Coronavirus news & views

COVID On The Heart

“We will see….”

I often end these blog posts that describe the confounding nature of this brand new SARS-CoV-2 virus and its novel disease, COVID, saying, “We will see.” The virus and its disease, both, have been very unusual and medical science has been continually trying to catch up with it and understand new issues they present. Hence, novel information we have been gathering takes a while to understand, so "We will see" is an appropriated disclaimer.

After four years dealing with all this, our vision is gradually improving. For instance, we are getting a better handle on how infection with the virus affects the heart.

Sadly, too many armchair medical conspiracists still frequently sound off that mRNA vaccines are causing thousands of deaths due to cardiovascular problems they cause. They do so without ever proffering credible evidence to support their notion--they simply claim that it is self evident. The truth is that the vaccines are not doing that in any significant number as I previously debunked here, here, here and especially here. Several clinical trials done before the vaccines were released demonstrated that cardio risk from the shot is negligible, and when it occurs it is inconsequential and usually accompanied by no symptoms. It is just detected via blood test. This has since been confirmed in a billion people around the world who have gotten several billion shots as investigators continue to follow the outcomes of vaccinated people in what are called, “post-market studies” or "phase 4 trials." Rather, it is the virus that is causing almost all the cardiovascular problems and this is well established by the research.

We do know that between March 2020 and March 2022, there were ~90,000 more cardio deaths in the US than expected. Most of these were in people 65 and older who have the highest risk for such problems, but heart-related deaths also jumped dramatically for healthy 25-44 year old COVID patients. How does the virus do this?

It is understood that CoV-2 infection and COVID disease cause widespread inflammation in the body, the vaccines, not so much in most recipients. General inflammation caused by viral infection is what increases cardio risk. The virus and disease stick around a while and so does the inflammation; the vaccine and its side effects do not. The immune system responds to this lasting infection, in part, by releasing hormone-like proteins that cause inflammation and blood clotting. Clotting and plaque accumulation in arteries lead to heart attacks or strokes. Smokers and those with high blood pressure often already have plaque in their arteries, so it is no surprise that these folks are at the highest risk for COVID-caused cardiovascular problems.

Even without pre-existing plaque, virus-induced inflammation in blood vessels alone can lead to clot formation, even in the absence of other high risk factors. That helps explain how younger, healthier people also show increased risk for cardio problems after infection with the virus.

We have also learned that even if you had COVID a year ago and cleared it, you remain at long-term risk for all cardiovascular problems according to a large study that analyzed medical records of almost 700,000 patients. The stroke risk is 1.5 times elevated; risk of heart attack is doubled; and the risk for different types of arrhythmias increases 1.6-2.4 times. Some of this elevated risk comes from the ability of COVID disease to induce new-onset high blood pressure in some people. Why this particular consequence to infection happens is another “we will see” question.

The good news is that vaccines reduce all this risk. Other studies showed that people who are vaccinated are roughly 40 to 60 percent less likely to have a heart attack or stroke following a COVID infection than those who are unvaccinated. This may be because vaccinated people are less likely to develop severe COVID. The greater the severity of disease means that the patient experiences much more inflammation which in turn leads to greater risk of cardio problems.

Again, the risk of the vaccine causing myocarditis is way overblown and those who continue to harp on this are spreading disinformation. The risk of myocarditis following infection is 4-8 times greater than following the vax, not the other way around. Don’t believe these lies, which cannot be supported by medical science, only by salacious rumor.

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SpaceX AND BioX Do It Again!!

“In science one tries to tell people, in such a way as to be understood by everyone, something that no one ever knew before. But in poetry, it's the exact opposite.

--Paul Dirac (1902-1984)

                                                                 

Backstory: Yup. SpaceX did it again. They landed a rocket booster on a bullseye; even catching it in the air with large mechanical arms they called “chopsticks.” The Brewers would love to have an outfielder like that!

BioX also did it again, following its last year’s Nobel Prize win for the mRNA technology that led to the very effective COVID vaccines. Just a few days before the SpaceX catch, it was announced that BioX won the 2024 Nobel Prize for using a computer, or artificial intelligence, to decipher the structure of ALL known proteins, and for using similar technology to create whole new functional proteins that promise to remediate environmental contamination and treat diseases. We are in a new brave world of science.

