key: cord-0853645-2e7ddt6u
authors: AlMulla, Ahmad; Mamtani, Ravinder; Cheema, Sohaila; Maisonneuve, Patrick; Daghfal, Joanne; Kouyoumjian, Silva
title: The association between tobacco use and COVID-19 in Qatar
date: 2022-05-19
journal: Prev Med Rep
DOI: 10.1016/j.pmedr.2022.101832
sha: ae6255e2ffbb79ade818c22db1c21375c45f101b
doc_id: 853645
cord_uid: 2e7ddt6u

The effects of smoking on COVID-19 are controversial. Some studies show no link between smoking and severe COVID-19, whereas others demonstrate a significant link. This cross-sectional study aims to determine the prevalence of tobacco use among COVID-19 patients, examine the relationship between tobacco use and hospitalized COVID-19 (non-severe and severe), and quantify its risk factors. A random sample of 7430 COVID-19 patients diagnosed between 27 February-30 May 2020 in Qatar were recruited over the telephone to complete an interviewer-administered questionnaire. The prevalence of tobacco smoking in the total sample was 11.0%, with 12.6% among those quarantined, 5.7% among hospitalized patients, and 2.5% among patients with severe COVID-19. Smokeless tobacco and e-cigarette use were reported by 3.2% and 0.6% of the total sample, respectively. We found a significant lower risk for hospitalization and severity of COVID-19 among current tobacco smokers (p <0.001) relative to non-smokers (never and ex-smokers). Risk factors significantly related to an increased risk of being hospitalized with COVID-19 were older age (aged 55+), being male, non-Qatari, and those with heart disease, hypertension, diabetes, asthma, cancer, and chronic renal disease. Smokeless tobacco use, older age (aged 55+), being male, non-Qatari, previously diagnosed with heart disease and diabetes were significant risk factors for severe COVID-19. Our data suggests that only smokeless tobacco users may be at an increased risk for severe disease, yet this requires further investigation as other studies have reported smoking to be associated with an increased risk of greater disease severity.

The Coronavirus disease 2019 , caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), was officially characterized as a pandemic by the World Health Organization (WHO) on 11 March 2020 [1] . COVID-19 is predominately a disease of the respiratory tract characterized by severe acute respiratory syndrome. The virus uses angiotensinconverting enzyme 2 (ACE2) as a host cellular entry receptor, which is found in mucosal epithelial cells and the lung alveolar tissue [2] .

There is an ongoing debate about the link between tobacco use and the risk of contracting COVID-19. The act of smoking involves bringing the fingers to the mouth, which may increase the possibility of virus transmission if cigarettes, electronic devices, waterpipes, or fingers are contaminated with the virus [3] . Long-term smoking may be a risk factor for COVID-19 due to the elevated expression of ACE2 among cigarette smokers [4, 5] . Tobacco smoke exposure initiates inflammation in the lung, increases mucosal inflammation, causes mucus overproduction, and impaired mucociliary clearance [6] . These processes may increase the risk of developing severe COVID-19 [7] .

The relationship between smoking and COVID-19 severity remains controversial with various studies publishing conflicting reports. Some studies show an increased risk of severe COVID-19 progression in smokers compared to non-smokers [8] [9] [10] . Smoking was associated with a poor prognosis of COVID-19 and serious adverse health outcomes, including death [11] [12] [13] .

According to a recent meta-analysis, smokers were 1.91 times more likely to develop severe COVID-19 than non-smokers [14] .Current research on the relationship between smoking and COVID-19 has yielded conflicting findings and some scholars have suggested that nicotine in tobacco may be considered as a potential treatment option for COVID-19 [15] [16] [17] [18] . However, the confusion is mainly driven by a lack of clarity about study endpoints. The literature available thus far is affected by several design issues, making study comparisons difficult. For instance, a positive association between smoking and risk of COVID-19-related severe outcomes including hospitalization and death was found in some studies [19] [20] [21] . Whereas, other studies have identified lower proportions of active smokers among patients diagnosed with COVID-19 [22] [23] [24] , and a significant lower prevalence of smoking among hospitalized COVID-19 patients than that expected on the basis of population smoking prevalence [25] [26] [27] .

