The association of smoking status with SARS-CoV-2 infection, hospitalisation and mortality from COVID-19: A living rapid evidence review

<jats:p>Background: SARS-CoV-2 is the causative agent of COVID-19, an emergent zoonotic disease which has reached pandemic levels and is designated a public health emergency of international concern. It is plausible that former or current smoking status are associated with infection, hospitalisation and/or mortality from COVID-19.

Objective: We aimed to estimate the association of smoking status with rates of i) infection, ii) hospitalisation, iii) disease severity, and iv) mortality from SARS-CoV-2/COVID-19.

Methods: We adopted recommended practice for rapid evidence reviews, which involved limiting the search to main databases and having one reviewer extract data and another verify. Published articles and pre-prints were identified via Ovid MEDLINE, medRxiv and expertise within the review team. We included observational studies with community-dwelling or hospitalised adults aged 16 years who had been tested for SARS-CoV-2 infection or diagnosed with COVID-19, providing that data on smoking status were reported. The National Institutes of Health’s Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies was used to divide studies into ‘good’, ‘fair’ and ‘poor’ quality. Studies were judged as ‘good’ quality if they: i) had low levels of missing data on smoking status, ii) used a reliable self-report measure that distinguished between current, former and never smoking status iii) used biochemical verification of smoking status and iv) adjusted analyses for potential confounding variables.

Results: Forty-one studies were included, 25 of which were conducted in China, seven in the US, three in France, two across multiple international sites and one each in the UK, Korea, Mexico and Spain. Nine studies did not state the source for information on smoking status. Thirty-one studies reported current and/or former smoking status but had high levels of missing data and/or did not explicitly state whether the remaining participants were never smokers. Notwithstanding recording uncertainties, compared with national prevalence estimates, recorded current and former smoking rates in 36 (5 ‘fair’ and 31 ‘poor’ quality) studies of hospitalised patients were generally lower than expected. In two ‘fair’ quality studies, current and former smokers appeared more likely to be tested for SARS-CoV-2 but there was no difference in the risk of testing positive in current (RR = 0.74, 95% CI = 0.31-1.73, p = .49) or former (RR = 1.18, 95% CI = 0.82-1.69, p = .37) compared with never smokers. In three ‘fair’ quality studies of people who tested positive in the community, there was no evidence for a decreased risk of hospitalisation among current (RR = 0.95, 95% CI = 0.76-1.18, p = .62) or former (RR = 1.04, 95% CI = 0.98-1.10, p = .26) smokers compared with never smokers. In three ‘fair’ quality studies, there was an increased risk of greater disease severity in hospitalised current (RR = 1.36, 95% CI = 1.07-1.74, p = .01) but not former (RR = 1.51, 95% CI = 0.86-2.65, p = .15) smokers compared with never smokers. Two ‘poor’ quality studies provided mixed evidence for the risk of death in current compared with former/never smokers.

Conclusions: Across 41 observational studies, there is substantial uncertainty about the associations between smoking and COVID-19 outcomes arising from the recording of smoking status. The recorded smoking prevalence in hospitalised patients across multiple settings was lower than national estimates but that observation is inconsistent with there being no evidence of increased admission to hospital from three ‘fair’ quality studies among people who tested positive in the community. There was limited evidence from ‘fair’ quality studies that current compared with never smoking is associated with greater disease severity in those hospitalised for COVID-19.

Implications: Unrelated to COVID-19, smokers are at a greater risk of a range of serious health problems requiring them to be admitted to hospital. Given uncertainty around the association of smoking with COVID-19, smoking cessation remains a public health priority and high-quality smoking cessation advice should form part of public health efforts during this pandemic.</jats:p>