Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 28
Filter
1.
Eur Rev Med Pharmacol Sci ; 26(2): 715-721, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1675570

ABSTRACT

OBJECTIVE: As N-acetylcysteine (NAC) is promising as a re-purposed drug for the adjunctive or supportive treatment of serious COVID-19, this article aimed to describe current evidence. MATERIALS AND METHODS: A search was performed in PubMed/Medline for "NAC", "viral Infection", COVID-19", oxidative stress", "inflammation", retrieving preclinical and clinical studies. RESULTS: NAC is a pleiotropic molecule with a dual antioxidant mechanism; it may neutralize free radicals and acts as a donor of cysteine, restoring the physiological pool of GSH. Serious COVID-19 patients have increased levels of reactive oxygen species (ROS) and free radicals and often present with glutathione depletion, which prompts a cytokine storm. NAC, which acts as a precursor of GSH inside cells, has been currently used in many conditions to restore or protect against GSH depletion and has a wide safety margin. In addition, NAC has anti-inflammatory activity independently of its antioxidant activity. CONCLUSIONS: Clinical and experimental data suggest that NAC may act on the mechanisms leading to the prothrombotic state observed in severe COVID-19.


Subject(s)
Acetylcysteine/therapeutic use , COVID-19/drug therapy , Acetylcysteine/chemistry , Antioxidants/chemistry , COVID-19/metabolism , COVID-19/virology , Glutathione/chemistry , Glutathione/metabolism , Humans , Oxidative Stress , Randomized Controlled Trials as Topic , Reactive Oxygen Species/metabolism , SARS-CoV-2/isolation & purification , Virus Diseases/drug therapy , Virus Diseases/metabolism
2.
Arch Ital Urol Androl ; 93(4): 465-467, 2021 Dec 21.
Article in English | MEDLINE | ID: covidwho-1597211

ABSTRACT

Male infertility is an important factor accounting for 40-50% of infertility cases that may be due to disturbance in one of the parameters as concentration, motility and morphology observed in one or two semen analysis with an interval of 1 and 4 weeks. COVID-19 may affect male fertility through virus division, cytotoxic effects on testicular tissue and immunopathological effect. N-acetyl cysteine (NAC) improved sperm concentration and acrosome reaction while reducing reactive oxygen species (ROS) and oxidation of sperm DNA. This interventional study was conducted on 200 men who were referred to private infertility clinics for female factor (their previous semen analysis was normal) and got COVID-19 infection in the last 3 months showing an impairment of the latest semen analysis due to COVID. Men were placed in two groups of control (n = 100) and intervention (NAC consumption). Subjects who got COVID-19 infection had a significant impairment of sperm quality (sperm concentration, sperm motility, and normal sperm morphology) compared to their semen analysis evaluated before the COVID-19 infection. NAC consumption significantly improved sperm total motility, sperm morphology and sperm concentration. COVID-19 infection has a negative effect on sperm parameters. NAC supplementation may have positive effect on sperm parameters.


Subject(s)
COVID-19 , Infertility, Male , Acetylcysteine/therapeutic use , Female , Humans , Infertility, Male/drug therapy , Male , SARS-CoV-2 , Semen , Semen Analysis , Sperm Count , Sperm Motility , Spermatozoa
3.
Ann Hepatol ; 24: 100340, 2021.
Article in English | MEDLINE | ID: covidwho-1453997

