French researchers to give nicotine patches to coronavirus patients, frontline workers after low infection rates found among smokers

Man with nicotine patch

French researchers are planning to trial whether nicotine patches will help prevent – or lessen the effects of – the deadly coronavirus.

Evidence is beginning to show the proportion of smokers infected with coronavirus is much lower than the rates in the general population.

Scientists are now questioning whether nicotine could stop the virus from infecting cells, or if it may prevent the immune system overreacting to the infection.

Doctors at a major hospital in Paris – who also found low rates of smoking among the infected – are now planning to give nicotine patches to COVID-19 patients.

They will also give them to frontline workers to see if the stimulant has any effect on preventing the spread of the virus, according to reports.

It comes after world-famous artist David Hockney last week said he believes smoking could protect people against the deadly coronavirus.

MailOnline looked at the science and found he may have been onto something, with one researcher saying there was ‘bizarrely strong’ evidence it could be true.

One study in China, where the pandemic began, showed only 6.5 per cent of COVID-19 patients were smokers, compared to 26.6 per cent of the population.

Another study, by the Centers for Disease Control in the US, found just 1.3 per cent of hospitalised patients were smokers – compared to 14 per cent of America.

And research by hospitals in Paris found that smokers were under-represented in both inpatients and outpatients, suggesting that any protective effect could affect anyone, not just those hospitalised by their illness.

The French study, performed at Pitié Salpêtrière – part of the Hôpitaux de Paris, used data from 480 patients who tested positive for the virus.

Three hundred and fifty were hospitalized and the remainder recovered at home.

Results showed that of the patients hospitalized, with a median age of 65, only 4.4 percent were regular smokers. But among those at home, with a median age of 44, 5.3 percent smoked.

By comparison, among the general population, 40 percent of those between ages 44 and 53 smoke, and around 11 percent of those aged 65 to 75 smoke.

The researchers determined that far fewer smokers appear to have contracted the virus or, if they have, their symptoms are less serious.

Smokers and the coronavirus

Research by the Hopitaux de Paris and Université Pierre et Marie Curie, in the French capital, has claimed a potential protective effect of smoking against COVID-19 could have benefits for people with mild or severe symptoms.

While many studies have focused on patients in hospital or intensive care units, this research looked at outpatients, too.

And they found that a disproportionately small number of those – patients who were not ill enough to need a hospital bed – were smokers. This was the same phenomenon observed among the more seriously ill inpatients.

They found 5.3 per cent of 139 outpatients were smokers, compared to 4.4 per cent of 343 inpatients. In the French population, the smoke rate was 25 per cent.

The researchers, led by Dr Makoto Miyara, wrote: ‘The [smoking rates] did not differ between outpatients and inpatients, suggesting that the protective effect of smoking covered the whole population of symptomatic (both non-severe and severe) patients.’

‘Our cross-sectional study strongly suggests that those who smoke every day are much less likely to develop a symptomatic or severe infection with Sars-CoV-2 compared with the general population,’ the study reads.

‘The effect is significant. It divides the risk by five for ambulatory patients and by four for those admitted to hospital. We rarely see this in medicine.’

The team says it is not advocating that anyone start smoking because cigarettes have fatal health risks.

However, French neurobiologist Jean-Pierre Changeux, who reviewed the study, told The Guardian that nicotine may be hindering the virus from entering the body’s cells.

In addition, the authors theorize nicotine could abate the immune system’s overreaction to the virus, which leads to serious complications in some patients.

The researchers will verify the study’s results by giving nicotine patches to hospital patients, those in intensive care and frontline workers.

This is not the first article to suggest that nicotine may ward off the coronavirus.

A French study from the Université Pierre et Marie Curie found that just 8.5 percent of 11,000 hospitalized coronavirus patients were smokers compared to 25.4 percent of the country’s population.

And it also found, albeit in a small study, that people who had milder coronavirus infections and didn’t need to be admitted to hospital had lower smoking rates, too.

Just 5.3 per cent of the 139 outpatients in the study were classed as active smokers – still a fifth of the proportion of smokers in the general public.

The paper focused on statistics but pointed to past research which suggested nicotine may alter receptors inside the body called ACE-2 receptors, which the coronavirus relies on as its gateway into the body.

Any protective effect, the researchers suggested, may therefore work for people with any level of infection, not just those with severe illness.

They wrote: ‘The [smoking rates] did not differ between outpatients and inpatients, suggesting that the protective effect of smoking covered the whole population of symptomatic (both non-severe and severe) patients.

However, the US Food and Drug Administration (FDA) has said that cigarettes can increase the risk of contracting the disease.

‘People who smoke cigarettes may be at increased risk of infection with the virus that causes COVID-19, and may have worse outcomes from COVID-19,’ the agency told Bloomberg News.

The FDA has previously warned about ‘worse outcomes’ for coronavirus among smokers but did not specify what that meant.

Does smoking PROTECT against coronavirus? That was the amazing claim from David Hockney but multiple scientific studies now suggest he might be on to something

David Hockney

The eccentric artist David Hockney, who is a smoker himself, asked in a letter to the Daily Mail ‘Could it not be that smokers have developed an immune system to this virus?’

