Smoking increases expression of the SARS-CoV-2 spike protein-binding long ACE2 isoform in bronchial epithelium.

After more than two years the COVID-19 pandemic, that is caused by infection with the respiratory SARS-CoV-2 virus, is still ongoing. The risk to develop severe COVID-19 upon SARS-CoV-2 infection is increased in individuals with a high age, high body mass index, and who are smoking. The SARS-CoV-2 virus infects cells of the upper respiratory tract by entering these cells upon binding to the Angiotensin-converting enzyme 2 (ACE2) receptor. ACE2 is expressed in various cell types in the lung but the expression is especially high in goblet and ciliated cells. Recently, it was shown that next to its full-length isoform, ACE2 also has a short isoform. The short isoform is unable to bind SARS-CoV-2 and does not facilitate viral entry. In the current study we investigated whether active cigarette smoking increases the expression of the long or the short ACE2 isoform. We showed that in active smokers the expression of the long, active isoform, but not the short isoform of ACE2 is higher compared to never smokers. Additionally, it was shown that the expression of especially the long, active isoform of ACE2 was associated with secretory, club and goblet epithelial cells. This study increases our understanding of why current smokers are more susceptible to SARS-CoV-2 infection, in addition to the already established increased risk to develop severe COVID-19.

Incidencia y factores asociados con las reacciones adversas tras la primera dosis de la vacuna Pfizer-BioNTech en trabajadores de la salud.

OBJECTIVE: To determine the incidence of adverse reactions (AR) after the first dose of Pfizer-BioNTech vaccine, and to identify some factors associated with AR. METHOD: A retrospective cohort study was conducted. Data were obtained through an epidemiological survey answered online. Multivariate analyses were performed to identify factors associated with early (< 2 h) and late (≥ 2 h) AR. RESULTS: A total of 2295 health care workers were included; in them, the cumulative incidence of AR was 18.2% (95% confidence interval: 16.6-19.8), where the majority were late (78.2%). The associated factors that increased the risk of early AR were being female (odds ratio [OR]: 2.23, p = 0.002) and belonging to the medical staff (OR: 1.56; p = 0.041). In late AR were being female (OR: 1.94; p < 0.0001); on the other hand, diabetes (OR: 0.46; p = 0.021), asthma (OR: 0.53; p = 0.040) and smoking (OR: 0.44, p = 0.002) were inversely associated factors. Interestingly, history of COVID-19 was not associated with either early or late AR. CONCLUSIONS: The risk of presenting some type of AR due to the Pfizer-BioNTech vaccine in health care workers is < 20%.

OBJETIVO: Determinar la incidencia de reacciones adversas (RA) tras la primera dosis de la vacuna Pfizer-BioNTech e identificar algunos factores asociados con ellas. MÉTODO: Se realizó un estudio de cohorte retrospectiva. Los datos fueron obtenidos mediante una encuesta epidemiológica contestada en línea. Se realizaron análisis multivariados para identificar factores asociados con las RA tempranas (< 2 h) y tardías (≥ 2 h). RESULTADOS: Se incluyeron 2295 trabajadores de la salud; en ellos, la incidencia acumulada de RA fue del 18.2% (intervalo de confianza del 95%: 16.6-19.8%) y la mayoría fueron tardías (78.2%). Las RA tempranas más frecuentes fueron dolor local, cefalea y mareo; en las tardías fueron dolor local, cefalea y fatiga. No se documentaron casos de anafilaxia; sin embargo, en el grupo de RA tempranas y tardías hubo un caso y tres casos, respectivamente, con síntomas sistémicos que afectaron a dos órganos diferentes. Los factores asociados que incrementaron el riesgo de RA tempranas fueron ser mujer (odds ratio [OR]: 2.23; p = 0.002) y pertenecer al personal médico (OR: 1.56; p = 0.041). En las RA tardías fue ser mujer (OR: 1.94; p < 0.0001); por su parte, la diabetes (OR: 0.46; p = 0.021), el asma (OR: 0.53; p = 0.040) y el tabaquismo (OR: 0.44; p = 0.002) fueron factores asociados inversamente. Es interesante que la historia de COVID-19 no se asoció con RA tempranas ni tardías. CONCLUSIONES: El riesgo de presentar algún tipo de RA debido a la vacuna Pfizer-BioNTech en trabajadores de la salud es < 20%.

