Managing Severe Acute Asthma Exacerbation in Pregnancy during the COVID-19 Pandemic: A Case Report from a Resource-limited Setting

BACKGROUND: One-third of pregnant women will experience worsening asthma requiring emergency hospitalization. However, no report comprehensively discussed the management of asthma attacks in pregnant women in impoverished settings. We attempt to illuminate what general practitioners can do to stabilize and improve the outcome of severe acute asthma exacerbations in primary care with resource limitations. CASE REPORT: A nulliparous 29-year-old woman in her 21st week of pregnancy presented severe acute asthma exacerbation in moderate persistent asthma with uncontrolled asthma status along with gestational hypertension, uncompensated metabolic acidosis with a high anion gap, anemia, respiratory infection, and asymptomatic bacteriuria, all of which influenced her exacerbations. This patient was admitted to our resource-limited subdistrict hospital in Indonesia during the COVID-19 pandemic for optimal stabilization. Crystalloid infusions, oxygen supplementation, nebulized beta-agonist with anticholinergic agents, inhaled corticosteroids, intravenous methylprednisolone, broad-spectrum antibiotics, subcutaneous terbutaline, mucolytics, magnesium sulphate, oral antihypertensives, and continuous positive airway pressure were used to treat her life-threatening asthma. After she was stabilized, we referred the patient to a higher-level hospital with more advanced pulmonary management under the supervision of a multidisciplinary team to anticipate the worst scenario of pregnancy termination. CONCLUSION(S): Limitations in primary care, including the lack of sophisticated intensive care units and laboratory panels, may complicate challenges in managing severe acute asthma exacerbation during pregnancy. To enhance maternal-fetal outcomes, all multidisciplinary team members should be well-informed about key asthma management strategies during pregnancy using evidence-based guidelines regarding the drug, rationale, and safety profile.Copyright © 2023 Muhammad Habiburrahman, Triya Damayanti, Mohammad Adya Firmansha Dilmy, Hariyono Winarto.

L-Ornithine-L-Aspartate and Intermittent Renal Replacement Therapy in Fulminant Hepatitis A: A Case Report

Hepatitis A is a common viral infection worldwide that is transmitted via the fecal-oral route. Since the introduction of an efficient vaccine, the incidence of infection has decreased but the number of cases has risen due to widespread community outbreaks among unimmunized individuals. Classic symptoms include fever, malaise, dark urine, and jaundice, and are more common in older children and adults. People are often most infectious 14 days prior to and 7 days following the onset of jaundice. We will discuss the case of a young male patient, diagnosed with acute hepatitis A, leading to fulminant hepatitis refractory to conventional therapy and the development of subsequent kidney injury. The medical treatment through the course of hospitalization was challenging and included the use of L-ornithine-L-aspartate and prolonged intermittent hemodialysis, leading to a remarkable outcome. Hepatitis A is usually self-limited and vaccine-preventable;supportive care is often sufficient for treatment, and chronic infection or chronic liver disease rarely develops. However, fulminant hepatitis, although rare, can be very challenging to manage as in the case of our patient.Copyright © 2023 The Author(s).

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).

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.

Effect of N-acetyl cysteine in a patient cohort with severe or very severe COVID-19 pneumonia

Introduction: COVID-19, as of 9 June 2020, had been responsible for 404,396 deaths worldwide. Throughout the pandemic, IRCU and ICU directly cared for patients with severe or very severe respiratory failure due to COVID19 pneumonia. Objective(s): To determine if N-acetyl-cysteine (NAC) could be associated with lower mortality risk. Methodology: 1141 patients from March to May 2020 admitted to the ICU and IRCU of the Fundacion Jimenez Diaz were analysed. Patients with <3 days of hospital admission and those with CURB-65 equal to or <0 were excluded. A multivariate regression logistics models have been used to respond to our hypothesis and investigate the relationship between each variable and the mortality. Result(s): Of all patients analyzed, 44% received treatment with NAC associated with other drugs according to established protocols. Of these, 55% were male, most non-smokers with a mean age of 74.43 years. In table 2 we describe statistically significant predictive parameters associated with a decreased risk of mortality in severe or very severe patients with an area AUC of 0.80 Conclusion(s): Adjuvant treatment with NAC in severe or very severe COVID-19 pneumonia is associated with a significantly lower risk of mortality by 30% in elderly patients, principally males, and with associated co-morbidities.

