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8.28.2020

Why Do Some People Get Through COVID19 Infections Unscathed?

 

Why Do Some People Weather Coronavirus Infection Unscathed?

August 24, 2020 by Emily Laber-Warren

One of the reasons Covid-19 has spread so swiftly around the globe is that for the first days after infection, people feel healthy. Instead of staying home in bed, they may be out and about, unknowingly passing the virus along. But in addition to these pre-symptomatic patients, the relentless silent spread of this pandemic is also facilitated by a more mysterious group of people: the so-called asymptomatics.

According to various estimates, between 20 and 45 percent of the people who get Covid-19 — and possibly more, according to a recent study from the Centers for Disease Control and Prevention — sail through a coronavirus infection without realizing they ever had it. No fever or chills. No loss of smell or taste. No breathing difficulties. They don’t feel a thing.

Asymptomatic cases are not unique to Covid-19. They occur with the regular flu, and probably also featured in the 1918 pandemic, according to epidemiologist Neil Ferguson of Imperial College London. But scientists aren’t sure why certain people weather Covid-19 unscathed. “That is a tremendous mystery at this point,” says Donald Thea, an infectious disease expert at Boston University’s School of Public Health.

The prevailing theory is that their immune systems fight off the virus so efficiently that they never get sick. But some scientists are confident that the immune system’s aggressive response, the churning out of antibodies and other molecules to eliminate an infection, is only part of the story.

These experts are learning that the human body may not always wage an all-out war on viruses and other pathogens. It may also be capable of accommodating an infection, sometimes so seamlessly that no symptoms emerge. This phenomenon, known as disease tolerance, is well-known in plants but has only been documented in animals within the last 15 years.

Disease tolerance is the ability of an individual, due to a genetic predisposition or some aspect of behavior or lifestyle, to thrive despite being infected with an amount of pathogen that sickens others. Tolerance takes different forms, depending on the infection. For example, when infected with cholera, which causes watery diarrhea that can quickly kill through dehydration, the body might mobilize mechanisms that maintain fluid and electrolyte balance. During other infections, the body might tweak metabolism or activate gut microbes — whatever internal adjustment is needed to prevent or repair tissue damage or to make a germ less vicious.

Researchers who study these processes rely on invasive experiments that cannot be done in people. Nevertheless, they view asymptomatic infections as evidence that disease tolerance occurs in humans. At least 90 percent of those infected with the tuberculosis bacterium don’t get sick. The same is true for many of the 1.5 billion of people globally who live with parasitic worms called helminths in their intestines. “Despite the fact that these worms are very large organisms and they basically migrate through your tissues and cause damage, many people are asymptomatic. They don’t even know they’re infected,” says Irah King, a professor of immunology at McGill University. “And so then the question becomes, what does the body do to tolerate these types of invasive infections?”

While scientists have observed the physiological processes that minimize tissue damage during infections in animals for decades, it’s only more recently that they’ve begun to think about them in terms of disease tolerance. For example, King and colleagues have identified specific immune cells in mice that increase the resilience of blood vessels during a helminth infection, leading to less intestinal bleeding, even when the same number of worms are present.

“This has been demonstrated in plants, bacteria, other mammalian species,” King says.

“Why would we think that humans would not have developed these types of mechanisms to promote and maintain our health in the face of infection?” he adds.

In a recent Frontiers in Immunology editorial, King and his McGill colleague Maziar Divangahi describe their long-term hopes for the field: A deeper understanding of disease tolerance, they write, could lead to “a new golden age of infectious disease research and discovery.”


Scientists have traditionally viewed germs as the enemy, an approach that has generated invaluable antibiotics and vaccines. But more recently, researchers have come to understand that the human body is colonized by trillions of microbes that are essential to optimal health, and that the relationship between humans and germs is more nuanced.

Meddlesome viruses and bacteria have been around since life began, so it makes sense that animals evolved ways to manage as well as fight them. Attacking a pathogen can be effective, but it can also backfire. For one thing, infectious agents find ways to evade the immune system. Moreover, the immune response itself, if unchecked, can turn lethal, applying its destructive force to the body’s own organs.