In this study, we examine the possible relationship between COVID-19 and tobacco (smoking and smokeless) and/or electronic cigarette use during the ongoing pandemic. The Tobacco Control Center (TCC) WHO-Collaborating Center (WHO-CC) at Hamad Medical Corporation (HMC) aimed to test the hypothesis that tobacco and/or electronic cigarette users are at an increased risk of hospitalization and progression to severe COVID-19 in Qatar. We defined severe COVID-19 as those hospitalized patients who were admitted to the intensive care unit (ICU), received oxygenation, and needed mechanical ventilation or if the outcome was death.

The other hospitalized patients were categorized as non-severe COVID-19 patients. Our objectives were the following: 1) determine the percentages of different types of tobacco and/or electronic cigarette use among all COVID-19 patients, 2) examine the relationship between tobacco (smoking and smokeless) and/or electronic cigarette use and hospitalization of COVID-19 (non-severe and severe), and 3) and quantify the risk factors for hospitalization and severe disease progression in COVID-19 patients.

A telephone-based, cross-sectional study was conducted among patients diagnosed with COVID-19 who had been quarantined in selected hotels/accommodation facilities and among inpatients admitted to one of the hospitals of HMC for treatment ranging from general care to ICU. HMC is a large Joint Commission International-accredited group of nine tertiary hospitals across different regions in Qatar affiliated with the government and is exclusively responsible for all COVID-19 testing during the pandemic. Patients (aged 18 years and above) with a confirmed positive test result for COVID-19 nucleic acids by real-time fluorescence reverse transcriptionpolymerase chain reaction (RT-PCR) based on HMC laboratory testing were eligible to participate.

The sample size was calculated using the most conservative hypothesized proportion of tobacco use (p=0.50) with z=2.58 for a 99% confidence interval and a margin of error of 1.40%. To account for a non-response of 20%, the minimum sample size required to estimate a population parameter was estimated at 10,158.

We randomly sampled all patients -regardless of their nationality -from the patient database of all COVID-19-positive cases diagnosed between February 27, 2020 and May 30, 2020 as provided by the Communicable Disease Center (CDC), HMC, Qatar (S1 Table in Supplementary  Information [SI] ). We aimed to represent all nationalities to achieve a balanced sample reflecting the population in Qatar as much as possible [28] . The contact information of COVID-19 patients was also provided by the CDC. Selected anonymous participants were recruited voluntarily to participate over the phone by telephone interviewers from the TCC. The telephone interviewers

were blinded of any personal information of COVID-19 patients. At the time of the telephone survey these participants were either: (1) quarantined and recovered, (2) hospitalized and discharged, or (3) still in hospital and were reachable by phone. For deceased cases, tobacco and/or electronic cigarette-related information was extracted from the patient's electronic health record. In some cases, we reached family members or friends/colleagues who shared accommodation with the deceased to answer the survey questions on their behalf.

A short telephone-based, questionnaire was developed with the support of the WHO Regional

Office for the Eastern Mediterranean (WHO-EMRO). The questionnaire was piloted among members of the TCC HMC and deemed suitable for the study. The survey tool was available in Arabic and English (S1 File and S2 File of SI). Verbal consent was taken from everyone before completing the questionnaire. Agreeing to complete the telephone-based questionnaire was considered as informed consent by the participant to be included in the study. It took approximately five minutes to complete the questionnaire.

Demographic, tobacco, and clinical data of patients included in the study were collected over the telephone. Demographic data included gender, age, education, and premarital status. History and questions on current tobacco (smoking and smokeless) status and/or e-cigarette use were also asked. Questions related to second-hand exposure to tobacco smoking and vaping in the house and/or at the workplace and comorbidities (e.g. COPD, cancer, hypertension, diabetes) were also asked. In case of hospitalization, data about admission to the ICU, respiratory support (use of mechanical ventilation and oxygenation), and disease outcomes (recovery, discharge from hospital, or death) were also collected.

Collected data were coded and entered into Statistical Package for Social Sciences (IBM SPSS statistics; version 27; Armonk, NY: IBM Corporation program). Fifty percent of data entry was reviewed and repeated by a different individual to verify and validate the accuracy of the process. The first outcome variable was hospitalization of COVID-19 (non-severe and severe) and the second outcome variable was the severity of COVID-19 both expressed as a proportion (%). We defined severe COVID-19 as those hospitalized patients who were admitted to the ICU, received oxygenation, needed mechanical ventilation, or if the outcome was death. The other hospitalized patients were categorized as having non-severe COVID-19. The status of tobacco smoking by the respondents was divided into three categories: current smokers, ex-smokers, and never-smokers. For smokeless tobacco/e-cigarette use: current users, ex-users, and never users.

