Coronavirus

The Intelligence of Artificial Intelligence And Blogging

“Do you ever make silly mistakes? It is one of my very few creative activities.”

–Len Deighton, British Author

Have you tried dabbling with artificial intelligence? I specifically refer to the type referred to as chatbots that use powerful generative artificial intelligence that you can really chat with to generate ideas. It is like the computer, Hal, in the movie 2001 a Space Odyssey. Remember? Remember too that Hal malfunctioned big-time?

I’ve been dabbling for a while. Here is my experience related to this blog.

I began dabbling over a year ago with OpenAI’s ChatGPT, using their GPT3.5 version, but soon graduated to GPT-4, which was released in 2023 and comes with a small subscription fee. I have since migrated to Bing, which is a collaboration between Microsoft and GPT-4 and comes without the fee. It is a powerful research and generative tool. It can generate text, art, compose music, diagnose and even treat a psychological illness with talk therapy. You can have these chatty things teach you a foreign language, and write a legal brief. Perhaps you also have read the reasonable concerns schools and colleges have with such smart tools doing homework for students and the worry about professionals using them to fake their work and the attendant ownership issues of work done.

There seems to be a lot of mischief your computer can cause with the right smart software, but it can also do a lot of good. I know. I have found these smart tools quite useful for my research and writing. Rest assured that I have NEVER used anything but natural intelligence to write any blog post or other article for me (you can tell by the typos in my finished products). This is because, while the bot can compose, it is not creative. As I write, I try to use subtle humor, irony, alliteration and other tools to make my prose interesting. Chatbots do not. At times, however, when writer’s block hit, I prompted the chatbot to write something, and after a few prompts, usually found something that primed the pump of my muse and I penned away using my own intelligence.

I can pose questions or hypotheticals to the computer tool and it comes back with answers. I then either refine my questions, or pose follow up queries. It is much like bouncing ideas off a collaborator. In this regard, I find it quite useful. Who else will talk with me about the value of the latest vaccine or whether Brock Purdy is really a good quarterback or the product of the great pieces around him without my having to buy them a beer? Although, I admit sometimes the latter is much preferable. I have discussed much science at a dive dart bar in Dallas, a surf bar in Malibu, and over a pool table at tavern near the medical center in Madison. Not much artificial intelligence there except after a few brews.

All good. Until this. The chatbot models are supposed to be self-learning. So, I decided to see what Bing had learned about my blog on the coronavirus pandemic. I queried it about a term I thought was pretty unique to the blog, BioX. Readers will recognize that that is what I have dubbed the revolutionary post-molecular biology that gave us a vaccine so rapidly and that is bringing other amazing types of new disease treatments and diagnostics at astounding rates.

Turns out Stanford University (a school you might have heard of, Bing certainly has) has a new bio program also called BioX. It has well publicized it too. Well, Bing kept telling be about Stanford’s BioX and not about mine. Not what I wanted to see.

I changed my query several times to ask Bing about my version of BioX and instructed it to ignore everything about Stanford. Like a hyperactive toy poodle, it completely ignored me. It was quite polite though, apologizing each time I said it was not responding to my query.

Finally, after arguing with this digital nitwit, it finally included me and my notion of BioX in its rendition. Below is what it came up with—be seated as you read what Bing wrote about BioX and me. It included me, but still could not ignore Stanford.

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Steven Clark, PhD, is a retired professor from the University of Wisconsin and a viral immunologist who has been blogging about his research on the new biology he dubbed “bioX”. BioX is a term that he uses to describe the emerging field of biotechnology that aims to harness the power of viruses and other biological agents to create novel solutions for human health and disease. He claims that bioX has the potential to revolutionize medicine and biotechnology by offering new ways of diagnosing, treating, and preventing infectious diseases, as well as creating new therapies for cancer, aging, and other chronic conditions. (So far so good. But the next paragraphs…)

One of his most notable achievements is the development of a vaccine against the SARS-CoV-2 virus, which causes COVID-19. He announced this breakthrough on his blog in December 2022, shortly after he received funding from Stanford Bio-X1, an interdisciplinary biosciences institute that supports research and educational opportunities that cross disciplines between the biological or biomedical sciences and fields of engineering, physics and computational science2. He explained that he used a novel approach to engineer a virus that could deliver a synthetic version of the spike protein of SARS-CoV-2 into human cells. The spike protein is responsible for binding to human cells and allowing the virus to enter and infect them. By introducing a modified spike protein that can evade some of the immune responses generated by previous COVID-19 vaccines3, Clark was able to elicit strong neutralizing antibodies in his volunteers without causing any adverse effects. He also demonstrated that his vaccine could protect against different variants of SARS-CoV-2, including Omicron3.

