Abstract
Background:
Smoking, alcohol use, and non-prescription drug use are associated with worsened COVID-19 outcomes in hospitalized patients. Whether there is an association between substance use and outcomes in patients with COVID-19 who visited the Emergency Department (ED) but did not require hospitalization has not been well established. We investigated whether smoking, alcohol, and non-prescription drug use were associated with worsened COVID-19 outcomes among such patients presenting to the ED.
Methods:
We conducted a secondary analysis of a clinical trial which sought to determine the effect of early convalescent plasma administration in patients presenting to the ED within 7 days of onset of mild COVID-19 symptoms. The study recruited 511 participants who were aged 50 years or older or had one or more risk factors for severe COVID-19. The primary outcome was disease progression within 15 days after randomization, which was defined as a composite of hospital admission for any reason, seeking emergency or urgent care, or death without hospitalization. Secondary outcomes included: no hospitalization within 30 days post-randomization, symptom worsening on the 5-category COVID-19 outpatient ordinal scale within 15 days post-randomization, and all-cause mortality. Substance use was categorized into either use or never use based on participant self-report. Logistic regression models were used to determine the association between substance use and outcomes.
Results:
The mean age of the 511 patients enrolled was 52 years and the majority were females (274, 54%). Approximately 213 (42%) were non-Hispanic Whites, 156 (30%) Hispanics, 100 (20%) non-Hispanic Blacks, 18 (4%) non-Hispanic Asian, 8 (1%) American Indian Alaskan, and 16 (3%) unknown race. Tobacco 152 (30%) was the most common substance use reported. Alcohol use 36 (7%) and non-prescription drug use 33 (6%) were less common. Tobacco use and non-prescription drug use were associated with an increased risk for meeting the primary outcome ((tobacco: adjusted odds ratio [aOR] =2.08; 95% confidence interval [CI]: 1.37–3.15) and (drug: aOR =2.41; 95%CI: 1.17–5.00)) and increased risk for symptom worsening on the 5-category COVID-19 outpatient scale ((tobacco: aOR=1.62; 95%CI: 1.09 – 2.42) and (drug: aOR=2.32 95% CI: 1.10– 4.87)) compared to non-use after adjusting for age, sex, plasma administration, and comorbidity.
Conclusion:
Tobacco and non-prescription drug use but not alcohol use were associated with worsened COVID-19 outcomes in patients who did not require hospitalization on their initial presentation. Future studies should determine the quantity, duration, and type of drug/tobacco use that may worsen COVID-19.
Keywords: Alcohol, drug, smoking, COVID-19, disease progression, hospitalization
1.1. Introduction
Smoking, alcohol, and drug use contribute to significantly increased morbidity and mortality. In the United States, smoking leads to 480,000 deaths per year [1]. Smoking can damage the airway epithelial barrier, delay mucociliary clearance, and weaken the immune system [2,3]. Smokers are more susceptible to infectious respiratory diseases and are also at increased risk for severe complications from infection [4–6]. Due to similar effects of COVID-19 and smoking on the respiratory system, it has been theorized that smoking may worsen COVID-19 outcomes. However, whether there is an association between smoking and COVID-19 severity, has not been fully established. While studies among hospitalized patients found that smokers are more likely to need mechanical ventilation, experience increases in disease progression, and have worsened in-hospital outcomes [7–9] others found no association between smoking and COVID-19 disease progression or mortality [10,11]. Not much is known about the effect of smoking on COVID-19 patients not initially requiring hospitalization.
Alcohol misuse is another public health concern in the United States. During the COVID-19 pandemic, an increase in alcohol consumption was observed among the US adult population that was attributed to the psychological and socioeconomic challenges that people faced during the pandemic [12]. Chronic high alcohol consumption (>4 drinks/day or >14 drinks/week) damages the lining of the lung surfaces, may impair immune functions,[13] and has been shown to be a risk factor for acute respiratory distress syndrome (ARDS)[14]. Increases in weekly alcohol consumption are associated with increasing risk of ARDS [15], and alcohol related diagnoses are also associated with more use of intensive care and longer hospital length of stay in individuals with pneumonia. Furthermore, excessive alcohol intake damages the host immune responses to bacterial pneumonia by inhibiting the release of cytokines and chemokines (essential for microbial killing and immune response) from alveolar macrophages and neutrophils [16]. Due to its impact on immune function, chronic alcohol consumption may increase the risk of infection with COVID-19 and increase the severity of COVID-19 infection.
