Coronavirus news & views

SARS-CoV-2, A Respiratory Virus That Messes With Your Gut

The CoV-2 virus that causes COVID is a respiratory bug, right? They say we catch it, not from surfaces or food, like we do norovirus, but from airborne exposure—we breathe it in. That of course, means that it causes respiratory problems. Makes sense, right? Well, Sarah Carter, 36, from San Mateo, CA, caught the virus in late 2023. Her main symptom was not respiratory but relentless diarrhea that became so sever she had to take an ambulance to the ER. The runs caused her to become dehydrated, which in turn caused a spike in her blood pressure and heart rate. She urgently needed IV fluids to treat it all. After three more days of diarrhea she finally felt better. But, six months later the GI symptoms reappeared overnight without her being infected again. Nearly everything she ate set off diarrhea. She also had bloating and pain so severe that she said it felt like acid was running through her intestines. A gastroenterologist eventually diagnosed her with post-infectious irritable bowel syndrome (IBS).

What in the world is a respiratory virus doing messing with her entrails, especially months after being infected? Did it make a wrong turn somewhere?

We have gotten accustomed to testing for COVID when we feel crummy and run a temperature, have a sore throat, runny nose, loss of smell, cough, etc.—all symptoms of respiratory infection. But Dr Rohit Jain, an internal medicine doc at PennState Health told Time that when someone complains of problems affecting the exit at the other exit of the body: i.e., nausea, diarrhea, vomiting, etc., he always tests for COVID. Another doctor, Mark Rudd, chief of infectious diseases at the U of Nebraska Medical Center also weighed in saying that, “COVID-19 is really a GI-tract disease.”

What??

If it “really is a GI disease” why are we wearing masks, distancing, and worried about respiratory infection rather than hand washing and sanitizers??

The SARS-CoV-2 virus and its disease, COVID, are very strange and threw the medical establishment for a loop after they first appeared on the scene at the end of 2019, and after COVID became a world-wide pandemic in early 2020. Docs dealt with myriad, seemingly unrelated symptoms in different patients; symptoms such as brain fog, loss of smell, severe pneumonia, hemorrhage issues that led to black toes and lungs that looked like they had filled with chocolate pudding, among many others; all from the same virus. Now add to that befuddling mix, GI problems to what was believed a respiratory virus,and COVID presents a conundrum. Docs have to now factor in the fact that many people experience no, or only mild gastrointestinal symptoms, while other patients experience significant digestive problems that can distract from the pulmonary problems which complicate diagnoses.

As we have learned more about COVID over the last few years, it has become clear that infection symptoms can also include loss of appetite, nausea, vomiting, diarrhea, and stomach pain, according to Jain’s research. A 2023 study published in Nature Communications reported that 36% of COVID patients are likely to develop GI disorders such as ulcers, pancreatitis, IBS, and acid reflux. Another recent study in Clinical Gastroenterology and Hepatology found that 40% of adults hospitalized with COVID, had at least one GI relapse a year or more later. While both of these were small studies, they are in close agreement regarding the incidence of COVID GI problems. And like other symptoms of long COVID, the GI problems can last many weeks. That is quite concerning. Weeks of diarrhea, for example, is much more than an immense inconvenience and major mess, it is a serious medical issue. But not all patients experience these symptoms, just like not all patients lose their sense of smell, had black toes, or developed long COVID. Try to diagnose and understand COVID with this range of variable symptoms! How confusing.

How can the same virus cause runs from both ends of the body; the nose and the other end?  Among the things we have learned over the last few years is that the CoV-2 virus infects cells that express the ACE-2 protein. While ACE-2 normally is important for certain cell functions, the virus decided to use it as a receptor on which to grab onto and then enter cells. The protein is found on many different types of cells throughout the body, but it is expressed in especially high levels in the lungs, which helps explain COVID’s respiratory symptoms. It turns out that ACE-2 is also highly expressed in cells of the GI tract. That explains the intestinal complications. Also, because it is found in the GI tract that could possibly make feces from infected animals, like bats, a great way to widely spread the virus to other animals, just like migrating birds spread the avian flu virus to poultry flocks and dairy herds. In fact, in 2012, six Chinese mine workers removing guano in a bat-filled cave where flying flittermice were found with COVID, developed severe respiratory symptoms. Three of them died. COVID infection from contaminated bat guano is suspected because the Wuhan lab eventually found evidence of an unknown coronavirus in the patient samples. But, this was years before the CoV-2 virus had been discovered, so the CoV-2 link to their disease comes with some uncertainty. Maybe the virus in ca-ca could be a way to spread it between people too, like norovirus is spread. To my knowledge, human-to-human spread this way has not been shown, but it makes sense to this scientist that it could. After all, since the virus is found in feces, wastewater surveillance has proven to a useful tool for tracking CoV-2 spread among human populations. It is routinely found in poop, and there is a good possibility that the Chinese workers caught it from the bat scat they were shoveling. Together, that makes it very likely that humans can spread it to other people via unsanitary practices. But, at this time, that is just the opinion of your sometimes humble correspondent. We will see.

We also now know that the virus can hide in the nooks and crannies of the  bowel for months, or even years, according to Ziyad Al-Aly, MD, an epidemiologist at the Washington University School of Medicine in St. Louis, who co-authored the Nature Communications study on chronic post-COVID GI symptoms that was cited above. This might explain why gut-related symptoms can long outlast the initial acute infection. But other possibilities to explain long-COVID GI problems continue to be investigated. This is another “we shall see” issue.

We also know that the virus can cause widespread and sometimes long-lasting inflammation, potentially affecting various organs throughout the body including the gut. GI inflammation can affect the gut microbiome, which is the collection of microbes that normally live in the GI tract and that are good for us. We have long known that changes in the gut microbiome can have manifold health effects affecting GI health, and even the well-being of the heart, kidneys and brain, including Alzheimer’s disease, which is a possible complication of COVID. Disruption of the GI microbiome also is related to obesity and diabetes and it is notable that COVID disease also is associated with new-onset diabetes. Inflammation in the gut can also damage the lining of the intestines, making them “leaky” so that nutritional goodies from foods you normally would absorb across your gut into the blood stream, instead escape into the abdomen, causing immune cells to mount an allergy-like response to foods. COVID-induced inflammation can also chew away at the nerves that control normal gut contractions (peristalsis) that move food along, and interfere with neurological signals in the gut causing pain. Not fun, ask Sarah Carter!