The pathogenetic influence of smoking on SARS-CoV-2 infection: Integrative transcriptome and regulomics analysis of lung epithelial cells.

Corona virus disease (COVID-19) has been emerged as pandemic infectious disease. The recent epidemiological data suggest that the smokers are more vulnerable to infection with COVID-19; however, the influence of smoking (SMK) on the COVID-19 infected patients and the mortality is not known yet. In this study, we aimed to discern the influence of SMK on COVID-19 infected patients utilizing the transcriptomics data of COVID-19 infected lung epithelial cells and transcriptomics data smoking matched with controls from lung epithelial cells. The bioinformatics based analysis revealed the molecular insights into the level of transcriptional changes and pathways which are important to identify the impact of smoking on COVID-19 infection and prevalence. We compared differentially expressed genes (DEGs) between COVID-19 and SMK and 59 DEGs were identified as consistently dysregulated at transcriptomics levels. The correlation network analyses were constructed for these common genes using WGCNA R package to see the relationship among these genes. Integration of DEGs with network analysis (protein-protein interaction) showed the presence of 9 hub proteins as key so called "candidate hub proteins" overlapped between COVID-19 patients and SMK. The Gene Ontology and pathways analysis demonstrated the enrichment of inflammatory pathway such as IL-17 signaling pathway, Interleukin-6 signaling, TNF signaling pathway and MAPK1/MAPK3 signaling pathways that might be the therapeutic targets in COVID-19 for smoking persons. The identified genes, pathways, hubs genes, and their regulators might be considered for establishment of key genes and drug targets for SMK and COVID-19.

The role of smoking in COVID-19 progression: a comprehensive meta-analysis.

The association between current smoking and coronavirus disease 2019 (COVID-19) progression remains uncertain. We aim to provide up-to-date evidence of the role of cigarette smoking in COVID-19 hospitalisation, severity and mortality. On 23 February 2022 we conducted an umbrella review and a traditional systematic review via PubMed/Medline and Web of Science. We used random-effects meta-analyses to derive pooled odds ratios of COVID-19 outcomes for smokers in cohorts of severe acute respiratory syndrome coronavirus 2 infected individuals or COVID-19 patients. We followed the Meta-analysis of Observational Studies in Epidemiology reporting guidelines. PROSPERO: CRD42020207003. 320 publications were included. The pooled odds ratio for current versus never or nonsmokers was 1.08 (95% CI 0.98-1.19; 37 studies) for hospitalisation, 1.34 (95% CI 1.22-1.48; 124 studies) for severity and 1.32 (95% CI 1.20-1.45; 119 studies) for mortality. Estimates for former versus never-smokers were 1.16 (95% CI 1.03-1.31; 22 studies), 1.41 (95% CI: 1.25-1.59; 44 studies) and 1.46 (95% CI 1.31-1.62; 44 studies), respectively. Estimates for ever- versus never-smokers were 1.16 (95% CI 1.05-1.27; 33 studies), 1.44 (95% CI 1.31-1.58; 110 studies) and 1.39 (95% CI 1.29-1.50; 109 studies), respectively. We found a 30-50% excess risk of COVID-19 progression for current and former smokers compared with never-smokers. Preventing serious COVID-19 outcomes, including death, seems the newest compelling argument against smoking.

Impact of accumulative smoking exposure and chronic obstructive pulmonary disease on COVID-19 outcomes: report based on findings from the Japan COVID-19 task force.