In addition to alcohol, use of other non-prescribed drugs, such as opioids, benzodiazepines, and methamphetamines, can damage the respiratory system and increase vulnerability to COVID-19 [17,18]. The mechanism by which non-prescribed drugs affect the lungs is not well understood, but it is theorized that the lungs may act as a metabolic site for certain substances, thus exposing them to a variety of toxic metabolites [19]. Similar to alcohol use, substance use disorders (SUD) create suppressive effects on the immune system, making patients more susceptible to diseases like COVID-19 [18,20–22]. COVID-19 patients with SUD have underlying comorbidities such as kidney, pulmonary, liver, metabolic, and immune-related disorders, which contribute to a higher risk of unfavorable outcomes compared to patients without SUD [18]. SUD has also been associated with increased: risk of hospitalization, length of stay, ventilator use, and mortality in patients with COVID-19 [17,23].
Patients who smoke or use alcohol or non-prescribed drugs may require increased hospitalizations and ICU admissions when sick with COVID-19 and ultimately may suffer from higher mortality rates during COVID-19 infection. However, this association has not been well studied among COVID-19 patients not initially requiring hospitalization. We conducted a secondary analysis of a multicenter, single-blinded randomized intervention trial that aimed to determine the effect of early convalescent plasma administration on COVID-19 outcomes in patients presenting to the ED with mild COVID-19 symptoms (C3PO Trial) [24]. Our secondary analysis assessed if smoking, alcohol, or non-prescribed drug use were related to disease progression among high-risk patients who presented to the Emergency Department (ED) with symptomatic COVID-19 but were not admitted to the hospital. Recognizing risk factors for COVID-19 progression is important to identify subjects who may benefit from enhanced monitoring or treatments for COVID-19.
2.1. Methods
2.1.1: Study Design and Population
A randomized controlled clinical trial was carried out in 48 hospital emergency departments across the United States to determine the effect of early convalescent plasma administration in patients presenting to the ED with mild COVID-19 symptoms; details of the study have been described elsewhere [24]. In brief, patients enrolled were: 1) positive for SARS-CoV-2 infection, 2) 50 years of age or older or had one or more risk factors for disease progression, 3) were stable enough to be discharged from the ED, and 4) presented within 7 days of symptom onset. Patients were excluded if they were: <18 years of age, incarcerated, deemed unable to complete follow-up, had received any blood product within the past 120 days, or had received another investigative intervention for COVID-19 (including monoclonal antibodies or vaccination). All patients provided written informed consent in English or Spanish and a central institutional review board (Advarra) reviewed and approved the trial for all participating sites.
2.1.2. Data Collection
Study enrollment was from August 2020 through February 2021, a period during which the SARS-COV-2 genetic type Wuhan (Wild type 2020–21) was dominant. A total of 511 patients were randomized to receive either plasma or placebo. Structured patient interviews and chart review were conducted to extract the patient’s medical and demographic information including age, sex (assigned at birth), race, ethnicity, preferred language, past medical history, substance use including non-prescribed drug, alcohol, and tobacco use, and clinical outcomes (previous comorbidity, all-cause mortality, and no hospitalization within 30 days post-randomization). Patients were contacted for either a telephone or in-person visit within 15-days post-randomization to complete a symptom inventory. Telephone calls were also conducted by the central call team every other day for the first 14 days post-randomization. Symptom inventories, combined with information regarding their subsequent medical care, were used to assign subjects a score on the 5-category COVID-19 outpatient ordinal scale assessment [25]. This scale ranges from 1 (indicating hospital admission) to 5 (indicating usual state of health). A standard case report form was used for data collection for all sites and for the central call team.
The central clinical and data coordinating centers for the trial provided overall trial management including protocol and data collection training, development and maintenance of the study database, central randomization, and data monitoring. Data monitoring and source data verification took place periodically for each site.
2.1.2.1. Blinding
The study participants and the follow up central call team were blinded to the intervention, however each site treating team was not blinded to the intervention.
2.1.2.2. Sampling
Sites were instructed to screen potential adult participants from their emergency departments if the participant had a symptomatic lab-confirmed SARS-COV2 infection and were being considered for outpatient management. Those who met the eligibility criteria and provided written informed consent were enrolled into the trial.