Clinical experience with the alpha2A-adrenoceptor agonist, guanfacine, and N-acetylcysteine for the treatment of cognitive deficits in "Long-COVID19"

Background: Prolonged cognitive deficits ("brain fog") following COVID19 infection (long-COVID) are common and debilitating, yet there are currently no approved treatments. Cognitive impairment particularly targets the working memory and executive functions of the prefrontal cortex (PFC). The PFC has unusual neurotransmission and neuromodulation that render it vulnerable to stressors, and basic research has identified mechanisms that protect PFC connections. Based on the basic neuroscience data, we tried a combined open label treatment to bolster prefrontal function: the alpha2A-adrenoceptor agonist, guanfacine, which strengthens prefrontal connectivity, and the anti-oxidant, N- acetylcysteine (NAC), which protects mitochondria and reduces kynurenic acid blockade of NMDA receptors. Case report: Twelve patients with "brain fog" including difficulties in executive functions were treated with guanfacine (1mg, PO bedtime for the first month, increased to 2mg after 1 month, if well-tolerated) and 600 mg NAC daily. Guanfacine+NAC improved cognitive abilities in eight of the twelve patients;four patients discontinued therapy, two for unspecified reasons and two due to hypotension and/or dizziness, common side effects of guanfacine. Those who stayed on guanfacine+NAC reported improved working memory, concentration, and executive functions, including a resumption of normal workloads. One patient briefly stopped taking guanfacine due to a hypotensive episode and reported a return of cognitive deficits that abated with resumed guanfacine treatment. Conclusion(s): Although placebo-controlled trials will be needed to more rigorously demonstrate efficacy, as these agents have established safety, they may be immediately helpful in treating the large number of patients suffering from prolonged cognitive deficits following COVID19 infection.Copyright © 2022 The Author(s)

COVID19-Far from Over: Call for Urgent Novel and Advanced Measures

The COVID19 pandemic that started in late 2019 has already killed millions people, it is yet far from over and the road to the COVID-free world is much tougher than we all imagined;however, it ends at a vaccine functional against all coronaviruses. In this article, we try to present the aetiology behind evolution of superior pathogenicity of SARS-CoV-2 and point out fundamen-tal and highly hazardous loopholes in the current vaccination regimens and propose new vaccination strategies. We also suggest societal and personal level management that are necessary to en-sure prevention and better recovery outcomes until the arrival of the vaccine. In turn, we apprise the physician for long-term and stringent management of certain chronic diseases, avoiding pre-scribing certain drugs and suggesting physical exercises and diets that are fortified with specific mi-cronutrients.Copyright © 2022 Bentham Science Publishers.

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.

The effect of N-acetylcysteine as adjuvant therapy of hypoxemia in COVID-19 patients, assessed by interleukin-6 level and PaO2/FiO2 ratio

Background: Interleukin 6 (IL-6) is a cytokine that plays an essential role in lung damage and mortality. Arterial-to-inspired oxygen (PaO2/FiO2) ratio, also known as the Horowitz index, is a measure of hypoxemia in respiratory failure. N-Acetylcysteine (NAC) might be helpful in managing coronavirus disease 2019 (COVID-19) patients by decreasing the cytokine storm, which will lead to a decrease in disease severity. This study aims to analyze the effect of NAC as adjuvant therapy on IL-6 level and PaO2/FiO2 ratio in COVID-19 patients. Methods: This is a quasi-experimental, non-equivalent control group designed study of confirmed COVID-19 patients moderate to critical in Saiful Anwar Hospital Malang. Seventy-five patients received NAC intravenously 5000 mg/72 hours as adjuvant therapy for seven days, and 16 subjects in the control group. IL-6 level and PaO2/FiO2 ratio were measured on day one and day 8 in both groups from blood samples. Wilcoxon, Mann-Whitney U Test, and Pearson correlation were conducted for statistical analysis. Results: The decrease in IL-6 level on days 1 to 8 in the NAC group is significantly lower (94.49+or-253.51) than in the control group (P=0.002). The increase in PaO2/FiO2 ratio from day 1 to day 8 in the NAC group is significantly improving (126.94+or-76.05), the same as the control group (P < 0.001). There is a weak correlation between IL-6 level and PaO2/FiO2 ratio after administration of NAC (r=0.154, P=0.186). Conclusion: There is a significant decrease in IL-6 level after administration of NAC. NAC has no significant effect on hypoxemia in COVID-19 patients.