OBJECTIVES: Smoking and chronic obstructive pulmonary disease (COPD) are risk factors for severe COVID-19. However, limited literature exists on the effect of COPD and smoking on COVID-19 outcomes. This study examined the impact of smoking exposure in pack-years (PY) and COPD on COVID-19 outcomes among smokers in Japan. METHODS: The study included 1266 smokers enrolled by the Japan COVID-19 task force between February 2020 and December 2021. PY and COPD status was self-reported by patients. Patients were classified into the non-COPD (n = 1151) and COPD (n = 115) groups; the non-COPD group was further classified into <10 PY (n = 293), 10-30 PY (n = 497), and >30 PY (n = 361). The study outcome was the need for invasive mechanical ventilation (IMV). RESULTS: The incidence of IMV increased with increasing PY and was highest in the COPD group (<10 PY = 7.8%, 10-30 PY = 12.3%, >30 PY = 15.2%, COPD = 26.1%; P <0.001). A significant association was found for IMV requirement in the >30 PY and COPD groups through univariate (odds ratio [OR]: >30 PY = 2.11, COPD = 4.14) and multivariate (OR: >30 PY = 2.38; COPD = 7.94) analyses. Increasing PY number was also associated with increased IMV requirement in patients aged <65 years. CONCLUSION: Cumulative smoking exposure was positively associated with COVID-19 outcomes in smokers.

Smoking and the Risk of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection.

INTRODUCTION: It is unclear whether smokers are more vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to evaluate the association between smoking and the risk of SARS-CoV-2 infection. METHODS: A matched case-control study was conducted using a large nationwide database. The case group included patients with SARS-CoV-2 infection confirmed by the Korea Centers for Disease Control and Prevention, and the control group was randomly sampled from the general Korean population in the National Health Insurance Service database by matching sex, age, and region of residence. Conditional logistic regression models were used to investigate whether the risk of infection with SARS-CoV-2 was affected by smoking status. RESULTS: A total of 4167 patients with SARS-CoV-2 infection and 20 937 matched controls were enrolled. The proportion of ex-smokers and current smokers was 26.6% of the total participants. In multivariate analysis, smoking was not associated with an increased risk of SARS-CoV-2 infection (odds ratio [OR] = 0.56, confidence interval [CI] = 0.50-0.62). When ex-smokers and current smokers were analyzed separately, similar results were obtained (current smoker OR = 0.33, CI = 0.28-0.38; ex-smoker OR = 0.81, CI = 0.72-0.91). CONCLUSIONS: This study showed that smoking may not be associated with an increased risk of SARS-CoV-2 infection. Smoking tends to lower the risk of SARS-CoV-2 infection; however, these findings should be interpreted with caution. IMPLICATIONS: It is unclear whether smokers are more vulnerable to coronavirus disease 2019. In this large nationwide study in South Korea, smoking tended to lower the risk of infection with severe acute respiratory syndrome coronavirus 2. However, these findings should be interpreted with caution, and further confirmatory studies are required.

Smoking modulates different secretory subpopulations expressing SARS-CoV-2 entry genes in the nasal and bronchial airways.

SARS-CoV-2 infection and disease severity are influenced by viral entry (VE) gene expression patterns in the airway epithelium. The similarities and differences of VE gene expression (ACE2, TMPRSS2, and CTSL) across nasal and bronchial compartments have not been fully characterized using matched samples from large cohorts. Gene expression data from 793 nasal and 1673 bronchial brushes obtained from individuals participating in lung cancer screening or diagnostic workup revealed that smoking status (current versus former) was the only clinical factor significantly and reproducibly associated with VE gene expression. The expression of ACE2 and TMPRSS2 was higher in smokers in the bronchus but not in the nose. scRNA-seq of nasal brushings indicated that ACE2 co-expressed genes were highly expressed in club and C15orf48+ secretory cells while TMPRSS2 co-expressed genes were highly expressed in keratinizing epithelial cells. In contrast, these ACE2 and TMPRSS2 modules were highly expressed in goblet cells in scRNA-seq from bronchial brushings. Cell-type deconvolution of the gene expression data confirmed that smoking increased the abundance of several secretory cell populations in the bronchus, but only goblet cells in the nose. The association of ACE2 and TMPRSS2 with smoking in the bronchus is due to their high expression in goblet cells which increase in abundance in current smoker airways. In contrast, in the nose, these genes are not predominantly expressed in cell populations modulated by smoking. In individuals with elevated lung cancer risk, smoking-induced VE gene expression changes in the nose likely have minimal impact on SARS-CoV-2 infection, but in the bronchus, smoking may lead to higher viral loads and more severe disease.