2.1.2.3. Missing Data Management
The trial analysis plan did include an approach to handle missing data for the primary outcome of disease progression; however, the trial concluded with no missing primary outcome data. In the event that sites could not contact a subject on day 15, they were instructed to obtain information on the event from the medical record.
2.1.2.4. Interobserver reliability
The study used a single database for data collection. Sites received protocol and data collection training. In addition, the trial had central data monitoring within and across sites as well as source data verification at each site.
2.1.3. Outcomes
The primary outcome was disease progression within 15 days after randomization, which was a composite of hospital admission for any reason, seeking emergency or urgent care (UC), or death without hospitalization. Secondary outcomes included: no hospitalization within 30 days post-randomization, symptom worsening on the 5-category COVID-19 outpatient ordinal scale within 15 days post-randomization, and death from all-cause mortality within 30 days post-randomization. Substance use was categorized either as use or never use based on participant self-report.
2.1.4. Statistical Analyses
The analysis was performed in the intent-to-treat population, which included all the patients who had undergone randomization. Demographic and clinical variables were presented as frequencies and percentages. Chi-squared test was used to compare outcomes in the overall sample by substance use while logistic regression models were used to determine the association between substance use and outcomes controlling for age, sex, plasma administration, and comorbidities (total number of comorbidities per subject). Statistical Analysis Software (SAS) version 9.4 (SAS Institute, Inc., Cary. NC, USA) was used for analysis.
3.1. Results
The mean age of the 511 patients sampled was 51.6 (standard deviation, SD 14.6) years and the majority were females (53.6%, Table 1). Most of these patients were of non-Hispanic White race n=213 (41.7%), followed by Hispanics 156 (30.5%), non-Hispanic Blacks 100 (19.6%), non-Hispanic Asians 18 (3.5%), American Indian or native Alaskan 8 (1.6%), and unknown race 16 (3.1%). The majority of patients preferred to speak English while 14.7% preferred Spanish.
Table 1:
Demographic and Clinical Characteristics of mildly ill COVID-19 patients, n=511
| Variables | N (%) |
|---|---|
| Age, mean years, (SD); range | 51.6 (14.6); 18–85 |
| Sex | |
| Male | 237 (46.4) |
| Female | 274 (53.6) |
| Race/Ethnicity | |
| American Indian or Alaskan Native | 8 (1.6) |
| Non-Hispanic Asian | 18 (3.5) |
| Non-Hispanic Black | 100 (19.6) |
| Hispanic | 156 (30.5) |
| Non-Hispanic White | 213 (41.7) |
| Unknown Race | 16 (3.1) |
| Preferred language | |
| English | 432 (84.5) |
| Spanish | 75 (14.7) |
| Other | 4 (0.8) |
| Comorbidities/coexisting illness | |
| Obesity (BMI ≥ 30 kg/m2) | 302 (59.1) |
| COPD or asthma | 124 (24.3) |
| Chronic lung disease | 31 (6.1) |
| Hypertension | 216 (42.3) |
| Coronary artery disease | 51 (10.0) |
| Congestive heart failure | 20 (3.9) |
| Chronic kidney disease | 28 (5.5) |
| Diabetes mellitus | 142 (27.8) |
| Immunosuppression | 29 (5.7) |
| Immune system disorder | 38 (7.4) |
| Active cancer | 4 (0.8) |
| Liver disease | 18 (3.5) |
| Hematological disorder | 18 (3.5 ) |
| Thromboembolic disorder | 25 (4.9) |
| Organ transplant recipient | 5 (1.0) |
| Comorbidities a | |
| 0 | 44 (8.6) |
| 1 | 163 (31.9) |
| 2 | 149 (29.2) |
| ≥3 | 155 (30.3) |
| Plasma or placebo (saline) administration | |
| Plasma | 257 (50.3) |
| Saline | 254 (49.7) |
| Substance use | |
| Non-prescription drug use | 33 (6.5) |
| Tobacco use | 152 (29.7) |
| Alcohol use | 36 (7.0) |
Total number of comorbid conditions per patient (including obesity, COPD (chronic obstructive pulmonary disease) or asthma, chronic lung disease, hypertension, coronary artery disease, chronic kidney disease, diabetes mellitus, immunosuppression, immune system disorder, active cancer, liver disease, hematological disorder, thrombotic disorder, organ transplant recipient).
