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1.
J. oral res. (Impresa) ; 11(6): 1-13, nov. 3, 2022. ilus, tab
Article in English | WHO COVID, LILACS (Americas) | ID: covidwho-20234393

ABSTRACT

Introduction: The consumption of alcoholic beverages reduces the body's ability to deal with dangerous situations and exposes people to trauma. Objective: To determine the association between the consumption of alcoholic beverages and the characteristics of maxillofacial fractures treated at a Cuban university hospital in the context of COVID-19. Material and Methods: An observational, analytical, and cross-sectional study was carried out in the Maxillofacial Surgery unit at the "Carlos Manuel de Céspedes" General University Hospital during the year 2020. Prevalence ratios, 95% confidence intervals and p-values were obtained using generalized linear models. Results: In 58.23% of the cases, fractures were related to the consumption of alcoholic beverages. The fundamental etiology was interpersonal violence (47.75%), regardless of the consumption of alcoholic beverages. There was a prevalence of patients with nasal fractures (n=98; 55.06%), among which, 35.71% had consumed alcoholic beverages at the time of the trauma. Being male (p=0.005), the lack of university studies (p=0.007), the need for surgical treatment (p<0.001), the fractures of the zygomaticomaxillary complex (p=0.023), and the traumas that occurred during the weekends (p<0.001) or during the month of June (p=0.029) were factors associated with a higher frequency of fractures related to the consumption of alcoholic beverages. There was a lower frequency of fractures associated with alcohol consumption during the months of January (p=0.006) and March (p=0.001). Conclusion: Six out of ten cases were under the influence of alcoholic beverages. There was a greater number of young and male patients, mainly due to interpersonal violence.


Introducción: La ingestión de bebidas alcohólicas disminuye la capacidad del organismo para enfrentar situaciones de peligro y lo predispone a sufrir traumatismos diversos. Objetivo: Determinar la asociación entre el consumo de bebidas alcohólicas y las características de las fracturas maxilofaciales atendidas en un hospital universitario cubano en el contexto de la COVID-19. Material y Métodos: Estudio observacional, analítico y transversal realizado en el servicio de Cirugía Maxilofacial del Hospital General Universitario "Carlos Manuel de Céspedes" durante el 2020. Se obtuvieron razones de prevalencia, intervalos de confianza a 95% y valores p mediante modelos lineales generalizados. Resultados: En el 58.23% de los casos las fracturas se relacionaron con la ingestión de bebidas alcohólicas. La etiología fundamental fue la violencia interpersonal (47.75%), independientemente del consumo o no de bebidas alcohólicas. Predominaron los pacientes con fracturas nasales (n=98; 55.06%), en los que el 35.71% había consumido bebidas alcohólicas en el momento del trauma. El sexo masculino (p=0.005), la carencia de estudios universitarios (p=0.007), la necesidad de tratamiento quirúrgico (p<0.001), las fracturas del complejo cigomático-maxilar (p=0.023), los traumas sucedidos durante los fines de semanas (p<0.001) o durante el mes de junio (p=0.029) fueron factores asociados a una mayor frecuencia de fracturas relacionadas con el consumo de bebidas alcohólicas. Hubo menor frecuencia de fracturas asociadas a este consumo durante los meses de enero (p=0.006) y marzo (p= 0.001). Conclusión: Seis de cada diez casos estuvieron bajo los efectos de la ingestión de bebidas alcohólicas. Existió una mayor afectación de pacientes jóvenes, masculinos, a causa principalmente de la violencia interpersonal.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Young Adult , Skull Fractures/etiology , Accidental Falls/statistics & numerical data , Alcohol Drinking/physiopathology , COVID-19 , Maxillofacial Injuries/etiology , Cross-Sectional Studies , Cuba/epidemiology , Alcoholic Beverages , Alcoholism/complications , Pandemics
3.
PLoS Med ; 20(2): e1004134, 2023 02.
Article in English | MEDLINE | ID: covidwho-2235368

