Symptomatic COVID-19 patients are less likely to be smokers


With the COVID-19 pandemic raging in many parts of the world, new research shows that smoking may not play an important role in increasing the severity of the disease in these patients. The study is published on the preprint server medRxiv * in May 2020.

It is now well known that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19 disease, is more likely to cause severe pneumonitis often leading to severe acute respiratory distress, multi-organ dysfunction, or both, leading to death. Predisposing factors for serious or critical illness include advanced age, underlying medical conditions like asthma, high blood pressure, diabetes, and cardiovascular disease.

However, does active smoking increase the risk? Little is known about the role of this factor, which motivated this study.

Smoking could increase viral entry – but does it?

Smoking increases the expression of molecule 2, the angiotensin converting enzyme (ACE2) in the tissues of smokers. ACE2 is known to be the primary receptor for viral attachment and entry into the host cell in humans. Logically, it would appear that smoking increases the risk of infection.

The SARS-CoV-2 virus binds to ACE-2 receptors on a human cell, the initial stage of COVID-19 infection. Image credit: Kateryna Kon / Shutterstock
The SARS-CoV-2 virus binds to ACE-2 receptors in a human cell, the initial stage of COVID-19 infection. Image credit: Kateryna Kon / Shutterstock

However, some studies contradict this hypothesis, indicating rather the opposite. In Chinese studies, for example, only 1.4% to 12.6% of COVID-19 patients are smokers. Similarly, only about 5% of New York patients, who are part of a very serious epidemic, were smokers.

Compared to national smoking statistics in the two countries, about 25% and 17% respectively, taken from, they are so low that the absence of a simple link becomes clear. The present study is motivated by the need to examine the presence of an inverse association between smoking and the risks of infection with COVID-19.

How was the Smoking-COVID-19 study?

The researchers conducted a retrospective study on approximately 440 patients with COVID-19, all admitted consecutively to a tertiary-level center in Parma, Italy. All had confirmed infection with nasopharyngeal swabs found to be positive by reverse transcriptase polymerase chain reaction (rt-PCR).

Investigators extracted demographic, clinical, laboratory and mortality data from the hospital’s electronic health records. They also tried to confirm smoking data by direct contact with patients or their loved ones, in 423 of 441 cases.

What did the smoking study show about COVID-19?

The results show that about 62% of the patients were men and that the median age was 71 years. 35% of patients died while in hospital, and 65% were discharged after clinical recovery.

About 5% of them were active smokers at the time of the study, while 10% were smokers but had quit. The others never smoked.

Upon closer analysis of the clinical features, it was observed that many more men died from the disease. Although they represent 62% of the total number of patients, they represent 72% of deaths and only 59% of survivors. Those who died were also older, at a median age of 76, compared to 67 for those who survived. However, this was not statistically significant.

Again, the presence of certain coexisting medical illnesses was significantly more common among deaths. For example, patients with a history of cardiovascular disease accounted for 21% and 10%, respectively, of those who died and survived.

While hypertension was present in 61% and 56% of deaths and survivors, respectively, while diabetes was present in 26% and 18% respectively, these were not significant.

Median levels of D-dimer, which is an inflammatory marker, were almost double the value in those who died compared to those who survived. There has been a much smaller but significant increase in the median level of reactive protein C, which also increases inflammation, in those who have died.

With smoking, however, about 6% and 4% of those who died and lived were current smokers, which meant there was no significant difference. Similarly, the number of ex-smokers and non-smokers was almost identical in the two groups.

What does this study mean for people exposed to COVID-19?

Italy has the second highest number of deaths from COVID-19 in the European Union (EU). However, in this retrospective study, only 5% of the patients were current smokers, although the prevalence of the smoking population was 24% in Italy. This finding is therefore consistent with previous studies in China and the United States.

The study did not include asymptomatic patients by conception, and therefore the conclusion should be limited to only hospitalized or symptomatic cases of COVID-19.

Researchers say, “The current study suggests that smokers may wear some type of protective mechanism against symptomatic SARS-CoV-2 infection.” However, as scientists warn, carefully designed controlled studies alone can validate this impression.

The mechanism underlying the low prevalence of smoking in this population of hospitalized COVID-19 patients is currently purely speculative. It can be argued, for example, that exposure to smoke suppresses immune responses, which contributes to low systemic inflammation compared to non-smokers.

By modulating the normal intensity and spectrum of the immune system to the virus, due to a “continuous inflammatory insult”, the cytokine storm may be less likely to occur in COVID-19 patients, making them less prone serious or symptomatic illnesses.

The importance of confirming a protective role of smoking in this pandemic is that, according to the researchers, “this could help to unravel the underlying molecular mechanism predisposing to infection by SARS-CoV-2, then also potentially exploitable by newly designed targeted protective drugs. “

*Important Notice

medRxiv publishes preliminary scientific reports which are not peer reviewed and therefore should not be considered conclusive, guide clinical practice / health related behaviors, or treated as established information.


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