Since the start of the pandemic in early 2020, GI docs have noticed an uptick in IBS in COVID patients. Medical scientists have long known that other gastrointestinal infections, like those from norovirus, giardia (a parasite), or salmonella (bacteria), can lead to IBS as well as functional dyspepsia, a type of chronic indigestion that causes frequent feelings of fullness and stomach pain or burning, like acid running through your innards. Does that sound familiar? Now we can add the respiratory virus, CoV-2, to the list of infectious agents that can cause IBS and other digestive problems.

Bottom line: So, gut problems are added to the manifold issues associated with COVID disease. CoV-2 is a nasty bug that you don’t want to catch. Get vaccinated and spare yourself all these problems!

Over 400 Studies Show Face Masks Protect Against Respiratory Infection

“Sometimes we need education in the obvious more than investigation of the obscure.”

–Oliver Wendell Holmes

In my meanderings across the blogosphere, opinion pages, talk radio, Facebook, and even chatting with friends and acquaintances, I continually encounter folks who assert that masking is ineffective for protection against respiratory infections. Of course they never provide evidence to support their claim beyond their confidence that they are correct. I often reply that they should invite their next surgeon to remove his mask during the operation. I have published in these pages a few articles showing how controlled trials and real-life empirical data show this to be wrong (see here, here and here).

Now a new meta-analysis by University of Oxford researchers, or an analysis of some 400 published studies on facemasks, further confirms that if they are correctly and consistently worn masks effectively protect against respiratory infections, including COVID. The study also concludes that mask mandates are effective in reducing community transmission of respiratory pathogens. Note that health mandates have long passed Constitutional muster as I reported earlier. This new analysis was triggered by the controversial 2023 Cochrane review of non-pharmaceutical interventions for COVID, which several publications reported showed that masks were ineffective. However, Cochrane’s editor-in-chief later stated publicly that the review did not support such a conclusion and issued an apology for the confusion and a clarification. Several scholars also questioned the review’s methods and found flaws in its meta-analysis and criticized it for omitting a vast body of non-trial evidence. Hence the Oxford study was undertaken to learn the truth about the efficacy of face masks.

Face masks, along with other non-pharmaceutical measures, such as social isolation, have long been used during infectious epidemics, especially when vaccines and antibiotics were not available. This goes back to the European bubonic plague in 1619, the Great Manchurian plague (1910), the 1918 Spanish flu, etc. When there is no vaccine or therapeutic intervention to treat an infectious disease, physical isolation measures, such as social distancing, quarantine, and masks are critical.

The Oxford study. The study examined the relevant literature in a wide range of disciplines (public health, epidemiology, infectious diseases, biosecurity, fluid dynamics, materials science, modeling, data science, clinical trials, sociology, anthropology, psychology, and occupational hygiene). This included numerous randomly controlled trials as well as observational, or “real-world,” evidence. The results convincingly showed that cloth face coverings and disposable medical masks that are handed out at your doctor’s office can reduce infection risk, but the N95 respirators are much better.

In the early COVID-19 pandemic, when randomly controlled trials of masks had not yet been done, the study’s authors found a systematic review and meta-analysis of observational studies reporting that respirators and masks decreased infection risk up to 85%. Further, in a school-based cohort study, the risk of COVID among the family members of students was reduced by 30% to 40% when teachers used masks.

Other case-control and cohort studies in healthcare workers provided additional evidence of substantial reductions in COVID-19 risk associated with use of respirators. In 2020, one study found over 400-times lower odds of occupational acquisition of COVID among hospital staff using N95 respirators in respiratory, intensive care, and infectious diseases departments compared to those from other departments without continuous masking.

While cloth face masks were proven to protect against airborne infection, N95 or FFP2 face-fitting respirators were most effective. The latter fit more closely to the face minimizing ambient air from leaking through the edges. They also work differently from cloth masks, which use multiple layers as a barrier to block pathogens. In contrast, respirators pass air through a specially designed filter that uses electrostatic charges to trap airborne particles, whether dust or bugs.

The pore size in typical surgical masks and respirators is larger than many viruses, like Cov-2, but, viruses do not float around the air on their own. They are carried as passengers via respiratory aerosols, which are blocked by masks. Note that the International Standards Organization (ISO) provides standards for optimum filtration for respirators. This includes lab testing for filtration efficiency. This also includes personal testing while exercising in the face of a challenge contaminant. A respirator is considered to meet requirements when it achieves a 100-fold reduction in the challenge contaminate penetrating the barrier. Respirators outperform surgical masks by 8-12-fold. These results were further confirmed with animal Cov-2 infection experiments. Infected hamsters were separated from uninfected ones by a partition make of surgical mask material, which reduced Cov-2 transmission by 75%.

Besides lab studies and randomly controlled trials of face mask use, the authors also conducted a systematic review of 44 observational studies involving SARS-1, MERS, and SARS-Cov-2. They concluded that masks and respirators reduced the risk of infection by 85%. Overall, respirators were 96% effective while surgical masks were 67% effective. This protection was “dose dependent,” meaning that protection increased with the frequency of use of masks. Masks were not only found to protect the wearer, but also were effective and preventing infection of non-mask wearers surrounding the masked person. But, the greatest protection was when both parties were masked.

In addition, the study examined the effects of mask mandates in several different settings. The first such analysis found a progressive decline in epidemic growth rates after mandates were enacted when compared to time frames immediately before the mandates. Also, masking was an effective predictor of lower infection rates in the US. An analysis of masking in Boston schools, found a surge in CoV-2 infections after February 2022, when mandates were lifted. Similar evidence demonstrating the efficacy of mask mandates was reported in many other studies. Importantly, the meta-analysis did not find any evidence for significant harm to the health of mask wearers even during strenuous exercise. Specifically, they do not increase the carbon dioxide content of inhaled air. The biggest impediment to using them was discomfort and communication difficulty for deaf people who are unable to read the lips of a mask wearer.