ABSTRACT

BACKGROUND: Meta-analyses have shown that preexisting mental disorders may increase serious Coronavirus Disease 2019 (COVID-19) outcomes, especially mortality. However, most studies were conducted during the first months of the pandemic, were inconclusive for several categories of mental disorders, and not fully controlled for potential confounders. Our study objectives were to assess independent associations between various categories of mental disorders and COVID-19-related mortality in a nationwide sample of COVID-19 inpatients discharged over 18 months and the potential role of salvage therapy triage to explain these associations. METHODS AND FINDINGS: We analysed a nationwide retrospective cohort of all adult inpatients discharged with symptomatic COVID-19 between February 24, 2020 and August 28, 2021 in mainland France. The primary exposure was preexisting mental disorders assessed from all discharge information recorded over the last 9 years (dementia, depression, anxiety disorders, schizophrenia, alcohol use disorders, opioid use disorders, Down syndrome, other learning disabilities, and other disorder requiring psychiatric ward admission). The main outcomes were all-cause mortality and access to salvage therapy (intensive-care unit admission or life-saving respiratory support) assessed at 120 days after recorded COVID-19 diagnosis at hospital. Independent associations were analysed in multivariate logistic models. Of 465,750 inpatients with symptomatic COVID-19, 153,870 (33.0%) were recorded with a history of mental disorders. Almost all categories of mental disorders were independently associated with higher mortality risks (except opioid use disorders) and lower salvage therapy rates (except opioid use disorders and Down syndrome). After taking into account the mortality risk predicted at baseline from patient vulnerability (including older age and severe somatic comorbidities), excess mortality risks due to caseload surges in hospitals were +5.0% (95% confidence interval (CI), 4.7 to 5.2) in patients without mental disorders (for a predicted risk of 13.3% [95% CI, 13.2 to 13.4] at baseline) and significantly higher in patients with mental disorders (+9.3% [95% CI, 8.9 to 9.8] for a predicted risk of 21.2% [95% CI, 21.0 to 21.4] at baseline). In contrast, salvage therapy rates during caseload surges in hospitals were significantly higher than expected in patients without mental disorders (+4.2% [95% CI, 3.8 to 4.5]) and lower in patients with mental disorders (-4.1% [95% CI, -4.4; -3.7]) for predicted rates similar at baseline (18.8% [95% CI, 18.7-18.9] and 18.0% [95% CI, 17.9-18.2], respectively). The main limitations of our study point to the assessment of COVID-19-related mortality at 120 days and potential coding bias of medical information recorded in hospital claims data, although the main study findings were consistently reproduced in multiple sensitivity analyses. CONCLUSIONS: COVID-19 patients with mental disorders had lower odds of accessing salvage therapy, suggesting that life-saving measures at French hospitals were disproportionately denied to patients with mental disorders in this exceptional context.


Subject(s)
Alcoholism , COVID-19 , Down Syndrome , Mental Disorders , Adult , Humans , COVID-19/complications , Cohort Studies , COVID-19 Testing , Retrospective Studies , Alcoholism/complications , Mental Disorders/diagnosis
4.
JAMA Netw Open ; 6(2): e2255496, 2023 02 01.
Article in English | MEDLINE | ID: covidwho-2233956

