Associations between COVID-19 infection, tobacco smoking and nicotine use, common respiratory conditions and inhaled corticosteroids: a prospective QResearch-Case Mix Programme data linkage study January-May 2020

Introduction Epidemiological and laboratory research seems to suggest that smoking and perhaps nicotine alone could reduce the severity of COVID-19. Likewise, there is some evidence that inhaled corticosteroids could also reduce its severity, opening the possibility that nicotine and inhaled steroids could be used as treatments. Methods In this prospective cohort study, we will link English general practice records from the QResearch database to Public Health England9s database of SARS-CoV-2 positive tests, Hospital Episode Statistics, admission to intensive care units, and death from COVID-19 to identify our outcomes: hospitalisation, ICU admission, and death due to COVID. Using Cox regression, we will perform sequential adjustment for potential confounders identified by separate directed acyclic graphs to: 1. Assess the association between smoking and COVID-19 disease severity, and how that changes on adjustment for smoking-related comorbidity. 2. More closely characterise the association between smoking and severe COVID-19 disease by assessing whether the association is modified by age (as a proxy of length of smoking), gender, ethnic group, and whether people have asthma or COPD. 3. Assess for evidence of a dose-response relation between smoking intensity and disease severity, which would help create a case for causality. 4. Examine the association between former smokers who are using NRT or are vaping and disease severity. 5. Examine whether pre-existing respiratory disease is associated with severe COVID-19 infection. 6. Assess whether the association between chronic obstructive pulmonary disease (COPD) and asthma and COVID-19 disease severity is modified by age, gender, ethnicity, and smoking status. 7. Assess whether the use of inhaled corticosteroids is associated with severity of COVID-19 disease. 8. To assess whether the association between use of inhaled corticosteroids and severity of COVID-19 disease is modified by the number of other airways medications used (as a proxy for severity of condition) and whether people have asthma or COPD. Conclusions This representative population sample will, to our knowledge, present the first comprehensive examination of the association between smoking, nicotine use without smoking, respiratory disease, and severity of COVID-19. We will undertake several sensitivity analyses to examine the potential for bias in these associations.