Hemoperfusion that was popular during the COVID-19 pandemic: A case series

The medical world has been seeking solutions in solving the Coronavirus disease 2019 (COVID-19) outbreak since 2019. Amongst several alter-natives, hemoperfusion therapy has been reported to be beneficial for alleviating symptoms and reducing mortality in severely ill COVID-19 patients. Hemoperfusion is a process of filtering blood to eliminate toxins and inflammatory factors from the body. This case series aims to high-light the unexpected adverse clinical and labora-tory outcomes in the majority of COVID-19 patients treated with hemoperfusion in our hospi-tal. We included fifteen patients admitted to the Intensive Care Unit (ICU) with moderate-to-se-vere COVID-19 between August and December 2020 and were all given two to four sessions of hemoperfusion using the MG150 cartridge. All ten men and five women showed no improve-ment in their neutrophil-lymphocyte ratio (NLR), ferritin, D-dimer, and C-reactive protein (CRP) values after the hemoperfusion regiments, both survivors and non-survivors. In addition, eleven out of twelve patients with respiratory failure who were then intubated resulted in death. Based on our findings and previous evi-dence, we recommended only performing hemoperfusion for investigational instead of therapeutic purposes due to its poorly under-stood pathophysiology in COVID-19. We also recommended further research regarding the us-age of hemoperfusion in COVID-19 patients, es-pecially in the matter of determining the best time to start the therapy.Copyright © 2023, The Indonesian Foundation of Critical Care Medicine. All rights reserved.

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.

Efficacy and safety of acetylcysteine for the prevention of liver injury in COVID-19 intensive care unit patients under treatment with remdesivir.

Aim: The present double-blinded placebo-controlled randomized clinical trial evaluated prophylactic use of acetylcysteine for the prevention of liver injury in patients with severe COVID-19 pneumonia under treatment with remdesivir. Background: Liver injury is reportedly common in patients with severe COVID-19 pneumonia and can occur not only as a result of disease progression, but as an iatrogenic reaction to remdesivir. Methods: A total of 83 adult patients with severe COVID-19 pneumonia were randomly assigned in parallel groups to receive either acetylcysteine or placebo. All the patients received standard care according to institutional protocols, including remdesivir for a total of five days. One gram acetylcysteine was administered intravenously every 12 hours for 42 patients, and 41 patients received the same volume of 0.9% sodium chloride as placebo (Trial Registration: www.irct.ir identifier, IRCT20210726051995N1). Results: After 5 days, median aspartate transaminase (AST) and alanine transaminase (ALT) levels were significantly lower in the acetylcysteine than in the placebo group. Of those who received the placebo, 30 (73.2%), 4 (9.7%), and 3 (7.3%) patients had serum AST levels elevated between 1-2.5, 2.5-5, and over 5 times the upper limit of normal (ULN), respectively; while in the acetylcysteine group, 33 (78.6%) and 0 patients had AST levels between 1-2.5 and over 2.5 times ULN, respectively (p-value=0.037). In the acetylcysteine group, 23 (54.8%), 1 (2.4%), and 1 (2.4%) patient had serum ALT levels elevated between 1-2.5, 2.5-5, and over 5 times ULN, respectively; in the placebo group, however, 24 (58.5%), 7 (17.1%), and 1 (2.4%) patient had serum ALT levels between 1-2.5, 2.5-5, and over 5 times ULN, respectively (p-value=0.073). Conclusion: Intravenous administration of acetylcysteine significantly prevents liver transaminases elevation and liver injury in seriously ill COVID-19 patients treated with remdesivir.

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.