ABSTRACT

The role of N-acetylcysteine (NAC) in the treatment of acetaminophen induced acute liver injury (ALI) is well established but its role in non-acetaminophen induced ALI is still elusive. We conducted this meta-analysis to evaluate the role of NAC in non-acetaminophen induced ALI. We searched electronic databases for studies published till Oct 25, 2020. We used RevMan v5.4 software to analyze the data extracted from selected studies by using Covidence systematic review software. Outcome estimation was done using Odds Ratio (OR) with 95% confidence interval (CI). The heterogeneity in various studies was determined using the I2 test. A total of 11 studies were included in quantitative analysis. Use of NAC in non-acetaminophen induced ALI showed 53% reduction in mortality compared to standard of care (OR, 0.47; CI, 0.29-0.75) and reduced mean duration of hospital stay by 6.52 days (95% CI, -12.91 to -0.13). Similarly, the rate of encephalopathy was 59% lower in the treatment group (OR, 0.41; CI, 0.20-0.83). However, the risk of developing nausea and vomiting (OR, 3.99; CI, 1.42-11.19), and the need for mechanical ventilation (OR 3.88; CI, 1.14-13.29) were significantly higher in the treatment group. These findings conclude use of NAC decreases mortality and hepatic encephalopathy compared to standard of care in patients with non-acetaminophen induced ALI. Although there is an increased risk of nausea and vomiting with the use of NAC, the majority of adverse events are transient and minor.


Subject(s)
Acetylcysteine/therapeutic use , Free Radical Scavengers/therapeutic use , Liver Failure, Acute/chemically induced , Liver Failure, Acute/drug therapy , Humans , Length of Stay , Liver Failure, Acute/mortality , Standard of Care , Survival Rate
4.
Infect Dis (Lond) ; 53(11): 847-854, 2021 11.
Article in English | MEDLINE | ID: covidwho-1286520

ABSTRACT

BACKGROUND: N-acetyl-cysteine (NAC) has been previously shown to exert beneficial effects in diverse respiratory diseases, through antioxidant and anti-inflammatory actions. Our aim was to evaluate NAC potential impact in hospitalised patients with COVID-19 pneumonia, in terms of progression to severe respiratory failure (SRF) and mortality. PATIENTS AND METHODS: This retrospective, two-centre cohort study included consecutive patients hospitalised with moderate or severe COVID-19 pneumonia. Patients who received standard of care were compared with patients who additionally received NAC 600 mg bid orally for 14 days. Patients' clinical course was recorded regarding (i) the development of SRF (PO2/FiO2 <150) requiring mechanical ventilation support and (ii) mortality at 14 and 28 days. RESULTS: A total of 82 patients were included, 42 in the NAC group and 40 in the control group. Treatment with oral NAC led to significantly lower rates of progression to SRF as compared to the control group (p < .01). Patients in the NAC group presented significantly lower 14- and 28-day mortality as compared to controls (p < .001 and p < .01 respectively). NAC treatment significantly reduced 14- and 28-day mortality in patients with severe disease (p < .001, respectively). NAC improved over time the PO2/FiO2 ratio and decreased the white blood cell, CRP, D-dimers and LDH levels. In the multivariable logistic regression analysis, non-severe illness and NAC administration were independent predictors of 28-days survival. CONCLUSION: Oral NAC administration (1200 mg/d) in patients with COVID-19 pneumonia reduces the risk for mechanical ventilation and mortality. Our findings need to be confirmed by properly designed prospective clinical trials.


Subject(s)
COVID-19 , Respiration, Artificial , Acetylcysteine/therapeutic use , Cohort Studies , Humans , Prospective Studies , Retrospective Studies , SARS-CoV-2
5.
Pharmacol Rep ; 73(6): 1650-1659, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1265619