Because one of the inclusion criteria for the study was to have one or more high-risk factors for COVID-19 disease progression, comorbid conditions were highly prevalent among study subjects (467, 91%). The most common comorbid conditions included obesity (302, 59%), hypertension (216, 42%), diabetes (142, 28%), and chronic obstructive pulmonary disease (COPD) or asthma (124, 24%). Approximately 30% (n=155) of the patients had 3 or more comorbid conditions. Of enrolled patients, 257 (50%) received plasma administration. Among the three substances, tobacco 152 (30%) was the most common substance use reported. Alcohol use 36 (7%) and non-prescribed drug use 33(6%) were less common.
3.1.1. Association between substance use and outcomes
Approximately half of the patients who reported non-prescribed drug use (51.5% vs. 29.5% no drug use, risk difference:22%; 95% CI: 4.5%, 39.6%) and tobacco use (44.7% vs. 25.5% of no tobacco use, risk difference:19.7%; 95% CI: 10.6%, 28.8%) were hospitalized or in ED/UC within 15 days post-randomization (Table 2). Tobacco use was associated with a decreased risk of reporting no hospitalization within 30 days of randomization. Fewer patients who use tobacco (67% vs. 82% never use, risk difference:14.9%; 95% CI: 6.4%, 23.3%) reported no hospitalization within 30 days post-randomization. Symptom worsening on the 5-category COVID-19 outpatient ordinal scale within 15 days post-randomization was more frequently observed with non-prescribed drug use (63.6% vs. 42.3% no drug use, risk difference:21.4%; 95% CI: 4.5%, 38.4%) and tobacco use (54% vs. 39.3% no tobacco use, risk difference:14.7%; 95% CI:5.3%, 24.1%). Alcohol use and never use did not differ by any of the primary or secondary outcomes assessed. Neither tobacco, alcohol, nor non-prescribed drug use showed a significant difference in all-cause mortality between current or past use and never use (Table 2). Mortality rate for the entire study was 1% (n=6).
Table 2:
Outcomes in overall sample by substance use in mildly ill COVID-19 patients.
| Outcomes | Non-prescription drug use | Alcohol use | Tobacco use | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| No (n=478) | Yes (n=33) | *Risk difference (95% CI) | No (n=475) | Yes (n=36) | *Risk difference (95% CI) | No (n=359) | Yes (n=153) | *Risk difference (95% CI) | ||
| Hospitalization, or ED/UC visit within 15 days post-randomizatio n | No (n=353) | 337 (70.5) | 16 (48.5) | 333 (70.1) | 20 (55.6) | 269 (74.9) | 84 (55.3) | |||
| No hospitalization within 30 days post-randomization | No (n=114) | 103 (21.7) | 11 (33.3) | 102 (21.7) | 12 (33.3) | 64 (18.0) | 50 (32.9) | |||
| All-cause mortality within 30 days post-randomization | No (n=505) | 472 (98.7) | 33 (100.0) | 469 (98.7) | 36 (100.0) | 354 (98.6) | 151 (99.3) | |||
| #Symptom worsening on the 5-category COVID-19 outpatient ordinal scale within 15 days post-randomization [25] | No (n=288) | 276 (57.7) | 12 (36.4) | 270 (56.8) | 18 (50.0) | 218 (60.7) | 70 (46.1) | |||
Risk difference and 95% CI in percentages.
Symptom worsening on the 5-category COVID-19 outpatient ordinal scale within 15 days post-randomization: This refers to any subject admitted to the hospital, seen in the ED, reported an increase in symptoms of 2 levels over a 24hr period, or 1 level over a 48hr period.
Patients who use non-prescribed drugs had twice higher odds of hospitalization or ED/UC visit within 15 days post-randomization (primary outcome) (aOR=2.41; 95% CI: 1.17–5.00) and a higher odds of symptom worsening on the 5-category COVID-19 outpatient ordinal scale within 15 days post-randomization (aOR=2.32 95% CI: 1.10–4.87) compared to those who denied drug use, both independently and after controlling for age, sex, plasma administration and comorbidity (Table 3). Alcohol use was not associated with any of the primary or secondary outcomes assessed, both independently, and after controlling for other variables (Table 3).