Clark’s vaccine has been hailed as a game-changer in the fight against COVID-19, but it has also raised some ethical and regulatory concerns. Some critics have questioned his motives for developing such a powerful bioweapon without proper oversight or consent from the public. Others have expressed doubts about his safety and efficacy claims, citing lack of peer-reviewed data or independent verification. Clark has defended his work as being based on rigorous scientific principles and ethical standards. He has also stated that he intends to share his vaccine with other researchers around the world who are interested in collaborating with him on bioX projects.

Clark’s blog posts on bioX have attracted millions of readers who are fascinated by his vision and achievements. He has also inspired many young scientists who aspire to follow in his footsteps and pursue careers in biotechnology. However, he has also faced some backlash from anti-vaccine activists who accuse him of being part of a conspiracy to create more deadly diseases or manipulate public opinion. Clark has dismissed these allegations as unfounded and irresponsible.

Clark’s blog posts on bioX are an example of how science can be used for both good and evil purposes. They show how innovation can lead to breakthroughs in medicine and biotechnology, but also how it can pose challenges for society and ethics. They also illustrate how different perspectives can influence how people perceive and evaluate scientific discoveries.

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Well dang. If I invented the damn vaccine, how come I was not included in the Nobel Prizes that were just awarded for the invention? I demand a recount. I did like the part about “millions of readers who are fascinated by my vision”. Notice the “references” Bing included citing my accomplishments. They must be true because Bing says so.

In the parlance of computer geeks, what Bing spit out above is called “hallucination.”

This is the intelligence of artificial intelligence.


‘Tis The Season To…..Mask Up Again??

"It's a bug hunt!"

-Private Hudson, in “Aliens”

"Influenza-like illnesses" are increasing at an alarming rate across the country. Yup, ‘tis the season for respiratory diseases and we have more than one to worry about. In years past we mostly worried only about the flu and, sometimes as an afterthought, colds, which aren’t of much concern. But in late 2019, a brand new and very weird bug appeared on the scene, SARS-CoV-2 that caused COVID. It seems that the bug and disease will be an annual guest from now on. This year, we also see a surge of a third bad bug, respiratory syncytial virus, or RSV. All these viruses cause what have been collectively labeled “flu-like illnesses” and together they seem to be worse this year than recent years. The CDC reports that hospitalizations for flu-like illnesses have been steadily rising and that the peak is still to come.

As a result, we are beginning to see increasing reports of a return to local mask mandates. In my own community of Madison, Wisconsin, two major health networks just announced their return, like a bad TV rerun. This includes the University of Wisconsin Health network, where I receive health care. Glad I kept a few masks on hand. What’s in your glove compartment?

I also have read where some grocery stores are now requiring masks. Some stores only require masks on certain days of the week so that customers can select to shop on mask-required vs mask-optional days. Some colleges and large companies reportedly also are beginning to require masks again. So far these mandates are very local and are not a national phenomenon. It is feasible that mask mandates in public spaces and especially for travel could increase if infections and hospitalizations get more serious.

As I often say in these blog posts, “we will see.”

Why is the flu and RSV, which have been around almost forever now causing more than their usual problems? A hint was presented in a blog post I published about a year-and-a-half ago, “What Happened To The Flu And Other Respiratory Diseases?”  In that apparently prescient post, I reported that the world had seen a huge reduction of all infectious respiratory diseases due to the protective non-pharmaceutical interventions (masking, sanitation, isolation, quarantines, closings, etc.) designed to physically protect people from the new coronavirus. They were so effective that some strains of other common infectious viruses are thought to have gone extinct!

That is great news! But, it also means that the world also missed its regular natural booster of common bugs and our herd immunity to them waned. Our youngest were never exposed to those bugs and the rest of us became less resistant to future exposure and that future is now. We are now paying the piper for that lapse in a “bug boost.” Hence, flu and RSV temporarily are having their way with us and enjoying it. At least they are not nearly as nasty as the coronavirus initially was and still could be with a couple of insouciant genetic tweaks.

“Influenza-like illness,” is a catch-all term coined by the CDC to corral COVID and the other two viral diseases. Together, the three have reached an epidemic point in the US and other places across much of the world. The Figure below shows that the US epidemic is currently hitting Southern States the hardest, but expect it to migrate Northward in the next few weeks.

What do the different colors in the Figure mean on a practical level? I can offer one anecdotal example. According to the map, New Jersey, while not a Southern State, still is being hit hard. A family doc wrote about a week ago that all the hospitals in his health system are at capacity. He was unable to send a patient to the preferred ER because its hospital was full due COVID, flu and RSV cases. And the patients with these flu-like respiratory infections who were filling the beds were not necessarily elderly. Most are in their 40’s-50’s. Unsurprisingly, the hospitals and clinics in his health system again require masks. Their staffing is becoming a critical issue as providers also become ill and turn into patients. This is becoming too reminiscent of the early stages of the COVID onslaught when hospitals where overwhelmed and medical personnel were dropping like flies. So far, this experience is sporadic across the US. But, it is becoming concerning.

