The association of smoking status with SARS-CoV-2 infection, hospitalization and mortality from COVID-19: a living rapid evidence review with Bayesian meta-analyses (version 7)

Abstract

Aims: To estimate the association of smoking status with rates of (i) infection, (ii) hospitalization, (iii) disease severity and (iv) mortality from SARS-CoV-2/COVID-19 disease.

Design: Living rapid review of observational and experimental studies with random-effects hierarchical Bayesian meta-analyses. Published articles and pre-prints were identified via MEDLINE and medRxiv.

Setting: Community or hospital, no restrictions on location.

Participants: Adults who received a SARS-CoV-2 test or a COVID-19 diagnosis.

Measurements: Outcomes were SARS-CoV-2 infection, hospitalization, disease severity and mortality stratified by smoking status. Study quality was assessed (i.e. 'good', 'fair' and 'poor').

Findings: Version 7 (searches up to 25 August 2020) included 233 studies with 32 'good' and 'fair' quality studies included in meta-analyses. Fifty-seven studies (24.5%) reported current, former and never smoking status. Recorded smoking prevalence among people with COVID-19 was generally lower than national prevalence. Current compared with never smokers were at reduced risk of SARS-CoV-2 infection [relative risk (RR) = 0.74, 95% credible interval (CrI) = 0.58-0.93, τ = 0.41]. Data for former smokers were inconclusive (RR = 1.05, 95% CrI = 0.95-1.17, τ = 0.17), but favoured there being no important association (21% probability of RR ≥ 1.1). Former compared with never smokers were at somewhat increased risk of hospitalization (RR = 1.20, CrI = 1.03-1.44, τ = 0.17), greater disease severity (RR = 1.52, CrI = 1.13-2.07, τ = 0.29) and mortality (RR = 1.39, 95% CrI = 1.09-1.87, τ = 0.27). Data for current smokers were inconclusive (RR = 1.06, CrI = 0.82-1.35, τ = 0.27; RR = 1.25, CrI = 0.85-1.93, τ = 0.34; RR = 1.22, 95% CrI = 0.78-1.94, τ = 0.49, respectively), but favoured there being no important associations with hospitalization and mortality (35% and 70% probability of RR ≥ 1.1, respectively) and a small but important association with disease severity (79% probability of RR ≥ 1.1).

Conclusions: Compared with never smokers, current smokers appear to be at reduced risk of SARS-CoV-2 infection, while former smokers appear to be at increased risk of hospitalization, increased disease severity and mortality from COVID-19. However, it is uncertain whether these associations are causal.

Keywords: COVID-19; SARS-CoV-2; e-cigarettes; hospitalization; infection; living review; mortality; nicotine replacement therapy; smoking; tobacco.

FIGURE 1

Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) flow diagram of included studies.

FIGURE 2

(a) Weighted mean prevalence of current smoking in included studies with 95% bootstrap confidence intervals (CIs) compared with national current smoking prevalence (solid red lines), split by country. Shape corresponds to study setting (community, community and hospital, hospital) and shape size corresponds to relative study sample size. (b) Weighted mean prevalence of former smoking in included studies (where this was reported) with 95% bootstrap CIs compared with national former smoking prevalence (solid red lines), split by country. Shape corresponds to study setting (community, community and hospital, hospital) and shape size corresponds to relative study sample size. [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 3

Forest plot for risk of testing positive for SARS‐CoV‐2 in current versus never smokers. *This was a ‘good’ quality study. [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 4

Forest plot for risk of testing positive for SARS‐CoV‐2 in former versus never smokers. *This was a ‘good’ quality study. [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 5

Forest plot for risk of hospitalization in current versus never smokers. [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 6

Forest plot for risk of hospitalization in former versus never smokers. [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 7

Forest plot for the risk of severe disease in current versus never smokers. [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 8

Forest plot for the risk of severe disease in former versus never smokers. [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 9

Forest plot for the risk of mortality in current versus never smokers. [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 10

Forest plot for the risk of mortality in former versus never smokers. [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 11

A schematic of some of the interpretation issues for the association of smoking and SARS‐CoV‐2/COVID‐19. *Indicates potential confounding with smoking status.