ABSTRACT

BACKGROUND: We designed this single-centre clinical trial to assess the potential benefits of N-Acetylcysteine (NAC) in patients with COVID19-associated acute respiratory distress syndrome (ARDS). METHODS: Ninety-two patients with mild-to-moderate COVID19-associated ARDS were allocated to the placebo (45-cases) or NAC groups (47-cases). Besides standard-of-care treatment, the patients received either intravenous NAC at a dose of 40 mg/kg/day or the placebo for three consecutive days. The efficacy outcomes were overall mortality over 28-day, clinical status on day 28, based on the WHO Master Protocol, the proportion of patients requiring mechanical ventilation, changes in ARDS-severity (based on the PaO2/FiO2 ratio), and Sequential Organ Failure Assessment (SOFA) scores 48 and 96 h after intervention, RESULTS: No differences were found in the 28-day mortality rate between the two groups (25.5% vs. 31.1% in the NAC and placebo groups, respectively). Although the distribution of the clinical status at day 28 shifted towards better outcomes in the NAC-treated group, it did not reach a statistical significance level (p value = 0.83). Similar results were achieved in terms of the proportion of patients who required invasive ventilator support (38.3% vs. 44.4%), the number of ventilator-free days (17.4 vs. 16.6), and median time of ICU and hospital stay. Results regarding the change in PaO2/FiO2 ratio and SOFA scores also showed no significant differences between the groups. CONCLUSIONS: Our pilot study did not support the potential benefits of intravenous NAC in treating patients with COVID-19-associated ARDS. More studies are needed to determine which COVID-19 patients benefit from the NAC administration. TRIAL REGISTRATION: The trial was registered at Clinicaltrials.gov (identifier code: IRCT20120215009014N355). Registration date: 2020-05-18.


Subject(s)
Acetylcysteine/therapeutic use , COVID-19/complications , COVID-19/drug therapy , Respiratory Distress Syndrome/drug therapy , Acetylcysteine/administration & dosage , Acetylcysteine/adverse effects , Administration, Intravenous , Adult , Aged , Aged, 80 and over , Double-Blind Method , Female , Humans , Male , Middle Aged , Mortality , Pilot Projects , Prospective Studies , SARS-CoV-2 , Severity of Illness Index , Treatment Outcome
6.
Clin Infect Dis ; 72(11): e736-e741, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1249285

ABSTRACT

BACKGROUND: A local increase in angiotensin 2 after inactivation of angiotensin-converting enzyme 2 by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may induce a redox imbalance in alveolar epithelium cells, causing apoptosis, increased inflammation and, consequently, impaired gas exchange. We hypothesized that N-acetylcysteine (NAC) administration could restore this redox homeostasis and suppress unfavorable evolution in patients with coronavirus disease 2019 (COVID-19). METHODS: This was a double-blind, randomized, placebo-controlled, single-center trial conducted at the Emergency Department of Hospital das Clínicas, São Paulo, Brazil, to determine whether NAC in high doses can avoid respiratory failure in patients with COVID-19. We enrolled 135 patients with severe COVID-19 (confirmed or suspected), with an oxyhemoglobin saturation <94% or respiratory rate >24 breaths/minute. Patients were randomized to receive NAC 21 g (~300 mg/kg) for 20 hours or dextrose 5%. The primary endpoint was the need for mechanical ventilation. Secondary endpoints were time of mechanical ventilation, admission to the intensive care unit (ICU), time in ICU, and mortality. RESULTS: Baseline characteristics were similar between the 2 groups, with no significant differences in age, sex, comorbidities, medicines taken, and disease severity. Also, groups were similar in laboratory tests and chest computed tomography scan findings. Sixteen patients (23.9%) in the placebo group received endotracheal intubation and mechanical ventilation, compared with 14 patients (20.6%) in the NAC group (P = .675). No difference was observed in secondary endpoints. CONCLUSIONS: Administration of NAC in high doses did not affect the evolution of severe COVID-19. CLINICAL TRIALS REGISTRATION: Brazilian Registry of Clinical Trials (REBEC): U1111-1250-356 (http://www.ensaiosclinicos.gov.br/rg/RBR-8969zg/).


Subject(s)
COVID-19 , Acetylcysteine/therapeutic use , Brazil , COVID-19/drug therapy , Double-Blind Method , Humans , Respiration, Artificial , SARS-CoV-2 , Treatment Outcome
7.
Trials ; 22(1): 271, 2021 Apr 12.
Article in English | MEDLINE | ID: covidwho-1181123

