The association between smoking, nicotine and SARS-CoV-2 infection in the UK ONS COVID-19 Infection Survey

The ongoing COVID-19 pandemic, caused by the SARS-CoV-2 virus, is placing an unprecedented burden on healthcare and social systems in the UK and globally: with community transmission established in February 2020, COVID-19 has led to >9 million infections in the UK, with >140,000 premature deaths as of November 2021. At the start of the pandemic, many researchers and healthcare professionals hypothesised that tobacco smoking would be a risk factor for SARS-CoV-2 infection and subsequent disease progression. This was based on prior knowledge of biological, social, and behavioural factors that increase the risk of viral transmission. First, SARS­CoV­2 enters epithelial cells through the angiotensin-converting enzyme 2 (ACE­2) receptor, with evidence suggesting that gene expression and subsequent receptor levels are elevated in smokers, thus potentially putting smokers at higher risk of contracting SARS­CoV­2 if exposed to the virus. However, reduced receptor levels in smokers have also been reported. Second, both current and former smoking increase the risk of other respiratory viral and bacterial infections. Third, behavioural factors involved in smoking (e.g. regular hand-to-mouth movements) may increase SARS­CoV­2 infection through increased exposure and onward transmission once infected. Fourth, individuals from lower (compared with higher) socioeconomic position (SEP) groups are more likely to be smokers and are also more likely to live in overcrowded housing and/or be employed in occupations with increased viral exposure (e.g., supermarkets, warehouses, public transport). If smoking confers an increased risk of infection, this would further emphasise the need for public health efforts to support smoking cessation, with campaigns potentially leveraging motivation to quit to protect oneself and others from COVID-19. We aim to examine, in the nationally representative UK Office for National Statistics (ONS) COVID-19 Infection Survey, whether 1) current vs. never smoking is associated with reduced risk of a) testing positive for SARS-CoV-2; and b) SARS-CoV-2 seropositivity; 2) former vs. never smoking is associated with increased risk of a) testing positive for SARS-CoV-2; and b) SARS-CoV-2 seropositivity; 3) among nicotine users, current cigarette smoking vs. no cigarette smoking is associated with equivocal risk of a) testing positive for SARS-CoV-2; and b) SARS-CoV-2 seropositivity; 4) among former and never smokers, e-cigarette use vs. no e-cigarette is associated with reduced risk of a) testing positive for SARS-CoV-2; and b) SARS-CoV-2 seropositivity; 5) for the above questions, whether associations vary over the course of the pandemic; and 6) in those testing positive for SARS-CoV-2, current smoking/nicotine use is associated with a) greater mean PCR cycle threshold values; and b) a lower number of self-reported symptoms.