“With things like Covid, I think it’s going to be very parallel to TB, where you have this Goldilocks situation,” says Andrew Olive, an immunologist at Michigan State University, “where you need that perfect amount of inflammation to control the virus and not damage the lungs.”

Some of the key disease tolerance mechanisms scientists have identified aim to keep inflammation within that narrow window. For example, immune cells called alveolar macrophages in the lung suppress inflammation once the threat posed by the pathogen diminishes.

Much is still unknown about why there is such a wide range of responses to Covid-19, from asymptomatic to mildly sick to out of commission for weeks at home to full-on organ failure. “It’s very, very early days here,” says Andrew Read, an infectious disease expert at Pennsylvania State University who helped identify disease tolerance in animals. Read believes disease tolerance may at least partially explain why some infected people have mild symptoms or none at all. This may be because they’re better at scavenging toxic byproducts, he says, “or replenishing their lung tissues at faster rates, those sorts of things.”

The mainstream scientific view of asymptomatics is that their immune systems are especially well-tuned. This could explain why children and young adults make up the majority of people without symptoms because the immune system naturally deteriorates with age. It’s also possible that the immune systems of asymptomatics have been primed by a previous infection with a milder coronavirus, like those that cause the common cold.

Asymptomatic cases don’t get much attention from medical researchers, in part because these people don't go to the doctor and thus are tough to track down. But Janelle Ayres, a physiologist and infectious disease expert at the Salk Institute For Biological Studies who has been a leader in disease tolerance research, studies precisely the mice that don't get sick.

The staple of this research is something called the “lethal dose 50” test, which consists of giving a group of mice enough pathogen to kill half. By comparing the mice that live with those that die, she pinpoints the specific aspects of their physiology that enable them to survive the infection. She has performed this experiment scores of times using a variety of pathogens. The goal is to figure out how to activate health-sustaining responses in all animals.


For all of Undark's coverage of the global Covid-19 pandemic, please visit our extensive coronavirus archive.

A hallmark of these experiments — and something that surprised her at first — is that the half that survive the lethal dose are perky. They are completely unruffled by the same quantity of pathogen that kills their counterparts. “I thought going into this … that all would get sick, that half would live and half would die, but that isn’t what I found,” Ayres says. “I found that half got sick and died, and the other half never got sick and lived.”

Ayres sees something similar happening in the Covid-19 pandemic. Like her mice, asymptomatics seem to have similar amounts of the virus in their bodies as the people who fall ill, yet for some reason they stay healthy. Studies show that their lungs often display damage on CT scans, yet they are not struggling for breath (though it remains to be seen whether they will fully escape long-term impacts). Moreover, a small recent study suggests that asymptomatics mount a weaker immune response than the people who get sick — suggesting that mechanisms are at work that have nothing to do with fighting infection.

“Why, if they have these abnormalities, are they healthy?” asks Ayres. “Potentially because they have disease tolerance mechanisms engaged. These are the people we need to study.”


The goal of disease tolerance research is to decipher the mechanisms that keep infected people healthy and turn them into therapies that benefit everyone. “You want to have a drought-tolerant plant, for obvious reasons, so why wouldn’t we want to have a virus-tolerant person?” Read asks.

A 2018 experiment in Ayres’ lab offered proof of concept for that goal. The team gave a diarrhea-causing infection to mice in a lethal dose 50 trial, then compared tissue from the mice that died with those that survived, looking for differences. They discovered that the asymptomatic mice had utilized their iron stores to route extra glucose to the hungry bacteria, and that the pacified germs no longer posed a threat. The team subsequently turned this observation into a treatment. In further experiments, they administered iron supplements to the mice and all the animals survived, even when the pathogen dose was upped a thousandfold.

When the pandemic hit, Ayres was already studying mice with pneumonia and the signature malady of Covid-19, acute respiratory distress syndrome, which can be triggered by various infections. Her lab has identified markers that may inform candidate pathways to target for treatment. The next step is to compare people who progressed to severe stages of Covid-19 with asymptomatics to see whether markers emerge that resemble the ones she’s found in mice.

If a medicine is developed, it would work differently from anything that’s currently on the market because it would be lung-specific, not disease-specific, and would ease respiratory distress regardless of which pathogen is responsible. 

