Angry Citizens Pressure the World Health Organization to Fully Recognize COVID’s Airborne Spread
A new citizen movement is gathering steam to try to convince the influential World Health Organization to change its messaging about how the coronavirus is transmitted.
The new petition "COVID is Airborne" (www.covidisairborne.org) started in early November and has approximately 3,000 signatures. During this particularly dangerous acceleration of the pandemic, the petition's backers allege that the WHO is failing the public with mixed messaging and thus inadvertently fueling the wildfire of transmission.
"Early on in the pandemic, [WHO Director General Dr. Tedros Adhanom Ghebreyesus] said that coronavirus is airborne, but then in March, WHO tweeted that COVID-19 is not airborne, saying that it is primarily transmitted via droplets that are too heavy to hang in the air," says petition co-creator Jessica Bassett Allen.
The organization's late March messaging, still available on social media, is a digital graphic saying, "FACT CHECK: COVID-19 is NOT Airborne".
Screenshot of WHO's Tweet from March 28, 2020 that is still published.
The petition asks for a course correct: "We, citizens of the world, request that the World Health Organization (WHO) recognize the compelling scientific evidence that SARS-CoV-2 spreads by aerosol transmission ("airborne") and urge the WHO to immediately develop and initiate clear recommendations to enable people to protect themselves."
In the vacuum of the WHO's inaction, aerosol scientists around the world scrambled to raise awareness of what they saw as a grave error.
"Almost immediately after that [March 28] announcement, we formed a group of 239 scientists from many countries and disciplines to convince them that they should acknowledge that there is airborne transmission, but we find that they are totally dead set against it," says Dr. Jose Jimenez, a chemistry professor at the University of Colorado at Boulder who has studied aerosols for 20 years. He supports the citizen petition.
In a letter to the WHO back in July, he and his colleagues wrote: "Studies by the signatories and other scientists have demonstrated beyond any reasonable doubt that viruses are released during exhalation, talking, and coughing in microdroplets small enough to remain aloft in air and pose a risk of exposure at distances beyond 1–2 m from an infected individual."
The scientists have also gone direct to the public with their findings: They published a comprehensive Google doc with detailed answers to many people's frequently asked questions about how to protect themselves, addressing issues ranging from the best masks and air filters to how to deal with passing someone outdoors and much more.
It's worth noting that the CDC has now modified its COVID FAQ to include airborne transmission as a "less common way" for the virus to spread. This update took place after the CDC stated in September that it is "possible" the virus spreads via airborne transmission – only to reverse course and remove the language from its website several days later. The CDC's website now states that some viruses, including SARS-Cov-2, "may be able to infect people who are further than 6 feet away from the person who is infected or after that person has left the space."
Basset Allen notes that after the scientists' open letter, the WHO "added ventilation to public communications about how to prevent infection, but they haven't explained why."
When contacted, a WHO representative had no specific comment and shared its late March announcement as well as its latest guidelines on transmission. In part, its statement says, "Current evidence suggests that the main way the virus spreads is by respiratory droplets among people who are in close contact with each other. Aerosol transmission can occur in specific settings, particularly in indoor, crowded and inadequately ventilated spaces, where infected person(s) spend long periods of time with others, such as restaurants, choir practices, fitness classes, nightclubs, offices and/or places of worship. More studies are underway to better understand the conditions in which aerosol transmission is occurring outside of medical facilities where specific medical procedures, called aerosol-generating procedures, are conducted."
A forceful and clear message acknowledging the evidence could make it easier to standardize school and office ventilation, petitioners argue.
Aerosol scientist Jimenez was dismayed by the WHO's response.
"The first part is an error in my opinion," he says. "Current evidence suggests that the main way the virus spreads is inhalation of aerosols.…WHO is way behind, unfortunately.
"The second part is incomplete," Jimenez continues. "Aerosol transmission can happen in those indoor crowded low-ventilation spaces. But if aerosols can accumulate under those conditions and cause infection, they must be extremely infective in close proximity when talking, since they are much more concentrated there. Just like talking close to a smoker you would inhale much more smoke (which is an aerosol) than if you were in the same room, but let's say 10 or 15 feet away."
He adds, "The WHO and others are making the assumption that if this goes through the air, then everyone who is infected is putting a lot of virus into the air at all times, but we know that's wrong: People are infectious for a short period of time before and during their symptoms. In China, they have measured how much virus comes out of people, and they see that the emission is sporadic: The virus can come out in millions of viral [particles] per hour, but it doesn't happen all the time."