ABSTRACT

Importance: The COVID-19 pandemic affects many diseases, including alcohol use disorders (AUDs). As the pandemic evolves, understanding the association of a new diagnosis of AUD with COVID-19 over time is required to mitigate negative consequences. Objective: To examine the association of COVID-19 infection with new diagnosis of AUD over time from January 2020 through January 2022. Design, Setting, and Participants: In this retrospective cohort study of electronic health records of US patients 12 years of age or older, new diagnoses of AUD were compared between patients with COVID-19 and patients with other respiratory infections who had never had COVID-19 by 3-month intervals from January 20, 2020, through January 27, 2022. Exposures: SARS-CoV-2 infection or non-SARS-CoV-2 respiratory infection. Main Outcomes and Measures: New diagnoses of AUD were compared in COVID-19 and propensity score-matched control cohorts by hazard ratios (HRs) and 95% CIs from either 14 days to 3 months or 3 to 6 months after the index event. Results: This study comprised 1 201 082 patients with COVID-19 (56.9% female patients; 65.7% White; mean [SD] age at index, 46.2 [18.9] years) and 1 620 100 patients with other respiratory infections who had never had COVID-19 (60.4% female patients; 71.1% White; mean [SD] age at index, 44.5 [20.6] years). There was a significantly increased risk of a new diagnosis of AUD in the 3 months after COVID-19 was contracted during the first 3 months of the pandemic (block 1) compared with control cohorts (HR, 2.53 [95% CI, 1.82-3.51]), but the risk decreased to nonsignificance in the next 3 time blocks (April 2020 to January 2021). The risk for AUD diagnosis increased after infection in January to April 2021 (HR, 1.30 [95% CI, 1.08-1.56]) and April to July 2021 (HR, 1.80 [95% CI, 1.47-2.21]). The result became nonsignificant again in blocks 7 and 8 (COVID-19 diagnosis between July 2021 and January 2022). A similar temporal pattern was seen for new diagnosis of AUD 3 to 6 months after infection with COVID-19 vs control index events. Conclusions and Relevance: Elevated risk for AUD after COVID-19 infection compared with non-COVID-19 respiratory infections during some time frames may suggest an association of SARS-CoV-2 infection with the pandemic-associated increase in AUD. However, the lack of excess hazard in most time blocks makes it likely that the circumstances surrounding the pandemic and the fear and anxiety they created also were important factors associated with new diagnoses of AUD.


Subject(s)
Alcoholism , COVID-19 , Humans , Female , Young Adult , Adult , Male , COVID-19/diagnosis , COVID-19/epidemiology , Alcoholism/complications , Alcoholism/epidemiology , COVID-19 Testing , Retrospective Studies , Pandemics , SARS-CoV-2
5.
Liver Transpl ; 29(5): 539-547, 2023 05 01.
Article in English | MEDLINE | ID: covidwho-2233255

ABSTRACT

Worsened by the COVID-19 pandemic, alcohol use is one of the leading causes of preventable death in the US, in large part due to alcohol-associated liver disease. Throughout history, liver transplantation for this population has been controversial, and many policies and regulations have existed to limit access to lifesaving transplant for patients who use alcohol. In recent years, the rates of liver transplantation for patients with alcohol-associated liver disease have increased dramatically; however, disparities persist. For instance, many criteria used in evaluation for transplant listing, such as social support and prior knowledge of the harms of alcohol use, are not evidence based and may selectively disadvantage patients with alcohol use disorder. In addition, few transplant providers have adequate training in the treatment of alcohol use disorder, and few transplant centers offer specialized addiction treatment. Finally, current approaches to liver transplantation would benefit from adopting principles of harm reduction, which have demonstrated efficacy in the realm of addiction medicine for years. As we look toward the future, we must emphasize the use of evidence-based measures in selecting patients for listing, ensure access to high-quality addiction care for all patients pretransplant and posttransplant, and adopt harm reduction beliefs to better address relapse when it inevitably occurs. We believe that only by addressing each of these issues will we be able to ensure a more equitable distribution of resources in liver transplantation for all patients.


Subject(s)
Alcoholism , COVID-19 , Liver Diseases, Alcoholic , Liver Transplantation , Humans , Alcoholism/complications , Alcoholism/epidemiology , Alcoholism/therapy , Liver Transplantation/adverse effects , Pandemics , COVID-19/epidemiology , Liver Diseases, Alcoholic/epidemiology , Liver Diseases, Alcoholic/surgery , Liver Diseases, Alcoholic/complications
7.
Hepatol Commun ; 6(12): 3433-3442, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2127708

