Comparison of the baseline characteristics and influencing factors of successful smoking cessation before and during the coronavirus disease pandemic.

INTRODUCTION: Travel and living environment restrictions, which may have positive or negative effects on smoking-related behaviors, were implemented to limit the COVID-19 pandemic. This study aimed to compare the baseline clinical characteristics and smoking cessation (SC) rate at 3 months of patients in an SC clinic in Hunan Province, China before and during the COVID-19 pandemic and identify influencing factors of successful SC. METHODS: Healthy patients at the SC clinic aged ≥18 years before the COVID-19 pandemic and during the COVID-19 pandemic were divided into groups A and B, respectively. The two groups' demographic data and smoking characteristics were compared, and SC interventions were applied by the same medical staff team through telephone follow-up and counselling during the SC procedure. RESULTS: Groups A and B included 306 and 212 patients, respectively, with no significant differences in demographic data. The SC rates of group A (pre COVID-19) and group B (during the COVID-19 pandemic) at 3 months were 23.5% and 30.7%, respectively, after the first SC visit. Those who chose to quit immediately or within 7 days were more successful than those who did not choose a quit date (p=0.002, p=0.000). Patients who learned about the SC clinic via network resources and other methods were more likely to succeed than those who learned about the clinic from their doctor or hospital publications (p=0.064, p=0.050). CONCLUSIONS: Planning to quit smoking immediately or within 7 days of visiting the SC clinic and learning about the SC clinic via the network media or other methods improved the likelihood of successful SC. SC clinics and the harm of tobacco should be promoted via network media. During consultation, the smokers should be encouraged to quit smoking immediately and establish an SC plan, which would help them to quit smoking.

Autoantibodies targeting G protein-coupled receptors: An evolving history in autoimmunity. Report of the 4th international symposium.

G protein-coupled receptors (GPCR) are involved in various physiological and pathophysiological processes. Functional autoantibodies targeting GPCRs have been associated with multiple disease manifestations in this context. Here we summarize and discuss the relevant findings and concepts presented in the biennial International Meeting on autoantibodies targeting GPCRs (the 4th Symposium), held in Lübeck, Germany, 15-16 September 2022. The symposium focused on the current knowledge of these autoantibodies' role in various diseases, such as cardiovascular, renal, infectious (COVID-19), and autoimmune diseases (e.g., systemic sclerosis and systemic lupus erythematosus). Beyond their association with disease phenotypes, intense research related to the mechanistic action of these autoantibodies on immune regulation and pathogenesis has been developed, underscoring the role of autoantibodies targeting GPCRs on disease outcomes and etiopathogenesis. The observation repeatedly highlighted that autoantibodies targeting GPCRs could also be present in healthy individuals, suggesting that anti-GPCR autoantibodies play a physiologic role in modeling the course of diseases. Since numerous therapies targeting GPCRs have been developed, including small molecules and monoclonal antibodies designed for treating cancer, infections, metabolic disorders, or inflammatory conditions, anti-GPCR autoantibodies themselves can serve as therapeutic targets to reduce patients' morbidity and mortality, representing a new area for the development of novel therapeutic interventions.

Air exposure and cell differentiation are essential for investigation of SARS-CoV-2 entry genes in human primary airway epithelial cells in vitro.

Background: In-vitro models of differentiated primary human airway epithelial cells are a valuable tool to study severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Through the use of these models, it has been shown that the expression of SARS-CoV-2 entry genes in human airway epithelia is influenced by various factors such as age, sex, smoking status, and pathogenic conditions. In this study, we aimed to determine the effects of cell culture conditions and donor demographic and clinical characteristics on the expression of SARS-CoV-2 entry genes including angiotensin converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2), cathepsin L (CTSL), and tyrosine protein kinase receptor UFO (AXL) in primary airway epithelial cells. Methods: Eleven lung cancer patients with or without chronic obstructive pulmonary disease (COPD) or asthma were recruited. Human bronchial epithelial cells (HBEC) or small airway epithelial cells (SAEC) isolated from submerged or air-liquid interface (ALI) cultures were analyzed by quantitative real-time PCR. We also tested for correlations with clinical data. Results: In ALI cultures, the expression of AXL was significantly higher in HBEC than in SAEC. In addition, the expression of ACE2, TMPRSS2, and CTSL was significantly increased in both HBEC and SAEC differentiated under ALI conditions compared with the submerged culture. Negligible association was found between the expression of SARS-CoV-2 entry genes in SAEC and the age, sex, smoking status, and complication of COPD, asthma or hypertension of the cell donors. Conclusion: These results demonstrate that the expression of SARS-CoV-2 entry genes in differentiated primary airway epithelial cells in-vitro is much more influenced by individual culture conditions than by specific characteristics of individual donors.

