E-cigarette vapour disables lung's protective cells

COVID-19 mostly kills through an overreaction of the immune system, whose function is precisely to fight infections, say scientists who have decoded the mechanisms, symptoms, and diagnosis of the disease caused by the SARS-Cov-2 coronavirus.

In a study published in the journal Frontiers in Public Health, the researchers explained step-by-step how the virus infects the airways, multiplies inside cells, and in severe cases causes the immune defences to overshoot with a "cytokine storm".

This storm is an over-activation of white blood cells, which release too-great amounts of cytokines -- inflammation-stimulating molecules --into the blood, they said.

"Similar to what happens after infection with SARS and MERS, data show that patients with severe COVID-19 may have a cytokine storm syndrome," said study author Daishun Liu, Professor at Zunyi Medical University in China.

"The rapidly increased cytokines attract an excess of immune cells such as lymphocytes and neutrophils, resulting in an infiltration of these cells into lung tissue and thus cause lung injury," Liu said.

The researchers explained that the cytokine storm ultimately causes high fever, excessive leakiness of blood vessels, and blood clotting inside the body.

It also causes extremely low blood pressure, lack of oxygen and excess acidity of the blood, and build-up of fluids in the lungs, they said.

The researchers noted that white blood cells are misdirected to attack and inflame even healthy tissue, leading to failure of the lungs, heart, liver, intestines, kidneys, and genitals.

This multiple organ dysfunction syndrome (MODS) may worsen and shutdown the lungs, a condition called acute respiratory distress syndrome, (ARDS), they said.

This, the researchers explained, happens due to the formation of a so-called hyaline membrane -- composed of debris of proteins and dead cells -- lining the lungs, which makes absorption of oxygen difficult.

Most deaths due to COVID-19 are therefore due to respiratory failure, they said.

The researchers explained that in the absence of a specific antiviral cure for COVID-19, the goal of treatment must be to the fight the symptoms, and lowering the mortality rate through intensive maintenance of organ function.

For example, an artificial liver blood purification system or renal replacement therapy can be used to filter the blood through mechanical means, they said.

The team noted that especially important are methods to supplement or replace lung function, for example with non-invasive mechanical ventilation through a mask, ventilation through a tube into the windpipe, the administration of heated and humidified oxygen via a tube in the nose, or a heart-lung bypass.

The researchers stressed the importance of preventing secondary infections.

They noted that SARS-Cov-2 also invades the intestines, where it causes inflammation and leakiness of the gut lining, allowing the opportunistic entry of other disease-causing microorganisms.

The researchers advocate that this should be prevented with nutritional support, for example with probiotics -- beneficial bacteria that protect against the establishment of harmful ones -- and nutrients and amino acids to improve the immune defences and function of the intestine.

"Because treatment for now relies on aggressive treatment of symptoms, preventative protection against secondary infections, such as bacteria and fungi, is particularly important to support organ function, especially in the heart, kidneys, and liver, to try and avoid further deterioration of their condition," Liu added.

Early treatment with the antiviral drug remdesivir has been found to reduce viral load and prevent lung disease in macaques infected with SARS-CoV-2 that causes COVID-19, according to a study.

The findings, published in the journal Nature on Tuesday, support the early use of remdesivir treatment in patients with COVID-19 to prevent progression to pneumonia.

Researchers from the National Institutes of Health in the US noted that remdesivir has broad antiviral activity and has been shown to be effective against infections with SARS-CoV and MERS-CoV in animal models.

The drug is being tested in human clinical trials for the treatment of COVID-19, they said.

Researcher Emmie de Wit and colleagues investigated the effects of remdesivir treatment in rhesus macaques, a recently established model of SARS-CoV-2 infection.

Two sets of six macaques were inoculated with SARS-CoV-2.

One group was treated with remdesivir 12 hours later -- close to the peak of virus reproduction in the lungs -- and these macaques received treatment every 24 hours until six days after inoculation.

In contrast to the control group, the researchers found that macaques that received remdesivir did not show signs of respiratory disease, and had reduced damage to the lungs.

Viral loads in the lower respiratory tract were also reduced in the treated animals; viral levels were around 100 times lower in the lower-respiratory tract of remdesivir-treated macaques 12 hours after the first dose, they said.

The researchers said that infectious virus could no longer be detected in the treatment group three days after initial infection, but was still detectable in four out of six control animals.

Despite this virus reduction in the lower respiratory tract, no reduction in virus shedding was observed, which indicates that clinical improvement may not equate to a lack of infectiousness, they said.

Dosing of remdesivir in the rhesus macaques is equivalent to that used in humans, the researchers noted.

They cautioned that it is difficult to directly translate the timing of treatment used in corresponding disease stages in humans, because rhesus macaques normally develop only mild disease.

However, researchers said the results indicate that remdesivir treatment of COVID-19 should be initiated as early as possible to achieve the maximum treatment effect.

The coronavirus can stay aloft for hours in tiny droplets in stagnant air, infecting people as they inhale, mounting scientific evidence suggests.

This risk is highest in crowded indoor spaces with poor ventilation, and may help explain superspreading events reported in meatpacking plants, churches and restaurants.