ABSTRACT

Naltrexone is an approved drug for management of alcohol use disorder (AUD), but data in patients with liver disease (LD) are limited. We aimed to evaluate the safety of naltrexone in those with LD. This is a retrospective cohort of adults with and without LD who were prescribed naltrexone for AUD from 2015 to 2019 in a safety-net setting. Naltrexone hepatic safety was determined by liver enzyme changes during and after compared to before naltrexone prescription as well as rates of subsequent hospitalization and death by Kaplan-Meier methods. Factors associated with hospitalization were examined by Cox regression. Of 160 patients prescribed naltrexone for AUD, 100 (63%) had LD and 47 (47%) of those with LD had cirrhosis (47% decompensated). The total cohort, LD, and cirrhosis groups had lower adjusted mean aspartate aminotransferase and alanine aminotransferase levels after versus before naltrexone prescription (p < 0.001). Two-year survival was 97.7% (95% confidence interval [CI], 84.6-99.7), 95.4% (95% CI, 82.8-98.8), 90.8% (95% CI, 73.5-97.0), and 81.3% (95% CI, 41.2-93.8) in those without LD, LD without cirrhosis, cirrhosis, and decompensated cirrhosis groups (p = 0.46), respectively. Alcohol-related 2-year hospitalization rates were 8.2% (95% CI, 2.7-24), 27.7% (95% CI, 16.6-44.0), 40.5% (95% CI, 24.8-61.6), and 41.7% (95% CI, 23.3-66.6) for the groups without LD, LD without cirrhosis, cirrhosis, and decompensated cirrhosis (p = 0.007), respectively. Independent predictors of subsequent hospitalization were LD, (hazard ratio [HR], 3.70; 95% CI, 1.19-11.51; p = 0.02), cirrhosis (HR, 5.16; 95% CI, 1.69-15.75), and shorter duration (≤30 days) of naltrexone prescription (HR, 2.50; 95% CI, 1.l2-5.20; p = 0.01). Conclusion: Naltrexone is safe to use in patients with underlying LD, including those with compensated cirrhosis. Although encouraging, more safety data are needed for those with decompensated cirrhosis.


Subject(s)
Alcoholism , Liver Diseases , Adult , Humans , Naltrexone/adverse effects , Alcoholism/complications , Retrospective Studies , Liver Cirrhosis/complications , Liver Diseases/complications
8.
Ann Intern Med ; 175(10): ITC145-ITC160, 2022 10.
Article in English | MEDLINE | ID: covidwho-2090814

ABSTRACT

Unhealthy alcohol use-the consumption of alcohol at a level that has caused or has the potential to cause adverse physical, psychological, or social consequences-is common, underrecognized, and undertreated. For example, data from the 2020 National Survey on Drug Use and Health indicate that 7.0% of adults reported heavy alcohol use in the previous month, and only 4.2% of adults with alcohol use disorder received treatment. Primary care is an important setting for optimizing screening and treatment of unhealthy alcohol use to promote individual and public health.


Subject(s)
Alcohol Drinking , Alcoholism , Adult , Alcohol Drinking/adverse effects , Alcohol Drinking/epidemiology , Alcoholism/complications , Alcoholism/epidemiology , Alcoholism/therapy , Ethanol , Humans , Mass Screening
9.
J Clin Psychiatry ; 83(5)2022 08 29.
Article in English | MEDLINE | ID: covidwho-2024669

ABSTRACT

Objective: While psychiatric disorders have been recognized as a risk factor for COVID-19 outcomes, the impact of substance use disorders (SUD) on COVID-19 outcomes has not, to date, been examined in a systematic manner. We examined the association between SUD (cannabis, cocaine, alcohol, opioid, and benzodiazepine) as well as psychiatric diagnoses (schizophrenia, mood disorders, anxiety disorders) and COVID-19 outcomes in a large, retrospective cohort study.Methods: COVID-19-positive patients admitted to a large health care system in the US between January and December 2020 were included in this study. SUD and psychiatric diagnoses were identified from urine toxicology reports and ICD-10 diagnosis codes in the electronic medical record, respectively. Multivariable logistic regression was performed controlling for potential confounders such as age, race, sex, smoking status, and medical comorbidities. COVID-19-relevant outcomes included mortality, need for intensive care unit (ICU) admission, need for ventilatory support, length of hospitalization, and number of hospitalizations.Results: Among COVID-19 patients (N = 6,291), those with SUD were more likely to require ICU admission (adjusted odds ratio [AOR] = 1.46, P = .003) and ventilatory support (AOR = 1.49, P = .01). The association between SUD and ICU admission was driven by alcohol use disorder (AUD), whereas that between SUD and ventilatory support was driven by both AUD and opioid use disorder (OUD). Patients with SUD were more likely to have a longer mean maximum length of hospitalization (11.32 vs 8.62 days, P < .0001) and a greater mean number of hospital admissions in 2020 (2.96 vs 2.33, P < .0001). These associations were significant for cannabis use disorder, AUD, OUD, and benzodiazepine use disorder. The association with greater number of admissions was also significant for cocaine use disorder. Patients with psychiatric diagnoses were also more likely to have a greater maximum length of hospitalization (11.93 vs 8.39 days, P < .0001) and hospital admissions (2.72 vs 2.31, P < .0001). These associations were significant for schizophrenia, mood disorders, and anxiety disorders.Conclusions: COVID-19 patients with SUD had greater likelihood of requiring critical interventions, such as ICU admission and ventilatory support. SUD and psychiatric diagnoses were also associated with a longer duration of hospitalization and greater number of hospital admissions. These findings identify COVID-19 patients with SUD and psychiatric comorbidities as a high-risk group.


