METHYLENE BLUE FOR TREATMENT OF HOSPITALIZED COVID-19 PATIENTS: A RANDOMIZED, CONTROLLED, OPEN-LABEL CLINICAL TRIAL, PHASE 2.

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.

Evaluation of oral nano-curcumin efficacy on respiratory function and quality of life in patients with bronchial non-atopic asthma: A randomized controlled trial.

Objective: Asthma is a common disease and curcumin has modest effect in inflammatory disorders. This study investigated the efficacy of nano-curcumin on asthma. Materials and Methods: In this double-blinded randomized clinical trial, 60 patients with non-atopic bronchial asthma were randomly stratified in two groups of intervention (N=30) and control (N=30) groups. Apart from their standard treatment, the intervention group received 40 mg nano-curcumin (soft gel) three times daily while the control group received placebo. During the 60-day study, patients were assessed using spirometry to measure Forced expiratory volume in first second (FEV1). Asthma control test (ACT) was completed every 30 days and asthma quality of life questionnaire (AQLQ) was completed at the first and end of the study. Results: Totally, 31 patients (51.7%) were male and the mean age was 51.45±12.58 years. FEV1 was improved but there was no significant difference between intervention and control groups. ACT and AQLQ domains scores significantly improved. However, it was not statistically different between control and intervention groups. Conclusion: Nano-curcumin at administered dosage had no additive effect on the standard treatment in asthmatic patients.

Clinical characteristics of 200 COVID-19 patients in Mashhad, Iran, February and March 2020.

Introduction: Coronavirus disease 2019 (COVID-19) is a pulmonary involvement which was reported for the first time in December 2019 in the city of Wuhan, Hubei province, China. The aim of the study was to describe the demographic, clinical, laboratory, and radiological characteristics of 204 definitive laboratory-confirmed COVID-19 patients hospitalized in Mashhad, Khorasan Razavi province, Iran. Patients and Methods: This study was performed on 204 laboratory-confirmed COVID-19 patients. A set of laboratory tests combined with various patient information and results from lung high-resolution computed tomography (HRCT) were gathered in a checklist and analyzed to give us a better view of patients who are hospitalized due to the complications caused by this disease. Results: The average age of our patients was 58.83 ± 15.93 years. There were 122 (59.8%) male and 82 (40.2%) female patients, and almost all of our patients had at least one underlying disease. Nine (4.4%) of our patients reported having gone for a trip to COVID-19-epidemic areas in the last 2 weeks. The most common signs shared among all our patients were cough, fever, and decreased O2 saturation; the average respiratory rate was 25.50 ± 6.74/min, average axillary body temperature was 37.69°C ± 0.69°C, and average O2 saturation was 88.34% ± 7.34%. Conclusion: Based on our results, the most common signs of this disease are fever, cough, and shortness of breath, similar to seasonal influenza. Our data on disease severity showed that 33 (16.2%) patients had moderate disease, 139 (68.1%) had severe disease, and 28 (13.7%) were critical; 22 (10.8%) of our hospitalized patients died due to the complications of this disease.

Comparative Study of Vascular Endothelial Growth Factor in Exudative and Transudative Pleural Effusion.

