-19 treatment, in particular clinical trials on glutathione and N-acetylcysteine.

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.

Reactive Sulfur Compounds in the Fight against COVID-19.

The SARS-CoV-2 coronavirus pandemic outbreak in 2019 resulted in the need to search for an effective and safe strategy for treating infected patients, relieving symptoms, and preventing severe disease. SARS-CoV-2 is an RNA virus that can cause acute respiratory failure and thrombosis, as well as impair circulatory system function. Permanent damage to the heart muscle or other cardiovascular disorders may occur during or after the infection. The severe course of the disease is associated with the release of large amounts of pro-inflammatory cytokines. Due to their documented anti-inflammatory, antioxidant, and antiviral effects, reactive sulfur compounds, including hydrogen sulfide (H2S), lipoic acid (LA), N-acetylcysteine (NAC), glutathione (GSH), and some other lesser-known sulfur compounds, have attracted the interest of scientists for the treatment and prevention of the adverse effects of diseases caused by SARS-CoV-2. This article reviews current knowledge about various endogenous or exogenous reactive sulfur compounds and discusses the possibility, or in some cases the results, of their use in the treatment or prophylaxis of COVID-19.

Intravenous N-Acetylcysteine in Management of COVID-19: A Case Series.

A novel coronavirus, severe acute respiratory syndrome coronavirus-2, was isolated from patients' lower respiratory tracts in December 2019. As of May 19, 2021, there were over 33 million reported infections and almost 600,000 deaths in the United States. The infection, coronavirus disease-19 (COVID-19), can lead to cytokine storm, with elevations in interleukin-6 (IL-6), IL-10, tumor necrosis factor-α, nuclear factor-kappaB (NF-kappaB), and glutathione reductase. NF-kappaB activation is necessary for further transcription of other pro-inflammatory markers. Glutathione may play a role in modulation of NF-kappaB activation and elevated glutathione reductase may indicate glutathione depletion. Administration of N-acetylcysteine (NAC) may replenish spent glutathione and attenuate over-activation of NF-kappaB. This retrospective case series included 10 patients who were COVID-19 positive and received intravenous NAC in an attempt to attenuate the cytokine storm. Patients' outcomes were graded based on the World Health Organization symptom severity scale from 0, no evidence of infection, to 8, death. Overall, the median WHO Scale prior to NAC was 6.5, and increased by day seven, which indicated clinical worsening. This retrospective case series showed no benefit of NAC; however, further studies are needed to elucidate if differences in drug regimens would lead to positive results.