Currently, the world is suffering from the pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that uses angiotensin-converting enzyme 2 (ACE2) as a receptor to enter the host cells. So far, 30 million people have been infected with SARS-CoV-2, and nearly 1 million people have died because of COVID-19 worldwide, causing serious health, economical, and sociological problems. However, the mechanism of the effect of SARS-CoV-2 on human host cells has not been defined. The present study reports that the SARS-CoV-2 spike protein alone without the rest of the viral components is sufficient to elicit cell signaling in lung vascular cells. The treatment of human pulmonary artery smooth muscle cells or human pulmonary artery endothelial cells with recombinant SARS-CoV-2 spike protein S1 subunit (Val16 - Gln690) at 10 ng/ml (0.13 nM) caused an activation of MEK phosphorylation. The activation kinetics was transient with a peak at 10 min. The recombinant protein that contains only the ACE2 receptor-binding domain of SARS-CoV-2 spike protein S1 subunit (Arg319 - Phe541), on the other hand, did not cause this activation. Consistent with the activation of cell growth signaling in lung vascular cells by SARS-CoV-2 spike protein, pulmonary vascular walls were found to be thickened in COVID-19 patients. Thus, SARS-CoV-2 spike protein-mediated cell growth signaling may participate in adverse cardiovascular/pulmonary outcomes, and this mechanism may provide new therapeutic targets to combat COVID-19.
There was performed a statistical analysis of 164 records of pathological examination of persons who died of coronavirus disease during April-November, 2020. It is determined that the share of males was 62.20%, and females – 37.80%; the average age of the deceased persons was 64.40 ± 13.79 years. The largest number of lethal cases (57.32%) falls on the age category of 60-79 years, and the smallest (6.71%) – on the age category of 20-39 years. It is important that men predominate in all age groups. The most common direct causes of death were: respiratory failure – 78.05%, multiorgan failure – 17.07%. At the same time, respiratory insufficiency was dominant in all age categories, while the share of multiorgan failure was the largest in the group of persons aged 20-39 years. As a result of the analysis of thromboembolic complications found in 10.37% of cases, there were 3.05% of cases of acute coronary syndrome and acute cerebrovascular disorder, 1.83% of cases – acute thrombosis of the arteries of the lower extremities, 1.22% of cases – acute thrombosis of the mesenteric vessels, and 0.61% – disseminated intravascular coagulation of blood and acute pulmonary thromboembolism. Morphological examination of the lung tissue of the deceased persons revealed signs of diffuse alveolar damage involving the microcirculatory bed vessels in the pathological process. According to the results of bacteriological examination of the lungs there were revealed some signs of bacterial infection in 51.83% of cases, and signs of fungal infection – in 15.85% of cases. The most common (23.78%) was the growth of Klebsiella pneumoniae. The most common comorbidities were: coronary heart disease – 62.20%, hypertension – 29.27%, non-insulin dependent diabetes mellitus – 11.59%, obesity – 10.37%, anemia – 6.71% and chronic obstructive pulmonary disease – 2.44%. In 10.98% of cases diabetes was the main underlying disease. The data obtained may indicate an adverse effect of these diseases on the course of coronavirus disease.
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