ORI
Outpatient Respiratory Illness Activity Map Determined by Data Reported to ILINet
This system monitors visits for respiratory illness that includes fever plus a cough or sore throat, also referred to as ILI, not laboratory confirmed influenza and may capture patient visits due to other respiratory pathogens that cause similar symptoms. From the CDC.

The incidence of RSV is high. RSV hospitalizations have increased 60% nationwide over the past four weeks. A couple of deaths in children have been reported in my state. The vaccine for RSV is brand new this year and recommended for people over 65 and for kids; i.e., those at highest risk for severe disease. It definitely is worth it.

Flu is moderate right now, but expect it to soon blossom. Hospitalizations among all age groups increased by 200% for influenza in the past four weeks but still remain below Covid-19 and RSV hospitalizations. For now. They are expected to increase as the peak flu season has yet to arrive.

And then there is our relatively new friend, COVID. On a national level, COVID virus transmission is “very high.” After the post-Thanksgiving surge, as determined by monitoring viral loads in wastewater samples (“take-your-kids-to-work” days in that profession must be fun!), virus levels plateaued. But expect another sharp rise after the Christmas/New Year’s holidays. We have consistently seen this pattern in previous years.

Cov-2 is one of the most mutable viruses that the world has inflicted on us. That means we are constantly seen new variants arising. Surprise, the Omicron subvariant JN.1 is coming onto the scene. It’s the spawn of variant BA.2.86, which was discovered over the summer and was concerning because it came out of nowhere with a whopping 35 mutations in the spike protein (the more mutations, the greater the chance for another very nasty bug). While BA.2.86 caused a comparatively mild disease, it quickly mutated to JN.1 with just an additional single change in the spike protein that made it much more infectious, but it still remains fairly mild. With just one mutation, it became the fastest-spreading CoV-2 variant in the past two years. With all its changes, JN.1 is so different from its Omicron grandparent that there is considerable scientific debate about whether JN.1 should be given its own Greek letter designation, Pi. A weighty debate indeed.

But, a bigger question is whether COVID hospitalizations will follow wastewater sampling trends that show JN.1 (or Pi) viral levels surging through the world, especially in the US where vaccination rates are low. It is concerning that the UK and Singapore, which have high vaccination rates, are now seeing a steep increase in hospitalizations due to JN.1 (or Pi). So why not expect the same or even worse in the undervaxed US? Last week, the CDC warned about such a potentially huge impact due to the wretched combination of low US vax rates and the highly infectious JN.1 (or Pi) virus. As Private Hudson (aka Bill Paxton) in the movie Aliens might say, thanks to the antivaxers, “Game over, man! Game over!”

Also of new concern is that some scientists are now beginning to believe that COVID infection could be damaging our immune systems. If true, that could make infected people even more vulnerable to the other bugs out there such as flu, RSV, and others including bacteria and fungi. COVID could also cause immune dysregulation leading to new-onset autoimmune diseases. So get your COVID vaccines! They can protect you against illness beyond COVID!!

Finally, another concern is that the rapid home tests for COVID are proving to be only 30% reliable very early after infection before symptoms start. In other words, if you believe you have been exposed to COVID, but your home test comes up negative, don’t necessarily believe it. Retest yourself 24, or preferably 48 hours later or when you show symptoms like a fever, cough, etc. If that second test also is negative, you have pretty good confidence you are COVID free and have some other bug.

The pragmatic bottom line. There is a lot of coughing, sneezing and other respiratory distress going around, and it will increase in coming cold weeks as we bundle up and crowd around others indoors. To improve your odds of staying healthy, remember these things:

  • Limit your time around indoor crowds.
  • If you have indoor gatherings, crack your windows and bring out the fans to increase air circulation and air exchange with the outdoors. There is very good evidence that good ventilation really matters and that the amount of viruses we breathe in makes a big difference in terms of whether we get sick and how sick we get. It is worth a few extra dollars on the heating or electricity bill to avoid nasty illness.
  • Room air filters are also a good idea.
  • Get vaccinated!
  • Wash your hands often.
  • If you do get sick, STAY HOME! I have always hated the “brave” soul who came to work with a cough and sneeze. Don’t share your agony!!
  • And there are the good old fashioned masks for use in crowded places, especially in auditoriums, on planes, and other packed indoor situations. I don’t care what the naysayers say about masks, they are flat wrong. They don’t think twice when a store sign requires shoes and shirts to enter. So why do masks bother them so much? They WORK as I have written here before, over and over. Empirical evidence proves masks work. That is why the entire medical profession continues to use them.

