Radoslav Bilyukov

The successful use of bromhexine hydrochloride (BRH) for COVID-19 prevention led us to apply the same method for flu prevention. The goal of this study is to observe whether BRH could protect people against influenza.This is non-interventional, observational, questionnaire-based survey. General practitioners informed their patients to take BRH 8 mg twice per day for at least 3 weeks if they want. The mean participant age was 58.9 years (95% CI: 57.4–60.5), with a median of 62 years, indicating that the sample predominantly consisted of individuals over 60 years of age.The average number of comorbidities was 0.98, and the mean duration of prophylactic use was 80 days (95% CI: 76.7–83.7). The reported influenza incidence within the sample was 10.6%.Influenza incidence among individuals taking BRH prophylactically was significantly lower compared to national data (36.15%). Longer use was associated with a modest reduction in risk. The number of comorbidities remained the strongest predictor of influenza occurrence. Age had no significant impact among those using BRH prophylactically. The model demonstrated good discriminative ability but limited calibration, and the results should be interpreted cautiously.

Colchicine has an excellent basis for being effective against COVID-19 due to its anti-inflammatory, immunomodulatory, and cardioprotective effects, as well as its role in preventing microvascular thrombosis. In addition, colchicine also has antiviral effects, an extremely favorable safety profile, and–since it does not exert any overt immunosuppressive activity–does not interfere with effective viral clearance, nor is it associated with the occurrence of secondary infections. However, all studies to date on the effects of low-dose colchicine for COVID-19 treatment are conflicting and rather disappointing. As colchicine has the remarkable ability to accumulate intensively in leukocytes–where the cytokine storm is generated–we initiated high but safe doses of colchicine for COVID-19 patient treatment. Our assumption was that a safe increase in colchicine dosage to reach micromolar concentrations in leukocytes would result in NLRP3 inflammasome/cytokine storm inhibition and would enhance its antiviral effect by inducing microtubule dissociation. Outpatients’ high-dose colchicine treatment practically prevents hospitalizations. Total colchicine uptake analysis demonstrates an inverse relationship with hospitalization. The duration of colchicine uptake also shows an inverse relationship with hospitalization and post-COVID-19 symptoms. Unlike the WHO-recommended antiviral preparations molnupiravir, remdesivir, and paxlovid, colchicine–in addition to its antiviral effect–prevents the cytokine storm and therefore has a strong effect not only in outpatients but also in inpatients. Unlike antivirals, colchicine significantly reduces post-COVID-19 symptoms. The side effects of colchicine are similar to those of paxlovid. The price of colchicine is incomparably lower, and it is also easily available.

Colchicine has an excellent basis for being effective against COVID-19 due to its anti-inflammatory, immunomodulatory, cardioprotective effects, and prevention of microvascular thrombosis. In addition colchicine has also antiviral effect, extremely favorable safety profile and since it does not exert any overt immunosuppressive activity, does not interfere with the effective viral clearing nor is associated with the occurrence of secondary infections.However, all studies to date on the effects of colchicine with low doses for COVID-19 treatment are conflicting and rather disappointing.As colchicine has the remarkable ability to accumulate intensively in leukocytes, where the cytokine storm is generated, we started high, but save doses colchicine for COVID-19 patient treatment. Our assumption was that a safe increase in colchicine doses to reach micromolar concentrations in leukocytes will result in NLRP3 inflammasome/cytokine storm inhibition and will enhance its antiviral effect by inducing microtubule dissociation.Outpatients’ high-dose colchicine treatment practically prevents hospitalizations. The total colchicine uptake analysis demonstrates reverse relationship with hospitalization. The period of colchicine uptake analysis demonstrates reverse relationship with hospitalization and post-COVID-19 symptomatics. Unlike the WHO-recommended antiviral preparations molnupiravir, remdesivir and paxlovid, colchicine, in addition to its antiviral effect, prevents the cytokine storm, and therefore has a strong effect not only in outpatients, but also in inpatients. Unlike antivirals, colchicine significantly reduces post-COVID-19 symptoms. The side effects of colchicine are similar to those of paxlovide. Colchicine price is incomparably lower and it is also easily available.

