Cilia impairment in bronchial epithelial cells detected in autopsy material of SARS-CoV-2-infected patient.

Recent studies indicate that cilia impairment, accompanied by the axonema loss and the basal body misorientation, is a common pathological feature of SARS-CoV-2-infected bronchial epithelial cells. However, these data were obtained using either cultured cells, or animal models, while in human postmortem material, cilia impairment has not been described yet. Here, we present direct observation of cilia impairment in SARS-CoV-2-infected bronchial epithelial cells using transmission electron microscopy of the autopsy material. We were able to observe only single infected cells with cilia impairment in one of twelve examined specimens, while the large number of desquamated bronchial epithelial cells with undisturbed ciliary layer was visible in the bronchial lumens. Thus, it seems that in the lungs of infected patients, the majority of bronchial cells do not die as a direct result of infection, which may explain the rarity of this finding in the autopsy material.

CTLs From Patients With Atherosclerosis Show Elevated Adhesiveness and Distinct Integrin Expression Patterns on 2D Substrates.

Atherosclerosis is the major cause of cardiovascular disease that is characterized by plaque formation in the blood vessel wall. Atherosclerotic plaques represent sites of chronic inflammation with diverse cell content that is shifted toward the prevalence of cytotoxic T-lymphocytes (CTLs) upon plaque progression. The studies of CTL recruitment to atherosclerotic plaques require adequate in vitro models accounting for CTL interactions with chemokine-ligands and extracellular matrix fibers via surface chemokine receptors and integrins. Here we applied such a model by investigating CTL adhesion and migration on six types of coated surfaces. We assessed adhesion and motility metrics, the expression of chemokine receptors, and integrins in CTLs of patients with atherosclerosis and healthy donors. Using fibronectin, platelet-poor plasma from patients with atherosclerosis, and conditioned medium from atherosclerotic plaques we revealed the role of substrate in CTL adhesiveness: fibronectin alone and fibronectin combined with platelet-poor plasma and conditioned medium elevated the CTL adhesiveness - in patients the elevation was significantly higher than in healthy donors (p = 0.02, mixed 2-way ANOVA model). This was in line with our finding that the expression levels of integrin-coding mRNAs were elevated in the presence of fibronectin (p < 0.05) and ITGB1, ITGA1, and ITGA4 were specifically upregulated in patients compared to healthy donors (p < 0.01). Our experimental model did not affect the expression levels of mRNAs CCR4, CCR5, and CX3CR1 coding the chemokine receptors that drive T-lymphocyte migration to plaques. Thus, we demonstrated the substrate-dependence of integrin expression and discriminated CTLs from patients and healthy donors by adhesion parameters and integrin expression levels.

Bromhexine Hydrochloride Prophylaxis of COVID-19 for Medical Personnel: A Randomized Open-Label Study.

BACKGROUND: Bromhexine hydrochloride has been suggested as a TMPRSS2 protease blocker that precludes the penetration of SARS-CoV-2 into cells. We aimed to assess the preventive potential of regular bromhexine hydrochloride intake for COVID-19 risk reduction in medical staff actively involved in the evaluation and treatment of patients with confirmed or suspected SARS-CoV-2 infection. METHODS: In a single-centre randomized open-label study, medical staff managing patients with suspected and confirmed COVID-19 were enrolled and followed up for 8 weeks. The study began at the initiation of COVID-19 management in the clinic. The study was prematurely terminated after the enrollment of 50 participants without a history of SARS-CoV-2 infection: 25 were assigned to bromhexine hydrochloride treatment (8 mg 3 times per day), and 25 were controls. The composite primary endpoint was a positive nasopharyngeal swab polymerase chain reaction (PCR) test for SARS-CoV-2 or signs of clinical infection within 28 days and at week 8. Secondary endpoints included time from the first contact with a person with COVID-19 to the appearance of respiratory infection symptoms; the number of days before a first positive SARS-CoV-2 test; the number of asymptomatic participants with a positive nasopharyngeal swab test; the number of symptomatic COVID-19 cases; and adverse events. RESULTS: The rate of the combined primary endpoint did not differ significantly between the active treatment group (2/25 [8%]) and control group (7/25 [28%]); P=0.07. A fewer number of participants developed symptomatic COVID-19 in the treatment group compared to controls (0/25 vs. 5/25; P=0.02). CONCLUSION: Although the study was underpowered, it showed that Bromhexine hydrochloride prophylaxis was associated with a reduced rate of symptomatic COVID-19. The prophylactic treatment was not associated with a lower combined primary endpoint rate, a positive swab PCR test, or COVID-19 (ClinicalTrials.gov number, NCT04405999).

Long-term Success of Cardioneuroablation in a Patient with Tachycardia-bradycardia Syndrome and Syncope.

A case of successful treatment for syncopal episodes caused by intermittent atrioventricular block in a patient with paroxysmal atrial fibrillation/atrial flutter using cardioneuroablation is presented.