Smoking cigarettes increases the risk of severe coronavirus infection by dampening the immune response of the body, a study suggests.
Lab studies on airway models made from human stem cells reveals smoking stops key immune system molecules, called interferons, from working properly.
Interferons are messengers that tell infected cells to make proteins to attack the invading pathogen, and are essential for fighting off initial infection.
They also summon support from the wider immune system and warn uninfected cells to prepare for the virus.
The study found smoking stops this pathway from working properly and this causes up to a threefold increase in the number of human cells infected by the virus.
There have been conflicting reports about the impact of smoking on a Covid patient’s prognosis, with some studies finding it reduces risk, and others finding the opposite.
Now, academics from the University of California Los Angeles have determined how smoking likely results in a more severe SARS-CoV-2 infection.
Pictured, microscopic images of human stem cell-derived airway tissue models with cell nuclei (blue) and SARS-CoV-2 virus infected cells (green); tissue exposed to cigarette smoke (right) had two to three times more infected cells than non-exposed tissue (left)
Smoking increases the risk of severe coronavirus infection by dampening the immune response. Lab studies on airway models made from human stem cells reveals smoking stops key immune system molecules, called interferons, from working properly (stock)
At the start of the pandemic, when little was known about SARS-CoV-2, the virus which causes Covid-19, researchers instinctively warned smokers would be at higher-risk due to the fact the coronavirus targets the respiratory system.
In June, The World Health Organization declared smoking — which impairs lung function — may make people more susceptible to COVID-19.
This graphic sums up how the presence of coronavirus and cigarette smoke impacts human airways. It shows more coronavirus infects cells if the cells have been exposed to cigarette smoke. It also shows that when interferons are artificially introduced (bottom), there is no infection. This proves that smoke inhibits the interferon pathway and that is why smokers are at more risk of severe Covid than non-smokers
There have been conflicting reports on the impact of smoking on a Covid patient’s prognosis, with some studies finding it reduces risk, and others finding the opposite. Now, academics from the University of California Los Angeles have determined how smoking likely results in a more severe SARS-CoV-2 infection
‘If you think of the airways like the high walls that protect a castle, smoking cigarettes is like creating holes in these walls,’ says author of the latest study Dr Brigitte Gomperts.
‘Smoking reduces the natural defenses and that allows the virus to set in.’
The scientists used human stem cells from donors to create an airways analogue, called an air-liquid interface culture.
The researchers focused on this part of the respiratory system before the lungs because it is where mucus is formed and the majority of cilia live, little hairs designed to help move cilia, and any trapped infections, out of the body.
Number of Britons who gave up smoking more than DOUBLED after March lockdown
Twice as many people completely quit smoking after the COVID-19 lockdown began in March as did before the restrictions, a study has found.
Researchers from University College London (UCL) analysed a series of surveys that are taken monthly to examine people’s smoking, drinking and quitting habits.
‘The fact we saw rates of quit attempts and cessation increase after the start of lockdown is encouraging,’ said paper author and behavioural scientist Sarah Jackson of University College London.
‘It may be that the pandemic has made people more concerned about the effects of smoking on their respiratory health.’
The World Health Organisation has warned that smoking — which impairs lung function — may make people more susceptible to COVID-19.
Some were left unabused, while some were exposed to cigarette smoke for three minutes every day over four days.
They were then both infected with SARS-CoV-2 to see how the virus behaved in both systems.
In the models exposed to smoke, the researchers state in their paper, published in Cell Stem Cell, there was between two and three times more infected cells.
In June, German researchers conducted a comprehensive review of the impact of smoking and vaping has on coronavirus infection.
Both harden the arteries and raise the risk of developing lung and heart diseases — two risk factors for coronavirus — by up to seven-fold, they found.
As a result, the team believe smokers and e-cigarette users would be more likely to suffer complications from Covid-19.
They admitted smoking is more toxic on the body than vaping but warned research suggested vaping was ‘not a healthy alternative’.
