Impaired immune response mediated by prostaglandin E2 promotes severe COVID-19 disease.

The SARS-CoV-2 coronavirus has led to a pandemic with millions of people affected. The present study finds that risk-factors for severe COVID-19 disease courses, i.e. male sex, older age and sedentary life style are associated with higher prostaglandin E2 (PGE2) serum levels in blood samples from unaffected subjects. In COVID-19 patients, PGE2 blood levels are markedly elevated and correlate positively with disease severity. SARS-CoV-2 induces PGE2 generation and secretion in infected lung epithelial cells by upregulating cyclo-oxygenase (COX)-2 and reducing the PG-degrading enzyme 15-hydroxyprostaglandin-dehydrogenase. Also living human precision cut lung slices (PCLS) infected with SARS-CoV-2 display upregulated COX-2. Regular exercise in aged individuals lowers PGE2 serum levels, which leads to increased Paired-Box-Protein-Pax-5 (PAX5) expression, a master regulator of B-cell survival, proliferation and differentiation also towards long lived memory B-cells, in human pre-B-cell lines. Moreover, PGE2 levels in serum of COVID-19 patients lowers the expression of PAX5 in human pre-B-cell lines. The PGE2 inhibitor Taxifolin reduces SARS-CoV-2-induced PGE2 production. In conclusion, SARS-CoV-2, male sex, old age, and sedentary life style increase PGE2 levels, which may reduce the early anti-viral defense as well as the development of immunity promoting severe disease courses and multiple infections. Regular exercise and Taxifolin treatment may reduce these risks and prevent severe disease courses.

Apoptosis of T-Cell Subsets after Acute High-Intensity Interval Exercise.

INTRODUCTION: High-intensity interval training (HIT) exercise has gained much interest in both performance and recreational sports. This study aims to compare the effect of HIT versus continuous (CONT) exercise with regard to changes of circulating T cells and progenitor cells. METHODS: Subjects (n = 23) completed an HIT test and an isocaloric CONT test. Blood samples were collected before, immediately after, and 3 and 24 h postexercise for the assessment of low differentiated (CD3CD28CD57), highly differentiated T cells (CD3CD28CD57), regulatory T cells (Tregs) (CD4CD25CD127), hematopoietic progenitor cells (CD45CD34), and endothelial progenitor cells (CD45CD34KDR) by flow cytometry. The detection of apoptosis was performed by using labeling with annexin V. To analyze potential mechanisms affecting T cells, several hormones and metabolites were analyzed. RESULTS: Both exercise tests induced an increase of catecholamines, cortisol, and thiobarbituric acid-reactive substances (P < 0.05). CONT induced a higher increase of apoptosis in low differentiated T cells compared with the HIT (CONT: 3.66% ± 0.21% to 6.48% ± 0.29%, P < 0.05; HIT: 3.43% ± 0.31% to 4.71% ± 0.33%), whereas HIT was followed by a higher rate of apoptotic highly differentiated T cells (CONT: 21.45% ± 1.23% to 25.32% ± 1.67%; HIT: 22.45% ± 1.37% to 27.12% ± 1.76%, P < 0.05). Regarding Tregs, HIT induced a mobilization, whereas CONT induced apoptosis in these cells (P < 0.05). The mobilization of progenitor cells did not differ between the exercise protocols. CONCLUSION: These results suggest that HIT deletes mainly highly differentiated T cells known to affect immunity to control latent infections. By contrast, CONT deletes mainly low differentiated T cells and Tregs, which might affect defense against new infectious agents.