Study conclusions. The claim that masks do not reduce transmission of airborne pathogens is incorrect. They work. Furthermore, the level of protection increases as adherence to masking increases. Masks are a critical part of infection control during a respiratory infection epidemic.

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Infections Can Cause Brain Atrophy And Dementia

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“We could certainly slow the aging process down if it had to work its way through Congress.”
 -Will Rogers

Two provocative areas of research have led to the notion that infection could be a risk factor for dementia. On one hand, some studies have directly suggested that there is a possible link between some infections and an increased risk for Alzheimer’s disease (AD). Then, other studies found that two vaccines, the flu shot and the shingles vaccine, reduced the risk of dementia. Together, all this led to the hypothesis that infection might play a role in neurodegenerative diseases. This is now bolstered by a new study published last August in Nature Aging that identifies possible post-infection immunological/inflammation drivers that lead to brain atrophy and subsequent cognitive decline.

Brain atrophy! It can easily be detected via modern imaging technology, and it is not good.

We have abundant evidence that even minor infections can change the way we think and behave. More-severe infections that result in delirium have long been associated with long-term cognitive problems. Even shingles, which is a very painful relapse of chicken pox (you never clear the virus, which resides in your nerves) also is associated with dementia. There is a very effective vaccine that stops shingles in its tracks and it has been shown to reduce the risk for dementia later in life by up to 50%. The more severe an acute infection or its relapse, the greater the inflammation caused by the immune response, and the greater the risk of Alzheimer’s and other types of dementia. Therefore, it makes abundant sense that vaccines, which greatly reduce the severity of infectious disease, would also lessen the risk for dementia as well as for other long term post-infection health problems such as diabetes, Parkinson’s diesease, and maybe cancer that I have mentioned in these pages.

The link between infection and cognitive problems seems to hold with different types of infections, whether they are bacterial or viral. Of the 15 types of infections studied, six—flu, herpes (which includes small pox, chicken pox, shingles, etc.), respiratory tract infections, and skin infections—were associated with increased risk of atrophy in the brain’s temporal lobe. This region includes the inner folds of the temporal lobe where a rather small organ called the hippocampus sits on each side of the brain. This is part of what is called the limbic system, which manages the functions of feeling and reacting, and helps us process and retrieve two types of memory, declarative memories and spatial relationships.

Declarative memories are those related to facts and events such as learning how to memorize speeches or lines in a play. Spatial relationship memories involve pathways or routes. For example, when a cab driver learns a route through a city, they use spatial memory and that learning can actually increase the size of the hippocampus. Spatial relationship memories appear to be stored in the right hippocampus. In addition, short-term memories are converted into long-term memories in the hippocampus, but are then filed away long-term elsewhere in the brain. So, with a malfunctioning hippocampus, these short term memories do not get stored. And we forget things.

We have known about the hippocampus (or hippocampi, since we have two of them) for more than four centuries. The surgeon, Julius Caesar Arantius, first discovered the hippocampus in 1587, coining the term from the Greek word for seahorse (hippokampos) based on its shape. It does resemble a seahorse. This region, critical for memory and learning, is strongly affected in AD where the shrinking size of the hippocampus can be used to monitor the progress of the disease.

The latest study relating infection to dementia was based on data from the Baltimore Longitudinal Study of Aging, one of the longest-running studies of human aging in the United States. They also used neuroimaging to track how brain volume changed in 982 adults, with or without a history of infection. This began in 2009 and its data confirmed findings from analyses of UK Biobank data of almost 500,000 people, and a Finnish dataset of almost 300,000 subjects, both of which identified these infections as risk factors for dementia.

Of course, most of these studies were done before COVID. COVID has not been around long enough to definitely tell us whether the disease is also linked with increased risk of dementia, but as a respiratory infection accompanied by severe systemic inflammation, we can expect it to be.

Bottom line: Vaccines not only protect against the acute infection they were made for, but they also protect against serious post-infection complications such as new onset diabetes, Parkinson’s disease, perhaps cancer, and other long term complications of infectious disease, which now also includes dementia.

Get vaccinated!

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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NIH Launches First Trial Of Nasal COVID Vaccine

"Taking a new step, uttering a new word, is what people fear most.”
― Fyodor Dostoevsky, Crime and Punishment

Earlier in these pages I described how the mucosal immune system is different from the general immune system of the body. Your mucosa (i.e., the lining of your nose, mouth, throat, sinuses, lungs, etc.) has its own robust immune defense and produces different types of antibodies in response to invaders. The nose, mouth and throat are often the first line of defense to airborne pathogens, such as the flu and SARS-CoV-2 viruses. So, when you are infected via the mucosa by an airborne pathogen, it activates a local immune response while eventually sounding an immune alarm for the body-whole. But by the time the infection settles in and the rest of your body responds, it is all-out immunological warfare and you feel crappy (hope I am not being to technical). Sometimes the bug wins too. Too often, especially before we had the vaccines, COVID won, and folks were hospitalized in dire straits with tubes attached to machines keeping them alive, too often failing.

The amazing vaccines we developed in record time were delivered into an arm muscle to stimulate our general body immune response, not our mucosal immunity. This meant that even though we had immunity, the virus could still enter us, set up shop and wait until the general body immune reinforcements arrived. Those reinforcements were quite effective at preventing serious disease, but you still would get ill.

Wouldn’t it be nice if a vaccine could be developed to nip the infection in the bud at the site of entry--in the mucosa--so it could not set up shop at all? That is an idea that has been percolating in the minds of immunologists for a while. It is the idea behind a mucosal vaccine that I described earlier.

But, if it is such a good idea for the CoV-2 coronavirus, why not for flu or other airborne pathogens that have been around much longer? Indeed efforts to develop nasal vaccines for influenza have been ongoing for a couple of decades. But, when is the last time you got a nasal spray vaccine for the flu? The track record has been mixed. The FluMist nasal flu vaccine was approved for kids in 2003. Initially it was a convenient alternative to the injected vaccine. But, it showed limited efficacy in adults. Early on it was deemed just as effective as the standard vaccine in kids, not better as hoped. More recently it was reported to not be so effective. As a result it is no longer recommended by the American Academy of Pediatrics. It clearly did not rise to the hope we had for a nasal flu vaccine.