When world-famous artist David Hockney wrote a letter to the Daily Mail saying he believes smoking could protect people against the coronavirus many scoffed.

Mr Hockney wrote: ‘Could it not be that smokers have developed an immune system to this virus? With all these figures coming out, it’s beginning to look like that to me.’

Understandably the claim was brushed off as laughable and ‘rubbish’ by many.

But is it?

A leading infectious disease expert at University College London, Professor Francois Balloux, said there is ‘bizarrely strong’ evidence it could be true.

And data from multiple Chinese studies shows that COVID-19 hospital patients contained a smaller proportion of smokers than the general population (6.5 per cent compared to 26.6 per cent), suggesting they were less likely to end up in hospital.

Another study, 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.

COVID outcomes

The study also found that the smokers stood no greater chance of ending up in hospital or an ICU.

The reasons for this are unclear.

Evidence coming out of scientific studies is conflicting and some say doctors are just too busy to be accurately noting down everyone’s smoking habits.

Some researchers suggest smoking could reverse one of the ways in which COVID-19 damages the lungs while others argue the lung damage caused by smoke makes the organs more susceptible to failure.

Governments in both the UK and US urge people to stop smoking to protect themselves from the virus, but scientists admit there is no clear proof cigarettes can worsen the disease.

In his letter, Mr Hockney wrote: ‘I used to joke that being a smoker in Malibu was the equivalent of being a non-smoker in Pasadena. They used to have very bad pollution there.

‘Could it not be that smokers have developed an immune system to this virus? With all these figures coming out, it’s beginning to look like that to me.’

The British artist, now 82 and living in France, adds ‘I’m serious’ and has in the past revealed he’s smoked for more than 60 years but still considers himself healthy.

Around 1.1 billion people around the world smoke cigarettes in spite of evidence they cause lung cancer, heart disease and numerous other life-threatening illnesses.

Whether they make people more likely to end up in hospital or die if they catch COVID-19, however, is unclear.

A study published earlier this month by scientists in New York and Athens claims the opposite.

It 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. An astonishingly small number in country where over half of all men still smoke.

‘This preliminary analysis does not support the argument that current smoking is a risk factor for hospitalization for COVID-19,’ it reads.

‘Instead, these consistent observations, which are further emphasized by the low prevalence of current smoking among COVID-19 patients in the US (1.3 per cent), raises the hypothesis that nicotine may have beneficial effects on COVID-19.’

Chart of studies on smoking status and COVID

A group of studies from China found that the average proportion of coronavirus patients who were classed as smokers – from a total of almost 6,000 people – was just 6.5 per cent. For comparison, more than 26 per cent of the country’s population as a whole are smokers.

The paper has not been reviewed by other scientists and admits that it is based on limited data, but says that nicotine and the coronavirus both interact with the same receptors on cells inside the lungs.

It was done by Dr Konstantinos Farsalinos and Dr Anastasia Barbouni, from the University of West Attica in Athens, and Dr Raymond Niaura of New York University.

They suggest that while the virus causes lung damage by depleting the numbers of those receptors – known as ACE-2 receptors – smoking can increase the number of them, reversing the effect.

ACE-2 receptors, which are found on cells in the airways and lungs, have been said to work as the coronavirus’s doorway into the body and to ‘facilitate’ infection.

Therefore having more of them would seem to be a bad thing, but scientists say they have a protective effect in the lungs and low levels are linked to worse damage from viral infection.

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. ACE-2’s function in human lungs is poorly understood.

Dr Farsalinos’s study was shared on Twitter by Professor Francois Balloux, director of the genetics institute at University College London.

Professor Balloux described the paper as ‘puzzling’ and added: ‘Whilst the study design is far from perfect – and the authors are clear about its limitations – the evidence for a protective effect of smoking (or nicotine) against COVID-19 is bizarrely strong… actually far stronger than for any drug trialled at this stage…’

It is a claim that has been emerging around the world.

French scientist Professor Jean-François Delfraissy, who is leading a scientific council advising the country’s government on COVID-19, said: ‘We have something very special with tobacco.

‘We have found that the vast majority of serious cases are not smokers, as if (…) tobacco protects against this virus, via nicotine,’ French news site Sud Ouest reported.

The study by Dr Farsalinos adds by way of explanation: ‘It has been observed that decreased ACE-2 availability contributes to lung injury and acute respiratory distress syndrome development.

‘Therefore, higher ACE-2 expression, while seemingly paradoxical, may protect against acute lung injury caused by COVID-19.’

This is a disputed area of science – there are studies which show smoking can both increase and decrease the levels of ACE-2 available on someone’s lung cells.

An increase before infection could allow more of the viruses to get into the body in the first place, making someone more vulnerable to the disease.

A paper published by scientists at University College London offers the opposite view to Dr Farsalinos.

It said: ‘SARS-CoV-2 has been shown to enter cells through the ACE-2 receptor​.

‘Some evidence suggests that gene expression and subsequent receptor levels are elevated in the airway and oral [cells] of current smokers​, thus putting smokers at higher risk of contracting SARS-CoV-2.