Effect of financial voucher incentives provided with UK stop smoking services on the cessation of smoking in pregnant women (CPIT III): pragmatic, multicentre, single blinded, phase 3, randomised controlled trial.

OBJECTIVE: To examine effectiveness, cost effectiveness, generalisability, and acceptability of financial incentives for smoking cessation during pregnancy in addition to variously organised UK stop smoking services. DESIGN: Pragmatic, multicentre, single blinded, phase 3, randomised controlled trial (Cessation in Pregnancy Incentives Trial phase 3 (CPIT III)). SETTING: Seven UK stop smoking services provided in primary and secondary care facilities in Scotland, Northern Ireland, and England. PARTICIPANTS: 944 pregnant women (age ≥16 years) who self-reported as being smokers (at least one cigarette in the past week) when asked at first maternity visit, less than 24 weeks' gestation, and notified to the trial team by routine stop smoking services. INTERVENTIONS: Participants in the control group were offered the standard stop smoking services, which includes the offer of counselling by specially trained workers using withdrawal orientated therapy and the offer of free nicotine replacement therapy. The intervention was the offer of usual support from the stop smoking services and the addition of up to £400 ($440; €455) of LoveToShop financial voucher incentives for engaging with current stop smoking services or to stop smoking, or both, during pregnancy. MAIN OUTCOME MEASURES: Self-reported smoking cessation in late pregnancy (between 34 and 38 weeks' gestation) corroborated by saliva cotinine (and anabasine if using nicotine replacement products). Results were adjusted for age, smoking years, index of multiple deprivation, Fagerström score, before or after covid, and recruitment site. Secondary outcomes included point and continuous abstinence six months after expected date of delivery, engagement with stop smoking services, biochemically validated abstinence from smoking at four weeks after stop smoking date, birth weight of baby, cost effectiveness, generalisability documenting formats of stop smoking services, and acceptability to pregnant women and their carers. RESULTS: From 9 January 2018 to 4 April 2020, of 4032 women screened by stop smoking services, 944 people were randomly assigned to the intervention group (n=471) or the control group (n=470). Three people asked for their data to be removed. 126 (27%) of 471 participants stopped smoking from the intervention group and 58 (12%) of 470 from the control group (adjusted odds ratio 2.78 (1.94 to 3.97) P<0.001). Serious adverse events were miscarriages and other expected pregnancy events requiring hospital admission; all serious adverse events were unrelated to the intervention. Most people who stopped smoking from both groups relapsed after their baby was born. CONCLUSIONS: The offer of up to £400 of financial voucher incentives to stop smoking during pregnancy as an addition to current UK stop smoking services is highly effective. This bolt-on intervention supports new guidance from the UK National Institute for Health and Care Excellence, which includes the addition of financial incentives to support pregnant women to stop smoking. Continuing incentives to 12 months after birth is being examined to prevent relapse. TRIAL REGISTRATION: ISRCTN Registry ISRCTN15236311.

The UK Coronavirus Job Retention Scheme and smoking, alcohol consumption and vaping during the COVID-19 pandemic: evidence from eight longitudinal population surveys.

