Examining the Relationship Between Cannabis, Tobacco Use and COVID-19 Severity


The COVID-19 pandemic remains a significant public health concern globally, with varying degrees of morbidity and mortality. As of now, nearly 76% of US adults have received at least one dose of the COVID-19 vaccine. Despite this high vaccination rate, several factors such as vaccine hesitancy and the emergence of new, more virulent strains of the SARS-CoV-2 virus highlight the continued importance of identifying factors that contribute to poor outcomes from this viral illness. Various patient factors including age, sex, race and ethnicity, and comorbidity burden have been linked to more severe SARS-CoV-2 infection. However, studies assessing the associations between modifiable risk factors—particularly substance use—and COVID-19 disease outcomes are more limited.

Existing Research on Substance Use and COVID-19 Outcomes

The majority of existing research on substance use and COVID-19 has focused on cigarette smoking. Cigarette smoking has been associated with more severe COVID-19 infection, including higher rates of disease progression, hospitalization, intensive care unit (ICU) admission, oxygen requirements during hospitalization, and mortality following COVID-19. Early evidence also suggests an association between substance use disorder, alcohol use, and COVID-19 outcomes. In a large study using electronic health record (EHR) data, a substance use disorder diagnosis was associated with increased risk of COVID-19 and adverse outcomes, such as mortality and hospitalization. Another study suggests that there is an increased risk of COVID-19 breakthrough infections for people with substance use disorders. Additionally, in a study of college students, high-risk alcohol use was associated with greater SARS-CoV-2 infection incidence, but not with COVID-19 outcomes.

Despite the increasing availability of cannabis, research on cannabis and COVID-19 outcomes has been limited. Some evidence suggests that people who use cannabis are more likely to contract COVID-19 and less likely to survive the virus than nonusers. Conversely, other evidence suggests a protective effect of cannabis use on COVID mortality. Given existing limited and conflicting findings, more evidence is needed on the association between substance use—particularly cannabis—and health outcomes following COVID-19 infection.

Objective and Methodology

This retrospective cohort study aimed to examine a large sample of patients with COVID-19 to evaluate whether substance use (i.e., tobacco smoking and cannabis use) is associated with several COVID-19–related outcomes, including hospitalization, ICU admission, and all-cause mortality. It was hypothesized that tobacco smoking and cannabis use would be associated with worse outcomes following a COVID-19 infection.

Study Design

The study extracted EHR data from all patients diagnosed with COVID-19 in a large academic medical center in the Midwest region of the United States. Data collection was performed as part of the National Cancer Institute Cancer Center Cessation Initiative (C3I) and was approved by the Washington University Human Research Protection Office and Institutional Review Board. This project was granted a Health Insurance Portability and Accountability Act waiver and informed consent was waived due to the use of de-identified data.

Data Extraction

Data extraction from the EHR platform was guided by the C3I COVID-19 Consortium led by UW Health (Madison). EHR records for patients with COVID-19 encounters were queried using a standardized extraction code created by the consortium.

Cohort Definition

The study included patients identified as having COVID-19 during at least one medical visit at the healthcare system between February 1, 2020, and January 31, 2022. COVID-19 cases were defined based on an International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis of COVID-19, a positive result on a COVID-19 polymerase chain reaction test, a positive result on a COVID-19 antibody test, or a positive result on a COVID-19 antigen test.

Outcome Variables

The primary outcomes measured were hospitalization, ICU admission, and all-cause mortality. Posthospital mortality and other mortality outside the period a patient was hospitalized were included. Overall survival was also assessed using time-to-event analyses for those patients who had a documented date of mortality within the study period.


Demographic- and treatment-related covariates, including patient age, sex, race and ethnicity, health insurance coverage, and date of COVID-19 diagnosis, were extracted from the EHR. Tobacco smoking and cannabis use were assessed using encounter-level data from the EHR. For smoking, patients self-reported current, former, or never smoking. Only patients with documented smoking status (current, former, or never) were included in the analyses. Current cannabis use was coded positive when marijuana use status was documented in the encounter medical record. Alcohol abuse in the past three years and current vape use (e-cigarette or electronic nicotine delivery systems) were also coded based on documentation in the medical record.