All the above negativity for the early nasal flu vax doesn’t mean that the idea of a nasal flu vaccine is invalid. Researchers will test different sorts of flu antigens for the nasal approach. FluMist used a live, but attenuated virus in its nasal vaccine. That means kids snorted a live virus that could infect cells but not cause disease. Perhaps a different flu antigen would be more effective? But, frankly, it is hard to get more realistic than a live-attenuated virus.

Nevertheless, another promising new flu nasal vaccine candidate is FluGen’s, M2SR, developed by researchers at the University of Wisconsin-Madison. This vaccine is a bit different because it uses a wholly live virus with an essential replication gene deleted from its DNA. This means the virus is fully functional except it can’t replicate and cause illness. That makes it a little different from the live-attenuated virus. It should stimulate the immune system like a natural infection, but begs the question: how will that be different from the immune response generated from a live attenuated virus? How will that crippled snuffed virus stimulate a different immune protection from the sniffled FluMist attenuated virus? We will see, won’t we? That is why we do such experiments.

Back to COVID. This summer, NIH launched the initial Phase 1 trial to begin testing such a nasal COVID vaccine.

The vaccine. The vaccine is a mouse virus (MPV) in which a piece of the CoV-2 spike protein is expressed. MPV does not cause human disease but does like to stick to human and primate mucosal epithelial cells and should be an effective vector for delivering the spike protein sequence where it can tickle an appropriate immune irritation. In animal studies, the experimental virus was safe and produced a robust immune response in the mucosa lining the nose and respiratory tract of experimental animals. All very encouraging, hence the move to human trials.

The human trial. This is a Phase 1 trial, the first step of any experimentation in humans. Phase 1 trials do not look for efficacy and are done on quite a small number of patients, anywhere from 20-100 subjects who are not tested at all for resistance to the disease. The purpose simply is to look for common safety issues like whether the vaccine causes a general adverse reaction with increasing doses and how well it induces an immune response (i.e., anti-spike protein antibodies) at different doses. Using this information, a Phase 2 study can be designed including more subjects, usually hundreds. This begins to look for more subtle side effects and is the first test of the ability of the vaccine to protect against COVID disease. This would be a controlled trial where experimental vaccine recipients are compared to a control cohort who do not get the nasal vaccine, but probably a placebo. If data collected from this study warrant, then a Phase 3 study is done on thousands of patients to further refine the safety and efficacy profile of the vaccine.

The Phase 1 study that is underway is being led by the National Institute of Allergy and Infectious Diseases and is enrolling 60 subjects at trial sites, which include the Baylor College of Medicine, Houston; The Hope Clinic at Emory University in Atlanta; and New York University on Long Island. The immune responses of volunteers will be followed for one year. So, it will be a while before investigators have the data to begin Phase 2 trials.

Bottom line. This is just the beginning and it will take several years to finish. If successful, this would represent the next generation of COVID vaccine. Finally, as I have often ended my blog posts…

…we will see.

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Deadly Vaccine Disinformation

“There is no vaccine that is safe and effective.”

-RFK, Jr.

Debut: On July 6, 2023, RFK, Jr. (aka “Junior”) made the above minatory quote on a podcast. It sums up his decades-long quixotic crusade against all vaccines and his many more screwball contrarian stands on various topics. Basically, if mainline medicine has an opinion on something, Junior, will claim to have some special knowledge that the opposite is true. For example, he believes that AIDS is not caused by the HIV virus, that 5G cell phone towers causes cancer, that an herbicide causes teens to become transgender, and so on. The reams of scientific evidence  contrary to these special insights of his he simply dismisses as vague, conspiratorial plots invented by “big” government, “big” pharma, and “big” others designed to control you and me, or depopulate the world,….or something.

Unfortunately, there are others like Junior who too readily eschew normal standards of logic and evidence and buy into such febrile musings. Also, unfortunately, such bias-confirming fabulism is dangerous—it costs people their health and lives. Junior is indeed directly responsible for misery and even deaths caused by his vaccine disinformation. I relate two such examples below.

Disinformation is false information which is deliberately intended to mislead. In contrast, misinformation is wrong information that is spread without malicious intent.

Measles: Kennedy played a part in one of the worst measles outbreaks in recent memory—one that caused the deaths of several children. It began in 2018 when two 12-month old infants in American Samoa tragically died when nurses mistakenly prepared the combined measles, mumps and rubella, or MMR, vaccine with expired muscle relaxant rather than with sterile water as they should have. The muscle relaxant killed the children. It was an egregious medical error that should not have happened. The Samoan government overreacted and temporarily suspended the entire vaccination program, which enticed anti-vaccine advocates—including Kennedy and his nonprofit, the Children’s Health Defense—to manipulate the Samoan tragedy for their own interests in order to spread their vaccine disinformation. Junior falsely claimed on his Facebook page that the Samoan tragedy “proved” that the MMR vaccine was deadly. Even after it had become abundantly evident that the MMR vaccine wasn’t responsible for the infant deaths, Junior visited Samoa and met with senior officials to convince them that the MMR vaccine was deadly. Influenced in part by his actions, the Samoan government suspended its measles vaccination program.

As a result, the vaccination rate dropped precipitously from 74 percent in 2017 to 31 percent in late 2018, well below the level needed for “herd immunity.” The next year, 2019, a traveler brought measles to the islands, which precipitated a rapid measles epidemic in the under-vaccinated population (note: measles is the most infectious virus we know. Measles epidemics are explosive). Between September and December of that year, at least 5,700 people contracted the disease and 83 died. Most deaths were in children under four years old, who should have just received their MMR vaccines. During the outbreak, in a 4-page letter to the Samoan prime minister, Junior claimed that the measles deaths were caused by the vaccine, not the virus. But, the deaths were in unvaccinated children! The deaths were wholly preventable and Kennedy should have been held at least partly culpable for this preventable tragedy and the deaths of the children.