BACKGROUND: Employment disruptions can impact smoking and alcohol consumption. During the COVID-19 pandemic, many countries implemented furlough schemes to prevent job loss. We examine how furlough was associated with smoking, vaping and alcohol consumption in the UK. METHODS: Data from 27,841 participants in eight UK adult longitudinal surveys were analysed. Participants self-reported employment status and current smoking, current vaping and alcohol consumption (>4 days/week or 5+ drinks per typical occasion) both before and during the early stages of the pandemic (April-July 2020). Risk ratios were estimated within each study using modified Poisson regression, adjusting for a range of potential confounders, including pre-pandemic behaviour. Findings were synthesised using random effects meta-analysis. RESULTS: Compared to stable employment and after adjustment for pre-pandemic characteristics, furlough was not associated with smoking (ARR = 1.05; 95% CI: 0.95-1.16; I2: 10%), vaping (ARR = 0.89; 95% CI: 0.74-1.08; I2: 0%) or drinking (ARR = 1.03; 95% CI: 0.94-1.13; I2: 48%). There were similar findings for no longer being employed, and stable unemployment, though this varied by sex: stable unemployment was associated with smoking for women (ARR = 1.35; 95% CI: 1.00-1.82; I2: 47%) but not men (0.84; 95% CI: 0.67-1.05; I2: 0%). No longer being employed was associated with vaping among women (ARR = 2.74; 95% CI: 1.59-4.72; I2: 0%) but not men (ARR = 1.25; 95% CI: 0.83-1.87; I2: 0%). CONCLUSIONS: We found no clear evidence of furlough or unemployment having adverse impacts on smoking, vaping or drinking behaviours during the early stages of the COVID-19 pandemic in the UK. Differences in risk compared to those who remained employed were largely explained by pre-pandemic characteristics.

The global burden of cancer attributable to risk factors, 2010-19: a systematic analysis for the Global Burden of Disease Study 2019.

BACKGROUND: Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. METHODS: The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. FINDINGS: Globally, in 2019, the risk factors included in this analysis accounted for 4·45 million (95% uncertainty interval 4·01-4·94) deaths and 105 million (95·0-116) DALYs for both sexes combined, representing 44·4% (41·3-48·4) of all cancer deaths and 42·0% (39·1-45·6) of all DALYs. There were 2·88 million (2·60-3·18) risk-attributable cancer deaths in males (50·6% [47·8-54·1] of all male cancer deaths) and 1·58 million (1·36-1·84) risk-attributable cancer deaths in females (36·3% [32·5-41·3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20·4% (12·6-28·4) and DALYs by 16·8% (8·8-25·0), with the greatest percentage increase in metabolic risks (34·7% [27·9-42·8] and 33·3% [25·8-42·0]). INTERPRETATION: The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. FUNDING: Bill & Melinda Gates Foundation.

Associated risks of smoking and possible benefits of cessation in Covid-19: a rapid narrative review.

OBJECTIVE: To describe the possible risks associated to smoking in the spread and complications of Covid-19, em-phasizing in the benefits of quitting smoking. MATERIALS AND METHODS: The narrative review methodology and the established process for Cochrane rapid reviews were used. RESULTS: The scientific evidence related to smoking and Covid-19 remains limited. However, there is an already documented trend in cross-sectional, clinical studies and meta-analyses on the increased risk of adverse outcomes with Covid-19 associated with tobacco use. CONCLUSIONS: It is necessary to issue a warning that persons who smoke would have greater risks in the Covid-19 pandemic, which add to the many already known risks of tobacco use. Thus, quitting smoking becomes a relevant preventive measure to better confront SARS-CoV-2.

Association between smoking and COVID-19 severity: A multicentre retrospective observational study.

The relationship between smoking and coronavirus disease 2019 (COVID-19) severity remains unclear. This study aimed to investigate the effect of smoking status (current smoking and a smoking history) on the clinical severity of COVID-19. Data of all enrolled 588 patients, who were referred to 25 hospitals in Jiangsu province between January 10, 2020 and March 14, 2020, were retrospectively reviewed. Univariate and multivariate regression, random forest algorithms, and additive interaction were used to estimate the importance of selective predictor variables in the relationship between smoking and COVID-19 severity. In the univariate analysis, the proportion of patients with a current smoking status in the severe group was significantly higher than that in the non-severe group. In the multivariate analysis, current smoking remained a risk factor for severe COVID-19. Data from the interaction analysis showed a strong interaction between the number of comorbidities in patients with COVID-19 and smoking. However, no significant interaction was found between smoking and specific comorbidities, such as hypertension, diabetes, etc. In the random forest model, smoking history was ranked sixth in mean decrease accuracy. Active smoking may be significantly associated with an enhanced risk of COVID-19 progression towards severe disease. However, additional prospective studies are needed to clarify the complex relationship between smoking and COVID-19 severity.

