enigma

Allerede tidlig i pandemiens forløp var det klart at det reseptfrie og billige medikamentet N-Acetyl Cysteine (Acetylcystein, Bronkyl, Mucomyst) hadde effekt ved Covid-19 infeksjon. Vel så interessent er å se på virkninger av NAC på  sekundære effekter fra spikeproteinet som mRNA vaksinen leder til ukontrollert og uforutsigbar produksjon av.

NAC er i seg selv en skånsom behandling som kan administreres i form av både brusetabletter, intravenøs injeksjon og forstøver. Det er knyttet svært få bivirkninger til medikamentet som er bygget på aminosyren L-Cystein – en sentral komponent i dannelsen av kroppens viktigste antioksidant; glutation.

Man har sett at spikeproteinet spesielt utøver en toksisk effekt på hjerte og blodkarsystemet, både som følge av vaksinene og infeksjonen. Kardiolog og epidemiolog Peter A. McCullough påpeker for øvrig at man får en lengre eksposisjonsfase fra vaksinen grunnet det syntetisk stabiliserte RNA`et.

Gjentatte studier har sett på NAC relatert til Covid-19, influensa og sepsis. Virkningsmekanismene kan tilskrives disse effektene:

• Hemmer virusreplikasjon
• Antiinflammatorisk effekt
• Antioksidativ effekt
• Antitrombotisk effekt (motvirker blodpropp)
• Redusert forekomst av ARDS (svært alvorlig lungeinflammasjon)
• Beskytter mot organsvikt
• Redusert dødelighet
• Færre liggedøgn på sykehus og intensivavdelinger
• Færre respiratordøgn
• Forebygger cytokinstorm (inflammatorisk blodbilde)
• Reduserer mottakelighet for smitte

Utdrag fra forskningsartikler med relevans for tematikken:

“The novel coronavirus disease (COVID-19) is caused by a virus (SARS-Cov-2) and is known for inducing multisystem organ dysfunction associated with significant morbidity and mortality. Current therapeutic strategies for COVID-19 have failed to effectively reduce mortality rate, especially for elderly patients. A newly developed vaccine against SARS-Cov-2 has been reported to induce the production of neutralizing antibodies in young volunteers. However, the vaccine has shown limited benefit in the elderly, suggesting an age-dependent immune response. As a result, exploring new applications of existing medications could potentially provide valuable treatments for COVID-19. N-acetylcysteine (NAC) has been used in clinical practice to treat critically ill septic patients, and more recently for COVID-19 patients. NAC has antioxidant, anti-inflammatory and immune-modulating characteristics that may prove beneficial in the treatment and prevention of SARS-Cov-2. This review offers a thorough analysis of NAC and discusses its potential use for treatment of COVID-19.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649937/?fbclid=IwAR0hLLiEajt3LIFD-ouHN_n7nu1vGUo_yD8kkesPuiE-MiQo0HpuvUBlV9s

“The infection caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) resulted in a pandemic with huge death toll and economic consequences. The virus attaches itself to the human epithelial cells through noncovalent bonding of its spike protein with the angiotensin-converting enzyme-2 (ACE2) receptor on the host cell. We hypothesized that perturbing the functionally active conformation of spike protein through reduction of its solvent accessible disulfide bond, thereby disintegrating its structural architecture, may be a feasible strategy to prevent infection. Proteomics data showed that N-acetyl cysteine (NAC), an antioxidant and mucolytic agent been widely in use in clinical medicine, forms covalent conjugates with solvent accessible cysteine residues of spike protein that were disulfide bonded in the native state. In silico analysisindicated that this covalent conjugation perturbed the stereo specific orientations of the interacting key residues of spike protein that resulted in threefold weakening in the binding affinity of spike protein with ACE2 receptor. Antiviral assay using VeroE6 cells showed that NAC caused 54.3% inhibition in SARS-CoV-2 replication. Interestingly, almost all SARS-Cov-2 variants conserved cystine residues in the spike protein. Our observed results open avenues for exploring in vivo pharmaco-preventive and therapeutic potential of NAC for Coronavirus Disease 2019 (COVID-19).”

https://chemrxiv.org/engage/chemrxiv/article-details/60c753ec4c89190f3bad43ca

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.

https://www.sciencedirect.com/science/article/pii/S1876034122003021?via%3Dihub

N-Acetylcysteine (NAC) has been proposed to be used to treat Coronavirus Disease 2019 (COVID-19). By reviewing the existing pathological studies of COVID-19, it was found that abundant mucus secretion, formation of a hyaline membrane (supportive of acute respiratory distress syndrome), and interstitial fibrous exudation may be important characteristics of COVID-19 and pathological targets of drug therapy. In addition, multiple extrapulmonary organ injuries in COVID- 19 may be associated with cytokine storm. NAC is an important antioxidant and anti-inflammatory drug. NAC has been demonstrated to have mucolytic effects in bronchitis, relieve respiratory failure in acute respiratory distress syndrome, and inhibit fibrous exudation in interstitial lung disease in clinical studies. These findings suggest that NAC may have a therapeutic effect on the pathological targets of COVID-19. Furthermore, NAC decreases TNF-α, IL-1β, IL-6, IL-8, IL-10, and IL-17 serum levels in patients with sepsis, severe burns, acute liver failure, or peritoneal dialysis and may also reduce cytokine storm in COVID-19. The antiviral effect of NAC on other respiratory viruses may also benefit COVID-19 patients. Summarizing the potential mechanisms of NAC in treating COVID-19 suggests that the role of NAC in COVID-19 treatment is worthy of further research.

https://www.eurekaselect.com/article/112762

Patients receiving N-acetyl-l-cysteine (NAC) during hospitalisation for #SARSCoV2 pneumonia and discharged alive present a significantly shorter length of hospital stay compared to those who did not receive NAC

https://openres.ersjournals.com/content/8/1/00542-2021

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.

https://journals.sagepub.com/doi/10.1177/00368504221074574

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.

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.

https://brieflands.com/articles/jjnpp-129817.html

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.

https://www.jhsci.ba/ojs/index.php/jhsci/article/view/1156

Severe acute respiratory infection (SARI) caused by the SARS-CoV-2 virus may cause lung failure and the need for mechanical ventilation. Infection with SARS-COV-2 can lead to activation of inflammatory factors, increased reactive oxygen species, and cell damage. In addition to mucolytic effects, N-Acetylcysteine has antioxidant effects that we believe can help patients recover. In this study, we evaluate the efficacy of N-Acetylcysteine in patients with severe COVID-19.

https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-021-05242-4

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.

https://www.dovepress.com/n-acetylcysteine-as-adjuvant-therapy-for-covid-19–a-perspective-on-th-peer-reviewed-fulltext-article-JIR

Artikkel fra Fritt Vaksinevalg

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