But intriguing as this prospect is, most experts caution that disease tolerance is a new field and tangible benefits are likely many years off. The work involves measuring not only symptoms but the levels of a pathogen in the body, which means killing an animal and searching all of its tissues. “You can’t really do controlled biological experiments in humans,” Olive says.

In addition, there are countless disease tolerance pathways. “Every time we figure one out, we find we have 10 more things we don’t understand,” King says. Things will differ with each disease, he adds, “so that becomes a bit overwhelming.”

Nevertheless, a growing number of experts agree that disease tolerance research could have profound implications for treating infectious disease in the future. Microbiology and infectious disease research has “all been focused on the pathogen as an invader that has to be eliminated some way,” says virologist Jeremy Luban of the University of Massachusetts Medical School. And as Ayres makes clear, he says, “what we really should be thinking about is how do we keep the person from getting sick.”


Emily Laber-Warren directs the health and science reporting program at the Craig Newmark Graduate School of Journalism at CUNY.

This article was originally published on Undark. Read the original article.

5.25.2020

No One Knows What the Future Holds

Early on, I started getting direct messages from friends and acquaintances asking what to expect when COVID19 hit our shores. How bad would it be? What should we do? Most often --once school and then other life started to close down -- how long will this last? 

I explained then -- and continue to explain today -- that this is a new and different disease and we are just learning as we go. We are learning how to treat it, how it spreads, how to recognize when it will be benign and when it will kill.

We don't know.

We react and act and our reaction and actions change what happens next. 

We cast about for someone to tell us what we want to hear. 

Between the Internet and Cable TV, we have grown accustomed to experts on tap, with a ready reassurance or a dire warning. So much so, that when they tell use that they don't really know, we feel that can't be true. There must be someone with a crystal ball. 

Enter the grifters, conspiracy theorists, end-times prophets and pundits to fill the void. 

As Mark Lilla writes in the New York Times, however, we don't know what the future holds:

"The pandemic has brought home just how great a responsibility we bear toward the future, and also how inadequate our knowledge is for making wise decisions and anticipating consequences. Perhaps that is why our prophets and augurs can’t keep up with the demand for foresight. At some level, people must be thinking that the more they learn about what is predetermined, the more control they will have. This is an illusion. Human beings want to feel that they are on a power walk into the future, when in fact we are always just tapping our canes on the pavement in the fog. 
A dose of humility would do us good in the present moment. It might also help reconcile us to the radical uncertainty in which we are always living. Let us retire our prophets and augurs. And let us stop asking health specialists and public officials for confident projections they are in no position to make — and stop being disappointed when the ones we force out of them turn out to be wrong.

A day in the ER fighting COVID19

Great storytelling of a doctor who fought Ebola and is now fighting COVID19 from AJ+

5.22.2020

EKG Interpretation by ... Ortho?

Sure you passed your ACLS class --barely -- but your specialty area doesn't deal with electro-physiology all that much and you have a hard time remembering what all those EKG rhythms mean. 

@TCKMed on twitter had a great thread to ... um .. help. 



Okay, that was easy, how about ... 
 
Let's slow this down ... 
 
 
Now it gets confusing, hang on ... 
 
 Danger ...


Now things get seriously ... anoying? 

 
Ummm ... crash cart squiggles?
 
The Final Squiggles!

 

3.13.2020

I Think it's going to rain today





I woke up with this song in my head.
This morning I realized it is Friday the 13th of March. Back in the ER tonight.

After a week of summer weather.

Woke up to rain.

Last night was a tipping point I think. People in the United States started to realize that -- regardless of whether they personally got sick -- the next few weeks or months were going to be disrupted. It was the cancellation of major sporting SEASONS -- not just events. The statewide school closures that likely got people's attention. On the way home from school yesterday, my 15 year old daughter said "it feels like this dystopian novel I read at the start of the year."

She said she felt that the coming days would be historic -- something that she would look back on and say that she remembered living through it. The weight of events, piling up one upon another on all of our minds.