Smoking and socioeconomic factors linked to acute exacerbations of COPD: analysis from an Asthma + Lung UK survey.

BACKGROUND: Understanding the factors driving acute exacerbations of chronic obstructive pulmonary disease (COPD) is key to reducing their impact on human health and well-being. METHODS: 5997 people with COPD, mean 66 years, 64% female, completed an online survey between December 2020 and May 2021 about living with COPD, developed by the charity Asthma + Lung UK. RESULTS: The 3731 (62.2%) survey participants reporting frequent (≥2/year) exacerbations were more likely to smoke (adjusted OR (AOR) 1.70, 95% CI 1.470 to 1.98), have lower annual household income (≤£20 000 (AOR 1.72, 95% CI 1.36 to 2.17), live in a cold and damp home (AOR 1.78, 95% CI 1.50 to 2.11) and report previous occupational exposure to dust, fumes and chemicals. Smokers were more likely to report attending hospital to manage their most recent acute exacerbation of COPD compared with ex-smokers (AOR 1.25, 95% CI 0.99 to 1.59). DISCUSSION: Strategies to improve COPD outcomes must address issues of deprivation and social justice.

Smoking is associated with increased risk of cardiovascular events, disease severity, and mortality among patients hospitalized for SARS-CoV-2 infections.

The clinical sequalae of SARS-CoV-2 infection are in part dependent upon age and pre-existing health conditions. Although the use of tobacco products decreases cardiorespiratory fitness while increasing susceptibility to microbial infections, limited information is available on how smoking affects COVID-19 severity. Therefore, we examined whether smokers hospitalized for COVID-19 are at a greater risk for developing severe complications than non-smokers. Data were from all hospitalized adults with SARS-CoV-2 infection from the American Heart Association's Get-With-The-Guidelines COVID-19 Registry, from January 2020 to March 2021, which is a hospital-based voluntary national registry initiated in 2019 with 122 participating hospitals across the United States. Patients who reported smoking at the time of admission were classified as smokers. Severe outcome was defined as either death or the use of mechanical ventilation. Of the 31,545 patients in the cohort, 6,717 patients were 1:2 propensity matched (for age, sex, race, medical history, medications, and time-frame of hospital admission) and classified as current smokers or non-smokers according to admission data. In multivariable analyses, after adjusting for sociodemographic characteristics, medical history, medication use, and the time of hospital admission, patients self-identified as current smokers had higher adjusted odds of death (adjusted odds ratio [aOR], 1.41; 95% CI, 1.21-1.64), the use of mechanical ventilation (aOR 1.15; 95% CI 1.01-1.32), and increased risk of major adverse cardiovascular events (aOR, 1.27; 95% CI 1.05-1.52). Independent of sociodemographic characteristics and medical history, smoking was associated with a higher risk of severe COVID-19, including death.

Evaluation of Japanese university students' perception of smoking, interest in quitting, and smoking behavior: An examination and public health challenges during the COVID-19 pandemic.

This study examined college students' perceptions of the association between smoking and novel coronavirus disease 2019 (COVID-19), changes in smoking behavior, and interest in quitting categorized by smoking device, to identify public health challenges. A questionnaire survey was conducted among 8,547 students in a Japanese university in March and April 2021. In response to "Awareness of the increased risk of COVID-19 infection due to smoking and the tendency to develop severe disease", current smokers (70.2%) were more aware of the risk than non-smokers (49.8%) (p < 0.001), with no significant difference according to smoking device (p = 0.213). "Interest in quitting smoking" (p = 0.323), and "Changes in smoking behavior during the COVID-19 pandemic" (p = 0.146) did not differ by smoking device. However, approximately 50% of the respondents answered that they were not interested in quitting smoking, while two-thirds reported that the number of cigarettes they smoked did not change during the pandemic. During the COVID-19 pandemic, college students were found to be less interested in quitting and not likely to change their smoking behavior, despite the knowledge of the increased risk of COVID-19 transmission and severity of disease from smoking, regardless of smoking device.