Descriptive categorical variables were expressed as proportions. Statistical analysis for the association of variables with COVID-19 hospitalization and severity was carried out using the Chi-square test using a significance level of less than 5%. Variables that showed significant association at the bivariate level were entered into a multivariate logistic regression to identify the risk factors for COVID-19 hospitalization (non-severe and severe) and COVID-19 severe disease progression. Age, gender, nationality, tobacco smoking, smokeless tobacco use, heart disease, hypertension, diabetes, asthma, cancer, obesity, chronic renal disease, and other diseases were the factors entered into the first model. For the second model all the aforementioned factors were entered except asthma, cancer, and obesity.

The study procedures were approved by the Institutional Review Board at the Medical Research

Center, HMC, Qatar.

Out of the 10,158 selected study sample population, 151 were non-responsive and 2577 were unreachable. The final sample size included in the analysis was 7430 (S2 Table of reporting that they do not work, and 78.2% (n=5718) stating they were not exposed in work.

Regarding 

Out of the total sample, 76.3% of individuals were quarantined and recovered without hospitalization (n=5668), while 23.7% (n=1762) were hospitalized ( In bivariate analyses, only the variables that were significantly associated with hospitalization of COVID-19 (non-severe and severe) and severe disease progression of COVID-19 were included in both models, respectively ( Table 1 ). The first model was found to be statistically significant, However, for smokeless users and ex-users, the odds of severe COVID-19 were significantly higher (AOR= 2.0, 95% CI 1.1-3.7 and AOR= 1.8, 95% CI 1.1-2.9) than non-users.

Among the hospitalized smokeless tobacco users, 51.8% (n=29) were severe COVID-19 patients.

The common nationalities were Asian countries as mentioned in S8 We investigated the effects of smoking in young patients aged 18-49 years and over 50 years.

These multivariable stratified analyses presented reduced risk of hospitalization associated with tobacco smoking in both age groups, but the inverse association of smokeless tobacco with severe disease was present for patients aged <50 years only. More details can be found in S11 

To our knowledge, this is the first study in Qatar and in the WHO's Eastern Mediterranean Region (EMR) examining the relationship between tobacco (smoking and smokeless) and/or electronic cigarettes and COVID-19. Our study demonstrates that the rate of smoking among COVID-19 patients is lower (11.0%) than the overall rate of smoking in Qatar's population.

According to a recent study, the rate of overall tobacco use among adults in Qatar was 25.2%, with 21.5% being tobacco smokers [29] . The smoking rate among COVID-19 patients reported in the literature is consistently lower than the population average [30] . Similarly, a recent metaanalysis reported a low prevalence of current smoking (5.7%) among hospitalized COVID-19

patients [25] . It might be that smokers adhere more to preventive measures, such as masking, social distancing, and/or other factors.

In our study, we found a significant lower risk for hospitalization and for severe COVID-19

among current tobacco smokers compared to non-smokers. However, smokeless tobacco use was associated with a greater risk for severe COVID-19 (AOR=2.0, 95% CI1.1-3.7). This is in line with published literature, which shows that all forms of tobacco increase the risk of mortality and serious complications [7, [30] [31] [32] [33] . Several studies have described a significant nicotine-induced reduction of membrane ACE-2 protein expression and an anti-inflammatory response due to nicotinic acetylcholine receptor and suggested a therapeutic value in COVID-19 patients [34] [35] [36] [37] .

However, according to a review, smokeless tobacco use seems to worsen the progression and prognosis of COVID-19 by nicotine-induced increased expression of the ACE2 receptor and action of the furin enzyme in the oral cavity [33] . or with a diagnosis of COVID-19 made in hospital was 73 years [38] . However, in our study, only two percent of our sample were aged over 70 years. This large difference may be responsible for the divergent result of the protective association of tobacco smoking with COVID-19 severity. This is a peculiarity of the population in Qatar, given the young age of the population, which has led to a relatively small number of deaths (119/7430=1.6%) compared to other countries [38] [39] [40] in which a larger proportion of the population is aged over 70 years.

