Tobacco Smoking and Risk of SARS-CoV-2 Infection and Disease Severity Among Adults in an Integrated Healthcare System in California

Abstract

Introduction The relationship between cigarette smoking status and SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19) severity is highly debated. We conducted a retrospective cohort study of >2.4 million adults in a large healthcare system to evaluate whether smoking is associated with SARS-CoV-2 infection and disease severity. Methods This retrospective cohort study of 2,427,293 adults in KPNC from 3/5/2020 (baseline) to 12/31/2020 (pre-vaccine) included smoking status (current, former, never), socio-demographics, and comorbidities from the electronic health record. SARS-CoV-2 infection (identified by a positive PCR test) and COVID-19 severity (hospitalization, ICU admission or death ≤30 days of COVID-19 diagnosis) were estimated in time-to-event analyses using Cox proportional hazard regression models adjusting for covariates. Secondary analyses examined COVID-19 severity among patients with COVID-19 using logistic regression. Results During the study, 44,270 patients had SARS-CoV-2 infection. Current smoking was associated with lower adjusted rates of SARS-CoV-2 infection (aHR=0.64 95%CI:0.61-0.67), COVID-19-related hospitalization (aHR=0.48 95%CI:0.40-0.58), ICU admission (aHR=0.62 95%CI:0.42-0.87), and death (aHR=0.52 95%CI:0.27-0.89) than never-smoking. Former smoking was associated with a lower adjusted rate of SARS-CoV-2 infection (aHR=0.96 95%CI:0.94-0.99) and higher rates of hospitalization (aHR=1.10 95%CI:1.03-1.08) and death (aHR=1.32 95%CI:1.11-1.56) than never-smoking. Logistic regression analyses among patients with COVID-19 found lower odds of hospitalization for current versus never-smoking and higher odds of hospitalization and death for former versus never-smoking. Conclusions In the largest US study to date on smoking and COVID-19, current and former smoking showed lower risk of SARS-CoV-2 infection than never-smoking, while a history of smoking was associated with higher risk of severe COVID-19. IMPLICATIONS In this cohort study of 2.4 million adults, adjusting for socio-demographics and medical comorbidities, current cigarette smoking was associated with a lower risk of both COVID-19 infection and severe COVID-19 illness compared to never-smoking. A history of smoking was associated with a slightly lower risk of COVID-19 infection and a modestly higher risk of severe COVID-19 illness compared to never-smoking. The lower observed COVID-19 risk for current versus never-smoking deserves further investigation. Results support prioritizing individuals with smoking-related comorbidities for vaccine outreach and treatments as they become available.

Tobacco product use and the risks of SARS-CoV-2 infection and COVID-19: current understanding and recommendations for future research

“…However, former smokers had higher rates of hospital admission (1·10, 1·03–1·08) and death (1·32, 1·11–1·56). 18 The findings highlight the need for further understanding of the mechanisms by which smoking affects the risk of worse outcomes in patients with COVID-19.…”

“…Infection rates were also slightly lower in former smokers than in never-smokers (0·96, 0·94–0·99). 18 Despite these few positive studies, as indicated above, our review identified many studies suggesting that smoking was not protective against COVID infection, in addition to many that indicated that it was protective, so the evidence remains conflicting (see appendix pp 3–6 ). It is also important to note that almost all the epidemiological studies were limited to adult participants, which limits our ability to comment on younger populations.…”

“…Of note, a study of more than 17 million patient records in England found that the increase in COVID-19-related mortality associated with smoking was no longer significant after controlling for the presence of chronic lung disease, suggesting that smoking-induced comorbidities might explain the overall increase in mortality associated with smoking. 23 In addition, a recent retrospective cohort study of 44 270 SARS-CoV-2-infected individuals 18 reported that, compared with never-smokers, current smokers had lower rates of hospital admission (adjusted HR 0·48, 95% CI 0·40–0·58), ICU admission (0·62, 0·42–0·87), and death (0·52, 0·27–0·89). However, former smokers had higher rates of hospital admission (1·10, 1·03–1·08) and death (1·32, 1·11–1·56).…”

Risk Factors of Severe COVID-19: A Review of Host, Viral and Environmental Factors

“…However, the frequency and duration of smoking, or time since quitting tobacco use also influence the increased risk posed by this habit. The long-term damaging effects of smoking have been studied by comparing never-smokers to former [ 204 , 789 , 790 , 791 , 792 ] or ever-smokers (former and current smokers combined) [ 124 , 204 , 793 , 794 , 795 ], which consistently showed more severe outcomes (e.g., hospitalization, ICU admission, MV and death) in the latter groups. However, although current smokers compared to (current) non-smokers seem to be more prone to experience severe symptoms and death [ 123 , 794 , 796 , 797 ], when comparing current smokers to never-smokers, some publications reported increased severity [ 204 , 788 , 796 , 798 ], while others no effect [ 791 , 792 , 799 ], and surprisingly, recent cohort studies found lower rates of severe outcomes [ 789 , 790 ] in the smoker group of the study.…”

“…The long-term damaging effects of smoking have been studied by comparing never-smokers to former [ 204 , 789 , 790 , 791 , 792 ] or ever-smokers (former and current smokers combined) [ 124 , 204 , 793 , 794 , 795 ], which consistently showed more severe outcomes (e.g., hospitalization, ICU admission, MV and death) in the latter groups. However, although current smokers compared to (current) non-smokers seem to be more prone to experience severe symptoms and death [ 123 , 794 , 796 , 797 ], when comparing current smokers to never-smokers, some publications reported increased severity [ 204 , 788 , 796 , 798 ], while others no effect [ 791 , 792 , 799 ], and surprisingly, recent cohort studies found lower rates of severe outcomes [ 789 , 790 ] in the smoker group of the study. The short-term effects of tobacco use are harder to measure in clinical settings, but ambiguous results on the effect of current smoking behavior on COVID-19 might imply further physiological and immunological effects that differ from the mechanisms responsible for long-lasting damage in the lungs.…”