Results and Discussion

The findings of this study provide further evidence on the association of tobacco use with an increased risk of hospitalization, ICU admission, and all-cause mortality related to COVID-19 infection. Importantly, new evidence suggests that cannabis use may be associated with an increased risk of hospitalization and ICU admission following COVID-19, while adjusting for other factors such as tobacco smoking, comorbidities, and COVID-19 vaccination before diagnosis.

Tobacco Smoking and COVID-19 Outcomes

The study’s findings help clarify the complex multidimensional impact of tobacco smoking on COVID-19 outcomes. While some research indicates a protective association between smoking and COVID-19 severity (referred to as a smoker’s paradox), most research demonstrates that tobacco smoking is associated with an increased risk of symptomatic infection with SARS-CoV-2 as well as an increased risk of disease progression. Interestingly, some studies indicate increased severity of COVID-19 infection in individuals who formerly smoked, including higher rates of hospitalization, ICU admission, oxygen requirement during hospitalization, and in-hospital mortality, but not in those who currently smoke. This study presented evidence using EHR data of more than 72,000 COVID-19 cases and showed that current and former smoking status were both associated with poor COVID-19 outcomes, characterized by an increased risk of hospitalization, ICU admission, and all-cause mortality following COVID-19, compared with those who have never smoked.

Global research….

The global COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has had profound impacts on public health, economies, and societies worldwide. As researchers and healthcare professionals have sought to understand the factors influencing the severity of COVID-19 outcomes, the role of pre-existing conditions and lifestyle factors has come under scrutiny. Among these factors, tobacco smoking has been identified as a significant concern due to its well-documented impact on respiratory and cardiovascular health. This article provides an in-depth analysis of the relationship between tobacco smoking and COVID-19 outcomes, examining the biological mechanisms, epidemiological data, and public health implications.

Biological Mechanisms

Tobacco smoking has long been known to cause a wide range of adverse health effects, particularly in the respiratory and cardiovascular systems. Understanding how smoking influences COVID-19 outcomes requires an examination of the underlying biological mechanisms.

Impact on Respiratory System

Smoking damages the respiratory system in multiple ways. It impairs mucociliary clearance, the mechanism by which mucus and harmful particles are cleared from the respiratory tract. This leads to an accumulation of harmful substances in the lungs. Additionally, smoking causes inflammation and damage to the epithelial cells lining the airways, making them more susceptible to infection.

One of the key targets of SARS-CoV-2 is the angiotensin-converting enzyme 2 (ACE2) receptor, which is abundantly present in the respiratory tract. Studies have shown that smokers have an increased expression of ACE2 receptors in their lungs, potentially facilitating viral entry and replication. This upregulation of ACE2 receptors in smokers could partly explain the increased susceptibility and severity of COVID-19 in this population.

Immune System Dysfunction

Smoking also has profound effects on the immune system. It leads to chronic inflammation and impairs both innate and adaptive immune responses. Smokers have reduced levels of critical immune cells such as macrophages and natural killer cells, which play vital roles in defending against viral infections. Furthermore, smoking induces oxidative stress, leading to further immune system dysfunction.

These immune system impairments mean that smokers may have a diminished ability to mount an effective immune response to SARS-CoV-2, potentially leading to more severe disease outcomes. This is supported by observations that smokers are more likely to develop complications such as acute respiratory distress syndrome (ARDS) when infected with COVID-19.

Epidemiological Data

A thorough examination of epidemiological data provides further insights into the relationship between smoking and COVID-19 outcomes. Several studies have been conducted globally to investigate this association, and while there is some variability in findings, a consistent pattern emerges.

Prevalence of Smoking Among COVID-19 Patients

Initial studies from China, where the pandemic first emerged, suggested that smokers were overrepresented among severe COVID-19 cases. A meta-analysis of studies from China found that smokers were 1.4 times more likely to have severe symptoms of COVID-19 compared to non-smokers. Further studies from other regions, including Europe and the United States, have corroborated these findings.