Subject(s)
Alcoholism , COVID-19 , Cannabis , Cocaine , Hallucinogens , Opioid-Related Disorders , Substance-Related Disorders , Alcoholism/complications , Benzodiazepines , COVID-19/epidemiology , Humans , Opioid-Related Disorders/complications , Opioid-Related Disorders/diagnosis , Opioid-Related Disorders/epidemiology , Retrospective Studies , Substance-Related Disorders/complications , Substance-Related Disorders/diagnosis , Substance-Related Disorders/epidemiology
11.
Dig Liver Dis ; 54(11): 1459-1468, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-1966491

ABSTRACT

The COVID-19 pandemic is having substantial impacts on the health status of individuals with alcohol use disorder (AUD) and alcohol-associated liver disease (ALD). AUD and ALD have both been impacted throughout the pandemic, with increases in alcohol use during the early stages of the pandemic, reduced access to treatment during the mid-pandemic, and challenges in managing the downstream effects in the post-COVID era. This review will focus on how the COVID-19 pandemic has impacted AUD and ALD epidemiology and access to treatment, and will discuss to address this rising AUD and ALD disease burden.


Subject(s)
Alcoholism , COVID-19 , Liver Diseases, Alcoholic , Humans , Pandemics , Liver Diseases, Alcoholic/complications , Liver Diseases, Alcoholic/epidemiology , Alcoholism/complications , Alcoholism/epidemiology , Alcoholism/therapy , Alcohol Drinking/adverse effects , Alcohol Drinking/epidemiology
12.
Hosp Pract (1995) ; 50(3): 189-195, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1882942

ABSTRACT

BACKGROUND: Several lines of evidence suggest that SARS-CoV-2 invasion of the central nervous system leads to meningitis and encephalopathy syndromes. Additionally, chronic alcoholics were found to be at a higher risk of developing mental health problems and serious neurological manifestations, if exposed to SARS-CoV-2 infection. METHODS: Herein, we studied RNA seq data from alcoholics' brain tissue and COVID-19 patient's brain tissue to identify the common differentially expressed genes. RESULTS: Overlap analysis depicted the expression of seven genes (GHRL, SLN, VGF, IL1RL1, NPTX2, PDYN, and RPRML) that were significantly upregulated in both groups. Along with these, protein-protein interaction analysis revealed 10 other key molecules with strong interactions with the aforementioned genes. CONCLUSIONS: Taken together with the functional effect of these genes, we suggest a strong molecular link between COVID-19-induced severities and neurological impairment in patients suffering from alcohol abuse disorder. These findings emphasize the importance of identifying chronic alcoholism as a risk factor for developing cognitive and memory impairment in COVID-19 patients.