ABSTRACT

OBJECTIVES: 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. TRIAL DESIGN: This is a prospective, randomized, single-blinded, phase 3 controlled clinical trial with two arms (ratio 1:1) parallel-group design of 40 patients, using the placebo in the control group. PARTICIPANTS: All severe COVID-19 patients with at least one of the following five conditions: (respiration rate > 30 per minute), hypoxemia (O2 ≤ saturation, arterial oxygen partial pressure ratio <300), pulmonary infiltration (> 50% of lung area during 24 48 h), Lactate dehydrogenase (LDH) > 245 U / l, Progressive lymphopenia, and admitted to the intensive care unit of Shahid Mohammadi Hospital in Bandar Abbas and have positive PCR test results for SARS-Cov-2 and sign the written consent of the study will be included. Patients will be excluded from the study if they have a history of hypersensitivity to N-Acetylcysteine, pregnancy, or refuse to participate in the study. INTERVENTION AND COMPARATOR: After randomization, participants in the intervention group receive standard of care (SOC) according to the National Committee of COVID-19 plus N-acetylcysteine (EXI-NACE 200mg/mL, in 10mL ampules of saline for parenteral injection (EXIR pharmaceutical company)) at a dose of 300 mg/kg equivalent to 20 gr as a slow single intravenous injection on the first day of hospitalization. In the control group patients receive SOC and placebo ( Sterile water for injection as the same dose). The placebo is identical in appearance to the N-acetylcysteine injection (EXIR pharmaceutical company as well). MAIN OUTCOMES: The primary endpoint for this study is a composite endpoint for the length of hospitalization in the intensive care unit and the patient's clinical condition. These outcomes were measured at the baseline (before the intervention) and on the 14th day after the intervention or on the discharge day. RANDOMISATION: Eligible participants (40) will be randomized in two arms in the ratio of 1: 1 (20 per arm) using online web-based tools and by permuted block randomization method. To ensure randomization concealment, random sequence codes are assigned to patients by the treatment team at the time of admission without knowing that each code is in the intervention or comparator group. BLINDING (MASKING): All participants will be informed about participating in the study and the possible side effects of medication and placebo. Patients participating in the study will not be aware of the assignment to the intervention or control group. The principal investigator, health care personnel, data collectors, and those evaluating the outcome are aware of patient grouping. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 40 patients participate in this study, which are randomly divided; 20 patients in the intervention group will receive SOC and N-acetylcysteine, 20 patients in the control group will receive SOC and placebo. TRIAL STATUS: First version of the protocol was approved by the Deputy of Research and Technology and the ethics committee of Hormozgan University of Medical Sciences on February 14, 2021, with the local code 990573, and the recruitment started on March 2, 2021 and the expected recruitment end date is April 1, 2021. TRIAL REGISTRATION: The protocol was registered before starting participant recruitment entitled: Evaluation of the efficacy of N-Acetylcysteine in severe COVID-19 patients: a randomized controlled phase III clinical trial, IRCT20200509047364N3 , at Iranian Registry of clinical trials on 20 February 2021. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).


Subject(s)
Acetylcysteine/therapeutic use , Antioxidants/therapeutic use , COVID-19/drug therapy , Clinical Trials, Phase III as Topic , Humans , Iran , Prospective Studies , Randomized Controlled Trials as Topic , Treatment Outcome
8.
Eur Rev Med Pharmacol Sci ; 25(6): 2802-2807, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1173130

ABSTRACT

Since November 2019, SARS Coronavirus 2 disease (COVID-19) pandemic has spread through more than 195 nations worldwide. Though the coronavirus infection affects all age and sex groups, the mortality is skewed towards the elderly population and the cause of death is mostly acute respiratory distress syndrome (ARDS). There are data suggesting the role of excessive immune activation and cytokine storm as the cause of lung injury in COVID-19. The excessive immune activation and cytokine storm usually occurs due to an imbalance in redox homeostasis of the individuals. Considering the antioxidant and free radical scavenging action of N acetyl cysteine (NAC), its use might be useful in COVID-19 patients by decreasing the cytokine storm consequently decreasing the disease severity. Therefore, we reviewed all the available resources pertaining to the role of reactive oxygen species (ROS) in cytokine storm and the mechanism of action of NAC in preventing ROS. We also reviewed the use of NAC in COVID-19.