The petition's co-creator, Basset Allen, says that her life experience showed her the best way to make a change. "My involvement with this effort is entirely personal," she says. "I was first introduced to HIV treatment activism as a college student and what I learned about campaigning and power has been relevant in almost every other project I've worked on since then. HIV activism taught me that everyday people can win big, life-saving policy changes if they build expertise and work strategically to push decision makers."
The petition and its advocates argue that the WHO's mixed messaging is causing real harm. For instance, a forceful and clear message acknowledging the evidence could make it easier to standardize school and office ventilation, they argue. Anecdotally, some schools have refused to install HEPA filtration in their classrooms due to a lack of specific guidance from health agencies. (Note: The CDC now recommends improving central air filtration and considering the use of portable HEPA filters in classrooms.)
As the holidays approach, a clear and unified message from all influential health agencies would also help people understand why it is still important to wear masks while physical distancing, especially indoors.
"Personally, I cheered when I heard President-Elect Biden mention ventilation upgrades in schools during the first 10 minutes of his October town hall event, and again in the second debate," Basset Allen says. "Unfortunately, we're still more than two months away from the Biden administration taking over the U.S. COVID-19 response and we have to do absolutely everything we can right now to save as many lives as possible. Increasing awareness of airborne transmission and mitigation strategies can't wait. WHO can use its power to help close that gap, here and around the world."
Scientists Are Working to Decipher the Puzzle of ‘Broken Heart Syndrome’
Elaine Kamil had just returned home after a few days of business meetings in 2013 when she started having chest pains. At first Kamil, then 66, wasn't worried—she had had some chest pain before and recently went to a cardiologist to do a stress test, which was normal.
"I can't be having a heart attack because I just got checked," she thought, attributing the discomfort to stress and high demands of her job. A pediatric nephrologist at Cedars-Sinai Hospital in Los Angeles, she takes care of critically ill children who are on dialysis or are kidney transplant patients. Supporting families through difficult times and answering calls at odd hours is part of her daily routine, and often leaves her exhausted.
She figured the pain would go away. But instead, it intensified that night. Kamil's husband drove her to the Cedars-Sinai hospital, where she was admitted to the coronary care unit. It turned out she wasn't having a heart attack after all. Instead, she was diagnosed with a much less common but nonetheless dangerous heart condition called takotsubo syndrome, or broken heart syndrome.
A heart attack happens when blood flow to the heart is obstructed—such as when an artery is blocked—causing heart muscle tissue to die. In takotsubo syndrome, the blood flow isn't blocked, but the heart doesn't pump it properly. The heart changes its shape and starts to resemble a Japanese fishing device called tako-tsubo, a clay pot with a wider body and narrower mouth, used to catch octopus.
"The heart muscle is stunned and doesn't function properly anywhere from three days to three weeks," explains Noel Bairey Merz, the cardiologist at Cedar Sinai who Kamil went to see after she was discharged.
"The heart muscle is stunned and doesn't function properly anywhere from three days to three weeks."
But even though the heart isn't permanently damaged, mortality rates due to takotsubo syndrome are comparable to those of a heart attack, Merz notes—about 4-5 percent of patients die from the attack, and 20 percent within the next five years. "It's as bad as a heart attack," Merz says—only it's much less known, even to doctors. The condition affects only about 1 percent of people, and there are around 15,000 new cases annually. It's diagnosed using a cardiac ventriculogram, an imaging test that allows doctors to see how the heart pumps blood.
Scientists don't fully understand what causes Takotsubo syndrome, but it usually occurs after extreme emotional or physical stress. Doctors think it's triggered by a so-called catecholamine storm, a phenomenon in which the body releases too much catecholamines—hormones involved in the fight-or-flight response. Evolutionarily, when early humans lived in savannas or forests and had to either fight off predators or flee from them, these hormones gave our ancestors the needed strength and stamina to take either action. Released by nerve endings and by the adrenal glands that sit on top of the kidneys, these hormones still flood our bodies in moments of stress, but an overabundance of them could sometimes be damaging.
Elaine Kamil
A study by scientists at Harvard Medical School linked increased risk of takotsubo to higher activity in the amygdala, a brain region responsible for emotions that's involved in responses to stress. The scientists believe that chronic stress makes people more susceptible to the syndrome. Notably, one small study suggested that the number of Takotsubo cases increased during the COVID-19 pandemic.
There are no specific drugs to treat takotsubo, so doctors rely on supportive therapies, which include medications typically used for high blood pressure and heart failure. In most cases, the heart returns to its normal shape within a few weeks. "It's a spontaneous recovery—the catecholamine storm is resolved, the injury trigger is removed and the heart heals itself because our bodies have an amazing healing capacity," Merz says. It also helps that tissues remain intact. 'The heart cells don't die, they just aren't functioning properly for some time."