Investigation of Interaction between the Spike Protein of SARS-CoV-2 and ACE2-Expressing Cells Using an In Vitro Cell Capturing System.

BACKGROUND: The Interaction between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein with Angiotensin converting enzyme 2 (ACE2) on the host cells is a crucial step for the viral entry and infection. Therefore, investigating the molecular mechanism underlying the interaction is of great importance for the prevention of the infection of SARS-CoV-2. In this study, we aimed to establish a virus-free in vitro system to study the interaction between the spike protein and host cells of SARS-CoV-2. RESULTS: Our results show that ACE2-overexpressing HEK293T cells are captured by immobilized spike S1 protein, and the cell capturing process can be inhibited by the receptor binding domain of the spike protein or antibodies against S protein. Furthermore, spike S1 protein variant with D614G mutant show a higher cell capturing ability than wild type spike S1 protein and stronger binding capacity of its receptor ACE2. In addition, the captured cells can be eluted as living cells for further investigation. CONCLUSIONS: This study provides a new in vitro system for investigating the interaction between SARS-CoV-2 and host cells and purifying ACE2-expressing cells.

High Levels of Circulating IL-8 and Soluble IL-2R Are Associated With Prolonged Illness in Patients With Severe COVID-19.

Objectives: The coordinated immune response of the host is the key of the successful combat of the body against SARS-CoV-2 infection and is decisive for the development and progression of COVID-19. In this study, we aimed to investigate whether the immunological phenotype of patients are associated with duration of illness in patients with severe COVID-19. Method: In this single-center study, 69 patients with severe or critical COVID-19 were recruited retrospectively. Immunological parameters including counts of white blood cells, neutrophils, lymphocytes, the neutrophil-to-lymphocyte ratio, and levels of circulating cytokines and cytokine receptors were screened for their association with disease severity, survival and duration of illness of COVID-19. Results: Our data confirmed previous results that neutrophil-to-lymphocyte ratio and circulating levels of IL-6 represent prominent biomarker for the prediction of disease severity and survival of COVID-19. However, this study shows for the first time that duration of illness in patients with severe COVID-19 is positively associated with serum levels of IL-8 (P=0.004) and soluble IL-2Rα (P=0.025). Conclusion: The significant association of duration of illness with circulating levels of IL-8 and soluble IL-2Rα in patients with severe COVID-19 implicates that neutrophils and T cells are involved in the evolution of COVID-19.

Association of Cigarette Smoking, COPD, and Lung Cancer With Expression of SARS-CoV-2 Entry Genes in Human Airway Epithelial Cells.

SARS-CoV-2 enters into human airway epithelial cells via membrane fusion or endocytosis, and this process is dependent on ACE2, TMPRSS2, and cathepsin L. In this study, we examined the expression profiles of the three SARS-CoV-2 entry genes in primary human airway epithelial cells isolated from smokers, non-smokers, patients with chronic obstructive pulmonary disease or lung cancer. An exhaustive search of the GEO database was performed to identify eligible data on 1st June 2020. In total, 46 GEO datasets comprising transcriptomic data of 3,053 samples were identified as eligible data for further analysis. All meta-analysis were performed using RStudio. Standardized mean difference was utilized to assess the effect size of a factor on the expression of targeted genes and 95% confidence intervals (CIs) were calculated. This study revealed that (i) cigarette smoking is associated with an increased expression of ACE2 and TMPRSS2 and a decreased expression of cathepsin L; (ii) significant alternations in expression of ACE2, TMPRSS2, and cathepsin L were observed between current smokers and former smokers, but not between former smokers and never smokers; (iii) when compared with healthy controls with identical smoking status, patients with COPD or lung cancer showed negligible changes in expression of ACE2, TMPRSS2, and cathepsin L. Therefore, this study implicates cigarette smoking might contribute to the development of COVID-19 by affecting the expression of SARS-CoV-2 entry genes, while smoking cessation could be effective to reduce the potential risk.