The adverse inflammatory response of tobacco smoking in COVID-19 patients: biomarkers from proteomics and metabolomics.

Whether tobacco smoking affects the occurrence and development of coronavirus disease 2019 (COVID-19) is still a controversial issue, and potential biomarkers to predict the adverse outcomes of smoking in the progression of COVID-19 patients have not yet been elucidated. To further uncover their linkage and explore the effective biomarkers, three proteomics and metabolomics databases (i.e. smoking status, COVID-19 status, and basic information of population) from human serum proteomic and metabolomic levels were established by literature search. Bioinformatics analysis was then performed to analyze the interactions of proteins or metabolites among the above three databases and their biological effects. Potential confounding factors (age, body mass index (BMI), and gender) were controlled to improve the reliability. The obtained data indicated that smoking may increase the relative risk of conversion from non-severe to severe COVID-19 patients by inducing the dysfunctional immune response. Seven interacting proteins (C8A, LBP, FCN2, CRP, SAA1, SAA2, and VTN) were found to promote the deterioration of COVID-19 by stimulating the complement pathway and macrophage phagocytosis as well as inhibiting the associated negative regulatory pathways, which can be biomarkers to reflect and predict adverse outcomes in smoking COVID-19 patients. Three crucial pathways related to immunity and inflammation, including tryptophan, arginine, and glycerophospholipid metabolism, were considered to affect the effect of smoking on the adverse outcomes of COVID-19 patients. Our study provides novel evidence and corresponding biomarkers as potential predictors of severe disease progression in smoking COVID-19 patients, which is of great significance for preventing further deterioration in these patients.

Association of smoking, lung function and COPD in COVID-19 risk: a two-step Mendelian randomization study.

BACKGROUND AND AIMS: Smoking increases the risk of severe COVID-19, but whether lung function or chronic obstructive pulmonary disease (COPD) mediate the underlying associations is unclear. We conducted the largest Mendelian randomization study to date, to our knowledge, to address these questions. DESIGN: Mendelian randomization study using summary statistics from genome-wide association studies (GWAS), FinnGen and UK Biobank. The main analysis was the inverse variance weighted method, and we included a range of sensitivity analyses to assess the robustness of the findings. SETTING: GWAS which included international consortia, FinnGen and UK Biobank. PARTICIPANTS: The sample size ranged from 193 638 to 2 586 691. MEASUREMENTS: Genetic determinants of life-time smoking index, lung function [e.g. forced expiratory volume in 1 sec (FEV1 )], chronic obstructive pulmonary disease (COPD) and different severities of COID-19. RESULTS: Smoking increased the risk of COVID-19 compared with population controls for overall COVID-19 [odds ratio (OR) = 1.19 per standard deviation (SD) of life-time smoking index, 95% confidence interval (CI) = 1.11-1.27], hospitalized COVID-19 (OR = 1.67, 95% CI = 1.42-1.97) or severe COVID-19 (OR = 1.48, 95% CI = 1.10-1.98), with directionally consistent effects from sensitivity analyses. Lung function and COPD liability did not appear to mediate these associations. CONCLUSION: There is genetic evidence that smoking probably increases the risk of severe COVID-19 and possibly also milder forms of COVID-19. Decreased lung function and increased risk of chronic obstructive pulmonary disease do not seem to mediate the effect of smoking on COVID-19 risk.

Potential role of astrocyte angiotensin converting enzyme 2 in the neural transmission of COVID-19 and a neuroinflammatory state induced by smoking and vaping.