That's the good news. The bad news is that takotsubo is likely to strike again—in 5-20 percent of patients the condition comes back, sometimes more severe than before.
That's exactly what happened to Kamil. After getting her diagnosis in 2013, she realized that she actually had a previous takotsubo episode. In 2010, she experienced similar symptoms after her son died. "The night after he died, I was having severe chest pain at night, but I was too overwhelmed with grief to do anything about it," she recalls. After a while, the pain subsided and didn't return until three years later.
For weeks after her second attack, she felt exhausted, listless and anxious. "You lose confidence in your body," she says. "You have these little twinges on your chest, or if you start having arrhythmia, and you wonder if this is another episode coming up. It's really unnerving because you don't know how to read these cues." And that's very typical, Merz says. Even when the heart muscle appears to recover, patients don't return to normal right away. They have shortens of breath, they can't exercise, and they stay anxious and worried for a while.
Women over the age of 50 are diagnosed with takotsubo more often than other demographics. However, it happens in men too, although it typically strikes after physical stress, such as a triathlon or an exhausting day of cycling. Young people can also get takotsubo. Older patients are hospitalized more often, but younger people tend to have more severe complications. It could be because an older person may go for a jog while younger one may run a marathon, which would take a stronger toll on the body of a person who's predisposed to the condition.
Notably, the emotional stressors don't always have to be negative—the heart muscle can get out of shape from good emotions, too. "There have been case reports of takotsubo at weddings," Merz says. Moreover, one out of three or four takotsubo patients experience no apparent stress, she adds. "So it could be that it's not so much the catecholamine storm itself, but the body's reaction to it—the physiological reaction deeply embedded into out physiology," she explains.
Merz and her team are working to understand what makes people predisposed to takotsubo. They think a person's genetics play a role, but they haven't yet pinpointed genes that seem to be responsible. Genes code for proteins, which affect how the body metabolizes various compounds, which, in turn, affect the body's response to stress. Pinning down the protein involved in takotsubo susceptibility would allow doctors to develop screening tests and identify those prone to severe repeating attacks. It will also help develop medications that can either prevent it or treat it better than just waiting for the body to heal itself.
Researchers at the Imperial College London found that elevated levels of certain types of microRNAs—molecules involved in protein production—increase the chances of developing takotsubo.
In one study, researchers tried treating takotsubo in mice with a drug called suberanilohydroxamic acid, or SAHA, typically used for cancer treatment. The drug improved cardiac health and reversed the broken heart in rodents. It remains to be seen if the drug would have a similar effect on humans. But identifying a drug that shows promise is progress, Merz says. "I'm glad that there's research in this area."
This article was originally published by Leaps.org on July 28, 2021.
Lina Zeldovich has written about science, medicine and technology for Popular Science, Smithsonian, National Geographic, Scientific American, Reader’s Digest, the New York Times and other major national and international publications. A Columbia J-School alumna, she has won several awards for her stories, including the ASJA Crisis Coverage Award for Covid reporting, and has been a contributing editor at Nautilus Magazine. In 2021, Zeldovich released her first book, The Other Dark Matter, published by the University of Chicago Press, about the science and business of turning waste into wealth and health. You can find her on http://linazeldovich.com/ and @linazeldovich.
Did Anton the AI find a new treatment for a deadly cancer?
Bile duct cancer is a rare and aggressive form of cancer that is often difficult to diagnose. Patients with advanced forms of the disease have an average life expectancy of less than two years.
Many patients who get cancer in their bile ducts – the tubes that carry digestive fluid from the liver to the small intestine – have mutations in the protein FGFR2, which leads cells to grow uncontrollably. One treatment option is chemotherapy, but it’s toxic to both cancer cells and healthy cells, failing to distinguish between the two. Increasingly, cancer researchers are focusing on biomarker directed therapy, or making drugs that target a particular molecule that causes the disease – FGFR2, in the case of bile duct cancer.
A problem is that in targeting FGFR2, these drugs inadvertently inhibit the FGFR1 protein, which looks almost identical. This causes elevated phosphate levels, which is a sign of kidney damage, so doses are often limited to prevent complications.
In recent years, though, a company called Relay has taken a unique approach to picking out FGFR2, using a powerful supercomputer to simulate how proteins move and change shape. The team, leveraging this AI capability, discovered that FGFR2 and FGFR1 move differently, which enabled them to create a more precise drug.