Finally, as I have repeatedly admonished, please get vaccinated. Vaccine and booster uptake for all three viruses has been dismal this year. Failure to vax is a major driver in the surge of the flu-like respiratory diseases we are seeing. If you have not gotten vaccinated for all three circulating viruses, why the heck not?? It is way better to prevent disease than to treat disease. A sore arm is much less of an inconvenience than suffering the flu, RSV or lying in a specialized hospital bed turned on your stomach breathing with a ventilator because of COVID.

As I have written in these pages, having COVID can be worse than any flu you ever had. It also puts adults at risk for dealing with weeks of long COVID and getting new-onset diabetes and immune dysfunction. COVID also is much worse than the flu for many kids and puts them at risk for multi-system inflammatory syndrome (MIS).

Why risk what can be prevented by a simple vaccination?

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US Life Expectancy Finally Bounces Back Up

Game over, man! Game over!” --Bill Paxton as Private Hudson in Aliens

As I wrote in these pages a couple of years ago, the US suddenly lost a whopping 1.3 years of average life expectancy due to COVID. It had that big of an impact on the country in excess deaths. And before some moron starts saying it was due to vaccine deaths, the down turn in life expectancy, or the increase in excess deaths (i.e., deaths more than expected based on actuarial predictions) began before the vaccines rolled out and just after the virus appeared. Furthermore, the upturn in life expectancy occurred after the vaccines were delivered, as well as after the virus evolved from Delta to a less lethal variant. In the early days of COVID vaccination before vaccines were widely distributed, data showed that unvaccinated people were 11 times more likely to die from the virus than vaccinated people. At one point, 95% of hospitalizations and 99% of deaths were in unvaccinated people. The vaccines clearly prevent death, they do not cause death (unless you listen to Robert F. Kennedy, Jr. or Marjorie Taylor Greene, more on her later).

The graph below shows the dramatic drop in life expectancy beginning in 2019 and reversing about 2021. If vaccines were killing rather than saving people, you would think the curve would continue downward.

Blog pic

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BioX Wins The Nobel!

“If you start to take Vienna, take Vienna”— Napoleon (reportedly)

What’s the fuss? BioX won the Nobel Prize….er rather it was the mRNA vaccine that won. Correction—it was the scientists, Katalin Karikó and Drew Weissman of the University of Pennsylvania, who developed the RNA technology that went into the novel vaccine who won the prize. But their work directly led to the vaccine, a first fruit of BioX.

Readers of these blog pages might remember that about this time in 2020, that year’s Nobel award for Medicine or Physiology went to three scientists for their decades-long search to discover what caused hepatitis type non-A, non-B. It turned out to be a whole new virus, the hepatitis C virus (or HCV) that took four decades to identify. Even though it still remains a huge health problem, there still is no vaccine for it. I compared that four decade slog just to find the pathogen to how fast the novel viral cause of COVID-19 was found and a vaccine developed—all done in less than a year! I anointed the new biology that did that amazing feat, ‘BioX.’ That was rather prescient of me, since three years later, the co-founders of the COVID vaccine using BioX too were awarded the Nobel Prize.

I dubbed the new amazing post-molecular biology science that enabled such a quick identification of the novel coronavirus and development of a vaccine against it, ‘BioX’ after SpaceX. SpaceX, of course, is the name for the new way space travel is now being done. Shortly before the Nobel award for the discovery of HCV, Elon Musk’s SpaceX took astronauts in an unpiloted vehicle to the International Space Station. Then the launch vehicle, rather than being discarded as usual, was landed, upright, in the center of a bullseye on a barge off the coast of Ireland, to be reused on a future space flight--maybe to Mars? The whole thing was developed in a fraction of the time at a fraction of the cost of what NASA had historically been doing. NASA’s technology was rendered archaic by SpaceX, which introduced us to a new era of space travel.

The breathtaking speed with which a new biology discovered the SARS-CoV-2 virus and then developed a safe and effective vaccine against it ushered in a new post-molecular biology world I dubbed ‘BioX’.

Now the details. But as breathtaking as SpaceX is, it was not developed overnight in a vacuum. It arose on the back of decades of NASA engineering R&D, which included some spectacular failures and even a few tragic deaths. Similarly, as breathtaking as BioX was with the rapid identification of a novel virus and development of the new mRNA vaccines to a wholly new disease, that technology too was built on the back of decades of hard work, punctuated with many failures, but also flavored with impressive perseverance on the part of a few individuals.

