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      COVID-19 risk and outcomes in patients with substance use disorders: analyses from electronic health records in the United States

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      Molecular Psychiatry
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          Abstract

          The global pandemic of COVID-19 is colliding with the epidemic of opioid use disorders (OUD) and other substance use disorders (SUD) in the United States (US). Currently, there is limited data on risks, disparity, and outcomes for COVID-19 in individuals suffering from SUD. This is a retrospective case-control study of electronic health records (EHRs) data of 73,099,850 unique patients, of whom 12,030 had a diagnosis of COVID-19. Patients with a recent diagnosis of SUD (within past year) were at significantly increased risk for COVID-19 (adjusted odds ratio or AOR = 8.699 [8.411–8.997], P < 10−30), an effect that was strongest for individuals with OUD (AOR = 10.244 [9.107–11.524], P < 10−30), followed by individuals with tobacco use disorder (TUD) (AOR = 8.222 ([7.925–8.530], P < 10−30). Compared to patients without SUD, patients with SUD had significantly higher prevalence of chronic kidney, liver, lung diseases, cardiovascular diseases, type 2 diabetes, obesity and cancer. Among patients with recent diagnosis of SUD, African Americans had significantly higher risk of COVID-19 than Caucasians (AOR = 2.173 [2.01–2.349], P < 10−30), with strongest effect for OUD (AOR = 4.162 [3.13–5.533], P < 10−25). COVID-19 patients with SUD had significantly worse outcomes (death: 9.6%, hospitalization: 41.0%) than general COVID-19 patients (death: 6.6%, hospitalization: 30.1%) and African Americans with COVID-19 and SUD had worse outcomes (death: 13.0%, hospitalization: 50.7%) than Caucasians (death: 8.6%, hospitalization: 35.2%). These findings identify individuals with SUD, especially individuals with OUD and African Americans, as having increased risk for COVID-19 and its adverse outcomes, highlighting the need to screen and treat individuals with SUD as part of the strategy to control the pandemic while ensuring no disparities in access to healthcare support.

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          Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

          Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
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            COVID-19 and smoking: A systematic review of the evidence

