ABSTRACT
We present a unique case of a male veteran with a history of Castleman disease, presenting with multiple arterial and venous vascular thromboses in the setting of recent Coronavirus (COVID-19)-disease diagnosis. We explore this patient's morbidity related to thrombotic complications of his COVID-19 diagnosis that were potentially avoidable with a comprehensive outpatient evaluation of his risk for thrombosis, as well as the initiation of anticoagulation and/or antiplatelet therapy given his high risk. Our case highlights the need for a standardized clinical workup of patients in the outpatient setting for risk assessment of vascular thrombosis associated with COVID-19 infection to direct medical management, in order to minimize adverse outcomes, complications requiring inpatient admission, and the need for additional yet limited medical resources and interventions. We propose a minimum of low-dose aspirin 81 mg daily as a reasonable approach for outpatient clinicians to consider, based on their best clinical judgement, when managing mild COVID-19, while other options, such as novel oral anticoagulants, are undergoing further investigation.
ABSTRACT
Bromhexine is a potential therapeutic option in COVID-19, but no data from a randomized clinical trial has been available. The present study aimed to evaluate the efficacy of bromhexine in intensive care unit (ICU) admission, mechanical ventilation, and mortality in patients with COVID-19. Methods: An open-label randomized clinical trial study was performed in Tabriz, NorthWest of Iran. They were randomized to either the treatment with the bromhexine group or the control group, in a 1:1 ratio with 39 patients in each arm. Standard therapy was used in both groups and those patients in the treatment group received oral bromhexine 8 mg three times a day additionally. The primary outcome was a decrease in the rate of ICU admissions, intubation/ mechanical ventilation, and mortality. Results: A total of 78 patients with similar demographic and disease characteristics were enrolled. There was a significant reduction in ICU admissions (2 out of 39 vs. 11 out of 39, P = 0.006), intubation (1 out of 39 vs. 9 out of 39, P = 0.007) and death (0 vs. 5, P = 0.027) in the bromhexine treated group compared to the standard group. No patients were withdrawn from the study because of adverse effects. Conclusion: The early administration of oral bromhexine reduces the ICU transfer, intubation, and the mortality rate in patients with COVID-19. This affordable medication can easily be administered everywhere with a huge positive impact(s) on public health and the world economy. Altogether, the verification of our results on a larger scale and different medical centers is strongly recommended.
ABSTRACT
BACKGROUND: Bromhexine is a potent inhibitor of transmembrane serine protease 2 and appears to have an antiviral effect in controlling influenza and parainfluenza infection; however, its efficacy in COVID-19 is controversial. METHODS: A group of hospitalized patients with confirmed COVID-19 pneumonia were randomized using 1:1 allocation to either standard treatment lopinavir/ritonavir and interferon beta-1a or bromhexine 8 mg four times a day in addition to standard therapy. The primary outcome was clinical improvement within 28 days, and the secondary outcome measures were time to hospital discharge, all-cause mortality, duration of mechanical ventilation, the temporal trend in 2019-nCoV reverse transcription-polymerase chain reaction positivity and the frequency of adverse drug events within 28 days from the start of medication. RESULTS: A total of 111 patients were enrolled in this randomized clinical trial and data from 100 patients (48 patients in the treatment arm and 52 patients in the control arm) were analyzed. There was no significant difference in the primary outcome of this study, which was clinical improvement. There was no significant difference in the average time to hospital discharge between the two arms. There were also no differences observed in the mean intensive care unit stay, frequency of intermittent mandatory ventilation, duration of supplemental oxygenation or risk of death by day 28 noted between the two arms. CONCLUSION: Bromhexine is not an effective treatment for hospitalized patients with COVID-19. The potential prevention benefits of bromhexine in asymptomatic postexposure or with mild infection managed in the community remain to be determined.
ABSTRACT
SARS-CoV-2 is a worldwide pandemic, that has led to the morbidity and mortality of millions of people. This virus rapidly proliferates and destroys lung epithelial cells directly, which is worsened by a subsequent cytokine storm. This cytokine storm diffusely damages the alveolar barriers and leads to fibrin and fluid exudation, hyaline membrane formation, and infiltration of inflammatory cells into the lung causing acute respiratory distress syndrome (ARDS). To date, there exists no medication to treat SARS-CoV-2 infection and novel new therapeutics are still being explored to prevent or limit the damage to the lung. Sphingosine 1-phosphate (S1P) is an effective bioactive lipid mediator and its related signaling pathways are vital for endothelial cell integrity. Stabilizing the pulmonary endothelial barrier and decreasing the inflammatory infiltrate by S1P analogs such as Fingolimod (FTY720-P) would be a new therapeutic approach for the hindrance of pulmonary exudation and subsequent ARDS.