Subject(s)
Acetylcysteine/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Cytokine Release Syndrome/prevention & control , SARS-CoV-2/drug effects , COVID-19/immunology , COVID-19/virology , Cytokine Release Syndrome/virology , Humans , Prognosis
9.
Vopr Virusol ; 66(1): 40-46, 2021 03 07.
Article in Russian | MEDLINE | ID: covidwho-1120830

ABSTRACT

INTRODUCTION: Analysis of the pathogenesis of coronavirus infection caused SARS-CoV-2 indicates a significant impact of hemorheological disorders on its course and outcomes. It is known that chronic cardiovascular diseases are associated with the risk of severe course and lethal outcomes both in COVID-19 and other infectious diseases. Therefore, in each case it is necessary to study the interaction and mutual influence of different components of the treatment program prescribed to such patients.The purpose of this work was to evaluate the effect of coagulation activity on the course of a novel coronavirus infection (COVID-19) and to justify the management of comorbid patients having been received novel oral anticoagulants (NOACs) in previously selected doses according to indications in concomitant somatic diseases. MATERIAL AND METHODS: Total 76 cases of confirmed coronavirus infection in patients who had been received initial therapy on an outpatient basis were analyzed. 26 patients who received NOACs (rivaroxaban, apixaban, dabigatran) made up the main group and 50 - the comparison (control) group in which patients had not been administered any drugs that affect blood clotting until the episode of COVID-19. All patients have been prescribed therapy following the Provisional guidelines «Prevention, diagnosis and treatment of coronavirus infection (COVID-19)¼ (https://static-0.minzdrav.gov.ru/system/attachments/attaches/). RESULTS AND DISCUSSION: The number of hospitalizations was significantly fewer in the group of patients who had been received NOACs (19 vs. 66% in the control group). No deaths or cases of severe respiratory and/or renal failure were observed in the main group, while adverse outcomes were noted in 14% of patients who had not been administered these drugs. CONCLUSION: Taking NOACs reduces the probability of severe course and adverse outcomes in the development of coronavirus infection caused by SARS-CoV-2, which indicates a significant contribution of coagulation mechanisms to the pathogenesis in COVID-19. There were no indications for drug replacement and correction of anticoagulant therapy regimens in patients who received adequate therapy with oral anticoagulants for treating a non-severe form of coronavirus infection in ambulatory patient settings.


Subject(s)
Anticoagulants/therapeutic use , Atrial Fibrillation/drug therapy , COVID-19/drug therapy , Coronary Disease/drug therapy , Disseminated Intravascular Coagulation/drug therapy , Hypertension/drug therapy , Intracranial Arteriosclerosis/drug therapy , Acetylcysteine/therapeutic use , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , Atrial Fibrillation/diagnosis , Atrial Fibrillation/mortality , Atrial Fibrillation/virology , Azithromycin/therapeutic use , COVID-19/mortality , COVID-19/pathology , COVID-19/virology , Cohort Studies , Comorbidity , Coronary Disease/diagnosis , Coronary Disease/mortality , Coronary Disease/virology , Dabigatran/therapeutic use , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/mortality , Disseminated Intravascular Coagulation/virology , Female , Humans , Hypertension/diagnosis , Hypertension/mortality , Hypertension/virology , Indoles/therapeutic use , Interferon alpha-2/therapeutic use , Intracranial Arteriosclerosis/diagnosis , Intracranial Arteriosclerosis/mortality , Intracranial Arteriosclerosis/virology , Male , Middle Aged , Pyrazoles/therapeutic use , Pyridones/therapeutic use , Rivaroxaban/therapeutic use , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity , Severity of Illness Index , Survival Analysis
10.
BMJ Case Rep ; 14(1)2021 Jan 18.
Article in English | MEDLINE | ID: covidwho-1066836