It’s unclear how often the virus is spread via these tiny droplets, or aerosols, compared with larger droplets that are expelled when a sick person coughs or sneezes, or transmitted through contact with contaminated surfaces, said Linsey Marr, an aerosol expert at Virginia Tech.

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Aerosols are released even when a person without symptoms exhales, talks or sings, according to Marr and more than 200 other experts, who have outlined the evidence in an open letter to the World Health Organization.

What is clear, they said, is that people should consider minimizing time indoors with people outside their families. Schools, nursing homes and businesses should consider adding powerful new air filters and ultraviolet lights that can kill airborne viruses.

What does it mean for a virus to be airborne?

For a virus to be airborne means that it can be carried through the air in a viable form. For most pathogens, this is a yes-no scenario. HIV, too delicate to survive outside the body, is not airborne. Measles is airborne, and dangerously so: It can survive in the air for up to two hours.

For the coronavirus, the definition has been more complicated. Experts agree that the virus does not travel long distances or remain viable outdoors. But evidence suggests it can traverse the length of a room and, in one set of experimental conditions, remain viable for perhaps three hours.

How are aerosols different from droplets?

Aerosols are droplets, droplets are aerosols — they do not differ except in size. Scientists sometimes refer to droplets fewer than 5 microns in diameter as aerosols. (By comparison, a red blood cell is about 5 microns in diameter; a human hair is about 50 microns wide.)

From the start of the pandemic, the WHO and other public health organizations have focused on the virus’s ability to spread through large droplets that are expelled when a symptomatic person coughs or sneezes.

These droplets are heavy, relatively speaking, and fall quickly to the floor or onto a surface that others might touch. This is why public health agencies have recommended maintaining a distance of at least 6 feet from others, and frequent hand washing.

But some experts have said for months that infected people also are releasing aerosols when they cough and sneeze. More important, they expel aerosols even when they breathe, talk or sing, especially with some exertion.

Scientists know now that people can spread the virus even in the absence of symptoms — without coughing or sneezing — and aerosols might explain that phenomenon.

Because aerosols are smaller, they contain much less virus than droplets do. But because they are lighter, they can linger in the air for hours, especially in the absence of fresh air. In a crowded indoor space, a single infected person can release enough aerosolized virus over time to infect many people, perhaps seeding a superspreader event.

For droplets to be responsible for that kind of spread, a single person would have to be within a few feet of all the other people, or to have contaminated an object that everyone else touched. All that seems unlikely to many experts: “I have to do too many mental gymnastics to explain those other routes of transmission compared to aerosol transmission, which is much simpler,” Marr said.

Can I stop worrying about physical distancing and washing my hands?

Physical distancing is still very important. The closer you are to an infected person, the more aerosols and droplets you may be exposed to. Washing your hands often is still a good idea.

What’s new is that those two things may not be enough. “We should be placing as much emphasis on masks and ventilation as we do with hand washing,” Marr said. “As far as we can tell, this is equally important, if not more important.”

Should I begin wearing a hospital-grade mask indoors? And how long is too long to stay indoors?

Health care workers may all need to wear N95 masks, which filter out most aerosols. At the moment, they are advised to do so only when engaged in certain medical procedures that are thought to produce aerosols.

For the rest of us, cloth face masks will still greatly reduce risk, as long as most people wear them. At home, when you’re with your own family or with roommates you know to be careful, masks are still not necessary. But it is a good idea to wear them in other indoor spaces, experts said.

As for how long is safe, that is frustratingly tough to answer. A lot depends on whether the room is too crowded to allow for a safe distance from others and whether there is fresh air circulating through the room.

What does airborne transmission mean for reopening schools and colleges?

This is a matter of intense debate. Many schools are poorly ventilated and are too poorly funded to invest in new filtration systems. “There is a huge vulnerability to infection transmission via aerosols in schools,” said Don Milton, an aerosol expert at the University of Maryland.

Most children younger than 12 seem to have only mild symptoms, if any, so elementary schools may get by. “So far, we don’t have evidence that elementary schools will be a problem, but the upper grades, I think, would be more likely to be a problem,” Milton said.

College dorms and classrooms are also cause for concern.

Milton said the government should think of long-term solutions for these problems. Having public schools closed “clogs up the whole economy, and it’s a major vulnerability,” he said.

“Until we understand how this is part of our national defense, and fund it appropriately, we’re going to remain extremely vulnerable to these kinds of biological threats.”

What are some things I can do to minimize the risks?

Do as much as you can outdoors. Despite the many photos of people at beaches, even a somewhat crowded beach, especially on a breezy day, is likely to be safer than a pub or an indoor restaurant with recycled air.

But even outdoors, wear a mask if you are likely to be close to others for an extended period.

When indoors, one simple thing people can do is to “open their windows and doors whenever possible,” Marr said. You can also upgrade the filters in your home air-conditioning systems, or adjust the settings to use more outdoor air rather than recirculated air.

Public buildings and businesses may want to invest in air purifiers and ultraviolet lights that can kill the virus. Despite their reputation, elevators may not be a big risk, Milton said, compared with public bathrooms or offices with stagnant air where you may spend a long time.

If none of those things are possible, try to minimize the time you spend in an indoor space, especially without a mask. The longer you spend inside, the greater the dose of virus you might inhale.