Hepatitis B: Junior often claims that the “big” US government is not to be trusted. We can go back and forth on that—it depends on what the topic is. An unfortunate topic of his at one point, however, was the hepatitis B vaccine. In the early 90s, the CDC recommended hep B vaccines for all newborns. Junior, of course, not believing that any vaccine is safe or effective needed to find some way to dissent.  He pointed out that there are only three ways to contract  hepatitis B: 1) from sharing needles as a drug addict, 2) from unprotected sex with a prostitute, or 3) unprotected gay sex. He was correct on these three points, but completely ignored an important fourth group, childen.

If sinning adults are the only ones at risk for catching hep B, why in the world would the CDC recommend the vaccine for newborns? According to Junior’s elastic logic, it was because the prostitutes, drug addicts and promiscuous gay males didn’t want to buy the vaccine so the vaccine makers, Merck and Glaxo, were losing money! And behold, a compliant “big” CDC began recommending the vaccine for newborns so “big” pharma could continue to rake in the dough. This was according to Junior, without any evidence.

Then, Junior also made the accusation that the hep B vaccine was the cause of sudden infant death syndrome, or SIDS! His “evidence” was that SIDS “first appeared” about the time the CDC recommended that infants be vaccinated for hep B. The problem is that SIDS, or crib death, was around way before infants were ever given the vaccine. It was just that the medical establishment was just then beginning to recognize crib death as a recurring pattern with a definite cause and the press began reporting on it. According to Junior’s simple logic, it would be more accurate to blame crib death on the press coverage of it instead of the vaccine itself. Junior and other vaccine disinformation spreaders tend to ignore such inconvenient facts that distract from their preconceived biases. Junior needed to find some way to make the hep B vaccine sinister so he invented a dishonest link between the vaccine and crib death that had just popped up in the news.

Here are more compelling facts that Junior ignored when he spread this disinformation. Before the hepatitis B vaccine was recommended for all infants, every year the virus infected about 18,000 children less than 10 years of age!! What?? If it only infects sexually active adults and drugs users, as Junior claimed, how does he account for this fact? He clearly chose to ignore it! Worse, infection with hep B virus early in life dramatically increases the chance of liver cancer or chronic liver disease later in life.

While it is true that hepatitis B virus usually is transmitted through sexual contact or needle sharing, that isn’t how the virus is transmitted to young children. Babies are infected with hepatitis B during birth to a mother who is infected. And young children can also contract hepatitis B when living with someone who is infected and sharing personal items like toothbrushes. Then, there are several studies that have confirmed that the hepatitis B vaccine is not at all related to SIDS. The most common cause of crib death occurs when babies sleep face down. For that reason, in the early 1990s, at the same time that the CDC recommended the hepatitis B vaccine for babies, the American Academy of Pediatrics launched its “Back to Sleep” program, encouraging parents to lay their babies on their backs at bedtime to prevent crib death. It worked.

So, RFK, Jr falsely claimed, with no data, that the infant hepatitis B vaccine caused SIDS. Meanwhile, the number of babies vaccinated with hep B increased, and the “Back to Sleep” program was implemented to prevent SIDS, and the incidence of SIDS sharply dropped clearly showing Kennedy’s lie. How many kids went unvaccinated and are now walking around with liver cancer thanks to RFK, Jr’s lies?

Other spreaders of deadly disinformation: RFK, Jr. a lawyer, and his anti-vaccine non-profit, the Children’s Health Defense, by far are not the only miscreants spreading anti-vaccine disinformation. But, they are among the top of the “Disinformation Dozen” according to The Hill. This “dozen” is responsible for 65% of the disinformation promulgated on social media platforms according to the Center for Countering Digital Hate. But, since the COVID vaccines arrived on the scene, a number of medical doctors also have jumped on the anti-vaccine bandwagon. A few have been professionally sanctioned. A short rogues’ gallery of the most notable MD scofflaws follows:

1. Sherri Tenpenny—said the COVID vaccines cause “magnetism” and that metal objects would stick to people, and that there was some sort of connection between vaccines and 5G towers. Her medical license was temporarily suspended until she paid a fine for these flagrant lies.

2. Joseph Mercola—one of the “Disinformation Dozen” called the vaccines a “medical fraud” in order to promote his own online supplement business that included unapproved treatments for COVID—a business worth $100 million! The FDA sent several letters warning him about selling unapproved health products and making false claims about COVID treatments. His YouTube account was permanently banned for this disinformation but his alternative drug business thrives.

3. Simone Gold—one of America’s Frontline Doctors, an anti-vaccine group that has been mentioned in these pages, discouraged the COVID vaccines while promoting hydroxychloroquine and ivermectin long after they were proven ineffective and disapproved by the CDC. She was disciplined by the California Medical Board, but kept her medical license.

4. Stella Immanuel—also one of America’s Frontline Doctors also promoted hydroxychloroquine after it had been disapproved. She was disciplined by the Texas Medical Board and had her social media posts removed. Amazingly, she has claimed that 1) alien DNA is being used in medical treatments, 2) gynecological problems are caused by having sex with demons and 3) that vaccines to prevent people from becoming religious are being developed. As of March 2023, she was, by several orders of magnitude, the highest prescriber of ivermectin and hydroxychloroquine in the US. For some reason, she retains her medical license.

5. Lee Merritt—claimed that COVID was a genetically engineered bioweapon designed to exert some sort of social control and that the vaccination dramatically increases the risk of death from COVID itself. The opposite clearly is true. She too  still has her license.

6. Paul Thomas—A pediatrician has spread general vaccine disinformation to his patients, including about the COVID vaccine, causing many of them to get vaccine-preventable diseases. His license was suspended by the Oregon Medical Board for violating standard medical practices.

7. Scott Jensen—A Minnesota state senator and family doc spread disinformation about COVID death certificates and the vaccines. He signed up with America’s Frontline Doctors and faced multiple investigations by the Minnesota Medical Board, which were eventually dropped. He has been banned from several social media platforms for promoting COVID disinformation. He is running for governor.

