Does smoking increase COVID-19 risk?

By Dr. Liji Thomas, MDJun 2 2020

The COVID-19 pandemic continues to smolder and smoke in many parts of the world, with over 100,000 cases, and more than 3,000 deaths reported every day. Many factors are responsible for the higher risk of infection in certain specific population subgroups are known.

Now, a new study published in the online preprint server medRxiv* in May 2020 shows that smoking may not be a risk factor for higher rates of infection or severity of disease in COVID-19.

The pandemic has led to over 380,000 deaths in just five months, especially among the elderly and sick.

Study: Smoking and the risk of COVID-19 in a large observational population study. Image Credit: Nopphon_1987 / Shutterstock

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Smoking and Disease

Smoking is a well-established risk factor for lung disease, both acute infections, and more chronic or complicated conditions such as asthma and chronic obstructive lung disease. However, reports on the role of smoking in COVID-19 have yielded unexpectedly contradictory conclusions.

While some reports point to a comparable risk among smokers and non-smokers, others demonstrate a lower rate of infection among COVID-19 positives. The clinical outcomes among this group are also not clear.

A review commissioned by the World Health Organization (WHO) brings these diverse conclusions together, emphasizing the need for more research to determine the level of risk in this subgroup.

How Was the Study Done?

The current study was a large population-based study carried out among 3 million adults who belonged to Clalit Health Services, the largest of Israel's four state-mandated health service organizations. Clalit has central electronic health records, which include data on its members stretching back for over 20 years, to provide a comprehensive timeline-based picture of the relationship between smoking and COVID-19 disease and severity of infection.

The study was designed to be a case-control study, among patients who were tested for the virus, to measure the impact of smoking on the incidence and severity of COVID-19, with five COVID-19-negative controls for each confirmed case. Cases and controls were matched for age, sex, and ethnic origin/religion.

Data on other existing medical conditions as well as smoking status was available for over 90% of the population. Hospital records provided by the Israeli Ministry of Health were accessed for information on disease severity, the number of patients on ventilation, and mortality.

The researchers constructed two models to estimate the odds of testing positive for the infection and to adjust for other illnesses such as hypertension, cancer, chronic respiratory disease, and obesity.

What Effect Did Smoking Have on COVID-19 Odds?

Since the beginning of the outbreak up to May 3, 2020, over 114,000 individuals have been tested for the infection, with a case-positive rate of 4%. Almost 10% of them were current smokers, and 12% had a history of smoking. This compares to current and past smoking rates of 19% and 14%, respectively, in the general population.

The same ratio was maintained in the matched control group, with a current smoking rate of 19%, thus leading to an odds ratio of 0.457. The odds for testing positive among past smokers were also slightly lower at 0.8.

When adjusted for the effect of other existing illnesses, the estimate remained robust. The odds for infection among those with cancer and asthma were significantly lower at 0.8 in both cases, compared to those with other conditions. On the other hand, obesity conferred higher odds of risk for infection.

When severe or fatal outcomes were compared, there was no significant effect of smoking, either current or past, on the odds of death due to infection. Being female was reduced with lower odds of death by almost half.

As shown by numerous other studies, being above 35 years increased the odds of death by 4-fold, 20-fold, and almost 70-fold, in the groups aged 35-54 years, 55-74 years, and above 75 years of age, compared to the 18-34 year age group.

Among the other illnesses, hypertension, cardiac arrhythmias, peripheral vascular disease, and cancer were the other conditions directly associated with significantly higher odds of death following COVID-19.

Possible Explanations for Smoking Effects on COVID-19

The current study included a considerable proportion of asymptomatic and mild cases that were not hospitalized. The results, therefore, reflect a large-scale effect, which may not have been the case with earlier studies based on hospitalized patient samples.

The current study did not differentiate between various levels of smoking, which rules out any dose-response effect for either risk or protection against COVID-19.

These findings may be the result of unique effects produced on the precise mechanisms of infection used by the novel coronavirus. One model depends on the presence of the nicotinic acetylcholine receptor, which is hypothesized to be vital for this infection to occur. In this model, the virus enters the central nervous system (CNS) via this receptor on the olfactory neurons.

This neurotropic model explains the neurologic symptoms seen with COVID-19 infection, including anosmia and ageusia, or severe tiredness.

Another theory is that the viral ACE2 receptor for the virus on the host cells is affected explicitly by smoking. Again, cytokines like IL-6, which are associated with an unfavorable cytokine storm syndrome, causing hyperinflammatory conditions which result in organ damage, might be lowered by smoking.

Importance of the Study

This is the first study to look at this association of smoking and COVID-19 on such a large scale. The reduced odds of infection by almost half in smokers seem to show that smoking does protect the individual against SARS-CoV-2 infection. A past history of smoking also appears to have a genuine, though less pronounced, protective effect. The question remains as to whether this is due to secret smoking at the present time in the "Past Smokers" group, or the residual effects of past smoking still acting on the lungs.

While smoking continues to be viewed as a destructive habit, with high addiction potential, the putative protective effect of smoking on infection with COVID-19 could offer researchers "promising new directions for fighting this disease, based on a better understanding of the mechanisms by which smoking reduces the risk of SARS-CoV-2 infection."

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.