For those new to these pages, “BioX” is what I earlier dubbed the new, post-molecular biology (mobio) science that has been absolutely amazing. And I speak as a molecular biologist who now feels like a scientific dinosaur. What we learned from the old-school mobio is now being fed into computers which do all the work for us. Much tedious lab work has now become obsolete, which means that we are learning about our bio-world at an unbelievable pace. It also means that we are translating all that information into useful tools, such as better vaccines and medicines, and into making new proteins that do what we wish—like digest plastics contaminating our environment.

The science of molecular biology began in the 1920s with really basic questions. Swedish chemist and Nobel Prize winner, Theodor Svedberg, developed the ultracentrifuge in 1924, which was then used to determine the size of biomolecules—the first major question in molecular biology. The centrifuges were also used to separate different cell components, which played a huge role in discovering how cells function. The ultracentrifuge was a major tool used by only a few of the most advanced labs at that time. Now, pretty much every bioscience department has at least one ultracentrifuge.

Three decades after the advent of ultracentrifuges, Jim Watson, an American, and Francis Collins, a Brit, at Cambridge University, reported on their seminal discovery of the structure of DNA, which unleashed a storm of research into how it functions and deciphering the genetic code. That in turn led to much research into the other nucleic acid molecules found in cells, RNA. And that guided research into the structure and function of proteins, the things that make cells function. All that mobio research led to many, many Nobel Prizes. All that information provides the basis for the new post-mobio science of BioX.

Current story: All this background is mentioned in order to introduce the latest Nobel Prize for Chemistry, announced October 8. Three BioX chemists share the award. Demis Hassabis and John Jumper of Google DeepMind used AI to decipher the structure of millions of proteins. David Baker of the University of Washington used similar computer software to invent new proteins. It is possible that none of them ever purified DNA from a cell culture, sequenced DNA, cloned a gene, inserted a gene into cells to determine its function, etc. All of that is mobio—old stuff. These post-mobio scientists showed us we really do not need to that anymore if you can use a computer. Boy, does that make me feel old.

It used to take decades and many thousands of dollars of high tech equipment and an army of lab techs, students and post-docs to learn how a single protein, like hemoglobin, was structured and functioned. Now it takes minutes and a lap top. Computers can be used to predict the structure of any protein in the human body, which can inform researchers how other molecules will bind or physically attach to it. This is the new path for drug discovery.

These are the 2024 BioX Nobel Prize winners:

Demis Hassabis was born in London, where his parents—one a Greek Cypriot, the other Singaporean—ran a toy store. At one time, he was the second-highest-ranked chess player under 14 in the world. He began designing video games professionally before attending college. After completing a computer science degree at the University of Cambridge, he founded a video game company then returned to academia for a PhD in neuroscience. He and a fellow academic, Shane Legg, and a childhood friend, Mustafa Suleyman, founded an AI start-up called DeepMind in 2010. About four years later, Google acquired it for $650 million.

DeepMind’s goal was to build an artificial machine that can do anything the human brain can do. It also explored other technologies that could solve particular scientific problems. One of those technologies was AlphaFold, the program used to solve the structure of millions of proteins and for which the Nobel Prize was awarded. AlphaFold is built using a mathematical system called a neural network. With neural networks, computers can analyze vast amounts of data to learn to perform many tasks that were once beyond their capacity.

John Jumper, the youngest chemistry laureate in over 70 years, was born in the United States. After finishing an undergraduate degree at Vanderbilt University and a master’s degree at the University of Cambridge, he earned a Ph.D. degree in theoretical chemistry at the University of Chicago.

He joined Hassabis at DeepMind as a researcher in 2017 after Google had acquired the technology. He soon began work on AlphaFold. In 2020, Google researchers unveiled an update of the AlphaFold technology and showed that it had fully cracked the problem of predicting shapes of proteins with an accuracy that rivaled physical experiments and made lab rats like me obsolete. Sigh....

With AlphaFold, the Google team was able to calculate the structure of all human proteins, and then, according to the Nobel committee, it deciphered “the structure of virtually all the 200 million proteins that researchers have so far discovered when mapping Earth’s organisms.” Holy moly!!

David Baker’s work preceded the emergence of these AI models and focused on creating novel proteins. A Seattle native, Baker earned his undergraduate degree from Harvard in 1984 and in 1989, a biochemistry PhD from the University of California, Berkeley. He now serves as the director of the Institute for Protein Design and is a professor of biochemistry at the University of Washington (the other UW). In 2003, Baker and his colleagues created the first entirely new protein: a molecule called Top7. The molecule was useless but symbolic.