8. Rashid Buttar—claimed that the vaccine was a depopulation plan and that most people who were vaccinated would be dead by 2025. He has been reprimanded more than once by the North Carolina Medical Board for unprofessional conduct and malpractice. He still practices medicine.

9. Christiane Northrup—Also one of the “Disinformation Dozen,” promotes alternative medicine and anti-vaccine conspiracy theories, especially disinformation about COVID vaccines. She has used Tarot cards to help her diagnose illness and believes that trauma from a past life can cause chronic illness, and that in a past life she lived in Atlantis, etc, etc, etc. She denied the existence of COVID and believes the vaccines contain artificial intelligence that integrates into DNA making the recipient the intellectual property of the vax patent holders. etc, etc, etc.  Her Instragram account was blocked. She voluntarily gave up medical practice in order to write and publicize these ideas.

Bottom line: The insidiousness and even silliness of anti-vaccine charlatans like RFK, Jr and the others is that while they claim to be saving peoples’ lives, they actually are causing deaths. The Kaiser Family Foundation found that in the nine months between June 2021 and March 2022, 234,000 deaths could have been prevented with the COVID vaccines that these charlatans actively worked to prevent.

How is a death caused by deceitful conspiracies about vaccines different from a death caused by criminally refusing to give insulin to a diabetic in crises, or after telling someone that a loaded gun is unloaded? Both are irresponsible and lead to great harm, just like vaccine disinformation does. Why hasn’t RFK, Jr been prosecuted for the preventable deaths of Samoan children from measles? Why do so many physicians engaging in medical malpractice keep their licenses?

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Tattoos and Vaccines: Muddled Thinking And A Good Idea

“Often wrong, never in doubt”  Anonymous

Muddled thinking. Despite reams of evidence to the contrary, including a recent Nobel Prize for the technology, vaccine fabulists, like RFK, Jr, , Robert De Niro, Jenny McCarthy, my own Senator Ron Johnson, and too many others continue to spread intentional disinformation about the safety and efficacy of the COVID mRNA vaccines. Despite these naysayers, mRNA vaccines are here to stay and new ones are being developed for many other maladies that have been hard to vaccinate for, like cancer, HIV, several animal diseases, etc.

I keep encountering people who belabor the same old disproven canards about millions of people falling dead from the vaccines, about the vaccines being “experimental,” and “gene therapy.” All this disinformation continues despite the fact that tens of billions of jabs have been given to 5.6 billion vax recipients around the world over the last 4+ years. At what point does  fact replace lie and truth supplant fable? The world’s entire medical establishment does not agree with these deceivers, yet they continue to sound the sham anti-vax alarm undaunted. I have pondered in these pages whether this willful dissemination of such disinformation that could affect peoples’ lives and health could be criminal. A case for this could be made.

The funny thing is that these alarmists are announcing the sky is falling over something well tested and vetted while ignoring another very common jab that many of them have likely have gotten without questioning, but that does have significant effects on one’s immune system: tattoos (see vocal anti-vaxer and celebrated tattoo artist, Kat Von D). When you stick hundreds of ink-filled needles into your skin, can it be good for you? Anti-vaxers worry about well tested and vetted vaccines, but never worry about tattoos. Why their selective outrage?

Much of tattooing remains mysterious: Scientists aren’t fully sure what makes certain tattoos fade fast, why others stick around when they’re supposed to disappear, or how they react to light. Given the fact that tat recipients are sitting for multiple injections of unknown substances into their bodies that last forever, tattooing would seem like a much better way than vaccines for someone like Bill Gates to poison us; or to use them for something sinister like mind control, or as a way to control the world population, as the vax chicken-littles often frett about with the mRNA vaccines. Why aren’t folks up in arms over this vast potential conspiracy? (Cynicism mine!)

What do tattoos do? The Atlantic recently ran an article about how tats mess with the immune system and a subsequent quick search found other concerning aspects about them. The practice involves poking dozens to thousands of holes into the middle layer of the skin, or dermis, and depositing different formulations of chemicals, or pigments, that permanently remain behind. Contrast that to the single shot of a typical vaccine that deposits into a muscle a single dose of an agent that has undergone extensive testing and approval for safety and that quickly is eliminated by the natural scavenger cells and processes of the body’s immune system so nothing remains soon after the shot is given. Both procedures irritate the immune system, but one is permanent, the other temporary.

When the hundreds of needle pricks deposit ink into the dermis for a tat, the immune system detects an assault on its body and jumps into action. The skin after all, is our immune system’s first barrier and it is well loaded with rapid-response defensive cells that lead the assault on the pigment intruder. This generally works well to heal wounds and clear infections, but the system breaks down trying to fight tat ink. The immune system simply cannot adequately clear that intruder. Rather, the pigments persist in the belly of the immune cells and skin cells, only to again be gobbled up when those cells die and disgorge their undigested contents. Then the process repeats, ad nauseam leaving a permanent stain in the skin.

Over time, the edges of tats fray and become fuzzy as ink particles are gradually shuttled away into the draining lymph nodes, which normally handle viruses, bacteria, fungi, etc. In the nodes, the immune system then revs up to recruit and deliver antibodies and T cells around the body to combat intruders that escape further into the interior. These nodes normally are pale white, but in tattooed people, they can be the color of the tattoo ink.

Thus not only is the skin tattooed, so are the lymph nodes!

It is not clear if all this misdirected immune response to tattoo ink throws the immune system off its game of surveillance against infectious pathogens. One study published last year found that tat ink can affect the function of immune cells. But, in another Australian study, tat ink was mixed with a vaccine in order to track the fate of the vaccine components after vaccination. There was no evidence of any untoward effect of the pigment on the vaccine itself. Other immunological differences between heavily tattooed and un-tattooed people have been noted but it remains unclear whether these are for the better or the worse. So, it remains uncertain whether tattoos are good or bad for one’s immune system.

However, tat ink can be harmful in other ways. The European Union banned certain pigments, that they believe are linked to bladder cancer. And a 2016 report from the Australian government found that >80% of black inks contained carcinogenic polycyclic aromatic hydrocarbons (PAHs). Other pigments may contain other harmful substances like barium, cadmium, lead, mercury, micro-plastics, etc. Then there always is the real risk of infection or allergic reaction when anything is injected into your body. Nice.