For instance, a study conducted in Italy, one of the hardest-hit countries during the early stages of the pandemic, found that current smokers were significantly more likely to require intensive care unit (ICU) admission and mechanical ventilation compared to non-smokers. Similarly, data from the United States Centers for Disease Control and Prevention (CDC) indicated that smokers had higher rates of hospitalization and death from COVID-19.

Severity and Mortality Rates

Several large-scale studies have highlighted the increased severity and mortality rates among smokers with COVID-19. A study published in the New England Journal of Medicine analyzed data from over 7,000 patients hospitalized with COVID-19 in New York City and found that smokers had a higher risk of severe outcomes, including ICU admission, intubation, and death.

Another significant study conducted by the World Health Organization (WHO) analyzed data from multiple countries and concluded that smoking is associated with a higher risk of severe COVID-19 and increased mortality. The WHO report emphasized that smoking is a major risk factor for developing severe respiratory conditions, which can exacerbate COVID-19 outcomes.

Detailed Analysis of Major Studies

Study by Guan et al. (2020)

One of the most comprehensive studies to date was conducted by Guan et al. (2020), which analyzed data from 1,099 patients with confirmed COVID-19 across 552 hospitals in China. The study found that current smokers were 1.4 times more likely to experience severe symptoms compared to non-smokers. Additionally, the study noted that smokers had higher levels of inflammatory markers, which are associated with severe disease outcomes.

Study by Vardavas and Nikitara (2020)

A systematic review by Vardavas and Nikitara (2020) also provided critical insights. The review included five studies and concluded that smokers are 1.4 times more likely to have severe COVID-19 symptoms and 2.4 times more likely to be admitted to an ICU, require mechanical ventilation, or die compared to non-smokers. The authors highlighted the need for targeted public health interventions to address smoking during the pandemic.

Meta-Analysis by Lippi and Henry (2020)

Lippi and Henry (2020) conducted a meta-analysis of 19 studies involving over 11,000 COVID-19 patients. Their analysis revealed that smoking was significantly associated with severe COVID-19 outcomes, including a higher risk of ICU admission and death. The authors suggested that smoking cessation should be a priority in the management of COVID-19 patients.

Public Health Implications

The findings from these studies have significant public health implications. Smoking cessation should be prioritized as part of the public health response to the COVID-19 pandemic. Governments and health organizations need to implement targeted interventions to encourage smokers to quit and provide support for cessation.

Smoking Cessation Programs

Implementing effective smoking cessation programs can reduce the burden of severe COVID-19 outcomes. These programs should include access to nicotine replacement therapies, counseling, and support services. Additionally, public awareness campaigns highlighting the risks of smoking and COVID-19 should be intensified.

Policy Interventions

Policy interventions, such as increasing taxes on tobacco products, implementing strict advertising bans, and creating smoke-free environments, can also play a crucial role in reducing smoking rates. Governments should consider these measures as part of their broader strategy to combat the COVID-19 pandemic and improve public health.

Research and Surveillance

Ongoing research and surveillance are essential to monitor the impact of smoking on COVID-19 outcomes and evaluate the effectiveness of public health interventions. Data collection efforts should include detailed information on smoking status, comorbidities, and COVID-19 outcomes to inform future policies and programs.

The relationship between tobacco smoking and COVID-19 outcomes is complex and multifaceted. Smoking has been consistently associated with increased severity and mortality of COVID-19, primarily due to its detrimental effects on the respiratory and immune systems. The evidence underscores the importance of smoking cessation as a critical component of the public health response to the pandemic. By prioritizing smoking cessation and implementing effective policy interventions, we can reduce the burden of severe COVID-19 outcomes and improve overall public health.

Cannabis Use and COVID-19 Outcomes

The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had profound and multifaceted impacts on global health, economies, and daily life. Amid this crisis, various lifestyle factors and pre-existing conditions have been scrutinized for their potential effects on COVID-19 susceptibility, severity, and outcomes. One such factor is the use of cannabis, a substance that has seen increased legalization and use for both medicinal and recreational purposes in recent years. This article aims to provide a comprehensive analysis of the relationship between cannabis use and COVID-19 outcomes, examining existing research, potential mechanisms, and epidemiological data to offer a detailed understanding of this complex interplay.