ABSTRACT

This case represents a rare fulminant course of fried-rice associated food poisoning in an immunocompetent person due to pre-formed exotoxin produced by Bacillus cereus, with severe manifestations of sepsis, including multi-organ (hepatic, renal, cardiac, respiratory and neurological) failure, shock, metabolic acidosis, rhabdomyolysis and coagulopathy. Despite maximal supportive measures (continuous renal replacement therapy, plasmapheresis, N-acetylcysteine infusion and blood products, and broad-spectrum antimicrobials) and input from a multidisciplinary team (consisting of infectious diseases, intensive care, gastroenterology, surgery, toxicology, immunology and haematology), mortality resulted. This case is the first to use whole genome sequencing techniques to confirm the toxigenic potential of B. cereus It has important implications for food preparation and storage, particularly given its occurrence in home isolation during the COVID-19 pandemic.


Subject(s)
Bacillus cereus/genetics , Exotoxins/genetics , Foodborne Diseases/diagnosis , Acetylcysteine/therapeutic use , Acidosis/physiopathology , Acidosis/therapy , Adult , Anti-Arrhythmia Agents/therapeutic use , Anti-Bacterial Agents/therapeutic use , Arrhythmias, Cardiac/physiopathology , Arrhythmias, Cardiac/therapy , Bacillus cereus/isolation & purification , Blood Coagulation Disorders/physiopathology , Blood Coagulation Disorders/therapy , Blood Transfusion , Brain Diseases , Continuous Renal Replacement Therapy , Fatal Outcome , Female , Foodborne Diseases/microbiology , Foodborne Diseases/physiopathology , Foodborne Diseases/therapy , Free Radical Scavengers/therapeutic use , Humans , Immunocompetence , Liver Failure/physiopathology , Liver Failure/therapy , Multiple Organ Failure/physiopathology , Multiple Organ Failure/therapy , Plasmapheresis , Renal Insufficiency/physiopathology , Renal Insufficiency/therapy , Rhabdomyolysis/physiopathology , Rhabdomyolysis/therapy , Sepsis/physiopathology , Sepsis/therapy , Shock/physiopathology , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Whole Genome Sequencing
11.
Curr Pharm Biotechnol ; 22(12): 1584-1590, 2021.
Article in English | MEDLINE | ID: covidwho-999940

ABSTRACT

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-1ß, 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.


Subject(s)
COVID-19 , Coronavirus Infections , Acetylcysteine/therapeutic use , COVID-19/drug therapy , Humans , SARS-CoV-2
12.
Eur J Pharmacol ; 885: 173494, 2020 Oct 15.
Article in English | MEDLINE | ID: covidwho-959753

ABSTRACT

COVID-19 is a global catastrophic event that causes severe acute respiratory syndrome. The mechanism of the disease remains unclear, and hypoxia is one of the main complications. There is no currently approved protocol for treatment. The microbial threat as induced by COVID-19 causes the activation of macrophages to produce a huge amount of inflammatory molecules and nitric oxide (NO). Activation of macrophages population into a pro-inflammatory phenotype induces a self-reinforcing cycle. Oxidative stress and NO contribute to this cycle, establishing a cascade inflammatory state that can kill the patient. Interrupting this vicious cycle by a simple remedy may save critical patients' lives. Nitrite, nitrate (the metabolites of NO), methemoglobin, and prooxidant-antioxidant-balance levels were measured in 25 ICU COVID-19 patients and 25 healthy individuals. As the last therapeutic option, five patients were administered methylene blue-vitamin C-N-acetyl Cysteine (MCN). Nitrite, nitrate, methemoglobin, and oxidative stress were significantly increased in patients in comparison to healthy individuals. Four of the five patients responded well to treatment. In conclusion, NO, methemoglobin and oxidative stress may play a central role in the pathogenesis of critical COVID-19 disease. MCN treatment seems to increase the survival rate of these patients. Considering the vicious cycle of macrophage activation leading to deadly NO, oxidative stress, and cytokine cascade syndrome; the therapeutic effect of MCN seems to be reasonable. Accordingly, a wider clinical trial has been designed. It should be noted that the protocol is using the low-cost drugs which the FDA approved for other diseases. TRIAL REGISTRATION NUMBER: NCT04370288.


