A double-blind, randomised, placebo-controlled parallel study to investigate the effect of sex and dietary nitrate on COVID-19 vaccine-induced vascular dysfunction in healthy men and women: protocol of the DiNOVasc-COVID-19 study.

BACKGROUND: Cardiovascular events, driven by endothelial dysfunction, are a recognised complication of COVID-19. SARS-CoV-2 infections remain a persistent concern globally, and an understanding of the mechanisms causing endothelial dysfunction, particularly the role of inflammation, nitric oxide, and whether sex differences exist in this response, is lacking. We have previously demonstrated important sex differences in the inflammatory response and its impact on endothelial function and separately that the ingestion of inorganic nitrate can protect the endothelium against this dysfunction. In this study, we will investigate whether sex or a dietary inorganic nitrate intervention modulates endothelial function and inflammatory responses after the COVID-19 vaccine. METHODS: DiNOVasc-COVID-19 is a double-blind, randomised, single-centre, placebo-controlled clinical trial. A total of 98 healthy volunteers (49 males and 49 females) will be recruited. Participants will be randomised into 1 of 2 sub-studies: part A or part B. Part A will investigate the effects of sex on vascular and inflammatory responses to the COVID-19 vaccine. Part B will investigate the effects of sex and dietary inorganic nitrate on vascular and inflammatory responses to the COVID-19 vaccine. In part B, participants will be randomised to receive 3 days of either nitrate-containing beetroot juice (intervention) or nitrate-deplete beetroot juice (placebo). The primary outcome for both sub-studies is a comparison of the change in flow-mediated dilatation (FMD) from baseline after COVID-19 vaccination. The study has a power of > 80% to assess the primary endpoint. Secondary endpoints include change from baseline in inflammatory and leukocyte counts and in pulse wave analysis (PWA) and pulse wave velocity (PWV) following the COVID-19 vaccination. DISCUSSION: This study aims to evaluate whether sex or dietary influences endothelial function and inflammatory responses in healthy volunteers after receiving the COVID-19 vaccine. TRIAL REGISTRATION: ClinicalTrials.gov NCT04889274. Registered on 5 May 2023. The study was approved by the South Central - Oxford C Research Ethics Committee (21/SC/0154).

Systematic identification and referral of smokers attending HIV ambulatory care highlights the failure of current service provision in an at-risk population.

Introduction: People living with HIV (PLWH) are more likely to smoke than the general population and are at greater risk of smoking-related illness. Healthcare services need to address this burden of preventable disease. Methods: We evaluated the impact of a brief intervention that asked service users about smoking when they attended for ambulatory HIV care in London, UK, and offered referral to smoking cessation. Results: Overall, 1548 HIV-positive individuals were asked about their smoking status over a 12-month period. Of this group, 385 (25%) reported that they were current smokers, 372 (97%) were offered referral to smoking cessation services and 154 (40%) accepted this. We established an outcome of referral for 114 (74%) individuals. A total of 36 (10% of smokers) attended stop smoking clinics and 16 (4%) individuals were recorded as having quit smoking. Discussion: The simple intervention of asking PLWH about tobacco smoking and offering referral to smoking cessation services rapidly identified current smokers, 40% of whom accepted referral to smoking cessation services. This highlights the importance of promoting behaviour and lifestyle changes with every contact with health services. However, a large proportion of those referred were either not seen in local services or the outcome of referral could not be ascertained. If the risk of smoking-related morbidity among PLWH is to be reduced, more sustainable referral pathways and ways of improving uptake of smoking cessation services must be developed.