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1.
J Stroke Cerebrovasc Dis ; 30(12): 106121, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1415617

ABSTRACT

BACKGROUND: There is little information regarding the safety of intravenous tissue plasminogen activator (IV-tPA) in patients with stroke and COVID-19. METHODS: This multicenter study included consecutive stroke patients with and without COVID-19 treated with IV-tPA between February 18, 2019, to December 31, 2020, at 9 centers participating in the CASCADE initiative. Clinical outcomes included modified Rankin Scale (mRS) at hospital discharge, in-hospital mortality, the rate of hemorrhagic transformation. Using Bayesian multiple regression and after adjusting for variables with significant value in univariable analysis, we reported the posterior adjusted odds ratio (OR, with 95% Credible Intervals [CrI]) of the main outcomes. RESULTS: A total of 545 stroke patients, including 101 patients with COVID-19 were evaluated. Patients with COVID-19 had a more severe stroke at admission. In the study cohort, 85 (15.9%) patients had a hemorrhagic transformation, and 72 (13.1%) died in the hospital. After adjustment for confounding variables, discharge mRS score ≥2 (OR: 0.73, 95% CrI: 0.16, 3.05), in-hospital mortality (OR: 2.06, 95% CrI: 0.76, 5.53), and hemorrhagic transformation (OR: 1.514, 95% CrI: 0.66, 3.31) were similar in COVID-19 and non COVID-19 patients. High-sensitivity C reactive protein level was a predictor of hemorrhagic transformation in all cases (OR:1.01, 95%CI: 1.0026, 1.018), including those with COVID-19 (OR:1.024, 95%CI:1.002, 1.054). CONCLUSION: IV-tPA treatment in patients with acute ischemic stroke and COVID-19 was not associated with an increased risk of disability, mortality, and hemorrhagic transformation compared to those without COVID-19. IV-tPA should continue to be considered as the standard of care in patients with hyper acute stroke and COVID-19.


Subject(s)
COVID-19/complications , Fibrinolytic Agents/administration & dosage , Ischemic Stroke/drug therapy , Thrombolytic Therapy , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/mortality , Disability Evaluation , Europe , Female , Fibrinolytic Agents/adverse effects , Hospital Mortality , Humans , Infusions, Intravenous , Intracranial Hemorrhages/chemically induced , Iran , Ischemic Stroke/complications , Ischemic Stroke/diagnosis , Ischemic Stroke/mortality , Male , Middle Aged , Risk Assessment , Risk Factors , Thrombolytic Therapy/adverse effects , Thrombolytic Therapy/mortality , Time Factors , Treatment Outcome
2.
Rev Invest Clin ; 73(3): 190-198, 2021.
Article in English | MEDLINE | ID: covidwho-1239310

ABSTRACT

BACKGROUND: There is no pharmacological intervention on the treatment of hypoxemia and respiratory distress in COVID-19 patients. OBJECTIVE: The objective of the study was to study the effect of the reduced form of methylene blue (MB) on the improvement of oxygen saturation (SpO2) and respiratory rate (RR). METHODS: In an academic medical center, 80 hospitalized patients with severe COVID-19 were randomly assigned to receive either oral MB along with standard of care (SOC) (MB group, n = 40) or SOC only (SOC group, n=40). The primary outcomes were SpO2 and RR on the 3rd and 5th days. The secondary outcomes were hospital stay and mortality within 28 days. RESULTS: In the MB group, a significant improvement in SpO2 and RR was observed on the 3rd day (for both, p < 0.0001) and also the 5th day (for both, p < 0.0001). In the SOC group, there was no significant improvement in SpO2 (p = 0.24) and RR (p = 0.20) on the 3rd day, although there was a significant improvement of SpO2 (p = 0.002) and RR (p = 0.01) on the 5th day. In the MB group in comparison to the SOC group, the rate ratio of increased SpO2 was 13.5 and 2.1 times on the 3rd and 5th days, respectively. In the MB group compared with the SOC group, the rate ratio of RR improvement was 10.1 and 3.7 times on the 3rd and 5th days, respectively. The hospital stay was significantly shortened in the MB group (p = 0.004), and the mortality was 12.5% and 22.5% in the MB and SOC groups, respectively. CONCLUSIONS: The addition of MB to the treatment protocols significantly improved SpO2 and respiratory distress in COVID-19 patients, which resulted in decreased hospital stay and mortality. ClinicalTrials.gov: NCT04370288.


Subject(s)
COVID-19/drug therapy , Methylene Blue/therapeutic use , Adult , Aged , Female , Hospitalization , Humans , Male , Middle Aged
3.
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
4.
Int Immunopharmacol ; 93: 107239, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-957148

ABSTRACT

Since SARS-CoV-2 infection is rapidly spreading all around the world, affecting many people and exhausting health care resources, therapeutic options must be quickly investigated in order to develop a safe and effective treatment. The present study was designed to evaluate the safety and efficacy of convalescent plasma (CP) for treating severe cases of COVID-19 who developed acute respiratory distress syndrome (ARDS). Among 64 confirmed cases of severe COVID-19 with ARDS in this study, 32 patients received CP besides first line treatment. Their clinical response and outcome in regard to disease severity and mortality rate were evaluated and compared with the other 32 patients in the control group who were historically matched while randomly chosen from previous patients with the same conditions except for receiving CP therapy. Analysis of the data was performed using SPSS software. Patients with plasma therapy showed improvements in their clinical outcomes including a reduction in disease severity in terms of SOFA and APACHE II scores, the length of ICU stay, need for noninvasive ventilation and intubation and also showed an increase in oxygenation. They also showed reduction in mortality which was statistically significant in less severe cases with mild or moderate ARDS. Early administration of the convalescent plasma could successfully contribute to the treatment of severe COVID-19 patients with mild or moderate ARDS at risk of progressing to critical state.