BACKGROUND: Knowledge of the entry receptors responsible for SARS-CoV-2 is key to understand the neural transmission and pathogenesis of COVID-19 characterized by a neuroinflammatory scenario. Understanding the brain distribution of angiotensin converting enzyme 2 (ACE2), the primary entry receptor for SARS-CoV-2, remains mixed. Smoking has been shown as a risk factor for COVID-19 severity and it is not clear how smoking exacerbates the neural pathogenesis in smokers. METHODS: Immunohistochemistry, real-time PCR and western blot assays were used to systemically examine the spatial-, cell type- and isoform-specific expression of ACE2 in mouse brain and primary cultured brain cells. Experimental smoking exposure was conducted to evaluate the effect of smoking on brain expression. RESULTS: We observed ubiquitous expression of ACE2 but uneven brain distribution, with high expression in the cerebral microvasculature, medulla oblongata, hypothalamus, subventricular zones, and meninges around medulla oblongata and hypothalamus. Co-staining with cell type-specific markers demonstrates ACE2 is primarily expressed in astrocytes around the microvasculature, medulla oblongata, hypothalamus, ventricular and subventricular zones of cerebral ventricles, and subependymal zones in rhinoceles and rostral migratory streams, radial glial cells in the lateral ventricular zones, tanycytes in the third ventricle, epithelial cells and stroma in the cerebral choroid plexus, as well as cerebral pericytes, but rarely detected in neurons and cerebral endothelial cells. ACE2 expression in astrocytes is further confirmed in primary cultured cells. Furthermore, isoform-specific analysis shows astrocyte ACE2 has the peptidase domain responsible for SARS-CoV-2 entry, indicating astrocytes are indeed vulnerable to SARS-CoV-2 infection. Finally, our data show experimental tobacco smoking and electronic nicotine vaping exposure increase proinflammatory and/or immunomodulatory cytokine IL-1a, IL-6 and IL-5 without significantly affecting ACE2 expression in the brain, suggesting smoking may pre-condition a neuroinflammatory state in the brain. CONCLUSIONS: The present study demonstrates a spatial- and cell type-specific expression of ACE2 in the brain, which might help to understand the acute and lasting post-infection neuropsychological manifestations in COVID-19 patients. Our data highlights a potential role of astrocyte ACE2 in the neural transmission and pathogenesis of COVID-19. This also suggests a pre-conditioned neuroinflammatory and immunocompromised scenario might attribute to exacerbated COVID-19 severity in the smokers.

Prevalence and Risk Factors of COPD in Nepal: A Systematic Review and Meta-Analysis.

BACKGROUND: Chronic Obstructive Pulmonary Disease is a common, preventable, and treatable disease. Here, we conducted a systematic review of Chronic Obstructive Pulmonary Disease and its risk factors in Nepal for the last two decades. METHODS: We systematically searched databases to find all relevant Chronic Obstructive Pulmonary Disease research papers from 2000 to 2020. Two reviewers screened the literature using Covidence based on the study protocol. Data extraction was done using Microsoft Excel from selected studies. Final data analysis was done using CMA v.3. Our review protocol is available in PROSPERO (CRD42020215486) on 20 November 2020. RESULTS: The database search revealed 1416 studies of which 13 were included in quantitative analysis. The prevalence of Chronic Obstructive Pulmonary Disease in the adult population was 22·7% (CI, 12·5-37·7) of whom 54·9% were female (CI, 51·9-57·9). Nearly three-fourth of the participants (73·1%) of Chronic Obstructive Pulmonary Disease patients had informal education (CI, 58·6-84·0). The commonest primary occupation was agriculture and farming in 39·4% (CI, 31·3-48·2), followed by homemaker (36·8%). It was observed that 28·5% of the Chronic Obstructive Pulmonary Disease patients were former smokers, 25·8% non-smokers, and 59·4% were current smokers. More than two-third (76·2%) of Chronic Obstructive Pulmonary Disease patients relied upon traditional firewood cooking, whereas only 14.6% was adopted fireless cooking. CONCLUSIONS: The pooled prevalence of Chronic Obstructive Pulmonary Disease in Nepal was significantly high with more cases in females compared to males. Smoking and traditional firewood cooking were major risk factors among Chronic Obstructive Pulmonary Disease cases in Nepal.