Preliminary studies have shown robust activity of this drug, called RLY-4008, in FGFR2 altered tumors, especially in bile duct cancer. The drug did not inhibit FGFR1 or cause significant side effects. “RLY-4008 is a prime example of a precision oncology therapeutic with its highly selective and potent targeting of FGFR2 genetic alterations and resistance mutations,” says Lipika Goyal, assistant professor of medicine at Harvard Medical School. She is a principal investigator of Relay’s phase 1-2 clinical trial.
Boosts from AI and a billionaire
Traditional drug design has been very much a case of trial and error, as scientists investigate many molecules to see which ones bind to the intended target and bind less to other targets.
“It’s being done almost blindly, without really being guided by structure, so it fails very often,” says Olivier Elemento, associate director of the Institute for Computational Biomedicine at Cornell. “The issue is that they are not sampling enough molecules to cover some of the chemical space that would be specific to the target of interest and not specific to others.”
Relay’s unique hardware and software allow simulations that could never be achieved through traditional experiments, Elemento says.
Some scientists have tried to use X-rays of crystallized proteins to look at the structure of proteins and design better drugs. But they have failed to account for an important factor: proteins are moving and constantly folding into different shapes.
David Shaw, a hedge fund billionaire, wanted to help improve drug discovery and understood that a key obstacle was that computer models of molecular dynamics were limited; they simulated motion for less than 10 millionths of a second.
In 2001, Shaw set up his own research facility, D.E. Shaw Research, to create a supercomputer that would be specifically designed to simulate protein motion. Seven years later, he succeeded in firing up a supercomputer that can now conduct high speed simulations roughly 100 times faster than others. Called Anton, it has special computer chips to enable this speed, and its software is powered by AI to conduct many simulations.
After creating the supercomputer, Shaw teamed up with leading scientists who were interested in molecular motion, and they founded Relay Therapeutics.
Elemento believes that Relay’s approach is highly beneficial in designing a better drug for bile duct cancer. “Relay Therapeutics has a cutting-edge approach for molecular dynamics that I don’t believe any other companies have, at least not as advanced.” Relay’s unique hardware and software allow simulations that could never be achieved through traditional experiments, Elemento says.
How it works
Relay used both experimental and computational approaches to design RLY-4008. The team started out by taking X-rays of crystallized versions of both their intended target, FGFR2, and the almost identical FGFR1. This enabled them to get a 3D snapshot of each of their structures. They then fed the X-rays into the Anton supercomputer to simulate how the proteins were likely to move.
Anton’s simulations showed that the FGFR1 protein had a flap that moved more frequently than FGFR2. Based on this distinct motion, the team tried to design a compound that would recognize this flap shifting around and bind to FGFR2 while steering away from its more active lookalike.
For that, they went back Anton, using the supercomputer to simulate the behavior of thousands of potential molecules for over a year, looking at what made a particular molecule selective to the target versus another molecule that wasn’t. These insights led them to determine the best compounds to make and test in the lab and, ultimately, they found that RLY-4008 was the most effective.
Promising results so far
Relay began phase 1-2 trials in 2020 and will continue until 2024. Preliminary results showed that, in the 17 patients taking a 70 mg dose of RLY-4008, the drug worked to shrink tumors in 88 percent of patients. This was a significant increase compared to other FGFR inhibitors. For instance, Futibatinib, which recently got FDA approval, had a response rate of only 42 percent.
Across all dose levels, RLY-4008 shrank tumors by 63 percent in 38 patients. In more good news, the drug didn’t elevate their phosphate levels, which suggests that it could be taken without increasing patients’ risk for kidney disease.
“Objectively, this is pretty remarkable,” says Elemento. “In a small patient study, you have a molecule that is able to shrink tumors in such a high fraction of patients. It is unusual to see such good results in a phase 1-2 trial.”
A simulated future
The research team is continuing to use molecular dynamic simulations to develop other new drug, such as one that is being studied in patients with solid tumors and breast cancer.
As for their bile duct cancer drug, RLY-4008, Relay plans by 2024 to have tested it in around 440 patients. “The mature results of the phase 1-2 trial are highly anticipated,” says Goyal, the principal investigator of the trial.
Sameek Roychowdhury, an oncologist and associate professor of internal medicine at Ohio State University, highlights the need for caution. “This has early signs of benefit, but we will look forward to seeing longer term results for benefit and side effect profiles. We need to think a few more steps ahead - these treatments are like the ’Whack-a-Mole game’ where cancer finds a way to become resistant to each subsequent drug.”
“I think the issue is going to be how durable are the responses to the drug and what are the mechanisms of resistance,” says Raymond Wadlow, an oncologist at the Inova Medical Group who specializes in gastrointestinal and haematological cancer. “But the results look promising. It is a much more selective inhibitor of the FGFR protein and less toxic. It’s been an exciting development.”