There are two major components to the novel COVID vaccines—the mRNA which generates the viral protein to which the immune response is made, and the lipid nanoparticles that encapsulate and protects the fragile mRNA from a world that is hostile to mRNA. Both components took very separate, decades long, twisting, uphill roads to develop. Both nearly met with failure. And both came together with spectacular success. BioX!

  • The mRNA. Weissman, and especially Karikó, languished for years on the fringes of science with a, then, very weird idea of using mRNA to produce drugs or vaccines. Their collaboration began with a chance encounter at a UPenn copy machine in the 90s and went downhill from there as recently told in the Wall Street Jounal. Funding for their work was hard to come by. Karikó was banished to an office on the outskirts of the campus and languished in a non-faculty position for years. At one point, she had to take a demotion to simply keep a job at Penn.

They just could not get their idea to work. The mRNA was too fragile and too short-lived to work with and produce the desired proteins when they tried to express it in cells or animals. The fact is that there are ubiquitous enzymes all around us called RNases that have a ravenous appetite for mRNA. RNA molecules, especially mRNA disappear almost as fast as one can purify or make them, let alone then try to get them into cells in tissue culture or into bodies. On top of that, when naked mRNA is injected into a body, it elicits a powerful immune response that further quickly degrades it. Note that there are several different types of RNA, and mRNA is the most fragile and hardest to work with, but it is the type that provides the message that turns a genetic code into a protein molecule like a spike protein, which is why it is used in the vaccine.

The researchers had great difficulty getting grant funding for their research because no one believed it would go anywhere. When they could produce some data, they had a very hard time finding journals to publish it. No one was interested because no one believe that there was any utility in the whole premise of using mRNA as a therapeutic tool. In the publish-or-perish world of academia, such negative peer pressure usually is the kiss of death. They should have seen the writing on the wall and been teaching high school biology. But for some reason, Karikó continued to have faith in her idea even though no one else did. For some reason, she persevered.

After dogged determination and ignoring all the naysayers, she eventually had a major breakthrough after a doing a simple experiment. They found a simple way to protect the mRNA from the immune response and published this in 2005. It opened the field and colleagues minds about using mRNA as a possible therapeutic tool. But there still was the problem that mRNA was exquisitely sensitive to RNase enzymes that were everywhere—on your fingers, in your breath and blood, even on sterilized surfaces—the enzymes are incredibly stable molecules and very hard to destroy. Life intended mRNA to be short lived molecules, not to be used in vaccines.

It wasn’t until folks paired the immune-stable mRNA of Karikó and Weissman with a way to protect the molecules from RNase enzymes that mRNA vaccines became possible so they could win the Nobel Prize. Lipid nanoparticles did the trick.

  • The lipid nanoparticles. The story behind the development of the lipid nanoparticles used to deliver the CoV-2 viral spike mRNA sequence to cells so they could use their normal gene expression machinery to put the spike protein on their surface and generate an immune response is a long one. In that regard it is quite similar to the long, arduous story behind the development of the therapeutic mRNA. Early on, neither technology was believed possible or useful by the scientists’ peers. Both groups had very hard times getting their scientific feet on the ground. Both nearly failed. I described Karikó’s struggle above and in March 2021 I wrote in these pages about the professional plight of Bob Langer who, in the 70s, had a vision for using liposomes (short for lipid nanoparticles) for delivering fragile bio-molecules and drugs to cells (you can read that post here). Briefly, his idea was to create mini-cells in which to package and protect fragile therapeutic molecules and then deliver them to cells and tissues in the body. The liposomes containing the fragile therapeutic molecules would fuse with the lipid membranes of cells and disgorge their contents into the cells. Many people told him it was not possible and he had his first nine grant applications rejected—and this was a time when medical science research grants were easy to get (when I was in graduate school in the early 80s, NIH grant applications had a 50% success rate. By the time I became a faculty member in the late 80s that dropped to 10%). Langer, like Karikó, also could not get a faculty position because people did not believe in his research. Also like Karikó, for some reason Langer persevered.

Also like Karikó, Langer too succeeded—eventually. It took a long time. The technology he successfully developed was first used to package a drug used to treat a rare genetic disease that causes nerve and heart damage. It also was used to package mRNA for an Ebola vaccine. From an ignominious beginning, Bob Langer became a professor at MIT where there now is a bioengineering lab named after him. That is not quite as nice as winning a Nobel prize, but high recognition still.

Along the way, he also co-founded a small biotech company named Moderna that was focused on developing mRNA vaccines for infectious diseases, cancer and other diseases. Then COVID came calling and Moderna immediately pivoted, and along with BioNTech, NIH, and Pfizer, quickly gave us mRNA vaccines delivered in liposomes that saved millions of lives from COVID.

