Is elevated ENA-78 serum level a link between obstructive sleep apnea and atherosclerosis?

Obstructive sleep apnea (OSA) is a risk factor for cardiovascular disease, inflammation, and oxidative stress. This study compared serum levels of different factors in patients with carotid artery stenosis and with or without coexisting OSA. It also aimed to identify a molecule that may be crucial for the inflammatory process correlated with intermittent hypoxia. Sixty-eight subjects scheduled for surgical treatment of carotid artery stenosis were enrolled. Polygraphy was performed the night before the surgery. Morning levels of proinflammatory cytokines and chemotactic and angiogenic factors were measured. The most profound differences between the groups were found for ENA-78 serum concentration. However, as many factors could affect the results, further studies are needed to investigate the role of ENA-78 in atherosclerosis in patients suffering from OSA.

Efficacy of oral amantadine among patients hospitalised with COVID-19: A randomised, double-blind, placebo-controlled, multicentre study.

BACKGROUND: Amantadine has been proposed as a treatment for COVID-19 because it shows anti-SARS-CoV-2 activity in vitro. However, to date, no controlled study has assessed the safety and efficacy of amantadine in COVID-19. RESEARCH QUESTION: Whether amantadine is effective and safe among patients with different COVID-19 severity classifications. STUDY DESIGN: and Methods: This was multi-centre, randomised, placebo-controlled study.Patients with oxygen saturation ≤94% and no need for high-flow oxygen or ventilatory support were randomly allocated to receive oral amantadine or placebo (1:1) for 10 days in addition to standard care. The primary endpoint was time to recovery assessed over 28 days since randomisation, defined as discharge from hospital or no need for supplemental oxygen. RESULTS: The study was terminated early due to a lack of efficacy after an interim analysis. Final data from 95 patients who received amantadine (mean age, 60.2 years; 65% male; 66% with comorbidities) and 91 patients who received placebo (mean age, 55.8 years; 60% male; 68% with comorbidities) were obtained. The median (95% CI) time to recovery was 10 days both in the amantadine (9-11) and placebo arms (8-11; subhazard ratio = 0.94 [95%CI 0.7-1.3]). The percentage of deaths and percentage of patients who required intensive care at 14 and 28 days did not significantly differ between the amantadine and placebo groups. INTERPRETATION: Adding amantadine to standard care in patients hospitalised with COVID-19 did not increase the likelihood of recovery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04952519; www. CLINICALTRIALS: gov.

Experimental Identification of Cross-Reacting IgG Hotspots to Predict Existing Immunity Evasion of SARS-CoV-2 Variants by a New Biotechnological Application of Phage Display.

Multiple pathogens are competing against the human immune response, leading to outbreaks that are increasingly difficult to control. For example, the SARS-CoV-2 virus continually evolves, giving rise to new variants. The ability to evade the immune system is a crucial factor contributing to the spread of these variants within the human population. With the continuous emergence of new variants, it is challenging to comprehend all the possible combinations of previous infections, various vaccination types, and potential exposure to new variants in an individual patient. Rather than conducting variant-to-variant comparisons, an efficient approach could involve identifying key protein regions associated with the immune evasion of existing immunity against the virus. In this study, we propose a new biotechnological application of bacteriophages, the phage display platform for experimental identification of regions (linear epitopes) that may function as cross-reacting IgG hotspots in SARS-CoV-2 structural proteins. A total of 34,949 epitopes derived from genomes of all SARS-CoV-2 variants deposited prior to our library design were tested in a single assay. Cross-reacting IgG hotspots are protein regions frequently recognized by cross-reacting antibodies in many variants. The assay facilitated the one-step identification of immunogenic regions of proteins that effectively induced specific IgG in SARS-CoV-2-infected patients. We identified four regions demonstrating both significant immunogenicity and the activity of a cross-reacting IgG hotspot in protein S (located at NTD, RBD, HR1, and HR2/TM domains) and two such regions in protein N (at 197-280 and 358-419 aa positions). This novel method for identifying cross-reacting IgG hotspots holds promise for informing vaccine design and serological diagnostics for COVID-19 and other infectious diseases.

Dynamics of anti-SARS-CoV-2 seroconversion in individual patients and at the population level.