This morning, Amy and I went to buy groceries after dropping our daughter off at school. A typical payday morning routine for us. Early morning shopping means empty stories and so we like getting what we need and getting back home before the rest of the world gets out the door. This morning, the stores were packed, but people were patient and courteous. Their smile and kindness reassuring, but I saw a lot of husbands out filling carts with lists from their wives. "Why am I buying bottled water?" asked one. "We have water at home, we never drink bottled water." Another complained that he thought it was all just a big hoax, his cart filled with supplies.

My daughter remarked on this too. Just like in the novel, she said, people fall into three categories -- those that worry and prepare, those that don't believe anything will happen and those that panic and act irrationally.

I've been in the medical field for 15 years, so I don't tend to panic. It doesn't accomplish much and burns energy that could be spent on other things. I also think in worst case scenarios -- because that has long been part of my job. A job I return to tonight.

I have plans to limit the spread to my family. Changing out of scrubs and decontaminating at work -- something I always do anyway. I even have our little camper prepared to go if I need to self-quarantine at home.

I go back to work tonight.

I work with a vulnerable population and I expect to see bad outcomes.
Additionally I worry about the stress all this will cause to compound things. Car accidents in busy grocery store parking lots, domestic violence and abuse. Quack cures that do more harm than good. Despair and the diseases that follow on from despair.

Randy Newman wrote "I Think It's Going to Rain Today" back in 1963 ... wrote it for someone else to sing. It is one of his most covered songs, recorded by dozens of acts in the 60s adn 70s. 

"The music is emotional – even beautiful – and the lyrics are not. The honest truth is the song bothered me because of the darkness."

Human kindness is overflowing.

And I think it's going to rain today.

-30-

7.17.2018

Think Fast: Understanding Stroke

When I was in nursing school, a friend of mine was walking out of a class when he suddenly couldn’t speak, his left arm and leg stopped working.
There were other students all around him, but they didn’t recognize what was happening and they kept asking him what they should do. Because the blood was cut off to a part of his brain that controlled speech he couldn’t tell them.  He knew that it was an emergency -- that they needed to call 911 and get help, but he couldn’t tell them.
He was in his second year of nursing school. He knew he was experiencing the symptoms of a stroke.

A stroke is a life threatening emergency and an life altering event.
Recognizing the signs and symptoms of stroke and understanding the importance of getting help fast can make a world of difference for you or someone you know.
It is estimated that every 40 seconds someone in the United States has a stroke. According to the Center for Disease Control, stroke is the leading cause of long term disability in the United States and it kills more than 140,000 people a year - that is one out of every 20 deaths. While risk of stroke increases with age, more than one third of people hospitalized after a stroke were younger than 65 years of age. Risk also varies by race, ethnicity and gender. More women than men suffer strokes and stroke kills twice as many women each year as breast cancer.
So what is it?
A stroke occurs when the flow of blood is interrupted a part of the brain. You might have also heard the more technical term CVA Cerebral Vascular Accident. It can occur from bleeding, but it is much more common for a stroke to be caused by a clot that blocks the blood supply to a part of the brain. So called ischemic strokes account for 87 percent of all strokes.
Because different parts of the brain control different parts of our body, often stroke symptoms appear as a problem on one side of the body. Often patients will have a facial droop, weakness, numbness or even paralysis on just one side of the body. It can start suddenly and when it does start, time is of the essence. The sooner the patient gets care, the better chance of restoring blood flow. The CDC reports that patients that receive care within the first three hours often have much less disability than those who delay care.

The American Heart Association has developed the act FAST campaign to emphasize what to look for.
  • Facial Droop on one side.
  • Arm drifts downward when raised.
  • Speech is slurred
  • Time is critical - call 911 immediately.