            COVID-19 is a coronavirus outbreak that initially appeared in Wuhan, Hubei Province, China, in December 2019, but it has already evolved into a pandemic spreading rapidly worldwide 1,2 . As of 18 March 2020, a total number of 194909 cases of COVID-19 have been reported, including 7876 deaths, the majority of which have been reported in China (3242) and Italy (2505) 3 . However, as the pandemic is still unfortunately under progression, there are limited data with regard to the clinical characteristics of the patients as well as to their prognostic factors 4 . Smoking, to date, has been assumed to be possibly associated with adverse disease prognosis, as extensive evidence has highlighted the negative impact of tobacco use on lung health and its causal association with a plethora of respiratory diseases 5 . Smoking is also detrimental to the immune system and its responsiveness to infections, making smokers more vulnerable to infectious diseases 6 . Previous studies have shown that smokers are twice more likely than non-smokers to contract influenza and have more severe symptoms, while smokers were also noted to have higher mortality in the previous MERS-CoV outbreak 7,8 . Given the gap in the evidence, we conducted a systematic review of studies on COVID-19 that included information on patients’ smoking status to evaluate the association between smoking and COVID-19 outcomes including the severity of the disease, the need for mechanical ventilation, the need for intensive care unit (ICU) hospitalization and death. The literature search was conducted on 17 March 2020, using two databases (PubMed, ScienceDirect), with the search terms: [‘smoking’ OR ‘tobacco’ OR ‘risk factors’ OR ‘smoker*’] AND [‘COVID-19’ OR ‘COVID 19’ OR ‘novel coronavirus’ OR ‘sars cov-2’ OR ‘sars cov 2’] and included studies published in 2019 and 2020. Further inclusion criteria were that the studies were in English and referred to humans. We also searched the reference lists of the studies included. A total of 71 studies were retrieved through the search, of which 66 were excluded after full-text screening, leaving five studies that were included. All of the studies were conducted in China, four in Wuhan and one across provinces in mainland China. The populations in all studies were patients with COVID-19, and the sample size ranged from 41 to 1099 patients. With regard to the study design, retrospective and prospective methods were used, and the timeframe of all five studies covered the first two months of the COVID-19 pandemic (December 2019, January 2020). Specifically, Zhou et al. 9 studied the epidemiological characteristics of 191 individuals infected with COVID-19, without, however, reporting in more detail the mortality risk factors and the clinical outcomes of the disease. Among the 191 patients, there were 54 deaths, while 137 survived. Among those that died, 9% were current smokers compared to 4% among those that survived, with no statistically significant difference between the smoking rates of survivors and non-survivors (p=0.21) with regard to mortality from COVID-19. Similarly, Zhang et al. 10 presented clinical characteristics of 140 patients with COVID-19. The results showed that among severe patients (n=58), 3.4% were current smokers and 6.9% were former smokers, in contrast to non-severe patients (n=82) among which 0% were current smokers and 3.7% were former smokers , leading to an OR of 2.23; (95% CI: 0.65–7.63; p=0.2). Huang et al. 11 studied the epidemiological characteristics of COVID-19 among 41 patients. In this study, none of those who needed to be admitted to an ICU (n=13) was a current smoker. In contrast, three patients from the non-ICU group were current smokers, with no statistically significant difference between the two groups of patients (p=0.31), albeit the small sample size of the study. The largest study population of 1099 patients with COVID-19 was provided by Guan et al. 12 from multiple regions of mainland China. Descriptive results on the smoking status of patients were provided for the 1099 patients, of which 173 had severe symptoms, and 926 had non-severe symptoms. Among the patients with severe symptoms, 16.9% were current smokers and 5.2% were former smokers, in contrast to patients with non-severe symptoms where 11.8% were current smokers and 1.3% were former smokers. Additionally, in the group of patients that either needed mechanical ventilation, admission to an ICU or died, 25.5% were current smokers and 7.6% were former smokers. In contrast, in the group of patients that did not have these adverse outcomes, only 11.8% were current smokers and 1.6% were former smokers. No statistical analysis for evaluating the association between the severity of the disease outcome and smoking status was conducted in that study. Finally, Liu et al. 13 found