Substance use treatment in Appalachian Tennessee amid COVID-19: Challenges and preparing for the future.

The COVID-19 pandemic created a number of rapidly emerging and unprecedented challenges for those engaged in substance use disorder (SUD) treatment, forcing service providers to improvise their treatment strategies as the crisis deepened. Drawing from five ongoing federally funded SUD projects in Appalachian Tennessee and hundreds of hours of meetings and interviews, this article explores the pandemic's impact on an already structurally disadvantaged region, its recovery community, and those who serve it. More specifically, we note detrimental effects of increased isolation since the implementation of COVID-19 safety measures, including stakeholders' reports of higher incidences of relapse, overdose, and deaths in the SUD population. Treatment providers have responded with telehealth services, but faced barriers in technology access and computer literacy among clients. Providers have also had to restrict new clients to accommodate social distancing, faced delays in health screening those they can accept, and denied family visitations, which has affected retention. In light of these challenges, several promising lessons for the future emerged--such as preparing for an influx of new and returning clients in need of SUD treatment; making arrangements for long-term housing and facility modification; developing a hybrid care delivery model, taking advantage of new regulations enabling telemedicine; budgeting for and storing personal protective equipment (PPE) and related supplies; and developing disaster protocols to withstand threats to intake, retention, and financial solvency.

Health service inequalities during the COVID-19 pandemic among elderly people living in large urban and non-urban areas in Florida, USA.

OBJECTIVE: Health inequalities were often exacerbated during the emerging epidemic. This study examined urban and non-urban inequalities in health services among COVID-19 patients aged 65 years or above in Florida, USA, from 2 March to 27 May 2020. METHODS: A retrospective time series analysis was conducted using individual patient records. Multivariable Poisson's and logistic models were used to calculate adjusted incidence of COVID-19 and the associated rates of emergency department visits, hospitalizations, and deaths. RESULTS: As of 27 May 2020, there were 13,659 elderly COVID-19 patients (people aged 65 years or above) in Florida and 14.9% of them died. Elderly people living in small metropolitan areas might be less likely to be confirmed with COVID-19 infection than those living in large metropolitan areas. The emergency department visit and hospitalization rates decreased significantly across metropolitan statuses for both men and women. Those patients living in small metropolitan or rural areas were less likely to be hospitalized than those living in large metropolitan areas (35% and 34% vs 41%). Elderly women aged 75 years or above living in rural areas had 113% higher adjusted incidence of COVID-19 than those living in large metropolitan areas, and the rates of hospitalizations were lower compared with those counterparts living in large metropolitan areas (29% vs 46%; odds ratio: 0.37 (0.25-0.54), p < 0.001). CONCLUSION: For elderly people living in Florida, USA, those living in small metropolitan or rural areas were less likely to receive adequate health care than those living in large or medium metropolitan areas during the COVID-19 pandemic.

Modeling return of the epidemic: Impact of population structure, asymptomatic infection, case importation and personal contacts.

BACKGROUND: Proactive interventions have halted the pandemic of coronavirus infected disease in some regions. However, without reaching herd immunity, the return of epidemic is possible. We investigate the impact of population structure, case importation, asymptomatic cases, and the number of contacts on a possible second wave of epidemic through mathematical modeling. METHODS: we built a modified Susceptible-exposed-Infectious-Removed (SEIR) model with parameters mirroring those of the COVID-19 pandemic and reported simulated characteristics of epidemics for incidence, hospitalizations and deaths under different scenarios. RESULTS: A larger percent of elderly people leads to higher number of hospitalizations, while a large percent of prior infection will effectively curb the epidemic. The number of imported cases and the speed of importation have small impact on the epidemic progression. However, a higher percent of asymptomatic cases slows the epidemic down and reduces the number of hospitalizations and deaths at the epidemic peak. Finally, reducing the number of contacts among young people alone has moderate effects on themselves, but little effects on the elderly population. However, reducing the number of contacts among elderly people alone can mitigate the epidemic significantly in both age groups, even though young people remain active within themselves. CONCLUSION: Reducing the number of contacts among high risk populations alone can mitigate the burden of epidemic in the whole society. Interventions targeting high risk groups may be more effective in containing or mitigating the epidemic.

