A genetically-informed study disentangling the relationships between tobacco smoking, cannabis use, alcohol consumption, substance use disorders and respiratory infections, including COVID-19

Db, Rosoff; Yoo, Juhyun; Fw, Lohoff

doi:10.1101/2021.02.11.21251581

Cited by 5 publications

(4 citation statements)

References 72 publications

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“…This reduction in causal effects might reflect greater precision in the GCP estimate or an increase in heterogeneity across the samples in the latest COVID-19 GWAS (e.g., of cases with varying degrees of illness severity). Nonetheless, the current non-significant causal results are consistent with another pre-print that utilized traditional Mendelian Randomization methods ( 29 ).…”

Section: Discussionsupporting

confidence: 84%

Genetic Liability to Cannabis Use Disorder and COVID-19 Hospitalization

Hatoum

Morrison

Colbert

et al. 2021

Biological Psychiatry Global Open Science

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Background Vulnerability to COVID-19 hospitalization has been linked to behavioral risk factors, including combustible psychoactive substance use (e.g., tobacco smoking). Paralleling the COVID-19 crisis have been increasingly permissive laws for recreational cannabis use. Cannabis Use Disorder (CUD) is a psychiatric disorder that is heritable and genetically correlated with respiratory disease, independent of tobacco smoking. We examined the genetic relationship between CUD and COVID-19 hospitalization. Methods We estimated the genetic correlation between CUD (n case=14,080, n control=343,726) and COVID-19 hospitalization (n case=9,373, n control=1,197,256) using summary statistics from genome-wide association studies (GWASs). Using independent GWASs conducted prior to the pandemic, we controlled for several covariates (i.e., tobacco use phenotypes, problematic alcohol use, BMI, fasting glucose, forced expiration volume, education attainment, risk-taking, ADHD, and Townsend Deprivation Index; as well as chronic obstructive pulmonary disease, hypertension and type 2 diabetes) using genomic structural equation modeling. Genetic causality between CUD and COVID-19 hospitalization was estimated using latent causal variable models. Results Genetic vulnerability to COVID-19 was correlated with genetic liability to CUD (rG=0.423(.0965), p=1.33e -6 ); this association remained when accounting for genetic liability to related risk factors and covariates (b = 0.381 - 0.539, p=0.012 - 0.049). Latent causal variable analysis revealed causal effect estimates that were not statistically significant. Conclusions Problematic cannabis use and vulnerability to serious COVID-19 complications share genetic underpinnings that are unique from common correlates. While CUD may plausibly contribute to severe COVID-19 presentations, causal inference models yielded no evidence of putative causation. Curbing excessive cannabis use may mitigate COVID-19’s impact.

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Section: Discussionsupporting

confidence: 84%

Genetic Liability to Cannabis Use Disorder and COVID-19 Hospitalization

Hatoum

Morrison

Colbert

et al. 2021

Biological Psychiatry Global Open Science

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“…Although tobacco smoking has long been known to increase susceptibility and severity of respiratory viral infection [5,6], the effect of cannabis smoke on the pulmonary antiviral response remains poorly understood. There is some evidence that cannabis users report increased incidence of respiratory symptoms associated with bronchitis and pneumonia [7,8] as well as increased rates of hospitalization and length of stay during respiratory infection compared to non-smokers [9,10]. Furthermore, clinical studies of HIV+ men have shown that cannabis smoke exposure worsened respiratory infections [11][12][13] and one multivariate Mendelian randomization study found that cannabis use disorder was associated with increased risk of chronic lower respiratory infections and asthma-related infections in the general population [10].…”

Section: Introductionmentioning

confidence: 99%

“…There is some evidence that cannabis users report increased incidence of respiratory symptoms associated with bronchitis and pneumonia [7,8] as well as increased rates of hospitalization and length of stay during respiratory infection compared to non-smokers [9,10]. Furthermore, clinical studies of HIV+ men have shown that cannabis smoke exposure worsened respiratory infections [11][12][13] and one multivariate Mendelian randomization study found that cannabis use disorder was associated with increased risk of chronic lower respiratory infections and asthma-related infections in the general population [10]. Therefore, in the wake of widespread legalization, it is crucial that we understand to what extent cannabis smoking might impact the pulmonary host-defense mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Cannabis smoke suppresses antiviral immune responses to influenza A in mice