Subject(s)
Alcoholism , COVID-19 , Nervous System Diseases , Alcoholism/complications , Alcoholism/genetics , COVID-19/complications , COVID-19/genetics , Gene Expression , Humans , Nervous System Diseases/genetics , Nervous System Diseases/metabolism , SARS-CoV-2
13.
BMJ Open ; 12(5): e060498, 2022 05 18.
Article in English | MEDLINE | ID: covidwho-1854359

ABSTRACT

INTRODUCTION: In the UK, alcohol use is the main driver of chronic liver disease and each year results in over 1 million unplanned hospital admissions and over 25 000 deaths from alcohol-related liver disease (ArLD). The only effective treatment to prevent progression of liver damage is reducing or ceasing alcohol consumption. Psychological and pharmacological therapies for alcohol misuse are ineffective in patients with ArLD. Functional imagery training (FIT) is a novel psychological therapy that builds on motivational interviewing techniques with multisensory imagery. This pilot trial aims to test the feasibility of training alcohol liaison nurses to deliver FIT therapy and of recruiting and retaining patients with ArLD and alcohol dependence to a randomised trial of FIT and treatment as usual (TAU) versus TAU alone. METHODS AND ANALYSIS: This is a randomised pilot trial of FIT and TAU versus TAU alone in 90 patients with ArLD and alcohol dependence admitted to one of four UK centres. The primary objectives are to estimate rates of screening, recruitment, randomisation, retention, adherence to FIT/TAU and a preliminary assessment of the FIT intervention in the ArLD population. Data from the pilot study will be used to finalise the design of a definitive randomised controlled trial to assess the effectiveness and cost-effectiveness of FIT. The proposed primary outcome measure for the definitive trial is self-reported alcohol use assessed using timeline follow-back. ETHICS AND DISSEMINATION: Research ethics approval was given by the Yorkshire and Humber-Bradford Leeds Research Ethics Committee (reference: 21/YH/0044). Eligible patients will be approached and written informed consent obtained prior to participation. Results will be disseminated through peer-reviewed open access journals, international conferences and a lay summary published on the Trials Unit website and made available to patient groups. TRIAL REGISTRATION NUMBER: ISRCTN41353774.


Subject(s)
Alcoholism , Liver Diseases, Alcoholic , Alcoholism/complications , Alcoholism/therapy , Cost-Benefit Analysis , Humans , Pilot Projects , Randomized Controlled Trials as Topic , Syndrome
14.
Gastroenterology ; 163(4): 840-851, 2022 10.
Article in English | MEDLINE | ID: covidwho-1852544

ABSTRACT

Alcohol use and consequent liver disease are major burdens that have worsened during the COVID-19 pandemic. There are several facets to the pathophysiology and clinical consequences of alcohol-use disorder (AUD) and progression to alcohol-associated liver disease (ALD) that require a concerted effort by clinicians and translational and basic science investigators. Several recent advances from bedside to bench and bench to bedside have been made in ALD. We focused this review on a case-based approach that provides a human context to these important advances across the spectrum of ALD.


Subject(s)
Alcoholism , COVID-19 , Liver Diseases, Alcoholic , Alcoholism/complications , Alcoholism/epidemiology , Humans , Liver Diseases, Alcoholic/epidemiology , Liver Diseases, Alcoholic/etiology , Liver Diseases, Alcoholic/therapy , Pandemics , Patient Care
15.
Acta Biomed ; 93(1): e2022081, 2022 03 14.
Article in English | MEDLINE | ID: covidwho-1754155

ABSTRACT

BACKGROUND AND AIM: The destructive impact of the still ongoing COVID-19 pandemic on those struggling with substance use disorders (SUD) stems from the daunting challenges which SUD patients experience in terms of coping with their condition and receiving care in a timely fashion. METHODS: Patients struggling with addiction are at particularly high risk, due to the underlying vulnerabilities in their conditions and the stigmatization they often suffer. New Psychoactive Substances stand out as a critical area of concern. The authors have conducted a broad-ranging search to assess the impact of SUDs, along with their related mental, physical, and behavioral symptoms, against the backdrop of the COVID-19, taking into account how drug trafficking and consumption trends have evolved as the emergency draws out, and the cyberspace comes to play an ever-bigger role. RESULTS: Given that roughly 1.5%-5% of the global burden of disease can be ascribed to alcohol abuse and substance addiction, the role of pandemic-related potential contributing factors in the exacerbation and relapse of SUDs and behavioral addiction cannot be discounted and needs targeted measures tailored to the special needs of SUD patients. Escalating environmental stressors stemming from abnormal circumstances can undermine recovery efforts and threaten the very survival of countless SUD patients, increasing the likelihood of relapsing for those in recovery. CONCLUSIONS: Policymakers and legislators have not yet put in place targeted measures and adjustments in the health care delivery mechanisms in order to countervail the pandemic impact on SUD sufferers, and the ever-evolving patterns of use and trafficking.