Introduction: Our study aimed to analyze virus-specific humoral immune responses in COVID-19 patients with varying disease severity. Methodology: A total of 109 serum samples from 87 patients, symptomatic for COVID-19 were studied using anti-SARS-CoV-2 immunoassays detecting different classes of immunoglobulins. Results: Clinical samples were divided into 2 groups - collected up to and more than 2 weeks post-onset of symptoms (PoS). In the first group, the highest percentage of positive samples was found for IgA class virus-specific antibodies (78.1%), followed by IgM (71.9%/59.4%) and IgG (56.3%/53.1%). In the second group, samples positive for virus-specific IgA class antibodies were also the most (97.7%) along with those positive for IgG. A total of 72 IgA and/or IgM and/or IgG positive samples were further tested for SARS-CoV-2 neutralizing antibodies (NAbs) - 89.1% and 100% of samples obtained up to and after 2 weeks PoS, respectively were positive. Serological test results were also analyzed depending on the severity of the disease - SARS-CoV-2 positive samples in mild forms of COVID-19 were fewer than in moderate and severe forms but this difference was not statistically significant. Conclusions: SARS-CoV-2 specific antibodies and a high virus neutralization capacity of these antibodies appear early PoS; Immunoglobulins of IgA class are of most significant diagnostic value for detection of SARS-CoV-2 infection; Timing of testing is the most important factor for positivity rate.

An otherwise healthy, 35-year-old man was hospitalized for the management of acute respiratory failure due to coronavirus disease 2019 (COVID-19)-related severe bilateral pneumonia and acute respiratory distress syndrome (ARDS). The patient therapeutic regimen included the widely accepted standard combination of oxygen, anticoagulation therapy; corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), and antibiotics. A novel combination of colchicine, hymecromone, and bromhexine inhalations was added to the therapeutic regimen as part of our unique COVID-19 management institutional protocol. COVID-19-related severe bilateral pneumonia and acute respiratory distress syndrome (ARDS). The patient therapeutic regimen included the widely accepted standard combination of oxygen, anticoagulation therapy, corticosteroids, NSAIDs, and antibiotics. A novel combination of colchicine, hymecromone, and bromhexine inhalations was added to the therapeutic regimen as part of our unique COVID-19 management institutional protocol. Rapid clinical response on day 2, with a significant improvement of radiographic pulmonary changes on day 5, and improvement of laboratory results on days 5-7 were observed. The administration of inhalatory bromhexine in combination with high-dose colchicine and hymecromone was crucial for the positive outcome of the disease. This treatment regimen resulted in a four to five-fold decrease in the mortality of hospitalized patients.

Asthma-COPD overlap (ACO) is a disorder that combines clinical signs of bronchial asthma and COPD - fixed airways obstruction and/or significant reversibility of the bronchial obstruction, rapid progression, poor quality of life, higher mortality, frequent and severe exacerbations compared to COPD and asthma alone. The aim of our study is to determine the neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-6 (IL-6) plasma levels and to analyze their association with peripheral eosinophilia and exacerbations of patients with asthma-COPD overlap (ACO), Chronic obstructive pulmonary disease (COPD) and asthma. Our results, based on 81 patients, indicate that the plasma levels of NGAL and IL-6 are significantly elevated in ACO and are associated with blood eosinophilia and exacerbations. NGAL and IL-6 may be useful biomarkers for differentiation of patients with frequent exacerbations and ACO.

Sleep-related breathing disorders could be accompanied by or caused by a variety of medical conditions. They are considered to be a significant medical and social problem. Together with excessive daytime sleepiness, patients with obstructive sleep apnea experience neuropsychological symptoms such as anxiety, attention deficits, cognitive impairment, depressive symptoms and other psychological disturbances leading to social adjustment difficulties. Patients diagnosed with obstructive sleep apnea demonstrate a decline in a wide spectrum of cognitive abilities, including memory, attention, psychomotor speed, executive, verbal and visual-spatial skills. The aim of this study is to investigate the cognitive functioning and affective disorders among patients with obstructive sleep apnea syndrome and to examine the frequency and severity of cases in comparison with a control group consisting of healthy volunteers. Our research has shown that there is a relation between sleep apnea and cognitive impairments and affective changes. This relation can be explained by the direct effect of the syndrome on the patient, where the main connecting factor is the severity and the distribution of excessive daytime sleepiness. Along with treatment of the somatic medical condition, it is extremely important that the patient's mental state is treated as well. Trial Registration: 57/2013, Medical University - Sofia, Bulgaria.