That is how BioX technology led to the Nobel prize this year.

The bottom line. BioX, like SpaceX, was built on decades of hard research that was punctuated by painful failures, but highlighted by dogged determination. Both technologies, BioX and SpaceX, are here to stay at least until the next amazing thing replaces them. You can bet that that next amazing thing will have been developed on the back of determined researchers who very possibly will be working at the fringe of their professions and may flirt with professional failure early on. You can also bet that the next amazing things will be built on the backbone of SpaceX and BioX. That is how science and engineering painfully progresses.

So, when you hear someone say that the mRNA vaccines are experimental like I very often do, tell them the truth. They were built on decades of hard research going back to the 70s.

Stay tuned for a coming post on the future of BioX, which is here to stay for a while. New mRNA vaccines are being developed for previously vaccine-impossible diseases including HIV, cancer, and various animal diseases. Work also is underway for a universal flu vaccine.

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Politics: A Risk Factor For Death From COVID?

What are you gonna believe, medical science or dubious talking heads?

In 2021 former Green Bay Packers quarterback, Aaron Rodgers, said he was “immunized” against COVID. He wasn’t. He claimed to have done “research” and learned how to get an infusion of antibodies and take some unproven ‘medicine.’ His ‘research’ was talking to radio pundit and hot-air purveyor, Joe Rogan. How many more people like Rodgers listen to the wisdom of the likes of Rogan or Tucker Carlson and think they know more than medical professionals and then rationalize their avoidance of COVID vaccines? And to what effect?

The Kaiser Family Foundation estimates that from June 2021 through March 2022 about 234,000 COVID deaths could have been prevented had the decedents been vaccinated against the SARS-CoV-2 virus. That protection was especially important during the more deadly Delta virus wave during the earlier stage of the pandemic, but it still extends into the Omicron era, which fortunately is not as deadly as Delta was, but still is not to be taken lightly. People are still dying from the virus.

How does politics come into this?

A 2022 study published in the journal, Lancet Regional Health-Americas, found higher COVID mortality rates in more conservative congressional districts across the US. And in another 2022 study using 2020 presidential election returns, researchers at the University of Maryland and the University of California at Irvine found that, through October 2021, Republican-majority counties across the US experienced nearly 73 additional COVID deaths per 100,000 people relative to majority Democratic counties.

These are correlations looking for a cause. A good causal candidate could be differences in vaccination rates between people who tend toward conservatism vs liberalism. The former are much less likely to get vaccinated than their left leaning neighbors. But, that connection needs to be made.

Sure enough, a July 2023 report by Yale researchers in the journal, JAMA Internal Medicine, compared COVID death rates in counties in Florida and Ohio that voted for Trump vs Biden before and after the vaccines came out. The bottom line was that after the vaccines rolled out, Trump voting counties saw 40% higher fatality rates per million residents. Before the vaccines, the COVID death rates were the same for all counties. Viral infection rates were similar for both types of counties throughout the period of analysis. Importantly, counties and individuals that went for Trump had lower vax rates than those that went for Biden.

That pretty much closes the circle on the causation. The greater reluctance of more conservative people to get vaccinated and boosted likely killed them at a greater rate.

Karma?

Now, don’t get me started on the conservative vs liberal attitudes on face masks and social distancing. Conservatives are wrong on these matters. I say this as a conservative myself. But, I also am a data driven scientist who believes data trumps partisanship.

How do you think SARS and MERS were stopped without a vaccine or anti-viral drugs? How do you think society stopped any epidemic such as small pox, influenza, bubonic plague, etc. throughout its history before modern medicine and effective vaccines? How do you think today we are handling Ebola for which there is no vaccine or drug? Non-pharmaceutical physical measures, like masks, gloves, sanitation, social distancing, etc. are effective ways to halt infectious diseases in lieu of vaccine and drug preventive measures.

Conservative resistance to these non-pharmaceutical physical protective measures also probably contributed to their higher death rates observed in the studies mentioned above.

Karma.


Part 3: Gain-Of-Function Research At The Wuhan Lab—Are The Chinese Hiding Something About The Lab?

This is a re-post of a blog, but with additional material. I added new information about the Chinese government response to the first SARS epidemic. You can find that section two-thirds of the way through the post under the headline in bold "The Chinese have done this before:"

“In a time of deceit telling the truth is a revolutionary act.”
― George Orwell

Yeah, I know, I said this would be a two-blog series about the research at the Wuhan Labs. But a comment a reader made on my second blog post made me think that I should make a third post to briefly address the apparent secrecy and lack of cooperation from the Chinese government regarding the research at the Wuhan Institute of Virology (WIV).