Tattoo-like vaccines: a good idea. In a typical vaccine, the shot is delivered into an arm muscle where the immune system is not as robust as in the skin. The skin being a primary barrier to a hostile outside world is well stocked with an armament of immune sentry cells, muscles deeper in the arm not so much. But, there are enough immune cells in muscles to get the job done and develop protective immunity to antigens which the vax delivers. For an intramuscular vaccine delivered to an arm muscle, usually a comparatively large antigen dose is used and it takes a bit of time to get the immune system in gear. Mobile immune cell cops where the vaccine bolus is deposited gobble up the material like a squirrel shovels nuts in its mouth, and then head to nearby lymph nodes to “report” that an intruder was encountered. This gets the army of T and B lymphocytes ginned up and pumping out antibodies, other immune molecules and cytokines, and other cells to respond the intruder. You are then “immunized.” This also sometimes causes the temporary malaise associated with vaccines—mild fever, fatigue, flu-like symptoms and maybe arm pain. In rare cases, allergies happen, which is a rapidly arising, acute immune response to a component in the vaccine, such as chicken egg material found in many, but not all, flu vaccines. 

However, a few vaccines are actually given in the skin, more like tattoos are administered. Currently this route is used to vaccinate for small pox, TB, rabies, and more recently, mpox (formerly called monkey pox). Some studies, but not all, have shown that the intradermal (ID) vaccine route can outperform the intramuscular (IM) vax route. For this reason, other vaccines are now being developed to be given this way simply because the skin immune system is more robust and this might provide a more effective way to vaccinate, and it uses less vaccine material. This is called intradermal vaccination.

But intradermal (ID) vaccines are not that easy to administer. If not done properly and the vax material is injected too deep, which is easy to do, their efficacy can drop precipitously, just like Biden’s presidential chances plummeted after the disastrous debate. So, medical folk are actually looking at different vaccine technologies, including using tattoo machines to administer effective ID vaxes on a large scale across many clinics large and small. One technique using a DNA vaccine, called DNA tattooing has been tested in animal models and human trials and was inspired by traditional tattoo machines, which are pretty easy to use.

Bottom line: The way that vaccinologists have taken notice of tattoo technology to improve vaccine efficacy is intriguing. They have taken their science knowledge of skin immunology and realized that the pop culture tattoo fad just might improve vaccine technology and public health. That is very cool.

The sad irony is that many people who get tattooed are also vax deniers. Their cognitive dissonance is disturbing. Vax deniers loudly spread disinformation about vaccine dangers, then are completely sanguine about tattoos which inject strange chemicals into their bodies, some of which have been clearly proven to be unhealthy.

That selective outrage betrays the intellectual dishonesty and lack of curiosity of anti-vaccine dissemblers. Too bad we can't vaccinate against that.

Acknowledgment: I am indebted to Frank C. (no relation) for helping procure an article needed to write this blog post, which I had a very hard time accessing without paying a full subscription to the journal. Thanks Frank!

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Coronaviruses, Colds And COVID: And Cool Immunology

“The most exciting phrase to hear in science…is not ‘Eureka!’ but ‘That’s funny…’”

–Issac Asimov

 

Background. Your run-of-the-mill common cold virus is sometimes related to its more infamous relative that caused the world all sorts of consternation between 2020-2023, and still demands respect like an aging rock star who might still have some chops left. I, of course, allude to SARS-CoV-2.

Yup, the now infamous family of deadly human coronaviruses, which includes the original bat-borne SARS-CoV-1 (which caused the first SARS pandemic in late 2002), its Middle-Eastern camel-riding cousin (that caused MERS in June 2012), and the recent, much more traveled, durable, and concerning SARS-CoV-2 (origins so far unknown and the cause of COVID-19), have some lesser known, ne’er-do-well cousins that have long traveled among us. I refer to certain viruses that visit us often and are as unwelcome as a distant cousin who arrives unannounced needing a place to crash for a few days. This is the “common cold virus” which actually is several different kinds of viruses. Cold viruses are all as irritating and inconvenient as said uninvited distant cousin, and about as enjoyable as a hangover; but seriously debilitating or life threatening? They are not.

The common cold is mostly caused by one of three families of viruses; rhinovirus (not related to any large mammal), adenovirus, or a coronavirus. Yup, a distant cousin to that bug that caused so much serious illness and death across this blue orb during the COVID pandemic also is one of the causes of the mostly benign, but very annoying common cold. In fact, there are four different types of coronavirus cousins that cause 15-30% of the “common colds” in adults. Isn’t it interesting that one coronavirus, like SARS-CoV-2, can kill you, but its cousins just make you sneeze and your nose run like a leaky faucet, but that is all. Aren’t viruses fascinating?

Facts. Just as between unwelcome distant cousins, there are genetic similarities between the dangerous CoV-2 and its nettlesome coronavirus kin that just cause colds. And recent studies found that infection with one of these coronavirus cousins can indeed confer some immune protection to the other distant cousins. In other words, if you were infected with CoV-2, you likely had a much milder cold, if you caught one at all. And vice versa! But the funny thing is that vaccination against COVID did not also protect you against a cold like an infection would. What??

This stuff makes viral immunology so much fun.

To confirm all this, one study showed that this cross protection only occurred in people who had a definite bout of COVID caused by the coronavirus, and the reduced incidence of colds only occurred for colds also caused by a coronavirus, and not for a cold caused by unrelated rhino or adenoviruses. Clearly prior exposure to a different member of the coronavirus family conferred some immunity to other members of that family, even to distant cousins. Also, just being vaccinated to the CoV-2 spike protein did not confer this sort of protection to future coronavirus-caused colds. Wow! This kind of discrimination and specificity gets immunologists salivating like a Pavlovian dog to a ringing bell. I know—I am wiping secretions off my keyboard as I type.

