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Hyperinflammation plays an important role in severe and critical COVID-19. Using inconsistent criteria, many researchers define hyperinflammation as a form of very severe inflammation with cytokine storm. Therefore, COVID-19 patients are treated with anti-inflammatory drugs. These drugs appear to be less efficacious than expected and are sometimes accompanied by serious adverse effects. SARS-CoV-2 promotes cellular ATP release. Increased levels of extracellular ATP activate the purinergic receptors of the immune cells initiating the physiologic pro-inflammatory immune response. Persisting viral infection drives the ATP release even further leading to the activation of the P2X7 purinergic receptors (P2X7Rs) and a severe yet physiologic inflammation. Disease progression promotes prolonged vigorous activation of the P2X7R causing cell death and uncontrolled ATP release leading to cytokine storm and desensitisation of all other purinergic receptors of the immune cells. This results in immune paralysis with co-infections or secondary infections. We refer to this pathologic condition as hyperinflammation. The readily available and affordable P2X7R antagonist lidocaine can abrogate hyperinflammation and restore the normal immune function. The issue is that the half-maximal effective concentration for P2X7R inhibition of lidocaine is much higher than the maximal tolerable plasma concentration where adverse effects start to develop. To overcome this, we selectively inhibit the P2X7Rs of the immune cells of the lymphatic system inducing clonal expansion of Tregs in local lymph nodes. Subsequently, these Tregs migrate throughout the body exerting anti-inflammatory activities suppressing systemic and (distant) local hyperinflammation. We illustrate this with six critically ill COVID-19 patients treated with lidocaine. [ABSTRACT FROM AUTHOR]

Background: Primary prevention programs at the worksite can improve employee health and reduce the burden of cardiovascular disease. Programs that include a web-based health risk assessment (HRA) with tailored feedback hold the advantage of simultaneously increasing awareness of risk and enhancing initiation of health-behaviour change. In this study we evaluated initial health-behaviour change among employees who voluntarily participated in such a HRA program. Methods: We conducted a questionnaire survey among 2289 employees who voluntarily participated in a HRA program at seven Dutch worksites between 2007 and 2009. The HRA included a web-based questionnaire, biometric measurements, laboratory evaluation, and tailored feedback. The survey questionnaire assessed initial self-reported health-behaviour change and satisfaction with the web-based HRA, and was e-mailed four weeks after employees completed the HRA. Results: Response was received from 638 (28%) employees. Of all, 86% rated the program as positive, 74% recommended it to others, and 58% reported to have initiated overall health-behaviour change. Compared with employees at low CVD risk, those at high risk more often reported to have increased physical activity (OR 3.36, 95% CI 1.52-7.45). Obese employees more frequently reported to have increased physical activity (OR 3.35, 95% CI 1.72-6.54) and improved diet (OR 3.38, 95% CI 1.50-7.60). Being satisfied with the HRA program in general was associated with more frequent self-reported initiation of overall health-behaviour change (OR 2.77, 95% CI 1.73-4.44), increased physical activity (OR 1.89, 95% CI 1.06-3.39), and improved diet (OR 2.89, 95% CI 1.61-5.17). Conclusions: More than half of the employees who voluntarily participated in a web-based HRA with tailored feedback, reported to have initiated health-behaviour change. Self-reported initiation of health-behaviour change was more frequent among those at high CVD risk and BMI levels. In general employees reported to be satisfied with the HRA, which was also positively associated with initiation of health-behaviour change. These findings indicate that among voluntary participating employees a web-based HRA with tailored feedback may motivate those in greatest need of health-behaviour change and may be a valuable component of workplace health promotion programs. [ABSTRACT FROM AUTHOR]