Possibly the last thing anyone would think of as protecting against COVID-19/Wikimedia Commons

Of all the strange twists and turns that have come out of the research into COVID-19 since the pandemic began to sweep the world six months ago, the strangest comes from Israel where scientists studied 3 million adult clients of  Clalit Health Services, the country’s largest health provider.

As the pandemic caused by SARS-CoV-2 was ruthlessly killing the obese, the asthmatic, and other with chronic medical problems, the Israel scientists were trying to determine the risk to smokers – usually easy targets for respiratory illnesses.

“Smokers are generally more susceptible to infectious respiratory diseases and are at higher risk of developing severe complications from these infections,” they noted. “Conflicting reports exist regarding the impact of smoking on the risk of coronavirus disease 2019 (COVID-19) infection.”

The data they collected eventually lead to a conclusion that can only be described as shocking:

“The risk of infection by COVID-19 appears to be reduced by half among current smokers.”

As a demonstrated protective measure that would put smoking ahead of public masking, the success of which scientists are still trying to sort out. But scientists writing in an “evidence review” at Research Gate in April reported that flu transmission in Hong Kong dropped 44 percent “after the implementation of changes in population behaviors, including social distancing and increased mask-wearing, enforced in most stores, during the COVID-19 outbreak.”

The flu virus is significantly larger than the SARS-CoV-2 virus, which would influence how much goes through a face covering, and there is no way to tell how much of a role social-distancing played in the reduction of transmission as opposed to masks. But flu provided scientists a mechanism for tracking changes in a known infectious disease as behaviors changed to respond to COVID-19.

Smoking remains unhealthy

What exactly to make of the smoking discovery, Dr. Ariel Israel and his colleagues admitted, nobody knows. They stressed it would be a bad idea to start smoking with the idea that it is a good way to beat SARS-CoV-2.

“Acknowledging the destructive effects of smoking on health, the importance of smoking prevention and cessation to preserve health, and the highly addictive nature of nicotine,” they wrote, “we strongly encourage all patients to refrain from smoking, as the long term effects of this hazardous habit far outweigh potential benefits in preventing SARS-CoV-2 infection.”

Even if someone were to start smoking for a time during the pandemic, however, the health consequences are unlikely to be as high as for drinking chloroquine phosphate, a chemical commonly used to clean fish tanks.

A 68-year-old Arizona man and his 61-year-old wife tried that as a possible prophylactic after President Donald Trump in March said chloroquine, an old malaria drug available only by prescription, had shown “very, very encouraging early results” in treating COVID-19.

The man died. His wife survived. Media widely blamed Trump for their deaths.

Subsequent research has found no evidence chloroquine works against COVID-19, a peer-reviewed study in the British journal The Lancet reported in late May, adding that there were indications the drug increased risks of heart failure.

“These findings suggest that these drug regimens should not be used outside of clinical trials and urgent confirmation from randomized clinical trials is needed,” those researchers concluded.

No clinical trials of smoking have been suggested, given the well-documented downsides to the use of tobacco. But the Israeli doctors said their findings could point to other areas worth further investigation. They readily conceded the connection between smoking and COVID-19 runs counter to what has been found in other studies of smokers and infectious, respiratory diseases of all sorts.

The COVID-19 data, they wrote, is in “contrast to what occurs in most respiratory
infections. (But) This intriguing observation confirms several recently published studies that also reported decreased disease incidence among smokers although on a smaller scale.”

No greater death risk

“Interestingly, even among SARS-CoV-2 positive patients, we found no evidence of significant association between current or past smoking and disease severity, as reflected by death during hospitalization or by need for mechanical ventilation,” the added.

At least one smaller, earlier study had shown that while smokers had less risk of catching COVID-19, they were at a somewhat greater risk of dying if the SARS-CoV-2 virus brought on symptoms. The Israelis did not find such a connection.

It is possible, they wrote, that smoking interferes with “unique infection mechanisms present in the novel coronavirus.”

French Dr. Jean-pierre Changeux and a team at the Pasteur Institute in France have suggested that nicotine might be protective. Their theory is that alterations to the “nicotinic acetylcholine receptor (nAChR) in smokers” in some way block the virus.

“According to their neurotropic hypothesis,” the Israelis wrote, “SARS-CoV-2 invades the central nervous system through the nAChR receptor, present in neurons of the olfactory system, as reflected by the frequent occurrence of neurologic symptoms, such as loss of smell or taste, or intense fatigue in patients affected by COVID-19.”

Other European researchers have also suggested nasal cells as “as a portal for initial infection and transmission.” There are other possibilities, however.

As Israel and his team wrote, “it is now widely accepted that the angiotensin
converting enzyme 2 (ACE2) represents the main receptor molecule for SARS-CoV-2, and smoking has been shown to differentially affect ACE2 expression in tissues. Other putative explanations could involve altered cytokine expression” in smokers.

Cytokines are proteins that cells use to communicate. Some COVID-19 deaths have been linked to what are called “cytokine storms.” In a cytokine storm, the immune system spins out of control in reaction to an infection.

Inflammation, a normal body reaction to naturally deal with disease or injury, progresses unchecked and can lead to the failure of major organs.

“Under normal circumstances, these cytokines help coordinate the response of your immune system to take care of infectious substances, like viruses or bacteria,” writes Dr. Ruth Jessen Hickman at Very Well Health. “The problem is that sometimes the body’s inflammatory response can get out of control, causing more harm than good. Sometimes the body produces too many inflammatory cytokines and not enough cytokines that modulate inflammation. The inflammatory cytokines start ‘storming’ out of control, without enough feedback from the anti-inflammatory cytokines.”