Association between initial use of e-cigarettes and subsequent cigarette smoking among adolescents and young adults a systematic review and meta-analysis

IMPORTANCE The public health implications of e-cigarettes depend, in part, on whether e-cigarette use affects the risk of cigarette smoking. OBJECTIVE To perform a systematic review and meta-analysis of longitudinal studies that assessed initial use of e-cigarettes and subsequent cigarette smoking. DATA SOURCES PubMed, EMBASE, Cochrane Library,Web of Science, the 2016 Society for Research on Nicotine and Tobacco 22nd Annual Meeting abstracts, the 2016 Society of Behavioral Medicine 37th Annual Meeting & Scientific Sessions abstracts, and the 2016 National Institutes of Health Tobacco Regulatory Science Program Conference were searched between February 7 and February 17, 2017. The search included indexed terms and text words to capture concepts associated with e-cigarettes and traditional cigarettes in articles published from database inception to the date of the search. STUDY SELECTION Longitudinal studies reporting odds ratios for cigarette smoking initiation associated with ever use of e-cigarettes or past 30-day cigarette smoking associated with past 30-day e-cigarette use. Searches yielded 6959 unique studies, of which 9met inclusion criteria (comprising 17 389 adolescents and young adults). DATA EXTRACTION AND SYNTHESIS Study quality and risk of biaswere assessed using the Newcastle-Ottawa Scale and the Risk of Bias in Non-randomized Studies of Interventions tool, respectively. Data and estimates were pooled using random-effects meta-analysis. MAIN OUTCOMES AND MEASURES Among baseline never cigarette smokers, cigarette smoking initiation between baseline and follow-up. Among baseline non-past 30-day cigarette smokers who were past 30-day e-cigarette users, past 30-day cigarette smoking at follow-up. RESULTS Among 17 389 adolescents and young adults, the ages ranged between 14 and 30 years at baseline, and 56.0%were female. The pooled probabilities of cigarette smoking initiationwere 30.4%for baseline ever e-cigarette users and 7.9%for baseline never e-cigarette users. The pooled probabilities of past 30-day cigarette smoking at follow-upwere 21.5%for baseline past 30-day e-cigarette users and 4.6%for baseline non-past 30-day e-cigarette users. Adjusting for knowndemographic, psychosocial, and behavioral risk factors for cigarette smoking, the pooled odds ratio for subsequent cigarette smoking initiationwas 3.62 (95%CI, 2.42-5.41) for ever vs never e-cigarette users, and the pooled odds ratio for past 30-day cigarette smoking at follow-up was 4.28 (95%CI, 2.52-7.27) for past 30-day e-cigarette vs non-past 30-day e-cigarette users at baseline.Amoderate level of heterogeneitywas observed among studies (I2 = 60.1%). CONCLUSIONS AND RELEVANCE e-Cigarette use was associated with greater risk for subsequent cigarette smoking initiation and past 30-day cigarette smoking. Strong e-cigarette regulation could potentially curb use among youth and possibly limit the future population-level burden of cigarette smoking

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

Accelarated immune ageing is associated with COVID-19 disease severity

Background The striking increase in COVID-19 severity in older adults provides a clear example of immunesenescence, the age-related remodelling of the immune system. To better characterise the association between convalescent immunesenescence and acute disease severity, we determined the immune phenotype of COVID-19 survivors and non-infected controls. Results We performed detailed immune phenotyping of peripheral blood mononuclear cells isolated from 103 COVID-19 survivors 3–5 months post recovery who were classified as having had severe (n = 56; age 53.12 ± 11.30 years), moderate (n = 32; age 52.28 ± 11.43 years) or mild (n = 15; age 49.67 ± 7.30 years) disease and compared with age and sex-matched healthy adults (n = 59; age 50.49 ± 10.68 years). We assessed a broad range of immune cell phenotypes to generate a composite score, IMM-AGE, to determine the degree of immune senescence. We found increased immunesenescence features in severe COVID-19 survivors compared to controls including: a reduced frequency and number of naïve CD4 and CD8 T cells (p < 0.0001); increased frequency of EMRA CD4 (p < 0.003) and CD8 T cells (p < 0.001); a higher frequency (p < 0.0001) and absolute numbers (p < 0.001) of CD28−ve CD57+ve senescent CD4 and CD8 T cells; higher frequency (p < 0.003) and absolute numbers (p < 0.02) of PD-1 expressing exhausted CD8 T cells; a two-fold increase in Th17 polarisation (p < 0.0001); higher frequency of memory B cells (p < 0.001) and increased frequency (p < 0.0001) and numbers (p < 0.001) of CD57+ve senescent NK cells. As a result, the IMM-AGE score was significantly higher in severe COVID-19 survivors than in controls (p < 0.001). Few differences were seen for those with moderate disease and none for mild disease. Regression analysis revealed the only pre-existing variable influencing the IMM-AGE score was South Asian ethnicity ( = 0.174, p = 0.043), with a major influence being disease severity ( = 0.188, p = 0.01). Conclusions Our analyses reveal a state of enhanced immune ageing in survivors of severe COVID-19 and suggest this could be related to SARS-Cov-2 infection. Our data support the rationale for trials of anti-immune ageing interventions for improving clinical outcomes in these patients with severe disease