Background: Increased vascular permeability is one of the main mechanisms in the production of pleural effusion (PE) and vascular endothelial growth factor (VEGF) has a significant role in its pathogenesis. This study aimed to compare pleural levels of VEGF in transudative and exudative PEs besides the other pleural markers. Materials and Methods: In this prospective cross-sectional study, 80 patients with PE were divided into 4 groups as transudative (N=15), parapneumonic (N=15), tuberculosis (N=25), and malignant (N=25) PE. Biochemical tests measured the pleural protein, LDH, cholesterol, glucose, polymorphonuclear cell (PMN), and lymphocyte. ELISA measured the pleural VEGF level. Results: Out of 80 patients, 51 were male, and the total mean age was 55.34±18.53. There were significant differences in pleural VEGF between exudative and transudative effusion (P<0.001) and between malignant and benign effusion (P=0.014). The highest mean difference in pleural VEGF levels was seen in the comparison of transudative and malignant groups (Mean difference=-136.56; P<0.002). The VEGF level in 3 groups was not significantly different; transudative vs tuberculous, parapneumonic vs tuberculous, and parapneumonic vs malignant. Furthermore, VEGF higher than 73.09 pg/ml had a 64% sensitivity and 82% specificity for the diagnosis of malignancy. Among pleural markers (VEGF, protein, LDH, and glucose), VEGF had the highest area under curve (AUC=0.734). Moreover, pleural protein, LDH, and glucose levels significantly correlated with pleural VEGF; however, pleural cholesterol, PMN, and lymphocyte were not correlated. Conclusion: VEGF is assumed as an important factor in the pathogenesis of exudative PE, especially malignant effusion. It can distinguish between lymphocytic exudative PEs.

Clinical features and disease severity in an Iranian population of inpatients with COVID-19.

Coronavirus disease 2019 (COVID-19) can present with a variety of symptoms. Severity of the disease may be associated with several factors. Here, we review clinical features of COVID-19 inpatients with different severities. This cross-sectional study was performed in Imam Reza hospital, Mashhad, Iran, during February-April 2020. COVID-19 patients with typical computed tomography (CT) patterns and/or positive reverse-transcriptase polymerase chain reaction (RT-PCR) were included. The patients were classified into three groups of moderate, severe, and critical based on disease severity. Demographic, clinical, laboratory, and radiologic findings were collected and compared. P < 0.05 was considered statistically significant. Overall, 200 patients with mean age of 69.75 ± 6.39 years, of whom 82 (41%) were female were studied. Disease was severe/critical in the majority of patients (167, 83.5%). Disease severity was significantly associated with age, malignant comorbidities, dyspnea, nausea/vomiting, confusion, respiratory rate, pulse rate, O2 saturation, extent of CT involvement, serum C-reactive protein (CRP), pH, pO2, and aspartate transaminase (P < 0.05). Moreover, complications including shock, coagulopathy, acidosis, sepsis, acute respiratory distress syndrome (ARDS), intensive care unit (ICU) admission, and intubation were significantly higher in patients with higher severities (P < 0.05). O2 saturation, nausea/vomiting, and extent of lung CT involvement were independent predictors of severe/critical COVID-19 (OR 0.342, 45.93, and 25.48, respectively; P < 0.05). Our results indicate O2 saturation, nausea/vomiting, and extent of lung CT involvement as independent predictors of severe COVID-19 conditions. Serum CRP levels and pO2 were also considerably higher patients with higher severity and can be used along with other factors to predict severe disease in COVID-19 patients.

Efficacy and safety of convalescent plasma therapy in severe COVID-19 patients with acute respiratory distress syndrome.

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.

Thrombotic events in COVID-19 patients: A case series and literature review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has rapidly emerged as a threatening pandemic. Clinical features of this pandemic involve a wide range of manifestations and are not completely known. Here, we present six cases of thrombotic events in patients with COVID-19. CASE PRESENTATION: In this case series, we present six patients with confirmed COVID-19, according to real-time polymerase chain reaction, who were referred to our emergency department and were found to have thrombotic events. Pulmonary thromboembolism was diagnosed in three patients by computed tomography (CT) angiography. One patient was found to have deep vein thrombosis in Doppler ultrasonography. Another patient who presented with loss of consciousness was finally diagnosed with a cerebrovascular accident using brain CT. One of the patients had developed a myocardial infarction evident on the electrocardiogram. CONCLUSION: It is ostensible that COVID-19 puts the patients at an increased risk for developing thrombotic conditions, possibly through formation of hyper-inflammatory and hyper-coagulative states. However, further prospective studies are recommended to confirm these findings.

Methylene blue for treatment of hospitalized Covid-19 patients: a randomized, controlled, open-label clinical trial, phase 2

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