Smokers are less likely to be diagnosed with Covid-19 compared to those who have never touched a cigarette, another study has claimed.
An array of research carried out since the pandemic began has shown smokers are at lower risk of getting the coronavirus.
Now researchers in Mexico have added more weight to the evidence, which experts have called bizarre and said warrants further investigation.
Scientists analysed data from almost 90,000 patients and found smokers were 23 per cent less likely than non-smokers to get diagnosed with Covid-19.
And the team also found smokers who did get infected were no more likely to need intensive care, be hooked up to a ventilator or die.
The findings support the theory that smokers are somehow protected from Covid-19, with data from Britain, the US, China and Italy all suggesting the same.
Scientists are starting to believe nicotine may be able to block the coronavirus from entering cells, preventing the infection in the first place.
Others say nicotine may control the immune system, stopping it from dangerously over-reacting to infection – a phenomenon found to be killing many Covid-19 patients.
Doctors are keen to trial nicotine patches in the fight against Covid-9. But they have warned against encouraging smoking tobacco because of its known dangers.
Smokers are 23 per cent less likely to be diagnosed with Covid-19 compared to those who have never touched a cigarette, a study claims. They are six per cent less likely to be admitted to hospital and no more at risk of ICU or death than non-smokers
The study was a joint investigation by scientists in Mexico, Greece and the US, led by Dr Theodoros Giannouchos of the University of Utah.
The team said to the best of their knowledge, this is the largest study of patients with a confirmed Covid-19 diagnosis.
It included 236,439 people who had been to a medical centre with a suspected viral respiratory illness – 89,756 tested positive for Covid-19 and 146,683 tested negative.
Any underlying health conditions, such as diabetes, were noted down. The team also identified whether or not the patient was a smoker.
People were classified as either a smoker or non-smoker – ‘former smoker’ was not an option but the scientists did not explain why.
Most patients were 18 to 44 years old and Mexican. Around 40 per cent of all patients had one or more co-morbidities.
Some 8.3 per cent who were diagnosed were current smokers. In contrast, around 14 per cent of adults in Mexico are estimated to smoke.
Researchers identified the main risk factors for Covid-19 by comparing the data of those with a positive or negative test.
Smokers were 23 per cent less likely to be diagnosed with Covid-19 compared to non-smokers, the findings claim.
Of those who were diagnosed, smokers were six per cent less likely to be admitted for hospital care compared to non-smokers.
No major differences were observed between the current smokers and non-smokers when looking at adverse outcomes, including ventilation and death.
The study found Covid-19 patients were most likely to be older, male, and have an underlying health condition.
Patients with diabetes, obesity, high blood pressure and COPD were the most vulnerable patients both to infection and death.
One in five patients with Covid-19 had at least one comorbidity – and they were three times more likely to end up hospitalised or dead.
The researchers, whose findings have yet to be peer-reviewed in a scientific journal, said the results were not ‘unexpected’.
They added that ‘multiple comorbidities contribute to disease complexity and such patients are more susceptible and vulnerable to adverse events’.
‘Notably, smoking was not associated with a higher risk for adverse outcomes and hospitalization,’ the team wrote in their paper published on medRxiv.
‘Smokers were also less likely to be diagnosed with Covid-19.’ The experts added that the findings were ‘in agreement’ with a study from Israel.
The Israeli study referenced, published last week, pooled data from more than three million people, including 115,000 swabbed for the virus.
Dr Ariel Israel and his colleagues uncovered a ‘genuine’ protective effect of smoking. They also published their findings on MedRxiv.
Ten per cent of patients who tested positive for Covid-19 were smokers, compared to 19 per cent in the general population.
The findings only add weight to a number of small studies from when the pandemic began, which say smokers are protected from the coronavirus.
Israeli researchers found 9.8 per cent of patients who had tested positive for SARS-CoV-2 were smokers compared to 18.5 per cent of people who had tested negative and 19 per cent in the general population. The findings were similar for past smokers but not as strong
British researchers have rubbished the claims, finding smokers were more at risk of the virus after looking at 2.4million people who self-reported symptoms. Among ‘standard users’ of an app – those who never actually had a test – current smokers were 14 per cent more likely to develop the classic triad of symptoms of COVID-19 than non-smokers. They found smokers were 50 per cent more likely to have more than 10 symptoms. Researchers said this indicated their disease was more severe because those that reported going to hospital tended to have more symptoms
WHY IS SMOKING THOUGHT TO PROTECT AGAINST THE CORONAVIRUS?
Swathes of 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 flouted 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.
The findings present a hypothesis that nicotine – the highly addictive compounds in tobacco – may exert protective effects.
It is broadly understood that SARS-CoV-2 – the virus that causes the disease – enters the body by binding to receptors in the body called ACE-2, which are found along the respiratory tract.
Some research suggests nicotine reduces the expression of ACE-2, which would suggest smokers have less entry points for the virus to begin with.
But other scientists, including Dr Giannouchos, say nicotine is thought to boost the expression of ACE-2 receptors which coat the cells.
