The association of smoking status with SARS-CoV-2 infection, hospitalisation and mortality from COVID-19: A living rapid evidence review (version 3)
Authors: Simons David , Shahab Lion , Brown Jamie , Perski Olga 
Published: May 2020

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 to address objectives of this review. 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: Sixty-seven studies were included, 30 of which were conducted in China, 12 in the US, six in the UK, four in France, three in Mexico, three in Spain, two across multiple international sites, two in Italy, and one each from Iran, Israel, Korea, Kuwait and Switzerland. Eleven studies did not state the source for information on smoking status. Fifty-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 most studies were lower than expected. In six ‘fair’ quality studies, no significant difference was observed between current and never (RR = 0.78, 95% CI = 0.55-1.11, p = .17, I2 = 92%) or former and never smokers (RR = 1.07, 95% CI = 0.95-1.20, p = .24, I2 = 61%) in the risk of testing positive for SARS-CoV-2. In five ‘fair’ quality studies, there was no significant difference between current and never (RR = 1.12, 95% CI = 0.74-1.69, p = .48, I2 = 84%) or former and never smokers (RR = 1.21, 95% CI = 0.82-1.79, p = .24, I2 = 81%) in the risk of requiring admission to hospital following diagnosis of COVID-19. In three ‘fair’ quality studies, current smokers were at increased risk of greater disease severity compared with never smokers (RR = 1.37, 95% CI = 1.07-1.75, p = .01, I2 = 0%). No significant difference was observed between former and never smokers (RR = 1.51, 95% CI = 0.82-2.80, p = .19, I2 = 81%). In three ‘fair’ quality studies, there were inconsistent results on mortality from COVID-19 in current and former compared with never smokers.

Conclusions: Across 67 observational studies, there is substantial uncertainty about the associations between smoking and COVID-19 outcomes. The recorded smoking prevalence in hospitalised patients was lower than national estimates but this observation is inconsistent with there being no evidence of increased admission to hospital from five ‘fair’ quality studies of people who tested positive. 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 including recommendations to use alternative nicotine should form part of public health efforts during this pandemic.