Table 3:
Association between substance use and outcome variables in mildly ill COVID-19 patients
| Substance use | Hospitalization, or ED/UC Visit within 15 days post-randomization | No hospitalization within 30 days post-randomization | All-cause mortality within 30 days post-randomization | Symptom worsening on the 5-category COVID-19 outpatient ordinal scale within 15 days post- randomization | ||||
|---|---|---|---|---|---|---|---|---|
| OR (95% CI) | aORa (95% CI) | OR (95% CI) | aOR (95% CI) | OR (95% CI) | aOR (95% CI) | OR (95% CI) | aOR (95% CI) | |
| Non-prescription drug use (Yes vs No) | 2.54 (1.25, 5.17) | 2.41 (1.17, 5.00) | 0.56 (0.26, 1.18) | 0.57 (0.26, 1.26) | Nab | NAb | 2.39 (1.15, 4.97) | 2.32 (1.10, 4.87) |
Adjusted odds ratio (aOR): controlling for age, sex, plasma/placebo administration, and comorbidity (total number of comorbid conditions per patient: including obesity, COPD or asthma, chronic lung disease, hypertension, coronary artery disease, chronic kidney disease, diabetes mellitus, use of immunosuppressant drugs, immune system disorder, active cancer, liver disease, hematological disorder, thromboembolic disorder, organ transplant).
Model did not converge due to 0 out of 6 deaths in the drug/alcohol use group. Symptom worsening on the 5-category COVID-19 outpatient ordinal scale within 15 days post-randomization: This refers to any subject admitted to the hospital, seen in the ED, reported an increase in symptoms of 2 levels over a 24hr period, or 1 level over a 48hr period.
Patients who use tobacco had twice higher odds of the primary outcome (aOR=2.08; 95% CI: 1.37–3.15); a 40% lower odds of no hospitalization within 30 days post-randomization (aOR=0.60; 95% CI: 0.38–0.95); and a higher odds of symptom worsening on the 5-category COVID-19 outpatient ordinal scale within 15 days post-randomization (aOR=1.62; 95% CI: 1.09–2.42) compared to never use, both independently and after controlling for age, sex, plasma administration and comorbidity. Neither tobacco, alcohol, nor non-prescribed drug use was associated with all-cause mortality within 30 days post-randomization. There was no interaction between tobacco, alcohol, or non-prescribed drug use and plasma/placebo administration (data not shown).
4.1. DISCUSSION
In this secondary analysis conducted as part of the C3PO trial, we found that tobacco and non-prescribed drug use were independently associated with increased hospitalization and symptom worsening on the 5-category COVID-19 ordinal scale, though not mortality, in patients presenting to the ED with mild COVID-19. When we controlled for age, sex, plasma or placebo administration, and comorbidities, these associations with increased hospitalization and symptom worsening persisted. Alcohol use was not associated with symptom worsening or hospitalization in our study sample. These findings have important implications for COVID-19 risk stratification, prevention efforts, and treatment.
Previous studies have shown that individuals with substance use disorders (SUD), especially those using non-prescribed drugs and tobacco, have increased hospitalization rates and a higher likelihood of mortality when infected with COVID-19 [17,26]. Our study showed an association between tobacco and non-prescribed drug, and worsened outcomes in mildly ill COVID-19 patients not requiring hospitalization at the first visit to the ED. However, our study did not find an association between substance use (alcohol, tobacco, or non-prescribed drugs) and mortality after COVID-19 infection. One possible explanation is that our study population consisted of mildly ill patients who were discharged from the ED and the overall study mortality rate was low. In addition, neither the duration nor quantity of substance use were captured in this study. This would be an important issue for a follow-up study as the effect of substance use on COVID-19 mortality may be more pronounced in individuals with more chronic use [17].
Previous studies examining the association between smoking and COVID-19 severity (including mortality) found that patients with any history of smoking are more vulnerable to severe COVID-19 outcomes [9]. A systematic review and meta-analyses also confirmed that former smokers are more likely to be at increased risk of COVID-19 disease progression compared with never smokers [27]. Our study is the first to examine substance use and COVID-19 severity on the COVID-19 outpatient ordinal scale and found an association for tobacco and non-prescribed drug use.
Substances like tobacco and drugs can damage the lungs, cause inflammation, diminish the lung’s capacity to respond to infection, and suppress the immune system [17]. Together, these processes make persons with substance use disorders more susceptible to viral and bacterial infections and can increase the risk of adverse outcomes in infected subjects. Like tobacco and drugs, alcohol use can affect lung function; prolonged and heavy exposure to alcohol impairs mucociliary clearance[28]. However, our study did not find an association between alcohol and hospitalization, symptom worsening, or 30-day mortality. Our findings may be the result of not differentiating past alcohol use from those with active long-term use who may be particularly susceptible to COVID-19 related hospitalizations, symptom worsening, and death [18]. This needs validation with future studies.