‘Other studies, however, show that nicotine downregulates the ACE-2 receptor.’

Professor Jamie Brown, an addiction researcher at UCL and one of the authors who wrote that paper, told MailOnline the link is ‘very difficult to understand’.

‘Everything we know about other respiratory viruses and comorbidities [health problems] suggests smokers will suffer worse outcomes,’ he said.

Only recently – a paper published this year claimed to be the first – have scientists started to record that smoking increases ACE-2 levels in the airways.

It had previously been reported to reduce levels, something that researchers have linked to worse lung damage in coronavirus infections.

While higher levels of the receptor may offer some protection in theory, they also offer more doorways through which the virus can enter the body.

The study in the European Respiratory Journal said: ‘While the up-regulation of ACE-2 may be useful in protecting the host against acute lung injury, chronically, this may predispose individuals to increased risk of coronavirus infections, which uses this receptor to gain entrance into epithelial cells.’

Professor Brown added that, considering how smoking influences other lung infections, he would be ‘very surprised’ if it didn’t make COVID-19 worse.

One paper suggested that a reason children appear not to be badly affected, in general, by the coronavirus could be that they have more ACE-2 receptors than adults, but it added there is ‘a lack of evidence to show that ACE-2 expression varies with age’.

Dr Farsalinos and his colleagues’ study even suggested that withdrawal symptoms from not being able to smoke in hospital could make cigarette users’ symptoms worse.

It added: ‘Hospitalization for COVID-19 will inevitably result in abrupt withdrawal of nicotine and its beneficial effect linked to this hypothesis in smokers or users of other nicotine products.

‘This could, at least partly, explain the association between smoking and COVID-19 severity among hospitalized patients.’

The theory of smokers having some level of protection from the virus stems from raw hospital data which suggested only small proportions of seriously-ill patients smoke.

Hospitals in China, the US, Germany and France have had hundreds of thousands of coronavirus patients but admitted disproportionately small numbers of smokers.

According to the campaign group, Foundation for a Smoke-Free World, early data showed that in Germany six percent to 21 percent; and in France six per cent compared to 27 per cent.

Data from the Centers for Disease Control and Prevention (CDC) in the US showed that of around 7,000 COVID-19 patients, former smokers were more likely to be hospitalised or taken into intensive care than current smokers.

Just 22 of the hospital patients and five of those in intensive care admitted to being smokers, while 45 in hospital and 33 in ICU said they were former smokers.

Public Health England has not published any information about the people diagnosed or hospitalised with coronavirus in the UK.

Why then, scientists have asked, do smokers make up such a small proportion of patients when there are significantly more of them in the countries?

Experts have knocked this theory down and say reporting of who smokes and who doesn’t has not been accurate enough.

UCL’s Professor Brown told MailOnline: ‘It’s difficult to assess how well smoking status has been recorded in an emerging epidemic and a lot of these people have been too sick to answer or have not replied totally honestly.’

He added: ‘We know generally smokers tend to come from lower income groups which have poorer access to healthcare… so may be more likely to die in the community.’

Professor Paul Hunter, a former NHS doctor and now medicine lecturer at the University of East Anglia, agreed that recording was likely to blame.

He told MailOnline: ‘One interpretation is that smokers are less likely to end up in hospital.

‘But actually it’s more of an indication that when you’ve got doctors who are unbelievably busy they don’t complete all of the questioning they would normally do.’

Professor Hunter added that the notion smoking could protect people from COVID-19 was ‘rubbish’, but admitted the ACE-2 receptor link deserved further study.

A researcher at Cold Spring Harbor Laboratory in New York, Jason Sheltzer, picked apart Dr Farsalinos paper on Twitter with similar logic, calling the study ‘severely flawed’.

He said that the measures for what defined a smoker varied across the world and across the multiple other studies that were referenced in the paper. One of them, he said, only classified very heavy smokers and not those with lighter habits.

A deeper dive into data, Mr Sheltzer wrote, revealed that smoking actually appeared to be linked to a higher risk of severe infection.

He said: ‘In order to further investigate, I emailed the authors of some of the studies on COVID-19 in China. One doctor replied that their smoking frequency was so low because some patients were literally too sick to answer the question.

‘So… it’s clear that in these studies, the definition of a smoker is neither consistent nor consistently applied. You can’t throw them all on a graph and call it a meta-analysis.’

He added: ‘In short, I think that this analysis is severely flawed. They’re comparing statistics that shouldn’t be compared.

‘I don’t think that there’s any convincing evidence that smoking protects against coronavirus.’

Government bodies are adamant that people should not consider the prospect of smoking being protective against the illness, which can be deadly, especially for people who already have health problems.

Both Public Health England and the Centers for Disease Control and Prevention (CDC) have urged people to stop smoking to protect their health.

British Health Secretary Matt Hancock last month said: ‘It is abundantly clear from the research into previous coronaviruses that smoking makes the impact of a coronavirus worse.’

And his chief medical adviser, Professor Chris Whitty, added: ‘If you are going to give up smoking, this is a very good moment to do it.’