Subject(s)
Alcoholism , COVID-19 , Substance-Related Disorders , Alcoholism/complications , Alcoholism/epidemiology , Humans , Pandemics , Recurrence , Substance-Related Disorders/complications , Substance-Related Disorders/epidemiology
16.
Ann Diagn Pathol ; 57: 151881, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1588329

ABSTRACT

Hepatic disease is common in severe COVID-19. This study compared the histologic/molecular findings in the liver in fatal COVID-19 (n = 9) and age-matched normal controls (n = 9); three of the fatal COVID-19 livers had pre-existing alcohol use disorder (AUD). Controls showed a high resident population of sinusoidal macrophages that had variable ACE2 expression. Histologic findings in the cases included periportal/lobular inflammation. SARS-CoV2 RNA and nucleocapsid protein were detected in situ in 2/9 COVID-19 livers in low amounts. In 9/9 cases, there was ample in situ SARS-CoV-2 spike protein that co-localized with viral matrix and envelope proteins. The number of cells positive for spike/100× field was significantly greater in the AUD/COVID-19 cases (mean 5.9) versus the non-AUD/COVID-19 cases (mean 0.4, p < 0.001) which was corroborated by Western blots. ACE2+ cells were 10× greater in AUD/COVID-19 livers versus the other COVID-19/control liver samples (p < 0.001). Co-expression experiments showed that the spike protein localized to the ACE2 positive macrophages and, in the AUD cases, hepatic stellate cells that were activated as evidenced by IL6 and TNFα expression. Injection of the S1, but not S2, subunit of spike in mice induced hepatic lobular inflammation in activated macrophages. It is concluded that endocytosed viral spike protein can induce hepatitis in fatal COVID-19. This spike induced hepatitis is more robust in the livers with pre-existing AUD which may relate to why patients with alcohol abuse are at higher risk of severe liver disease with SARS-CoV2 infection.


Subject(s)
Alcoholism/pathology , COVID-19/pathology , Liver Diseases/pathology , Aged , Alcoholism/complications , Animals , COVID-19/complications , Female , Humans , Liver Diseases/complications , Male , Mice , Middle Aged
17.
PLoS One ; 16(10): e0259061, 2021.
Article in English | MEDLINE | ID: covidwho-1496526

ABSTRACT

Effective, low-cost therapeutics are needed to prevent and treat COVID-19. Severe COVID-19 disease is linked to excessive inflammation. Disulfiram is an approved oral drug used to treat alcohol use disorder that is a potent anti-inflammatory agent and an inhibitor of the viral proteases. We investigated the potential effects of disulfiram on SARS-CoV-2 infection and disease severity in an observational study using a large database of clinical records from the national US Veterans Affairs healthcare system. A multivariable Cox regression adjusted for demographic information and diagnosis of alcohol use disorder revealed a reduced risk of SARS-CoV-2 infection with disulfiram use at a hazard ratio of 0.66 (34% lower risk, 95% confidence interval 24-43%). There were no COVID-19 related deaths among the 188 SARS-CoV-2 positive patients treated with disulfiram, in contrast to 5-6 statistically expected deaths based on the untreated population (P = 0.03). Our epidemiological results suggest that disulfiram may contribute to the reduced incidence and severity of COVID-19. These results support carefully planned clinical trials to assess the potential therapeutic effects of disulfiram in COVID-19.