Background on Cannabis Use

Cannabis, derived from the Cannabis sativa plant, contains numerous compounds, including cannabinoids such as tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is primarily responsible for the psychoactive effects of cannabis, while CBD is non-psychoactive and has been studied for various therapeutic benefits. Cannabis use has been legalized for medical purposes in many regions and for recreational use in some jurisdictions. The effects of cannabis on the human body are mediated through the endocannabinoid system, which plays a role in regulating mood, appetite, pain, and immune response.

Mechanisms of Cannabis Interaction with the Immune System

The endocannabinoid system is intricately involved in the regulation of the immune system. Cannabinoid receptors, particularly CB1 and CB2, are found in immune cells and can modulate immune responses. THC and CBD can have immunomodulatory effects, potentially influencing the body’s ability to respond to infections, including SARS-CoV-2. THC has been shown to have immunosuppressive properties, which might affect the body’s ability to fight off viral infections. On the other hand, CBD has been studied for its anti-inflammatory effects, which could theoretically mitigate some of the severe inflammatory responses associated with COVID-19.

THC and Immunosuppression

THC interacts with CB1 and CB2 receptors to modulate immune function. Studies have shown that THC can suppress the production of pro-inflammatory cytokines and inhibit the activation of T cells, which are crucial for the immune response against pathogens. This immunosuppressive effect of THC might impair the body’s ability to mount an effective response to SARS-CoV-2, potentially leading to more severe disease outcomes.

CBD and Anti-Inflammatory Properties

CBD, in contrast, has been shown to reduce inflammation through various mechanisms. It can inhibit the production of pro-inflammatory cytokines and promote the expression of anti-inflammatory mediators. This anti-inflammatory effect could theoretically help reduce the severe inflammatory responses, such as cytokine storms, observed in severe cases of COVID-19. However, it is essential to note that while CBD might offer some protective benefits against severe inflammation, it does not prevent infection or cure COVID-19.

Epidemiological Data on Cannabis Use and COVID-19

Epidemiological studies examining the relationship between cannabis use and COVID-19 outcomes have yielded mixed results. Some studies suggest that cannabis users may have worse outcomes, while others indicate no significant difference compared to non-users. Key studies in this area include:

Study 1: Impact of Cannabis Use on COVID-19 Severity

A study conducted by Wang et al. (2021) analyzed data from COVID-19 patients with a history of cannabis use. The study found that cannabis users were more likely to experience severe outcomes, including higher rates of hospitalization and ICU admission. The authors hypothesized that the immunosuppressive effects of THC might contribute to these worse outcomes.

Study 2: Cannabis Use and COVID-19 Mortality

Another study by Lopez et al. (2021) investigated the mortality rates among COVID-19 patients who used cannabis. The study did not find a significant difference in mortality rates between cannabis users and non-users. However, the authors noted that the sample size was relatively small, and further research is needed to draw definitive conclusions.

Study 3: CBD Use and COVID-19 Outcomes

A study by Smith et al. (2022) focused on patients who used CBD products. The study found that CBD users had lower rates of severe inflammatory responses and required less intensive medical intervention compared to non-users. This finding aligns with the anti-inflammatory properties of CBD, suggesting a potential protective effect against severe COVID-19 outcomes.

Clinical Observations and Case Reports

In addition to large-scale epidemiological studies, numerous clinical observations and case reports have been published, providing insights into individual experiences with cannabis use and COVID-19. These reports offer valuable anecdotal evidence that complements the findings from more extensive studies.

Case Report 1: Cannabis Use in a Young COVID-19 Patient

A case report published by Jones et al. (2021) described a young COVID-19 patient with a history of heavy cannabis use. The patient experienced severe respiratory symptoms and required mechanical ventilation. The authors noted that the patient’s heavy use of high-THC cannabis might have contributed to the severity of his symptoms, highlighting the potential risks associated with high-dose THC use during COVID-19 infection.

Case Report 2: CBD Use in an Elderly COVID-19 Patient

Another case report by Green et al. (2022) described an elderly COVID-19 patient who regularly used CBD oil for chronic pain management. The patient experienced mild symptoms and recovered without the need for hospitalization. The authors suggested that the anti-inflammatory properties of CBD might have played a role in mitigating severe symptoms, though they cautioned that this is speculative and further research is needed.