In our study, individuals were more vulnerable to hospitalization and severe COVID-19 with increasing age, as reported that the elderly and those with pre-existing multi-morbid conditions may be at higher risk of developing severe health consequences from COVID-19 [41] . We found that primarily heart disease and diabetes were risk factors for severe COVID-19, similar to previously published literature [7, [42] [43] [44] . Smoking is a well-recognized risk factor for preexisting comorbidities such as cardiovascular disease and diabetes, which seem to contribute to worse outcomes [45] . It may be that smoking played some sort of mediational role in the development of severe disease. Of the total sample, the higher prevalence of co-morbidities (heart disease, hypertension, and diabetes) among smokeless tobacco users might explain why they were at an increased risk of severe COVID-19. Moreover, this subgroup was older in age compared to smokers. Yet, further investigation is warranted.

There is a close relationship between respiratory diseases, smoking and ACE2 modulation that could increase the risk for developing severe COVID-19 outcomes [46] . However, our study reported a very low prevalence of COPD (0.1%), much lower than the literature [30, 47] . As previously discussed, this may be because our sample mainly consists of the younger population in Qatar, with a mean age of 38.8 (±12.6) years. COPD is considered a disease of the elderly and is not common in young adults and usually diagnosed after the age of 45 years [48] .

In our study, men had higher risk of being hospitalized and higher risk of severe COVID-19, consistent with published studies [8, 42, 49, 50] . Additionally, based on a global large-scale meta-analysis, a higher severity of COVID-19 in male gender was associated with an odds ratio of 2.84, like what was reported in our study (AOR=2.6, 95% CI 1.9-3.5). Some studies proposed that higher risk among men can be due to smoking; in our study, the smoking rate was higher among males (13.8% vs. 2.8%) and similarly among smokeless tobacco and e-cigarette users.

However, there might be other unidentified factors playing a role.

Similar to our findings, several other studies reported low odds of testing positive for COVID-19

and of disease severity among current smokers [51] [52] [53] [54] [55] or found negative or no relationship between the severity of COVID-19 and smoking [42, 56] . However, tobacco smoking should not be considered as an efficient protection against COVID-19, as has been suggested [57, 58] .

There is insufficient evidence to confirm any link between tobacco or nicotine use for the prevention or treatment of COVID-19 [13, 59] . On the contrary, smokers appear to have an increased risk of hospitalization and severe COVID-19 [60] [61] [62] .

The COVID-19 pandemic presents a unique opportunity to motivate tobacco users to quit and to offer advice, medication, and support by offering evidence-based tobacco cessation services.

Tobacco dependence treatment services across Qatar provide full cost cessation support and treatment for all Qataris and non-Qataris [63] , and, in response to the pandemic, the Tobacco Control Center WHO Collaborating Center in Hamad Medical Corporation provided tobacco cessation services by phone consultations [64] . Smoking cessation services providing counseling and pharmacological interventions are proven to be cost-effective and improve success rates compared to unaided quit attempts [65, 66] . Fortunately, a recent study among healthcare workers in Qatar showed that almost 60% of them provided tobacco cessation interventions to patients [67] .

In this cross-sectional study, COVID-19 patients who smoked or used tobacco accounted for a relatively small proportion of the total sample, and the relationship between these behaviors and the severity of COVID-19 may be affected by other confounding factors. It is also possible that some patients may have been in critical condition at the time they were hospitalized, which could have compromised their communication capacity and their ability to report their correct smoking status, particularly for the deceased cases. The study sample does not reflect the true proportion of nationality stratification in the country; therefore, the results may not be generalizable to the wider population.

This study indicates that only smokeless tobacco users may be at an increased risk for severe disease; however, this requires further investigation as other studies have reported smoking to be associated with an increased risk of greater disease severity. Smoking prevention initiatives among never smokers should be promoted, and healthcare practitioners must continue to identify, advise, and engage smokers/users and support them in cessation efforts. Patients with underlying disease, such as diabetes and heart disease, should follow preventive measures for COVID-19, such as social distancing, facemask use, avoiding social gatherings, and vaccination and must be monitored for COVID-19 and disease progression. 

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The authors are thankful for the support provided by the World Health Organization Eastern Mediterranean Regional Office (EMRO), particularly in reviewing the survey instrument. We thank the Communicable Disease Center in Hamad Medical Corporation in Qatar for extracting and providing data for analysis. The assistance in data collection provided by the staff of Tobacco Control Center was greatly appreciated. We also wish to express our gratitude to the consenting participants in our study. We would like to thank Ms. 

None to declare