Subject(s)
COVID-19 Drug Treatment , Disulfiram/therapeutic use , Adult , Alcoholism/complications , COVID-19/epidemiology , COVID-19/metabolism , Cohort Studies , Disulfiram/metabolism , Female , Humans , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Risk Factors , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity , Severity of Illness Index , Veterans
18.
Minerva Gastroenterol (Torino) ; 67(3): 283-288, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1485664

ABSTRACT

World Gastroenterology Organization define acute on chronic liver failure (ACLF) a syndrome in patients with chronic liver disease with or without previously diagnosed cirrhosis, characterized by acute hepatic decompensation resulting in liver failure and one or more extrahepatic organ failures, associated with increased mortality up to three months. A-56-year-old gentleman with alcohol related liver cirrhosis (ARLC) and history of variceal bleeding with insertion of transjugular intrahepatic porto-systemic stent shunt presented with two days history of fever, dry cough and worsening of the sensory. The severe acute respiratory coronavirus-2 (SARS-CoV-2) nasopharingeal C-reactive protein test was positive. X-ray showed multiple patchy ground glass opacities in both lungs. Despite the therapy, the clinical and laboratory picture deteriorated rapidly. The patient succumbed on day 14 with multi-organ-failure. SARS-Cov-2 infection can overlap with pre-existing chronic liver disease or induce liver damage directly or indirectly. From the data of the literature and from what is inferred from the case report it clearly emerges that alcohol related liver disease (ALD) patients are particularly vulnerable to SARS-Cov-2 infection. Thereafter, some considerations can be deduced from the analysis of the case report. In subjects with pre-existing cirrhosis hepatologists should play more attention to hepatic injury and monitor risk of hepatic failure caused by coronavirus disease 2019 (COVID-19). It is appropriate to promptly define the alcoholic etiology and investigate whether the patient is actively consuming. In fact, withdrawal symptoms may be present, and the prognosis of these patients is also worse. Physicians should be alerted to the possibility of the development of ACLF in this population, hepatotoxic drugs should be avoided, it is recommended to use of hepatoprotective therapy to mitigate the negative impact of COVID-19, and it is mandatory to administer anti COVID-19 vaccine to patients with alcohol related liver cirrhosis.


Subject(s)
Acute-On-Chronic Liver Failure/etiology , Alcoholism/complications , COVID-19/complications , Liver Cirrhosis/complications , Humans , Male , Middle Aged
20.
AIDS Behav ; 26(2): 523-536, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1333082

ABSTRACT

This randomized controlled trial tested the efficacy of a multi-session, evidence-based, lay counselor-delivered transdiagnostic therapy, the Common Elements Treatment Approach (CETA), in reducing unhealthy alcohol use and comorbidities among persons living with HIV (PLWH) in Zambia. Adult PLWH with (a) unhealthy alcohol use plus mental health or substance use comorbidities, or (b) severe unhealthy alcohol use were randomized to receive a single-session alcohol brief intervention (BI) alone or BI plus referral to CETA. Outcomes were measured at baseline and a 6-month follow-up and included Alcohol Use Disorders Identification Test (AUDIT) score (primary), depression and trauma symptoms, and other substance use (secondary). We enrolled 160 participants; 78 were randomized to BI alone and 82 to BI plus CETA. Due to COVID-19, the trial ended early before 36 participants completed. Statistically and clinically significant reductions in mean AUDIT score from baseline to 6-month follow-up were observed in both groups, however, participants assigned to BI plus CETA had significantly greater reductions compared to BI alone (- 3.2, 95% CI - 6.2 to - 0.1; Cohen's d: 0.48). The CETA effect size for AUDIT score increased in line with increasing mental health/substance use comorbidity (0 comorbidities d = 0.25; 1-2 comorbidities d = 0.36; 3+ comorbidities d = 1.6). Significant CETA treatment effects were observed for depression, trauma, and several other substances. BI plus referral to CETA was feasible and superior to BI alone for unhealthy alcohol use among adults with HIV, particularly among those with comorbidities. Findings support future effectiveness testing of CETA for HIV outcomes among PLWH with unhealthy alcohol use.Clinical Trials Number: NCT03966885.


Subject(s)
Alcoholism , COVID-19 , HIV Infections , Adult , Alcoholism/complications , Alcoholism/epidemiology , Alcoholism/therapy , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Pilot Projects , SARS-CoV-2 , Zambia/epidemiology
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