Milad,

Fantauzzi,

McGrath

et al. 2023

ERJ Open Res

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RationaleDespite its increasingly widespread use, little is known about the impact of cannabis smoking on the response to viral infections like influenza A virus (IAV). Many assume that cannabis smoking will disrupt antiviral responses in a manner similar to cigarette smoking, however, since cannabinoids exhibit anti-inflammatory effects, it suggests that cannabis smoke exposure may impact viral infection in distinct ways.MethodsMale and female BALB/c mice were exposed daily to cannabis smoke and concurrently intranasally instilled with IAV. Viral burden, inflammatory mediator levels (multiplex ELISA), lung immune cells populations (flow cytometry) and gene expression patterns (RNAseq) were assessed in the lungs. Plasma IAV-specific antibodies were measuredviaELISA.ResultsWe found that cannabis smoke exposure increased pulmonary viral burden while decreasing total leukocytes, including macrophages, monocytes, and dendritic cell populations in the lungs. Furthermore, infection-induced upregulation of certain inflammatory mediators (IFNγ and CCL5) was blunted by cannabis smoke exposure, which in females was linked to the transcriptional downregulation of pathways involved in innate and adaptive immune responses. Finally, plasma levels of IAV-specific IgM and IgG1 were significantly decreased in cannabis smoke-exposed, infected mice compared to infected controls, only in female mice.ConclusionsOverall, cannabis smoke exposure disrupted host-defense processes, leading to increased viral burden and dampened inflammatory signaling. These results suggest that cannabis smoking is detrimental to the maintenance of pulmonary homeostasis during viral infection and highlight the need for data regarding the impact on immune competency in humans.

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“…In addition, obesity is associated with the risk of hospitalization and mortality due to COVID-19 [ 3 , 5 ]. Behavioral risk factors have also been found to be associated with COVID-19 outcomes, above all in some regions where the prevalence of tobacco and alcohol use is high [ 7 ]. A systematic review suggested that smokers appear to be at a low risk of SARS-CoV-2 infection, while former smokers appear to be at increased risk of hospitalization, increased disease severity, and mortality from COVID-19 [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

COVID-19, Non-Communicable Diseases, and Behavioral Factors in the Peruvian Population ≥ 15 Years: An Ecological Study during the First and Second Year of the COVID-19 Pandemic

Canorio

Sánchez

Ramírez-Soto

2022

IJERPH

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A range of health-related and behavioral risk factors are associated with COVID-19 incidence and mortality. In the present study, we assess the association between incidence, mortality, and case fatality rate due to COVID-19 and the prevalence of hypertension, obesity, overweight, tobacco and alcohol use in the Peruvian population aged ≥15 years during the first and second year of the COVID-19 pandemic. In this ecological study, we used the prevalence rates of hypertension, overweight, obesity, tobacco, and alcohol use obtained from the Encuesta Demográfica y de Salud Familiar (ENDES) 2020 and 2021. We estimated the crude incidence and mortality rates (per 100,000 habitants) and case fatality rate (%) of COVID-19 in 25 Peruvian regions using data from the Peruvian Ministry of Health that were accurate as of 31 December 2021. Spearman correlation and lineal regression analysis was applied to assess the correlations between the study variables as well as multivariable regression analysis adjusted by confounding factors affecting the incidence and mortality rate and case fatality rate of COVID-19. In 2020, adjusted by confounding factors, the prevalence rate of obesity (β = 0.582; p = 0.037) was found to be associated with the COVID-19 mortality rate (per 100,000 habitants). There was also an association between obesity and the COVID-19 case fatality rate (β = 0.993; p = 0.014). In 2021, the prevalence of obesity was also found to be associated with the COVID-19 mortality rate (β = 0.713; p = 0.028); however, adjusted by confounding factors, including COVID-19 vaccination coverage rates, no association was found between the obesity prevalence and the COVID-19 mortality rate (β = 0.031; p = 0.895). In summary, Peruvian regions with higher obesity prevalence rates had higher COVID-19 mortality and case fatality rates during the first year of the COVID-19 pandemic. However, adjusted by the COVID-19 vaccination coverage, no association between the obesity prevalence rate and the COVID-19 mortality rate was found during the second year of the COVID-19 pandemic.

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A genetically-informed study disentangling the relationships between tobacco smoking, cannabis use, alcohol consumption, substance use disorders and respiratory infections, including COVID-19

Cited by 5 publications

References 72 publications

Genetic Liability to Cannabis Use Disorder and COVID-19 Hospitalization

Genetic Liability to Cannabis Use Disorder and COVID-19 Hospitalization

Cannabis smoke suppresses antiviral immune responses to influenza A in mice

COVID-19, Non-Communicable Diseases, and Behavioral Factors in the Peruvian Population ≥ 15 Years: An Ecological Study during the First and Second Year of the COVID-19 Pandemic

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