The immune response and specific antibody production in COVID-19 are among the key factors that determine both prognostics for individual patients and the global perspective for controlling the pandemics. So called "dark figure", that is, a part of population that has been infected but not registered by the health care system, make it difficult to estimate herd immunity and to predict pandemic trajectories. Here we present a follow up study of population screening for hidden herd immunity to SARS-CoV-2 in individuals who had never been positively diagnosed against SARS-CoV-2; the first screening was in May 2021, and the follow up in December 2021. We found that specific antibodies targeting SARS-CoV-2 detected in May as the "dark figure" cannot be considered important 7 months later due to their significant drop. On the other hand, among participants who at the first screening were negative for anti-SARS-CoV-2 IgG, and who have never been diagnosed for SARS-CoV-2 infection nor vaccinated, 26% were found positive for anti-SARS-CoV-2 IgG. This can be attributed to of the "dark figure" of the recent, fourth wave of the pandemic that occurred in Poland shortly before the study in December. Participants who were vaccinated between May and December demonstrated however higher levels of antibodies, than those who undergone mild or asymptomatic (thus unregistered) infection. Only 7% of these vaccinated participants demonstrated antibodies that resulted from infection (anti-NCP). The highest levels of protection were observed in the group that had been infected with SARS-CoV-2 before May 2021 and also fully vaccinated between May and December. These observations demonstrate that the hidden fraction of herd immunity is considerable, however its potential to suppress the pandemics is limited, highlighting the key role of vaccinations.

Correlation between COVID-19 severity and previous exposure of patients to Borrelia spp.

Predictors for the risk of severe COVID-19 are crucial for patient care and control of the disease. Other infectious diseases as potential comorbidities in SARS-CoV-2 infection are still poorly understood. Here we identify association between the course of COVID-19 and Lyme disease (borreliosis), caused by Borrelia burgdorferi transmitted to humans by ticks. Exposure to Borrelia was identified by multi-antigenic (19 antigens) serological testing of patients: severe COVID-19 (hospitalized), asymptomatic to mild COVID-19 (home treated or not aware of being infected), and not infected with SARS-CoV-2. Increased levels of Borrelia-specific IgGs strongly correlated with COVID-19 severity and risk of hospitalization. This suggests that a history of tick bites and related infections may contribute to the risks in COVID-19. Though mechanisms of this link is not clear yet, screening for antibodies targeting Borrelia may help accurately assess the odds of hospitalization for SARS-CoV-2 infected patients, supporting efforts for efficient control of COVID-19.

Hidden fraction of Polish population immune to SARS-CoV-2 in May 2021.

Population immunity (herd immunity) to SARS-CoV-2 derives from two sources: vaccinations or cases of infection with the virus. Infections can be diagnosed as COVID-19 and registered, or they can be asymptomatic, oligosymptomatic, or even full-blown but undiagnosed and unregistered when patients recovered at home. Estimation of population immunity to SARS-CoV-2 is difficult and remains a subject of speculations. Here we present a population screening for SARS-CoV-2 specific IgG and IgA antibodies in Polish citizens (N = 501) who had never been positively diagnosed with or vaccinated against SARS-CoV-2. Serum samples were collected in Wroclaw (Lower Silesia) on 15th and 22nd May 2021. Sera from hospitalized COVID-19 patients (N = 22) or from vaccinated citizens (N = 14) served as positive controls. Sera were tested with Microblot-Array COVID-19 IgG and IgA (quantitative) that contain specific SARS-CoV-2 antigens: NCP, RBD, Spike S2, E, ACE2, PLPro protein, and antigens for exclusion cross-reactivity with other coronaviruses: MERS-CoV, SARS-CoV, HCoV 229E Np, HCoV NL63 Np. Within the investigated population of healthy individuals who had never been positively diagnosed with or vaccinated against SARS-CoV-2, we found that 35.5% (178 out of 501) were positive for SARS-CoV-2-specific IgG and 52.3% (262 out of 501) were positive for SARS-CoV-2-specific IgA; 21.2% of the investigated population developed virus-specific IgG or IgA while being asymptomatic. Anti-RBD IgG, which represents virus-neutralizing potential, was found in 25.6% of individuals (128 out of 501). These patients, though positive for anti-SARS-CoV-2 antibodies, cannot be identified in the public health system as convalescents due to undiagnosed infections, and they are considered unaffected by SARS-CoV-2. Their contribution to population immunity against COVID-19 should however be considered in predictions and modeling of the COVID-19 pandemic. Of note, the majority of the investigated population still lacked anti-RBD IgG protection (74.4%); thus vaccination against COVID-19 is still of the most importance for controlling the pandemic.