among their population of 78 patients with COVID-19 that the adverse outcome group had a significantly higher proportion of patients with a history of smoking (27.3%) than the group that showed improvement or stabilization (3.0%), with this difference statistically significant at the p=0.018 level. In their multivariate logistic regression analysis, the history of smoking was a risk factor of disease progression (OR=14.28; 95% CI: 1.58–25.00; p= 0.018). We identified five studies that reported data on the smoking status of patients infected with COVID-19. Notably, in the largest study that assessed severity, there were higher percentages of current and former smokers among patients that needed ICU support, mechanical ventilation or who had died, and a higher percentage of smokers among the severe cases 12 . However, from their published data we can calculate that the smokers were 1.4 times more likely (RR=1.4, 95% CI: 0.98–2.00) to have severe symptoms of COVID-19 and approximately 2.4 times more likely to be admitted to an ICU, need mechanical ventilation or die compared to non-smokers (RR=2.4, 95% CI: 1.43–4.04). In conclusion, although further research is warranted as the weight of the evidence increases, with the limited available data, and although the above results are unadjusted for other factors that may impact disease progression, smoking is most likely associated with the negative progression and adverse outcomes of COVID-19. Table 1 Overview of the five studies included in the systematic review Title Setting Population Study design and time horizon Outcomes Smoking rates by outcome Zhou et al. 9 (2020)Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Jinyintan Hospital and Wuhan Pulmonary Hospital, Wuhan, China All adult inpatients (aged ≥18 years) with laboratory confirmed COVID-19 (191 patients) Retrospective multicenter cohort study until 31 January 2020 Mortality 54 patients died during hospitalisation and 137 were discharged Current smokers: n=11 (6%)Non-survivors: n=5 (9%)Survivors: n=6 (4%)(p=0.20) Current smoker vs non-smokerUnivariate logistic regression(OR=2.23; 95% CI: 0.65–7.63; p=0.2) Zhang et al. 10 (2020)Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China No. 7 Hospital of Wuhan, China All hospitalised patients clinically diagnosed as ‘viral pneumonia’ based on their clinical symptoms with typical changes in chest radiology (140 patients) Retrospective 16 January to 3 February 2020 Disease Severity Non-severepatients: n=82Severe patients:n=58 Disease Severity Former smokers: n=7Severe: n=4 (6.9%)Non-severe: n=3 (3.7%) (p= 0.448) Current smokers: n=2Severe: n=2 (3.4%)Non-severe: n=0 (0%) Guan et al. 12 (2019)Clinical Characteristics of Coronavirus Disease 2019 in China 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China Patients with laboratory-confirmed COVID-19 (1099 patients) Retrospective until 29 January 2020 Severity and admission to an ICU, the use of mechanical ventilation, or death Non-severe patients: n=926 Severe patients: n=173 By severity Severe cases16.9% current smokers5.2% former smokers77.9% never smokers Non-severe cases11.8% current smokers1.3% former smokers86.9% never smokers By mechanical ventilation, ICU or death Needed mechanical ventilation, ICU or died25.8% current smokers7.6% former smokers66.7% non-smokers No mechanical ventilation, ICU or death11.8% current smokers1.6% former smokers86.7% never smokers Huang et al. 11 (2020)Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China A hospital in Wuhan, China Laboratory-confirmed 2019-nCoV patients in Wuhan (41 patients) Prospective from 16 December 2019 to 2 January 2020 Mortality As of 22 January 2020, 28 (68%) of 41 patients were discharged and 6 (15%) patients died Current smokers: n=3ICU care: n=0Non-ICU care: n=3 (11%) Current smokers in ICU care vs non-ICU care patients (p=0.31) Liu et al. 13 (2019)Analysis of factors associated with disease outcomes in hospitalised patients with 2019 novel coronavirus disease Three tertiary hospitals in Wuhan, China Patients tested positive for COVID-19 (78 patients) Retrospective multicentre cohort study from 30 December 2019 to 15 January 2020 Disease progression 11 patients (14.1%) in the progression group 67 patients (85.9%) in the improvement/stabilization group 2 deaths Negative progression group: 27.3% smokersIn the improvement group: 3% smokers The negative progression group had a significantly higher proportion of patients with a history of smoking than the improvement/stabilisation group (27.3% vs 3.0%)Multivariate logistic regression analysis indicated that the history of smoking was a risk factor of disease progression (OR=14.28; 95% CI: 1.58–25.00; p= 0.018)
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              Tobacco Product Use and Cessation Indicators Among Adults — United States, 2018