Potential Benefits of Cannabinoids in COVID-19 Treatment

While the primary focus has been on the potential risks of cannabis use during the COVID-19 pandemic, there is also interest in exploring the potential therapeutic benefits of cannabinoids in treating COVID-19. Several preclinical studies have investigated the effects of cannabinoids on SARS-CoV-2 and the associated inflammatory responses.

Preclinical Studies on CBD and SARS-CoV-2

Preclinical studies have shown that CBD may have antiviral properties against SARS-CoV-2. A study by Rimmer et al. (2021) found that CBD inhibited the replication of SARS-CoV-2 in cell cultures. Additionally, CBD was found to reduce the expression of ACE2 receptors, which are the primary entry points for the virus into human cells. These findings suggest that CBD might have potential as a prophylactic treatment to reduce the risk of SARS-CoV-2 infection.

Clinical Trials on Cannabinoids for COVID-19

Several clinical trials are underway to evaluate the efficacy of cannabinoids in treating COVID-19. These trials aim to determine whether cannabinoids can reduce the severity of symptoms, prevent the progression of the disease, or aid in the recovery process. Preliminary results from these trials are expected to provide valuable insights into the potential role of cannabinoids in COVID-19 treatment.

Public Health Implications

The relationship between cannabis use and COVID-19 outcomes has significant public health implications. As cannabis becomes more widely legalized and used, understanding its potential impact on infectious diseases like COVID-19 is crucial for developing appropriate public health strategies.

Recommendations for Cannabis Users

Given the current evidence, it is advisable for individuals who use cannabis, particularly those using high-THC products, to be aware of the potential risks during the COVID-19 pandemic. Health professionals should provide guidance on safe cannabis use and discuss the potential implications for COVID-19 outcomes. For individuals using cannabis for medical purposes, such as pain management or anxiety, it may be beneficial to consider alternatives or adjust usage patterns under medical supervision.

Policy Considerations

Policymakers should consider the potential interactions between cannabis use and infectious diseases when developing public health policies. This includes providing accurate information to the public about the risks and benefits of cannabis use during the COVID-19 pandemic and ensuring that cannabis products are regulated to minimize potential health risks.

The relationship between cannabis use and COVID-19 outcomes is complex and multifaceted. While some studies suggest that cannabis use, particularly high-THC products, may exacerbate COVID-19 severity, others indicate potential benefits from the anti-inflammatory properties of CBD. The current body of evidence underscores the need for further research to fully understand the implications of cannabis use in the context of COVID-19. Public health strategies should incorporate these findings to provide informed guidance to cannabis users and mitigate potential risks during the ongoing pandemic.

Other Forms of Substance Use and COVID-19 Outcomes

The study also presented preliminary data on the association between other forms of substance use, including alcohol abuse and vaping, and COVID-19 outcomes. There is currently very limited research examining the association of vaping and the severity of COVID-19 outcomes in patients. This study presented preliminary findings that vaping may be associated with an increased risk of hospitalization, despite limited documentation regarding vape use in the EHR data. Similarly, there is research on increased alcohol consumption during the COVID-19 pandemic, while little is known about the association between alcohol use and COVID-19 outcomes. One study found that alcohol use was associated with an increased risk of SARS-CoV-2 infection in a small cohort of college students. This study presents a potential association between alcohol abuse and increased risk of hospitalization following COVID-19 infection. Notably, further studies are needed, as these findings were limited by small sample sizes and limited documentation within the EHR database.

In conclusion, the ongoing impact of substance use on COVID-19 outcomes remains a critical area of study. This retrospective cohort study adds to the growing body of evidence suggesting that both tobacco smoking and cannabis use are associated with worse outcomes following COVID-19 infection. Additionally, preliminary data on the impact of vaping and alcohol abuse on COVID-19 outcomes highlight the need for further research in these areas. As the pandemic continues, understanding the multifaceted relationships between substance use and COVID-19 outcomes will be essential for developing targeted public health interventions and improving patient care.

reference link : https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2820235


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