ABSTRACT
Interleukin 6 (IL-6) is a cytokine with dual functions of pro-inflammation and anti-inflammation. It is mainly produced by mononuclear macrophages, Th2 cells, vascular endothelial cells and fibroblasts. IL-6 binds to glycoprotein 130 and one of these two receptors, membrane-bound IL-6R or soluble IL-6R, forming hexamer (IL-6/IL-6R/gp130), which then activates different signaling pathways (classical pathway, trans-signaling pathway) to exert dual immune-modulatory effects of anti-inflammation or pro-inflammation. Abnormal levels of IL-6 can cause multiple pathological reactions, including cytokine storm. Related clinical studies have found that IL-6 levels in severe COVID-19 patients were much higher than in healthy population. A large number of studies have shown that IL-6 can trigger a downstream cytokine storm in patients with COVID-19, resulting in lung damages, aggravating clinical symptoms and developing excessive inflammation and acute respiratory distress syndrome (ARDS). Monoclonal antibodies against IL-6 or IL-6R, such as tocilizumab, sarilumab, siltuximab and olokizumab may serve as therapeutic options for COVID-19 infection.
ABSTRACT
People living with (PLWH) and at risk for HIV and people who use drugs (PWUD) are at heightened risk for health consequences of COVID-19 because of compromised immunity and high comorbidities. We studied their use of COVID-19 testing during the first year of the COVID-19 pandemic. Eight NIDA funded cohorts across North America in the Collaborating Consortium of Cohorts Producing NIDA Opportunities (C3PNO) administered multiple waves of a COVID-19 survey. Respondents were at least 18 years of age, half PLWH, and many active substance users. Wave one of the COVID-19 survey was May-November, 2020 and wave two October 2020-April 2021. Associations of COVID-19 testing with demographics, socio-demographics, substance use, and HIV-status were assessed. Of the 3762 responses from 2331 individuals, half reported ever COVID-19 testing (49.1 %), with 4.3 % reporting a positive test (163/3762 surveys=4.3 %) and 41.5 % of people reporting current symptoms reported having been tested. In multivariable analysis adjusting for age, sex, and cohort type associations with COVID-19 testing included African American/Black identification compared to Caucasian/white (adjusted odds ratio (AOR)= 0.68; 95 % confidence interval (CI) 0.53, 0.88); being unemployed (AOR=0.61; 95 % CI 0.51, 0.73), and living with HIV (AOR=0.76; 95 % CI0.65, 0.90). Findings from these C3PNO COVID-19 modules suggests that in the first year of the pandemic COVID-19 testing was not broadly accessed by these marginalized populations including PLWH and those unemployed. Factors associated with not testing may also parallel those for vaccination and identify populations needing better access to COVID-19 prevention.
ABSTRACT
Nitric oxide (NO) is a free radical playing an important pathophysiological role in cardiovascular and immune systems. Recent studies reported that NO levels were significantly lower in patients with COVID-19, which was suggested to be closely related to vascular dysfunction and immune inflammation among them. In this review, we examine the potential role of NO during SARS-CoV-2 infection from the perspective of the unique physical, chemical and biological properties and potential mechanisms of NO in COVID-19, as well as possible therapeutic strategies using inhaled NO. We also discuss the limits of NO treatment, and the future application of this approach in prevention and therapy of COVID-19.