Vaccines to just the spike protein quickly generates antibodies that neutralize the virus and thus prevent serious disease. But, that only offers short term protection to just that coronavirus from whence the spike protein sequence came. The viruses quickly mutate their spike surface proteins so the viral cousins cannot be recognized by the spike protein alone. That is why anti-spike immunity and the vaccines are not very good at protecting against re-infection for very long and why the vaccines don’t confer immunity to distant coronavirus cousins.

However, the immune system is a multi-layered security system. Besides these short-lived neutralizing antibodies that target the coronavirus spike protein (or similar surface proteins in other viruses), other layers of the immune security system can also be generated to other molecules across the SARS-CoV-2 genome following infection with the whole virus (see here and here). These other genome sequences are often more conserved and less likely to change between distant coronavirus cousins, than the highly variable spike protein sequence. This means that any immune response generated to one of these more boring, unchangable sites on a given coronavirus, can also recognize similar sequences on distant cousin coronaviruses.

But who, other than an immunology nerd really cares if having COVID protects you against a future cold? What about the reverse? Can having a cold caused by a coronavirus cousin generate some protective immunity to the nastier SARS-CoV-2 and protection from COVID and future coronaviruses that will emerge? Some, but not all research has indeed shown that people without prior exposure to CoV-2 do indeed show immune reactivity to the virus (see here and here). This means that folks who haven’t been infected with SARS-CoV-2 must have been exposed to another coronavirus that gave them a bit of cross protective immunity to the COVID virus. Other studies confirmed that prior infection with cold-causing coronaviruses can reduce COVID severity following infection with CoV-2 (here and here).

Bottom line.  What this means is that if you have been infected with some sort of mild coronavirus in the past, you just might be able to show some immunity to future infections with distant coronavirus cousins. Vaccination with the spike protein mRNA just doesn’t do the same. You need to be exposed to the whole kit and caboodle to enjoy all this immune goodness.

The responsible part of the immune system for this cross-over immune response is CD8⁺ T cells, also known as cytotoxic T lymphocytes, or CTLs. These immune cells are assassins that seek out other cells infected with a virus and they kill those cells. So, immunologists get all atwitter and think, “Hellz bellz, why don’t we make vaccines using parts of these boring, but conserved virus pieces that generate CTLs to different viral cousins, instead of the ever changing spike proteins to make vaccines? We could make one vaccine for all coronaviruses! Or flu, or whatever virus….”

It is a great idea and that research is well underway. The goal is to make a single coronavirus vaccine that would be long lasting and target many coronavirus cousins to prevent any future pandemic (believe me, another one is sure to come).

Back to earth. As interesting and hopeful as this sounds for making a single vaccine against multiple coronaviruses so we don’t have to continually try different boosters each year, don’t get your hopes up just yet. Similar immuno-optimism has been going on with influenza for decades and what do we have to show for that? We still have the annual guessing game of which flu strain will pester us each winter and then feverishly roll out millions of vaccines to try to nip that particular one in the bud. Meanwhile its flu cousins chortle and conspire in the Southern Hemisphere on how to mix and mutate their genes so they can surprise us again in the Northern Hemisphere the following year with a sufficiently new variation to vex us again.

But, flu, like coronaviruses also has important proteins that are not changeable, and very constant between distant flu cousins. These too can be seen by the immune system’s T cells. Flu immunology’s Holy Grail has long been to make a vaccine to a conserved flu virus genomic sequence so we can use just one vaccine to immunize against all flu strains once and for all for all time. A pan-flu vaccine.

Well, we are still trying to do that. This makes the idea of finding a pan-coronavirus vaccine using similar immunology daunting. Still, these recent studies showing that cross-reactive immunity between distant cousin coronaviruses does exist, just stokes an Immunologist’s stubborn resolve to solve the problem. As I have written before in these pages, amazing science advances have often come from the long, dogged pursuit of goals that very stubborn scientists believe they can see right in front of them, even when others cannot. It often takes a long time to prove what is so clearly obvious to one or two science visionaries yet so oblivious to the rest of us. That often is how science progresses. Thank goodness for these obstinate scientists who see things the rest of us cannot.

Once again, We will see.

Personal note. These anti-viral CD8⁺ or cytotoxic T lymphocytes are near and dear to this correspondent’s heart since I got my PhD in Immunology studying how these immune cells in mice recognize cells infected with viruses. It is a lot more complicated than you would think. In fact, in 1996 two immunologists, Peter Doherty and Rolf Zinkernagel were awarded the Nobel Prize for work they did on this problem in the early 70s, and that work drove my PhD research (and a lot more!).

Doherty and Zinkernagel discovered that T cells have to simultaneously identify two different molecules on an infected cell surface before they actually know a cell is infected with a virus. They made a head-scratching observation that turned viral immunology upside down. It was one of those observations that I bet made them say, “That is funny.” Basically, they found that your T cells that can recognize flu infecting your cells would not recognize flu infecting my cells or anyone else’s cells. And vice versa. You would think flu is flu and that a T cell that can see flu in an infected cell would not care whose cell it came from. But it does care. It turns out that T cells can only see virus within the genetic background from whence they came. They cannot see the same virus on a cell from a different genetic background! How strange is that? An antibody does not care where it sees a virus. T cells do. Picky little suckers.

It gets even crazier. Doherty and Zinkernagel, mapped this genetic restriction in virus recognition to the same genes that the immune system also use to determine whether a tissue or organ is its own or is foreign! For example, the genes your immune cells recognize as a password to determine friend vs foe in a skin graft (do we accept it or reject it?) are the same genes the immune cells use to help them know if your cells are infected with a virus! Tell me that doesn’t make you scratch your head and mutter, “That’s funny?” That is exactly how the world of immunology reacted to Doherty and Zinkernagel’s findings. It was a beautiful time for immunology science. That launched a tsunami of research, my PhD effort included.

This is personal note because I earned my PhD further probing the mechanism of what Doherty and Zinkernagel stumbled on. I used a large panel of mice that had been engineered to carry single point mutations in different parts of these genes that immune system used to ascertain tissue compatibility, and detect viral invasion. This helped us learn what part of these molecules the T cells recognized and how their folding was important for this recognition. It was a grand time!

Immunology is so doggone interesting!

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