While this would imply smokers are at more risk of catching Covid-19, there is evidence that they are less likely to be hit by a severe bout of the disease.
‘ACE-2 deficiency’ may be detrimental to Covid-19 patients, Dr Giannouchos wrote, noting that risk factors for severe illness from Covid-19, such as age, male gender, and some diseases, are linked with lower levels of ACE-2.
Nicotine has been shown to prevent lung damage in animals with acute respiratory syndrome, a life-threatening condition the coronavirus can lead to.
It’s been suggested that if smokers do see their disease progress while in hospital, it is due to withdrawal from nicotine, exacerbating lung damage.
Another theory is that the virus first enters via the nicotinic acetylcholine receptor (nAChR), which is present around the nose and mouth.
This would explain why the virus causes a loss of taste and smell and in some cases, headaches, dizziness and intense fatigue.
Researchers from Paris wrote in a paper published on Qeios that nicotine would compete with the virus to bind to nAChR, and therefore may prevent the virus from latching on.
Severe Covid-19 has been shown to cause a ‘cytokine storm’ – a hyper activation of the immune response which can be fatal to healthy organs.
Research also suggests nicotine may prevent this severe over-reaction of the immune system by reducing the levels of cytokines circulating in the body.
Dr Giannouchos and colleagues concluded in their paper: ‘It is still not clear whether nicotine exerts any positive effect or not.
‘However, there is no doubt that smoking cannot be used as a protective measure and smoking cessation should be encouraged during the Covid-19 pandemic.
‘The potential value of nicotine or other nicotinic agonists in Covid-19 is expected to be determined through clinical trials.’
Indeed, researchers are pushing for clinical trials of nicotine patches, with the hope they can determine exactly what is going on.
Jonathan Davies, a consultant trauma surgeon at The Royal Glamorgan Hospital, Wales, told MailOnline the hospital is looking at a number of possible points at which nicotine might be a valid intervention.
He said: ‘In a nutshell, the question is: Are people who smoke see to be less likely to catch it? Does nicotine given to people who don’t smoker offer some sort of protection?
‘I would like to get a cohort of people in the general population and give half a nicotine patch for six week and the other half a placebo path and then see if there is a difference in antibodies [which indicate coronavirus infection].’
It follows the lead of researchers in France, who are also planning a trial after finding low levels of smokers in a hospital in Paris.
Only one notable study so far has thrown out the claims smoking is protective against Covid-19.
A team at Imperial College London looked at 2.4million users of the COVID Symptom Study app, developed by King’s College London and Zoe. Some 11 per cent of the group were smokers.
Among ‘standard users’ – those who never actually had a test – current smokers were 14 per cent more likely to develop the classic triad of symptoms of Covid-19 than non-smokers.
They were also 29 per cent more likely to have more than five symptoms, and 50 per cent more likely to have more than 10 symptoms, such as diarrhoea, loss of appetite and delirium.
The researchers said this indicated their disease was more severe because those that reported going to hospital tended to have more symptoms.
The World Health Organization (WHO) said on May 26 there is a lack of knowledge about whether smoking alters the risk of catching the coronavirus or being hospitalised.
There are currently no peer-reviewed papers on the matter published in medical journals, meaning none have been looked over and critiqued by other scientists.
The data up until this point has been full of holes – which could skew findings – because doctors are not always able to find out if someone severely sick is a smoker, either because they are too busy or the patient is so unwell they cannot speak.
Low smoking rates may be explained by differences in smoking rates between age groups, with middle-aged people more likely to have the habit, but elderly people more likely to be hospitalised with Covid-19.
When it comes to disease severity and death, the WHO reports that available evidence so far suggests that smoking increases the risk, having looked over 35 published studies.
A review of five early studies on the topic early in the pandemic made the exact same conclusions – that smokers may avoid serious infection, but their outlook is worse if they do.
The team at Harvard University in Boston and the University of Crete in Greece reviewed five Chinese studies in March and said so far say the proof smoking raises the risk of coronavirus is limited, after finding as little as 1.4 per cent of hospitalised patients were smokers.
The group of experts even admitted warnings made by health chiefs were based mainly on assumptions, given the known infection risks of smoking.
A recent Italian study found half of infected smokers died – compared to 35 per cent of the rest of the patients.
Fewer than five per cent of 441 Covid-19 patients who needed to be admitted to hospital were smokers – a ‘very low’ number, given that a quarter of the general population are known to be hooked on cigarettes.
But once smokers are in hospital, they may be more likely to see their disease rapidly progress and lead to death.
Information about smoking was taken from medical records, and efforts were made to directly contact the patients or their relatives for confirmation.
A leading infectious disease expert at University College London, Professor Francois Balloux, has also previously said there is ‘bizarrely strong’ evidence smoking may be protective.
And Linda Bauld, a professor of public health at the University of Edinburgh, said ‘there’s something weird going on with smoking and coronavirus’ on Good Morning Britain.
