Systematic review with meta-analysis of the epidemiological evidence in Europe,Israel,America and Australasia on smoking and COVID-19

BACKGROUND Previous meta-analyses related smoking to death or severe infection from coronavirus disease 2019(COVID-19)in hospitalized patients,but considered only a few studies,did not adjust for demographics and comorbidities,and inadequately defined smoking.AIM To review and meta-analyse epidemiological evidence on smoking and COVID-19,considering a range of endpoints,populations and smoking definitions and the effect of adjustment.METHODS Studies were identified from publications in English up to 30 September,2020 involving at least 100 individuals,carried out in Europe,Israel,America or Australasia,not restricted to those with specific other diseases,and providing information relating smoking to various COVID-related endpoints.Meta-analyses were carried out for combinations of population and endpoint,with variation studied by smoking definition,adjustment level and other factors.RESULTS From 96 publications,74 studies were identified,37 in the United States,10 in the United Kingdom,with up to four in the other countries.Three involved over a million individuals,and 37 involved less than a thousand.Adjusted results for smoking were available in 42 studies,with adjustment not considered in 20 studies.Results were considered by endpoint.No significant effect of smoking on COVID-19 positivity was seen in the general population,but there was a reduced risk in those tested.Best-adjusted estimates for current(vs never)smoking were 0.87(95%confidence interval:0.52-1.47)in the general population and 0.52(0.43-0.64)in those tested.For those hospitalized due to COVID-19,unadjusted rates were significantly increased in current smokers(1.20,1.01-1.42)and ever smokers(1.64,1.41-1.91),but those adjusted for comorbidities showed no increase for current(0.82,0.52-1.30)or ever smokers(1.00,0.76-1.32).There was little evidence to suggest that smoking was associated with intensive care admission.For those hospitalized with COVID-19,best-adjusted estimates were 0.88(0.72-1.08)for current smokers and 1.10(0.99-1.22)for ever smokers.In those hospitalized with COVID-19,smoking was not significantly related to subsequent mechanical ventilation,with best-adjusted estimates of 1.12(0.60-2.09)for current smokers and 1.05(0.88-1.25)for ever smokers.For those hospitalized with severe COVID-19,best-adjusted estimates were 0.74(0.49-1.12)for current smokers and 1.15(0.87-1.51)for ever smokers;few estimates were adjusted for comorbidities.While smoking was associated with increased mortality in unadjusted analyses,the association disappeared after adjustment for comorbidities.For example,in those hospitalized with COVID-19,the unadjusted estimate for ever smokers of 1.59(1.37-1.83)reduced to 1.07(0.82-1.38)when adjusted for comorbidities.Studies on those with severe COVID-19 showed that smoking tended to be associated with worsening of the disease.However,no estimate was adjusted,even for demographics.Estimates did not clearly vary by location or study size,and there was too little evidence to usefully study variations by age,amount smoked or years quit.CONCLUSION The increased COVID-19 death rate in smokers seen in unadjusted analyses disappears following adjustment for demographics and comorbidities.Among those tested,smoking is associated with lower COVID-19 infection rates.