Subject(s)
COVID-19/therapy , Respiratory Distress Syndrome/therapy , Adult , Aged , Antiviral Agents/therapeutic use , COVID-19/immunology , COVID-19/virology , Female , Humans , Immunization, Passive/adverse effects , Immunization, Passive/methods , Male , Middle Aged , Respiratory Distress Syndrome/immunology , Respiratory Distress Syndrome/virology , SARS-CoV-2/isolation & purification , Severity of Illness Index , Treatment Outcome , Young Adult
5.
Arch Bone Jt Surg ; 8(Suppl1): 291-294, 2020 Apr.
Article in English | MEDLINE | ID: covidwho-621858

ABSTRACT

The severe acute respiratory syndrome caused by COVID-19 is now a global catastrophic event. Currently there is no approved drug or vaccine for the disease. Methylene blue (MB, oxidized form, blue color) has been used in many different areas of clinical medicine, ranging from malaria to orthopedics. Leucomethylene Blue (reduced form of MB, colorless) may be applied for the treatment of COVID-19 according to the scientific evidences. In severe patients, there is a cytokine storm (hyperinflammation) and high oxidative stress (OS). Inflammation and OS has a mutual correlation and exacerbate each other. In human body, MB first induces OS through absorbing electron (like a free radical) from other molecules, if the body could counteract to this OS, then reduced MB decreases OS through other mechanisms. Reduced MB could prevent inflammation, propagation of the virus RNA, and also improves hypoxia through reducing methemoglobin. Therefore, to avoid the increment of OS, we suggest using Leucomethylene Blue through the following protocol: The IV cocktail contains 50 mg MB (1mg/kg, 50-kg weight), 1000-2000 mg vitamin C, 500-1000 mg N-Acetylcysteine (or glutathione or cysteine or α-lipoic acid) and 10-20 gr urea (optional) in 100 ml dextrose 5%. Before the injection, the cocktail should be kept in a dark place for 1-2 hour to become fade or colorless.

6.
Ocul Immunol Inflamm ; 28(5): 739-744, 2020 Jul 03.
Article in English | MEDLINE | ID: covidwho-610309

ABSTRACT

PURPOSE: To evaluate ocular findings in patients with Coronavirus Disease 2019 (COVID-19) in the Northeast of Iran. METHODS: In a cross-sectional, observational study all consecutive patients with confirmed COVID-19 diagnosis at the central referral center of these patients in northeast of Iran were included. Ocular examinations (external and slit) were randomly performed for the patients who were admitted to the Intensive Care Unit (ICU) and six COVID wards of the hospital. Moreover, Chart records and serum chemistry results were collected. RESULTS: A total of 142 patients with the mean age of 62.6 ± 15 years (range: 23-96 years) and almost equal gender distribution (male: N = 77, 54.2%) were included in the study. During the initial external examination by the ophthalmologist, 44 (31%) patients were found to have conjunctival hyperemia and 22 (15.5%) patients had chemosis. Consecutive slit examination showed 41 (28.9%) conjunctival hyperemia, 22 (15.5%) chemosis, 11 (7.7%) cataract, and 9 (6.3%) diabetic retinopathy. The patients with at least one ocular manifestation had significantly higher blood urea levels at the time of admission compared to those with no obvious ocular involvement (median: 41.5, IQR: 28-66.3 vs. median: 33, IQR: 23.8-51.8, P = .023). Moreover, a significant difference was observed in the total white blood cell count, lymphocyte percent, neutrophil count, Erythrocyte Sedimentation Rate (ESR), and blood urea level between patients with positive and negative Polymerase Chain Reaction (PCR) for SARS-CoV-2 virus. None of the patients reported ocular symptoms prior to systemic involvement. The proportion of patients with at least one ocular manifestation was significantly higher in those admitted in the ICU compared to the non-ICU wards. wards. While conjunctival hyperemia was the most prevalent ocular finding in all patients, chemosis was the most common ocular manifestation in ICU admitted patients. CONCLUSION: Ocular manifestation was observed in more than half of our COVID-19 patients. Hence, it seems important to involve ophthalmologist in the diagnosis and management of these patients.


Subject(s)
Betacoronavirus/pathogenicity , Conjunctivitis, Viral/diagnosis , Coronavirus Infections/diagnosis , Eye Infections, Viral/diagnosis , Pneumonia, Viral/diagnosis , Adult , Aged , Aged, 80 and over , COVID-19 , Conjunctivitis, Viral/epidemiology , Coronavirus Infections/epidemiology , Cross-Sectional Studies , Eye Infections, Viral/epidemiology , Female , Hospitalization , Humans , Hyperemia/diagnosis , Hyperemia/epidemiology , Iran/epidemiology , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , SARS-CoV-2 , Slit Lamp Microscopy , Young Adult
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