Because most strokes are caused by a clot in the brain, hospitals can give clot-busting medications to break up the clot, but these medications are only effective within a few hours of the start of the stroke.
Moreover, if the patient is bleeding in their brain, those clot-busting medications can make the problem much much worse. So a CT scan looking for bleeding must rapidly be performed before any medication is given. Cut off from its oxygen supply, brain tissue can die and leave permanent damage, so every second counts in getting oxygenated blood flowing again.
Ocean Beach Hospital’s medical staff train to respond quickly to help a patient presenting with symptoms of a stroke. Our hospital works with Providence’s telestroke system so a remote neurologist can examine the patient in the Emergency Room using a direct video connection. While we make sure that all happens as quickly as possible, it all takes time - so it is important to recognize the stroke symptoms and call 911 to get help immediately.
There are other, less common symptoms of strokes that occur in different parts of the brain. A sudden headache or loss of vision can be the first sign of a stroke. An inability to speak, or understand language in a fully awake patient can mean a clot in the part of the brain that controls language. That said, the vast majority of strokes have symptoms that only affect one side of the body.
Sometimes the stroke symptoms may occur and resolve without medical intervention. These are called “mini-strokes” or TIA - Transient Ischemic Attacks. TIAs are strokes but temporary. However, they shouldn’t be ignored because they are highly associated with strokes that cause permanent damage. Don’t delay calling 911 hoping the symptoms just go away.  TIAs are warning signs for a full blown stroke.
It is important to note the time that the stroke symptoms started. Paramedics or nurses may ask when was the patient last seen normal -- this time is what we use when the start the clock ticking for the clot busting medications.
There are a number of factors that increase our risk for stroke. High blood pressure, high cholesterol, diabetes, lack of physical activity and being overweight all put you at increased risk.
An irregular heart rhythm known as atrial fibrillation can also increase the risk of stroke. Smoking -- particularly when combined with pregnancy or oral contraceptives -- greatly increases the risk of stroke. Excessive drinking and recreational drugs also increase stroke risk.
Effort to raise awareness have been working. According to the American Stroke Association, stroke mortality rates have decreased 39 percent from 1999 to 2016 and awareness of the need to call 911 at the first symptoms of a stroke has doubled since 2012.

-30-

Ed Hunt is an Emergency Room nurse at Ocean Beach Hospital.





4.16.2018

It's the Prices, Stupid

There are a lot of problems with the US Healthcare system that prevent the ideal capitalist model from transferring its invisible-hand efficiencies to make us all well at minimal cost. 

The most obvious problem is people rarely price-shop prior to purchasing healthcare services. Moreover, even if they did, no one knows how much anything costs

Instead, a parasitic multilayered economy has evolved around the confusing and wasteful billing systems. Costs vary wildly based on insurance negotiations, not quality or efficacy. 

Now California wants to control prices directly - using the Medicare payment rate as a baseline. Proposed legislation would employ a nine member comission to set hospital charges and doctor fees.

It would be sort of a back door way to achieving the same effect of a single payer healthcare system, writes Vox's Sarah Kliff.

This system would be similar — but not quite the same — to something we usually call all-payer rate setting, where the government doesn’t run all the health care insurance plans but does tightly regulate the prices they charge. 
All-payer rate setting essentially shares the same goals of single-payer: It aims to increase efficiency and reduce insurer overhead in the health care system. Single-payer does this by eliminating private plans for one government plan. All-payer rate setting gets there by setting one price that every health insurer pays for any given medical procedure.
What's interesting is that this is not a new idea. Apparently Maryland has been using a sort of all-payer rate setting for years under a federal waiver. It is the only state currently doing so, but other states tried it in the 1980s.  That said, countries like Germany and Switzerland also use all payer rate setting to keep costs under control.

Why does setting one price reduce costs? Studies have found that a the same procedure may vary in cost by thousands of dollars based on the size and negotiating skill of the insurance carrier. This creates an inefficient system that requires a whole sub-economy of billing clerks and subcontractors just to figure out what to charge for each procedure.

Single-payer health care systems save money in two ways: reducing administrative costs and increasing the bargaining power of health insurers. This is true of all-payer rate setting systems, too.
Healthcare prices are rising at the fastest level in years, California's proposed legislation may be once politically feasible way to try and reign those prices in.

Required Reading:

All Rate Payer Setting: Back Door to Single Payer? 
California's Ambitious Plan to Set Healthcare Prices
 

Why Do Some People Get Through COVID19 Infections Unscathed?

  Why Do Some People Weather Coronavirus Infection Unscathed? August 24, 2020 by Emily Laber-Warren O ne of the reasons Covid-19 has spre...