Subject(s)
Acetylcysteine/therapeutic use , Ascorbic Acid/therapeutic use , Clinical Trials, Phase I as Topic , Coronavirus Infections/drug therapy , Critical Illness , Methylene Blue/therapeutic use , Pneumonia, Viral/drug therapy , COVID-19 , Compassionate Use Trials , Coronavirus Infections/complications , Female , Humans , Hypoxia/complications , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications
13.
J Med Virol ; 92(10): 2238-2242, 2020 10.
Article in English | MEDLINE | ID: covidwho-935131

ABSTRACT

A healthy patient presented to Klinikum Altmühlfranken Weißenburg Hospital, Germany, with two morning attacks of painful muscle spasm in the left upper and lower limbs, without altered consciousness. Full examinations, radiological imaging, electroencephalography, lumbar puncture, and autoimmune profile were either normal or not consistent with patient's complaint. Subsequent epileptic episodes were observed on admission day and the following days; thus, the patient was diagnosed with focal epilepsy. The patient started to develop a fever and severe cough on day 4, and SARS-coronavirus-2 was confirmed through a nasopharyngeal swap. She received anticonvulsants and symptomatic treatments and completely recovered. This report emphasizes the potential nervous system involvement in severe acute respiratory syndrome-coronavirus-2 pathogenesis.


Subject(s)
COVID-19/complications , Epilepsies, Partial/complications , SARS-CoV-2/pathogenicity , Acetaminophen/therapeutic use , Acetylcysteine/therapeutic use , Aged , Ambroxol/therapeutic use , Anticonvulsants/therapeutic use , COVID-19/diagnostic imaging , COVID-19/drug therapy , COVID-19/virology , Cough/diagnosis , Cough/physiopathology , Dipyrone/therapeutic use , Epilepsies, Partial/diagnostic imaging , Epilepsies, Partial/drug therapy , Epilepsies, Partial/virology , Female , Fever/diagnosis , Fever/physiopathology , Humans , Nasopharynx/virology , Radiography, Abdominal , Treatment Outcome
14.
Medicine (Baltimore) ; 99(42): e22577, 2020 Oct 16.
Article in English | MEDLINE | ID: covidwho-933919

ABSTRACT

RATIONALE: The new coronavirus pneumonia Corona Virus Disease 2019 (COVID-19) has become a global pandemic. Patients with critically COVID-19 usually require invasive respiratory support, and the airway management is particularly important and the prognosis is poor. PATIENT CONCERNS: A 64-year-old man with an anastomotic fistula after radical treatment of esophageal cancer and right-side encapsulated pyopneumothorax was admitted with cough and dyspnea. DIAGNOSIS: The patient was diagnosed with novel coronavirus pneumonia and right-side encapsulated pyopneumothorax by pharyngeal swab nucleic acid test in combination with chest computed tomography (CT). INTERVENTIONS: The patient was treated with antibiotics, antiviral and antibacterial medications, respiratory support, expectorant nebulization, and nutritional support. But he expressed progressive deterioration. Endotracheal intubation and mechanical ventilation were performed since the onset of the type - respiratory failure on the 13th day of admission. The patient had persistent refractory hypercapnia after mechanical ventilation. Based on the treatment mentioned above, combined with repeated bronchoalveolar lavage by using N-acetylcysteine (NAC) inhalation solution, the patients refractory hypercapnia was gradually improved. OUTCOMES: The patient was cured and discharged after being given the mechanical ventilation for 26 days as well as 46 days of hospitalization, currently is surviving well. LESSONS: Patients with severe conditions of novel coronavirus pneumonia often encounter bacterial infection in their later illness-stages. They may suffer respiratory failure and refractory hypercapnia that is difficult to improve due to excessive mucus secretion leading to small airway obstruction. This study provided a new insight on the proper treatment severe COVID-19 patients. The use of reasonable antibiotics and symptomatic respiratory support and other treatment, timely artificial airway and repeated bronchoalveolar NAC inhalation solution lavage, expectorant and other airway management are essential for such patients.