The Chinese have failed to cooperate to help us find the origin of the SARS-CoV-2 virus that caused COVID. They have denied access to WIV lab records or research personnel beyond what was posted on their coronavirus database as I mentioned in my prior blog post. This secrecy and lack of cooperation began in early January 2020 immediately after Chinese officials realized that they had a coronavirus superspreader event at the Wuhan wet market as I described almost three years ago in these pages.

This apparent secrecy on the part of the Chinese has led many people to jump to the conclusion that the Chinese are hiding something sinister—sinister like they secretly created SARS-CoV-2 and accidentally released it and don’t want the world to find out. But, as I have posted several times in these pages, most recently here, there is precious little evidence that supports the notion that the virus came out of a lab. On the other hand, there are several pieces of consistent, but still circumstantial evidence for its natural origin. However, that conclusion is not definitive and could change with new evidence. Hence, we cannot say with certainty that we know where the virus came from. But, remember, it took 14 years and a LOT of work to learn the origin of the virus that caused the first SARS outbreak; it took much longer to discover the source of HIV, and we still do not know where the Ebola virus came from. These things are very hard to learn and take time to figure out.

However, I don’t believe that the best explanation for the Chinese lack of cooperation is that they are hiding something sinister from the world because it seems very unlikely that the virus was man-made. After all, we have several examples of novel coronaviruses popping up in animals and humans, and all have had natural origins. And as I described in my prior post in this series, it is next to impossible that the virus was accidentally released from the Wuhan labs since they really did not work live viruses at all. I think one of two other explanations for Chinese intransigence is more plausible.

The least likely alternative explanation is that WIV lab safety protocols for handling dangerous pathogens were substandard and for the Chinese to allow access to lab records would reveal to the world how careless they were. Perhaps they were concerned about their world image and did not want to be embarrassed. It could deleteriously affect their R&D collaborations with other countries. But, we already had an idea that their safety protocols were not up to Western standards so this would not have been a terribly shocking revelation. That is why I don’t think this is the most likely explanation for the lack of cooperation and transparency.

More likely, however, I think the lack of cooperation probably reflects the general and significant deterioration in science and technology collaboration between China and the US that has been going on for five years. This was the topic of a long article in the Wall Street Journal just a few days ago. In fact, US-China science and tech cooperation has gotten so bad in recent years that US lawmakers are pushing to let a long-standing agreement between the two counties to cooperate broadly on science and technology lapse. It was originally signed in 1979 and renewed every five years since, but will expire this month if not renewed as several lawmakers are pushing.

A once highly productive cooperative science and technology agreement between the US and China seems to have begun falling apart in 2018, before COVID, according to the WSJ article. That is when the US DoJ launched its China Initiative to ferret out Chinese economic espionage. Over time the program increasingly focused on interactions between US universities and Chinese institutions. NIH also launched hundreds of investigations into ties between US science and China. While all these investigations largely failed to turn up criminal conduct, they understandably put a major damper on further cooperation between China and the US. They also led to an exodus of Chinese scientists from American labs. Given all that, it is not surprising that Chinese officials are not opening the doors and books of the Wuhan labs to us.

Thus, this lack of cooperation regarding access to the Wuhan labs is happening as cooperation is seriously deteriorating across the scientific spectrum, not just at the Wuhan labs.

The Chinese have done this before: The Communist Chinese government also has a long history of invoking repressive secrecy in order to prevent itself from looking bad. For example, they also clammed up during the first SARS outbreak back in November 2002 and it threw the country into its worst political crisis since the 1989 Tienanmen Square uprising. The government’s first response to the emerging epidemic was to hide the outbreak from its people, and even from its own public health officers. Despite the cloak of a news blackout, SARS spread throughout the country, reaching Beijing that March (viruses don’t read the newspapers!). But doctors do, and the cloak worked on them. Because of all the secrecy, they were caught by surprise by the sudden and prolific appearance of a new disease, and only learned what was going on via surreptitious text messaging.

In April, WHO officials finally were allowed into the country to inspect Beijing hospitals in order to assess what was going on, but sick patients were shuttled out of the hospitals in ambulances to different hospitals or checked into hotels to hide them from inspectors. Because Beijing tried to hide all this from the world, the epidemic, which might have been limited to that city, found its way into 32 countries around the world (viruses are very slippery). Fortunately, those other countries were not as furtive and were able to nip their infections in the bud with public health measures such as quarantines, contact tracings and isolation, and public closings.

SARS allowed the world to see and compare how repressive and self-sensitive China vs other world countries handle a deadly contagion. China was afraid of losing face and tried to hide its problem from public exposure. However, this backfired and showed China to be a repressive country that was willing to risk the safety of its people and the world in order to avoid accountability for the first SARS outbreak.