Since then, the researchers have used a computer model called Rosetta, which searches databases of existing proteins to find a sequence that might create a desired structure. Baker realized that if he could create a novel protein structure, he should also be able to create proteins “that actually do things,” like break up the amyloid fibrils that are thought to cause Alzheimer’s disease. Or digest plastic bottles. Or oil contamination from spills.

So far, his lab’s novel proteins—created with a more advanced iteration of Rosetta—have already been the basis of several potential medical treatments, like an antiviral nasal spray for Covid-19 (on which I will soon blog) and a medication for celiac disease. A Covid-19 vaccine, SKYCovione, based on his one of his lab’s proteins, was approved for use in South Korea in 2022.

Baker is also a co-founder of more than 20 biotechnology companies.

Congratulations, BioX! Stay tuned, more is sure to come.

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Still Digging Into Long COVID

It is the glory of God to conceal a matter; to search out a matter is the glory of kings.

            --Solomon

…such is the mystery of long COVID; a malady with many symptoms and no simple diagnosis—not a blood test, not even an easily agreed upon constellation of symptoms to define the malady. Yet it has a  single name, Long COVID. A simple name for a hodge-podge of unrelated health problems for which patients very often complain to their docs who very often wave off as malingering, or “in your mind”, or simply by shrugging. It is the lucky long COVID patient who presents with specific symptoms that their physician can write in Latin in their chart.

COVID itself began as a mysterious disease—THAT is one of the biggest understatements of recent memory! Long COVID has proven an even greater mystery. We have gotten a good handle on COVID itself, but still struggle to understand what long COVID is all about, what causes it (probably many different things, depending on the person), who will get it and why, who will not get and why not, how long will it last, can it be prevented, how do we accurately identify it, how can we treat it once we identify it, and so on? Medical science struggles to answer these questions.

Yet, some progress is being made; probably not fast enough if you are a long COVID sufferer, but medical science often moves at a glacial pace. Here, I describe some of our recent advances in learning about the problem.

Earlier, as the pandemic was fulminating and the health community was frantically trying to wrap its head around weird things like black toes, lungs filled with what looked like chocolate pudding,  loss of smell, etc, etc, people were other getting odd symptoms that were not resolving even after they cleared the virus: brain fog, fatigue, chronic cardiovascular problems, hard-to-describe general malaise, and other unconnected symptoms that lingered like a bellhop waiting for tip. At a loss for specific diagnosis, the maladies were deemed, long COVID.

I earlier wrote about this mystery malady and speculated on the high incidence of the illness around the world. Extrapolating the numbers, I predicted it could have a huge impact on world health and economics in coming years. I was right according to a new study reported in the prestigious journal, Nature. About 400 million people in the world (or 6% of the world’s population) have had long COVID since the pandemic began. About 13.7 million people in the US currently have long COVID. The study cited other studies suggesting that only 7 percent to 10 percent of long Covid patients fully recovered two years after developing long Covid. They added that “some manifestations of long Covid, including heart disease, diabetes, myalgic encephalomyelitis and dysautonomia (a dysfunction of the autonomic nervous system that can affect the heart, bladder, intestines, sweat glands, pupils) are chronic conditions that last a lifetime.” A lifetime of long COVID?! How to treat long COVID remains very elusive because of its plethora of unrelated health problems.

Long COVID unsurprisingly has a huge financial cost as well. It costs the global economy about $1 trillion each and every year! This includes direct health costs incurred by patients with long COVID, but also the cost of their not being able to work. This expense will continue as long as long COVID remains, which, in turn, will continue as long as we have COVID.

While our inability to effectively deal with long COVID remains an elusive goal, there is some good news. The rate of long COVID cases has sharply declined with the appearance of the vaccines according to a large new study. It appears that vaccination prevents long COVID by preventing severe illness. Unfortunately, vaccines do not eliminate all the risk of long COVID since even some people with mild illness can develop long-term complications. This study was based on an examination of medical record data from about 450,000 VA patients who had contracted COVID between March 1, 2020 and the end of January 2022. About 3.5% of vaccinated people in the database had long COVID, compared to about 7.8% of unvaccinated people. The rates of long COVID also varied with the strain of virus contracted. The Delta version, which produced more serious disease also produced more long COVID cases than did Omicron, which caused milder COVID.

And the beat goes on. Will we ever get a handle on long COVID so it can be better prevented, diagnosed, and treated?

We will see, won’t we?

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