Washington - With thousands of deaths already in the raging coronavirus pandemic, it's clear the disease is worse for the elderly and those with preexisting health problems.
But scientists are considering whether more subtle factors may also intensify the disease or increase the initial chances of infection - including smoking and air pollution.
There are no large scale studies from the current outbreak of coronavirus, which causes a disease known as covid-19, that directly support this conclusion - and only a few hints from smaller studies.
But experts note that damage to the lungs from pollutants that result from combustion - whether inhaled deliberately by smokers, or inadvertently by those in regions with poor air quality - may increase the risk of respiratory tract infections from viruses such as the novel coronavirus. Poor air can also cause lung inflammation that could worsen the symptoms of covid-19.
"Given what we know now, it is very likely that people who are exposed to more air pollution and who are smoking tobacco products are going to fare worse if infected with covid than those who are breathing cleaner air, and who don't smoke," said Aaron Bernstein, the interim director of the Center for Climate, Health, and the Global Environment at Harvard University's T.H. Chan School of Public Health.
Not everyone is convinced that there is a link.
"I would still treat this as a hypothesis - a reasonable one, but still a hypothesis," said Anna Hansell, an expert in environmental epidemiology at the University of Leicester in the United Kingdom.
The evidence for this hypothesis comes from two sources. First, there are a number of imperfect studies conducted during outbreaks caused by the evolutionary cousins of the current coronavirus. And second, there's more basic medical reasoning about how coronavirus and the products of combustion - a noxious mix of chemicals and gases - affect the lungs.
Studying the SARS (severe acute respiratory syndrome) outbreak in China in 2003, a team of scientists from the University of California at Los Angeles and several Chinese institutions found that cases tended to be more deadly in regions of China with poor air quality. But they warned that they had only found an "association," not causation, and that the result could be confounded by variables such as socioeconomic conditions and health practices.
With the similar MERS (Middle East respiratory syndrome) outbreak, meanwhile, several smaller studies showed that smokers had more deadly outcomes from the disease in South Korea and the Middle East, and a greater risk of contracting the disease in the first place in Saudi Arabia.
And then, there's basic biology about the impact of the novel coronavirus on the way lungs function.
More-severe covid-19 infections often feature pneumonia, an infection in the lungs that causes swelling and sometimes difficulty breathing. Some of those cases worsen further and produce acute respiratory distress syndrome, or ARDS, in which fluid in the lungs blocks breathing, requiring intensive care and sometimes leading to death.
Research shows that smokers tend to be more prone to pneumonia, including its most severe and deadly forms.
Air pollution, too, has been linked to a greater risk of respiratory infection. One reason, says John Balmes, a professor of occupational and environmental medicine at the University of California at San Francisco, is cells in our lungs known as "alveolar macrophages." They remove particles, microbes and bacteria that make their way deep into the airways. But pollution particles slow down the alveolar macrophages.
"Inorganic carbon particles, which they can't kill, they just accumulate in the macrophages," Balmes said. "So the macrophages get a little bit sick, and they're not as good at fighting infection.
White blood cells, which also battle infection, "are also interfered with by a lot of air pollution exposure. And smoking. So I do lump smoking and air pollution together when talking about their impacts on lung infection," Balmes said. ". . . That's an overly simplified way of describing how smoking and air pollution can inhibit the first line of defense in the lungs."
The coronavirus could amplify the existing strain on the lungs from smoking and air pollution, said Christopher Carlsten, who heads the respiratory medicine division at the University of British Columbia's department of medicine. "When you've already started the inflammatory machinery of the lungs, when you have another insult on top of it, it simply sets up a situation where you've kind of got a two-hit scenario," he said.
If this is correct, other factors such as wildfires and indoor stoves that cause air pollution, could also intensify the coronavirus risk. Smoking marijuana and vaping could also potentially be grouped as risks, though less is known about the latter's consequences on the lungs at this point.
"There is fairly strong evidence that air pollution increases the risk of acute low respiratory infections," said Balmes, a volunteer medical spokesman for the American Lung Association. "And it may have contributed to the extent of the outbreak in Wuhan."
This potential link between air quality in Wuhan and the novel coronavirus outbreak requires further study, researchers said.
These would be short term or acute effects, in which bad air pollution or a history of smoking worsens disease. But there is also a long-term picture that may be even clearer, and which at least puts smoking and air pollution two steps away from worse cases of covid-19.
It's clear that air pollution, over a period of time, leads to a higher risk of chronic obstructive pulmonary disease, or COPD, a condition that constricts the airways, Hansell said. And it's also becoming clear that people with COPD tend to have more severe disease when they contract covid-19.
Similarly, she notes, smoking leads to heart and lung disease, which also leaves one predisposed toward worse covid-19 outcomes.
What's missing is proof of the more direct causal linkage, rather than what Hansell described as these "two-stage processes."
"This sets up a hypothesis that smoking/air pollution may worsen outcomes but doesn't establish directly that smoking/air pollution worsens covid-19 and would need to be evaluated in further study," Hansell said.