Subject(s)
Acetylcysteine/therapeutic use , Airway Management/methods , Bronchoalveolar Lavage/methods , Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Acetylcysteine/administration & dosage , Administration, Inhalation , Anastomosis, Surgical , Betacoronavirus , COVID-19 , Coronavirus Infections/complications , Humans , Intubation, Intratracheal/methods , Length of Stay , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications , Pneumothorax/complications , Respiration, Artificial , SARS-CoV-2
16.
Pharmacotherapy ; 40(11): 1166-1171, 2020 11.
Article in English | MEDLINE | ID: covidwho-812649

ABSTRACT

Remdesivir is a direct-acting nucleoside RNA polymerase inhibitor with activity against the novel severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) virus used in the treatment of coronavirus disease 2019 (COVID-19) pneumonia. Here, we present two cases of suspected remdesivir-associated acute liver failure (ALF) in which the liver failure improved after continuous infusion acetylcysteine and withdrawal of remdesivir. Both patients had significant increases in transaminases between day 3 and day 10 of remdesivir therapy accompanied by coagulopathy and encephalopathy. After initiation of continuous infusion acetylcysteine, the transaminases of both patients rapidly improved. Ultimately, one patient fully recovered while the other died of suspected septic shock. Due to its novel nature and only recent widespread use, there are very little data on the risk of ALF from remdesivir. Additionally, the data for the use of acetylcysteine to manage non-acetaminophen-induced ALF are limited. It is important to consider the risk of remdesivir-associated ALF when weighing the risk versus benefits of use, and acetylcysteine may have a role in its management.


Subject(s)
Acetylcysteine/therapeutic use , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/adverse effects , COVID-19/drug therapy , Liver Failure, Acute/drug therapy , Acetylcysteine/administration & dosage , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/therapeutic use , Aged , Aged, 80 and over , Alanine/administration & dosage , Alanine/adverse effects , Alanine/therapeutic use , Antiviral Agents/administration & dosage , Antiviral Agents/therapeutic use , Fatal Outcome , Female , Humans , Liver Failure, Acute/chemically induced , Liver Failure, Acute/diagnosis , Liver Function Tests , SARS-CoV-2 , Treatment Outcome
20.
FASEB J ; 34(10): 13185-13193, 2020 10.
Article in English | MEDLINE | ID: covidwho-704967

ABSTRACT

COVID-19 may cause pneumonia, acute respiratory distress syndrome, cardiovascular alterations, and multiple organ failure, which have been ascribed to a cytokine storm, a systemic inflammatory response, and an attack by the immune system. Moreover, an oxidative stress imbalance has been demonstrated to occur in COVID-19 patients. N- Acetyl-L-cysteine (NAC) is a precursor of reduced glutathione (GSH). Due to its tolerability, this pleiotropic drug has been proposed not only as a mucolytic agent, but also as a preventive/therapeutic agent in a variety of disorders involving GSH depletion and oxidative stress. At very high doses, NAC is also used as an antidote against paracetamol intoxication. Thiols block the angiotensin-converting enzyme 2 thereby hampering penetration of SARS-CoV-2 into cells. Based on a broad range of antioxidant and anti-inflammatory mechanisms, which are herein reviewed, the oral administration of NAC is likely to attenuate the risk of developing COVID-19, as it was previously demonstrated for influenza and influenza-like illnesses. Moreover, high-dose intravenous NAC may be expected to play an adjuvant role in the treatment of severe COVID-19 cases and in the control of its lethal complications, also including pulmonary and cardiovascular adverse events.


Subject(s)
Acetylcysteine/therapeutic use , Antioxidants/therapeutic use , COVID-19 , SARS-CoV-2/metabolism , Virus Internalization/drug effects , Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/drug therapy , COVID-19/metabolism , COVID-19/pathology , Chemotherapy, Adjuvant , Humans , Oxidative Stress/drug effects
SELECTION OF CITATIONS
SEARCH DETAIL