Impact of mitigating interventions and temperature on the instantaneous reproduction number in the COVID-19 pandemic among 30 US metropolitan areas.

BACKGROUND: After more than six months into the coronavirus disease (COVID-19) pandemic, as of August 10, 2020, over 734,664 people had died worldwide. The current study aims to evaluate how mitigating interventions affected the epidemic process in the 30 largest metropolitan areas in the US and whether temperature played a role in the epidemic process. METHODS: Publicly available data for the time series of COVID-19 cases and deaths and weather were analyzed at the metropolitan level. The time-varying reproductive numbers (Rt) based on retrospective moving average were used to explore the trends. Student t-tests were used to compare temperature and peak Rt cross-sectionally. RESULTS: We found that virus transmissibility, measured by instantaneous reproduction number (Rt), had declined since the end of March for all areas and almost all of them reached a Rt of 1 or below after April 15, 2020. The timing of the main decline was concurrent with the implementation of mitigating interventions. However, the Rts remained around 1 for most areas since then and there were some small and short rebounds in some areas, suggesting a persistent epidemic in those areas when interventions were relaxed. Cities with warm temperature also tended to have a lower peak Rt than that of cities with cold temperature. However, they were not statistically significant and large geographic variations existed. CONCLUSIONS: Aggressive interventions might have mitigated the current pandemic of COVID-19, while temperature might have weak effects on the virus transmission. We may need to prepare for a possible return of the coronavirus outbreak.

Risk Interactions of Coronavirus Infection across Age Groups after the Peak of COVID-19 Epidemic.

BACKGROUND: The COVID-19 pandemic has incurred significant disease burden worldwide, particularly on the elderly population. This study aims to explore how risks of coronavirus infection interact across age groups using data from South Korea. METHODS: Daily new COVID-19 cases from 10 March to 30 April 2020 were scraped from online open sources. A multivariate vector autoregressive model for time series of count data was used to examine the risk interactions across age groups. Case counts from previous days were included as predictors to dynamically examine the change of risk patterns. RESULTS: In South Korea, the risk of coronavirus infection among elderly people was significantly affected by other age groups. An increase in virus infection among people aged 20-39 was associated with a double risk of infection among elderly people. Meanwhile, an increase in virus infection among elderly people was also significantly associated with risks of infection among other age groups. The risks of infection among younger people were relatively unaffected by that of other age groups. CONCLUSIONS: Protecting elderly people from coronavirus infection could not only reduce the risk of infection among themselves but also ameliorate the risks of virus infection among other age groups. Such interventions should be effective and for the long term.

Distinctive trajectories of the COVID-19 epidemic by age and gender: A retrospective modeling of the epidemic in South Korea.

OBJECTIVES: Elderly people had suffered a disproportionate burden of COVID-19. We hypothesized that males and females in different age groups might have different epidemic trajectories. METHODS: Using publicly available data from South Korea, daily new COVID-19 cases were assessed using generalized additive models, assuming Poisson and negative binomial distributions. Epidemic dynamics by age and gender groups were explored using interactions between smoothed time terms and age and gender. RESULTS: A negative binomial distribution fitted the daily case counts best. The relationship between the dynamic patterns of daily new cases and age groups was statistically significant (p<0.001), but this was not the case with gender groups. People aged 20-39 years led the epidemic processes in South Korean society with two peaks - one major peak around March 1 and a smaller peak around April 7, 2020. The epidemic process among people aged 60 or above trailed behind that of the younger age group, and with smaller magnitude. After March 15, there was a consistent decline of daily new cases among elderly people, despite large fluctuations in case counts among young adults. CONCLUSIONS: Although young people drove the COVID-19 epidemic throughout society, with multiple rebounds, elderly people could still be protected from infection after the peak of the epidemic.