The review — published in the European Heart Journal — did not actually analyse the hospital records of Covid-19 patients, however.
Paradoxically, a growing body of research has indicated that cigarette users are actually less likely to be diagnosed with Covid-19 or be hospitalised, compared to non-smokers.
And hospital records have also suggested smokers who do catch the virus are no more likely to need intensive care, be hooked up to a ventilator or die.
Others say nicotine may control the immune system, stopping it from dangerously over-reacting to infection – a phenomenon found to kill many Covid-19 patients.
SMOKING AND THE CORONAVIRUS
Many studies have shown a low prevalence of smokers in hospitals with COVID-19.
When smokers do get diagnosed with the virus, however, they appear to be more likely to get so sick that they need ventilation, two studies in the review showed.
If the findings are proven, scientists say it’s likely that it is not cigarettes – filled with thousands of harmful chemicals – that would offer a potential protection, but the nicotine that is beneficial.
A theory touted by scientists is that nicotine reduces ACE-2 receptors, which are proteins in the body the virus binds to in order to infect cells.
The coronavirus enters cells inside the body via the structures, which coat the surface of some cells, including in the airways and lungs.
If nicotine does lowers ACE-2 expression, it makes it harder for viral particles to gain entry into cells and therefore cause an infection.
On the other hand, other studies show that nicotine enhances the action of the ACE-2 receptor, which in theory, puts smokers at a higher risk of contracting the coronavirus.
Other scientists say low levels of ACE-2 expression as a result of nicotine may prevent worse damage from viral infection, and there is no evidence that says higher quantities of ACE-2 receptors increases the risk of SARS-CoV-2 infection in the first place.
Dr Konstantinos Farsalinos, from the University of West Attica, Greece, who queried whether nicotine could be a cure for COVID-19 in a paper published on May 9, said: ‘Up-regulation of ACE2, though seemingly paradoxical, may in fact protect patients from severe disease and lung injury.’
A 2008 study in mice found that getting rid of ACE-2 made the animals more likely to suffer severe breathing difficulties when infected with the SARS virus, which is almost identical to COVID-19.
Other scientists have turned their head towards nicotine’s ability to prevent inflammation, where evidence is more robust.
Nicotine has been shown inhibit the production of pro-inflammatory cytokines, such as TNF, IL-1 and IL-6, which are involved in promoting an inflammatory response.
A ‘cytokine storm’ is a phenomenon in which an abundance of cytokines are released in response to infection.
Doctors have previously said that it’s often the body’s response to the virus, rather than the virus itself, that plays a major role in how sick a person gets.
A cytokine storm can lead to respiratory failure and the attack of healthy tissues, causing multi-organ failure.
Therefore, the cytokine storm is being looked at as a target for COVID-19 treatment.
‘Nicotine has effects on the immune system that could be beneficial in reducing the intensity of the cytokine storm,’ Dr Farsalinos wrote in Internal and Emergency Medicine.
‘The potential benefits of nicotine…. could explain, at least in part, the increased severity or adverse outcome among smokers hospitalized for COVID-19 since these patients inevitably experience abrupt cessation of nicotine intake during hospitalization.
‘This may be feasible through repurposing already approved pharmaceutical nicotine products such as nicotine patches.’
Dr Nicola Gaibazzi, who recently published findings on MedRxiv of ‘very low’ numbers of smokers in Italian COVID-19 patients, speculates smoke exposure may bolster the immune system.
He said exposure to cigarette smoke reduces the body’s immune system over time, measured by lower inflammatory markers.
Therefore, when smokers are infected with a virus like SARS-CoV-2, their immune system is more ‘tolerant’ and does not overreact.
On the other hand, non-smokers may be more prone to having the sudden and deadly cytokine storm when they are infected with the virus.
Scientists have stressed that the evidence supporting nicotine as a medicine does not mean everyone should take up smoking.