Less than five per cent of 441 hospitalised Covid-19 patients in an Italian study were smokers – compared with 24 per cent in the population
But more smokers succumbed to the disease – almost half compared to 35 per cent of those who had never touched a cigarette
WHAT HAVE STUDIES IN EACH COUNTRY SHOWN?
Italy
A recent Italian study found fewer than five per cent of 441 Covid-19 patients who needed to be admitted to an Italian hospital were smokers.
The scientists described it as a ‘very low’ number, given that a quarter of the general population are known to be hooked on cigarettes.
The Italian study led by Dr Nicola Gaibazzi looked at patients admitted to hospital in Parma, Northern Italy.
It means the findings can only be applied to those with symptoms severe enough to seek medical attention – thousands of patients escape suffering any symptoms.
Information about smoking was taken from medical records, and efforts were made to directly contact the patients or their relatives for confirmation.
Previous research on the topic has been full of holes because researchers admit data had been missing.
But in this study, a total of 423 out of 441 patients or their relatives were spoken to on the phone, which strengthens the data.
Non-smokers made up 85 per cent of deaths, smokers 6 per cent and ex-smokers 9 per cent – which was not significantly different to the total cohort.
However, active smokers had a 50/50 chance of survival once hospitalised – 47 per cent of those admitted died. In comparison, just over a third of non-smokers died.
China
The UCL review included 22 studies conducted in hospitals in China, which showed that 3.8 to 17.6 per cent of Covid-19 patients were current smokers and fewer than five per cent were former smokers.
However, 2018 data shows more than half the population of the country are current smokers (50.5 per cent of men and 2.1 per cent of women).
And almost one in 10 of non-smokers in China are former smokers (8.4 per cent of men and 0.8 per of women).
A separate study published in early April by scientists in New York and Athens looked at 13 Chinese studies that had registered smoking as a precondition and found that the number of smokers across the whole sample of 5,300 patients was 6.5 per cent.
It’s an astonishingly small number in country where half of all men still smoke.
South Korea
In one South Korean study looked at by UCL, 18.5 per cent were current smokers, which almost matches the smoking prevalence of 19.3 per cent in 2016.
France
In a study conducted in France, 7.1 per cent were current smokers, 6.1 per cent of whom were hospitalised. But much higher smoking rates are recorded in the population – 32 per cent.
However the results were different for former smokers, of which there are 31.4 per cent in France. A much higher 59.1 per cent of Covid-19 patients were former smokers.
University of College London found smoking rates were lower than expected among Covid-19 patients. The graph shows the smoking rate of each country against the percentage of smokers among Covid-19 patients. The lowest figure has been chosen for each country to show the stark comparison discovered by some studies
UK
In the international study with participants predominantly from the UK in a hospital setting, five per cent were current or former smokers.
This compares with a current and former smoking prevalence of 14.4 and 25.8 per cent in England in 2018, ‘suggesting a lower than expected proportion of current and former smokers in the included study’, UCL wrote.
Another study by Imperial College London, led by Dr Nicholas Hopkinson, used information from a symptom tracker app – rather than hit-and-miss hospital data – to try and solve whether smokers are at risk of catching the coronavirus.
The team looked at 2.4million users of the COVID Sympto Study app, developed by King’s College London and Zoe. All participants had regularly reported their health and if they have symptoms of the coronavirus with the app, helping to build a clearer picture of the UK’s outbreak.
Some 11 per cent of the group were smokers. The researchers said this may be lower than the national average (14 per cent) because wealthier people are less likely to smoker while also be more likely to have a smartphone.
Among ‘standard users’ – those who never actually had a test – current smokers were 14 per cent more likely to develop the classic triad of symptoms of Covid-19 than non-smokers. These were a fever, persistent cough and shortness of breath.
They were also 29 per cent more likely to have more than five symptoms, and 50 per cent more likely to have more than 10 symptoms, such as diarrhoea, loss of appetite and delirium.
The researchers said this indicated their disease was more severe because those that reported going to hospital tended to have more symptoms.
In addition, current smokers who actually tested positive, receiving a formal Covid-19 diagnosis, were more than twice as likely to need to attend hospital due to Covid-19.
The authors concluded in their pre-print paper, which has not been peer reviewed by other scientists: ‘Our results provide compelling evidence for an association between current smoking and individual risk from Covid-19, including symptom burden and risk of attending hospital.’
US
One study conducted by America’s Centers for Disease Control of over 7,000 people who tested positive for coronavirus, found that just 1.3 per cent of them were smokers – against the 14 per cent of all Americans that the CDC says smoke.
The study also found that the smokers stood no greater chance of ending up in hospital or an ICU.
In US studies reviewed by UCL, 1.3 to 27.2 per cent were current smokers, in contrast to a smoking prevalence of 13.8 per cent in 2018.
And 2.3 to 30.6 per cent were former smokers, compared with the 20.9 per cent of former smokers across the states.
Similarly, data published in the The New England Journal of Medicine from New York City, the epicentre of the US epidemic, shows just 5.1 per cent of patients are smokers.