Although the association between substance use and symptom worsening (particularly mortality) was not as strong in our study compared to studies of hospitalized patients, substance use should be considered as a risk stratification factor in clinical care of patients with COVID-19. Early risk stratification of these patients can also help direct treatment efforts such as anti-viral agents, symptom monitoring, and management. Public health practitioners and policy makers should invest in continuous education efforts to promote prevention of respiratory infectious diseases among persons with substance use disorders, including vaccination campaigns and other prevention efforts. Improved preventive measures and treatments for substance use disorders may prevent worse outcomes in respiratory diseases.
There are several limitations to our study. First, our study was limited in sample size for drug and alcohol use. Second, substance use was combined as past or current use, as such the effect we saw in our study may not be a true reflection of those who are current substance use only. Third, the quantity, duration of use, and frequency of substance used were not documented in the patient medical records, so we could not control these in our study. Fourth, the type of non-prescribed substance use was not captured and may influence patient outcomes. For example, the route of substance use (injection vs. inhalation or oral ingestion) may have different outcomes.
The strength of our study is the fact that our patient population consisted of mildly ill patients who were discharged from the ED and not only hospitalized patients. Also, this study examined the association between COVID-19 and worse symptoms on a COVID-19 outpatient ordinal scale showing that the assessment of worse symptoms may be applicable in both COVID-19 hospitalized and outpatients.
5.1. CONCLUSIONS
Tobacco and non-prescribed drug use but not alcohol use are associated with an increased risk for COVID-19 hospitalizations and worse symptoms in patients who presented to the ED who did not require hospitalization. Substance use should be considered as an important risk stratification in clinical practice. Future studies are needed to determine the quantity, duration, and type of substance use that may worsen COVID-19 outcomes.
Highlights:
Tobacco and drug use are associated with worse outcomes in COVID-19 patients.
Alcohol use was not associated with symptom worsening or hospitalization.
Tobacco, drug, & alcohol use were not associated with increased all-cause mortality.
Substance use should be considered in COVID-19 risk stratification.
Acknowledgements:
We acknowledge The SIREN-C3PO investigators for the hard work and dedication to this trial.
Funding:
Research reported in this publication was supported by the National Institutes of Health (NIH) under Awards U24NS100659, U24NS100655 and agreement 1OT2HL156812 through the National Heart, Lung, and Blood Institute (NHLBI) CONNECTS program. The views and conclusions contained in this document are those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of the NIH
Footnotes
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Declaration of Interest Statement
Authors have no declaration.
Article Presentation
American Society for Nutrition 2023: Accepted for Poster presentation July 22–24, 2023.
2023 Food & Nutrition Conference & Expo : Accepted for poster presentation October 7–10, 2023.
Contributor Information
Ruth Pobee, UI Health/University of Illinois Chicago College of Medicine, Departments of Emergency Medicine, 808 S. Woods St. Chicago, IL 60612..
Tracy Cable, University of Cincinnati Medical Center, Infectious Disease, 234 Goodman St Cincinnati, OH 45219 United States..
David Chan, University of Illinois Chicago, Department of Pharmacy Practice, 833 S Wood St, Chicago, IL 60612 United States..
Jesica Herrick, UI Health/University of Illinois Chicago College of Medicine, Medicine Infectious Disease, 1740 W Taylor St, Chicago, IL 60612. United States..
Valerie Durkalski-Mauldin, Medical University of South Carolina, Department of Public Health Sciences, 135 Cannon St, Ste 303 Charleston, SC 29425. United States..
Frederick Korley, University of Michigan, Departments of Emergency Medicine, 1500 E Medical Center Dr Spc 5301, Ann Arbor, MI 48109. Michigan, United States..
Clifton Callaway, University of Pittsburgh, Departments of Emergency Medicine, 400A Iroquois, 3600 Forbes Avenue, Pittsburgh, PA 15260, United States..
Marina Del Rios, UI Health/University of Illinois Chicago College of Medicine, Departments of Emergency Medicine, 808 S. Woods St. Chicago, Illinois, IL 60612, United States.; University of Iowa Hospitals and Clinics, Department of Emergency Medicine, Iowa City, Iowa United States.
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