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
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Abstract
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 England’s 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:
Assess the association between smoking and COVID-19 disease severity, and how that changes on adjustment for smoking-related comorbidity.
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.
Assess for evidence of a dose-response relation between smoking intensity and disease severity, which would help create a case for causality.
Examine the association between former smokers who are using NRT or are vaping and disease severity.
Examine whether pre-existing respiratory disease is associated with severe COVID-19 infection.
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.
Assess whether the use of inhaled corticosteroids is associated with severity of COVID-19 disease.
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.
Article activity feed
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SciScore for 10.1101/2020.06.05.20116624: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis To detect a HR of ≥1.2 with 90% power, 1% significance, for an exposure with 20% exposed then 2515 outcome events are needed. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources This protocol is written following RECORD guidance[28]. RECORDsuggested: (RECORD, RRID:SCR_009097)The outcomes are: Exposures: Exposuressuggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the …SciScore for 10.1101/2020.06.05.20116624: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis To detect a HR of ≥1.2 with 90% power, 1% significance, for an exposure with 20% exposed then 2515 outcome events are needed. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources This protocol is written following RECORD guidance[28]. RECORDsuggested: (RECORD, RRID:SCR_009097)The outcomes are: Exposures: Exposuressuggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Our study is observational with strengths and inherent limitations since the data were collected as part of routine NHS care. Key strengths include the use of high quality, established validated databases, size, representativeness, lack of selection, recall and respondent bias. UK general practices have good levels of accuracy and completeness in recording clinical diagnoses and prescriptions and provide the ability to update analyses as data changes over time[35]. It is therefore likely to be representative of the population of England. It has good face validity since it has been conducted in the setting where most patients in the UK are assessed, treated and followed up. It is likely that prescribed NRT will under-ascertain exposure to nicotine replacement therapies because most NRT is purchased not prescribed and this may particularly have been the case during the early stages of the COVID-19 pandemic. However, this does not invalidate the analysis because it is likely that the majority of people prescribed NRT will be using it and therefore the association will be largely unbiased. We cannot exclude the possibility that smoking history is related to being kept at home and/or not given ICU care because of the degree of underlying chronic disease and that this will affect our findings. However, we will explore this possibility by examining the presence of smoking-related co-morbidities in the primary care and hospital COVID positive populations. There may be some over-ascer...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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