Prevalence and Risk of Obstructive Sleep Apnea and Arterial Hypertension in the Adult Population in Poland: An Observational Subset of the International Prospective Urban Rural Epidemiology (PURE) Study.

Obstructive sleep apnea (OSA) is a common breathing disorder affecting millions of people worldwide. The disorder is connected with serious consequences including hypertension, myocardial infarction, arrhythmias, coronary disease, cardiac insufficiency, stroke, transient ischemic attack, and cognitive decline. Epidemiological data assessing the prevalence of OSA in different countries vary in methodology, size, and characteristics of population chosen and thus are hardly comparable. There are very few reports on the prevalence of OSA and on the diagnostic accuracy of sleep questionnaires available in Poland. In this report we present the analysis of the prevalence of, and risk factors for OSA in the Polish adult population consisting of 613 community-based subjects (227 men and 386 women). The study was based on the STOP-BANG questionnaire, a validated Screening Tool for OSA in primary care. It is a part of Polish subset of the Prospective Urban Rural Epidemiology (PURE) study, an ongoing population cohort study of individuals from urban and rural communities from 21 countries. We took into account age, gender, body mass index (BMI), and antihypertensive treatment. The findings are that over one half of the Polish population investigated had a moderate to high risk of OSA (66.5% of men and 60.1% of women). After the adjustments for age, gender, and BMI we noticed a dose-response relationship between arterial blood pressure behavior and OSA. The association was significant among women, but not men. Based on previous studies we can assume that one half of this high risk group would be further diagnosed for OSA. This study, the first large scale screening for OSA in Poland, shows a substantial, much higher than previously appreciated, prevalence of risk for OSA in the population at large.

Effectiveness of Bronchofiberoscopy in Diagnosis of Lung Lesions.

Lung cancer is the most common cause of cancer-related deaths. A short survival rate often results from belated diagnosis made in advanced stages. Therapy individualization requires the collection of a viable material for histopathological examination, which often brings difficulties. This study was performed in a group of 110 patients suspected of malignancy in chest computed tomography. All subjects underwent bronchofiberoscopy. Bronchoalveolar lavage (BAL) and endobronchial brushing were performed in all cases, whereas forceps tissue biopsy was taken if mucous membrane abnormalities were observed. In case of a negative result of bronchofiberoscopy invasive methods were implemented. A malignant neoplasm was diagnosed in 106 cases. Overall, cancer cells (positive result) were found in 45 patients (42.0%) subjected to bronchofiberoscopy. Cytology was positive in 38 (35.8%) and histopathological examination in 30 (28.3%) specimens. Eleven samples of BAL (10.3%) were positive. Endobronchial brushing was more effective, with 27 positive samples (25.5%). Forceps tissue biopsy was performed in 33 cases with 90% sensitivity. The most frequent cancer subtype found was squamous cell carcinoma. No severe complications of bronchofiberoscopy were observed. We conclude that bronchofiberosocpy is a safe diagnostic procedure for lung lesions, but its sensitivity and specificity are low. Only when there are mucous macroscopic changes observed, a precise diagnosis is possible.

Cranial dural arteriovenous fistula as a rare cause of tinnitus - case report.

BACKGROUND: Tinnitus, occurring at least once in a lifetime in about 10-20% of the population, is an important clinical problem with complex etiology. Rare causes of tinnitus include cranial dural arteriovenous fistulas (DAVFs), which are usually small lesions consisting of abnormal connections between branches of dural arteries and venous sinuses or veins. CASE REPORT: Authors present a case of a 44-year-old woman with persistent, unilateral, treatment-resistant pulsatile tinnitus caused by a small dural arteriovenous fistula revealed in computed tomography angiography. CONCLUSIONS: Computed tomography angiography is a useful diagnostic method that in some cases allows for establishing the cause of unilateral, pulsatile tinnitus.