Normal circadian rhythm in Obstructive Sleep Apnea (OSA) is impaired by changes in various hormones and the Vitamin D level related with them: Aim: To evaluate parathyroid hormone (PTH) and 25-hydroxyvitamin D (25(OH) D) serum levels in patients with newly diagnosed OSA in the winter: Materials and Methods: From December 2015 to February 2016 50 people were included in a prospective study – 30 patients with OSA (24 men, 6 women), mean age 49.91 ± 14.15 years, and 20 healthy controls (12 men, 8 women; 53.54 ± 11.57 years). Polysomnography, assessment of daytime sleepiness, blood tests, including 25(OH) D and PTH, were performed: Results: There were no significant differences in the demographic data between both groups. Patients with OSA had significantly higher serum levels of PTH (5.93 ± 1.82 pmol/L), compared to controls (3.13 ± 0.97 pmol/L), p<0.001. We found low levels of 25(OH) D (deficiency) in both groups (18.90 ± 8.36 nmol/L in the OSA patients versus 19.80 ± 13.69 nmol/L in the controls). The average oxygen desaturation during sleep in the OSA patients with 25(OH) D above and below 25 nmol/L differs significantly (12.50 ± 5.41 % versus 7.60 ± 3.72 %, p = 0.036). We found a significant negative correlation (r = - 0.398, p = 0.036) between the lower levels 25(OH) D (severe deficiency) and the average oxygen desaturation: Conclusions: OSA can lead to vitamin D deficiency and secondary hyperparathyroidism that requires CPAP and substitutional therapy.

The diagnosis of pulmonary embolism (PE) is usually determined by a combination of clinical investigations, D-dimer assay, and different imaging tests. The aim of this study was to compare the diagnostic value of perfusion lung scintigraphy in SPECT and low-dose CT (SPECT/CT), and Computed tomography pulmonary angiography (CTPA) for patients with suspected PE. Material and Methods: In a prospective one-year study 76 hospitalized patients suspected for PE were included. Clinical assessment, D –dimer assay, perfusion SPECT/CT and CTPA were carried out. Results: PE was diagnosed in 50 of 76 patients (66%) by perfusion SPECT/CT and 26 of 76 patients (34%) by CTPA. The sensitivity and specificity of perfusion SPECT/CT was 93%, respectively 64%. For CTPA they are 54%, respectively 93%. There is no significant difference regarding the diagnosis of PE at subsegmental and segmental level between both used methods. The sensitivity of perfusion SPECT/CT is significantly higher compared with CTPA, while the specificity is significantly higher at CTPA for diagnosis of PE. Conclusion: The perfusion SPECT/CT has an excellent diagnostic performance and should therefore be considered first-line imaging in the work up of PE in most cases.

Obstructive sleep apnea syndrome (OSAS) is associated with increased risk of different cardiovascular complications such as arterial hypertension, ischemic heart disease, rhythm disorders. Pericardial effusion (PE) is common condition in patients with OSAS, but usually in correlation with respiratory failure and pulmonary arterial hypertension (PAH). The aim of the study is to evaluate the presence of PE in OSAS patients without PAH and/or daily hypoxemia, and to assess the possible factors associated with it. 279 consecutive patients (162 men and 117 women, mean age 42.76 ± 12.44 years) with newly diagnosed OSAS were included. Different laboratory tests, 2-D echocardiography with Doppler-sonography to exclude other diseases that can lead to chronic PE were provided in all patients. PE was found in 102 (36.56%) of the patients.The mean effusion volume was small (150-250 ml). The PE significantly correlated with severity of OSA (r = 0.374, p<0.001), body mass index (r=0.473, p<0.001) and duration of sleep desaturation (r = 0.289, p<0.001). Persistent pericardial effusion is common in patients with OSAS. Although it is usually not life-threatening condition, the PE could be very resistant to treatment. The exact mechanisms for the development of PE in many patients with OSAS are still unclear but the correlation with obesity and desaturation time during sleep show that PE may be as a result of chronic low-grade inflammation and elevated systemic oxidative stress.