              Cigarette smoking is the leading cause of preventable disease and death in the United States ( 1 ). The prevalence of adult cigarette smoking has declined in recent years to 14.0% in 2017 ( 2 ). However, an array of new tobacco products, including e-cigarettes, has entered the U.S. market ( 3 ). To assess recent national estimates of tobacco product use among U.S. adults aged ≥18 years, CDC, the Food and Drug Administration (FDA), and the National Cancer Institute analyzed data from the 2018 National Health Interview Survey (NHIS). In 2018, an estimated 49.1 million U.S. adults (19.7%) reported currently using any tobacco product, including cigarettes (13.7%), cigars (3.9%), e-cigarettes (3.2%), smokeless tobacco (2.4%), and pipes* (1.0%). Most tobacco product users (83.8%) reported using combustible products (cigarettes, cigars, or pipes), and 18.8% reported using two or more tobacco products. The prevalence of any current tobacco product use was higher in males; adults aged ≤65 years; non-Hispanic American Indian/Alaska Natives; those with a General Educational Development certificate (GED); those with an annual household income 30% that are not presented. ††† Hispanic persons could be of any race. All other racial/ethnic groups were non-Hispanic. §§§ Northeast: Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, and Vermont; Midwest: Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, Ohio, South Dakota, and Wisconsin; South: Alabama, Arkansas, Delaware, District of Columbia, Florida, Georgia, Kentucky, Louisiana, Maryland, Mississippi, North Carolina, Oklahoma, South Carolina, Tennessee, Texas, Virginia, and West Virginia; West: Alaska, Arizona, California, Colorado, Hawaii, Idaho, Montana, Nevada, New Mexico, Oregon, Utah, Washington, and Wyoming. ¶¶¶ Based on income variables from the family file (n = 8,310 missing valid income data). Imputed income files were not used in this analysis. **** Private coverage: includes adults who have any comprehensive private insurance plan (including health maintenance organizations and preferred provider organizations). Medicaid: for adults aged 30%; neither daily use nor nondaily use is presented. The figure is a bar chart showing the prevalence of daily and nondaily use of selected tobacco products among adults aged ≥18 years who currently use each tobacco product, in the United States, during 2018. The prevalence of any current tobacco product use was higher among males (25.8%) than among females (14.1%) and among persons aged 25–44 years (23.8%), 45–64 years (21.3%), and 18–24 years (17.1%) than among those aged ≥65 years (11.9%) (Table). Current tobacco product use was also higher among non-Hispanic American Indian/Alaska Native adults (32.3%), non-Hispanic multiracial adults (25.4%), non-Hispanic whites (21.9%), non-Hispanic blacks (19.3%), and Hispanic adults (13.8%) than among non-Hispanic Asian adults (10.0%), as well as among those who lived in the Midwest (23.6%) or the South U.S. Census regions (21.4%) than among those who lived in the West (15.3%) or the Northeast (17.5%). The prevalence of current tobacco product use was also higher among persons who had a GED (41.4%) than among those with other levels of education and among those who were divorced, separated, or widowed (22.6%) or single, never married, or not living with a partner (21.1%) than among those married or living with a partner (18.4%). Current tobacco product use was higher among persons with an annual household income 1 day during the past 12 months because they were trying to quit smoking and former smokers who quit during the past year. † Percentage of former cigarette smokers who quit smoking for ≥6 months during the past year, among current smokers who smoked for ≥2 years and former smokers who quit during the past year. § Percentage of persons who ever smoked (≥100 cigarettes during lifetime) who have quit smoking. The figure is a line chart showing the prevalence of past-year quit attempts and recent cessation and quit ratio among cigarette smokers aged ≥18 years, in the United States, during 2009–2018. Discussion The approximate two thirds decline in adult cigarette smoking prevalence that has occurred since 1965 represents a major public health success ( 1 ). In 2018, 13.7% of U.S. adults aged ≥18 years currently smoked cigarettes, the lowest prevalence recorded since 1965. However, no significant change in cigarette smoking prevalence occurred during 2017–2018. Most cigarette smokers and smokeless tobacco users reported daily use, whereas most e-cigarette and cigar users reported nondaily use. Even nondaily use of cigarettes has been linked to increased mortality risk ( 6 ). Quitting smoking at any age is beneficial for health ( 1 , 4 ). During 2009–2018, significant linear increases occurred in quit attempts, recent successful cessation, and quit ratio. Population-based tobacco control interventions, including high-impact tobacco education campaigns like CDC’s Tips From Former Smokers (https://www.cdc.gov/tobacco/campaign/tips/index.html) campaign and FDA’s Every Try Counts campaign (https://www.fda.gov/tobacco-products/every-try-counts-campaign), combined with barrier-free access to evidence-based cessation treatments, can both motivate persons who use tobacco products to try to quit and help them succeed in quitting. The prevalence of adult e-cigarette use increased from 2.8% in 2017 to 3.2% in 2018 but was much lower than the 20.8% ( 7 ) of U.S. high school students reporting past 30-day e-cigarette use in 2018. The prevalence of e-cigarette use among persons aged 18–24 years is higher than that among other adult age groups, and e-cigarette use in this age group increased from 5.2% in 2017 ( 2 ) to 7.6% in 2018. During 2014–2017 there had been a downward trajectory of adult e-cigarette use ( 2 , 8 ), but during 2017–2018 a significant increase in adult e-cigarette use was detected for the first time. This increase might be related to the emergence of new types of e-cigarettes, especially “pod-mod” devices, which frequently use nicotine salts as opposed to the free-base nicotine used in other e-cigarettes and tobacco products. Sales of JUUL, a pod-mod device, increased by approximately 600% from 2016 to 2017, making it the dominant e-cigarette product in the United States by the end of 2017 ( 9 ). Further research is needed to monitor patterns of e-cigarette use and the relationship between use of e-cigarettes and other tobacco products (e.g., cigarette smoking). The findings in this report are subject to at least three limitations. First, responses were self-reported and were not validated by biochemical testing. However, self-reported smoking status correlates highly with serum cotinine levels ( 10 ). Second, because NHIS is limited to the noninstitutionalized U.S. civilian population, the results are not generalizable to institutionalized populations and persons in the military. Finally, the NHIS Sample Adult response rate of 53.1% might have resulted in nonresponse bias. Coordinated efforts at the local, state, and national levels are needed to continue progress toward reducing tobacco-related disease and death in the United States. Proven strategies include implementation of tobacco price increases, comprehensive smoke-free policies, high-impact antitobacco media campaigns, barrier-free cessation coverage, and comprehensive state tobacco control programs, combined with regulation of the manufacturing, marketing, and distribution of all tobacco products ( 1 , 4 ). Summary What is already known about this topic? Cigarette smoking is the leading cause of preventable disease and death in the United States. Adult cigarette smoking prevalence has declined; however, new tobacco products, including e-cigarettes, have entered the U.S. market. What is added by this report? In 2018, approximately 20% of U.S. adults currently used any tobacco product; cigarette smoking reached an all-time low (13.7%). During 2009–2018, significant increases in three cigarette cessation indicators occurred. During 2017–2018, e-cigarette and smokeless tobacco product use prevalence increased. What are the implications for public health practice? Continued surveillance is critical to informing tobacco control efforts at the national, state, and local levels. Coordinated efforts and regulation of all tobacco products are needed to reduce tobacco-related disease and death in the United States.
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                Contributors
                Journal
                Molecular Psychiatry
                Mol Psychiatry
                Springer Science and Business Media LLC
                1359-4184
                1476-5578
                September 14 2020
                Article
                10.1038/s41380-020-00880-7
                8dd8199a-aa31-4cc7-89e5-1adea690cc6f
                © 2020

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