Therefore, it is not terribly surprising that the Chinese government again is using repressive means to avoid being put into a position of accountability for the second SARS outbreak.

The bottom line is that to think the Chinese are hiding something nefarious and conspiratorial at the WIV is pure speculation and is backed by no evidence at all. So far. There are alternative explanations for the lack of cooperation by the Chinese that are more feasible and reasonable to believe at this point. New information could change this assessment of course, but evidence that the Chinese are hiding something is lacking. Too bad they won't let us confirm that.

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Part 2: Gain-Of-Function Research At The Wuhan Lab—What Exactly Was The Wuhan Lab Doing With Coronaviruses?

“I’m just a soul whose intentions are good; Oh Lord, please don’t let me be misunderstood.”  —The Animals

In the first part of this two-part blog series, I described what gain-of-function research entails in order to set the stage for this blog post which describes the coronavirus research that went on in the Wuhan labs. So, was it dangerous and risky? Did it likely lead to the release of SARS-CoV-2 that caused COVID? Let me try to clarify all that now.

Coronavirus research at the Wuhan lab: After the first SARS epidemic in China in 2002, the Wuhan Institute of Virology (WIV) had established itself as a world class coronavirus research lab. It was from their diligent work that the world learned that the first SARS virus came from a horseshoe bat via other animals such as civets and raccoon dogs. That was the result of years of arduous research trudging through bat guano muck in hundreds of caves throughout China to collect samples from thousands of bats. They reported their finding 14 years after SARS appeared and shortly after another strange, lethal flu popped up in the Middle East that was soon attributed to yet another bat-borne coronavirus that came via camel intermediate hosts—MERS.

Before these two coronaviruses that jumped from animals to cause significant disease in humans, the viruses were only known to cause mild human maladies; basically, the common cold. Therefore, when it was learned that the deadly SARS and MERS diseases were caused by coronaviruses, it rattled the cages of health experts around the world. This was brand new!

Hence, even before COVID struck, bat-born coronaviruses were hot on the radars of infectious disease nerds and public health worrywarts. The WIV, as one of the world’s preeminent labs for identifying novel coronaviruses was given international funds to continue their efforts to identify and catalog bat coronaviruses. As they did years earlier when they identified the origin of the SARS virus in horseshoe bats, WIV scientists traveled to far-flung Chinese caves to collect bat guano and biological samples (blood, saliva, fecal) from captured bats. The samples were brought back to the lab in Wuhan for analysis.

Since it is exceedingly difficult and potentially very dangerous to grow wild viruses from such samples (failure is the norm even when many viruses are present in the samples) the lab resorted to their previous tried and true methods of searching the samples for viral genome sequences. They found a LOT of new ones!

Their first and primary order of business in this research was the very mundane task to sequence and catalog all the different coronaviruses they found. They then colligated these genomes into trees of different virus families and posted all the data in a vast database for world scientists to use. They were coronavirus genealogists.

The database is an enormously useful research tool for scientists around the world studying the origins and evolution of coronaviruses in animals and humans. (Coronaviruses also cause significant animal disease, so they also are of great agricultural interest around the world.)

The Wuhan lab also was charged with predicting which of the new virus sequences they found might pose future health threats to humans.

This is where all the controversy begins.

Remember that the Wuhan scientists actually did not have these viruses on hand, just their genome sequences. So, without the actual virus, how could they evaluate the ability of new coronaviruses to infect humans? To do this WIV scientist, Zhengli Shi, used a genetic engineering technique first published in 2015 by Univ. of North Carolina Scientist Ralph Baric to study coronaviruses from their genome sequences (she was a collaborator on Baric’s 2015 paper, so was quite familiar with the approach). It was a technique that also was in use at the time by several labs around the world. It is notable that NIH funded this coronavirus research conducted by Baric at UNC well before COVID appeared and didn’t consider it to be GoF research then.

Using Baric’s genetic engineering technique, Shi’s lab at the WIV used as a tool, a benign coronavirus that they could grow in the lab that was only distantly related to the first SARS virus, but was not known to cause human disease. Its genome sequence was not at all related to SARS-CoV-2 that caused COVID, and which had not yet appeared.

Shi’s lab removed the spike protein gene sequence from the genome of this benign lab virus tool and methodically replaced it with spike protein sequences from each new virus they sequenced. They then grew the lab virus tool carrying the new spike protein and tested its ability to infect human cells in tissue culture.

It is the spike protein that determines whether a coronavirus can infect human cells. Therefore, if the chimeric lab virus carrying the new spike gene infected human cells, it would indicate that the virus the spike protein sequence came from was a likely human pathogen and that virus sequence was then listed on the database as a potential human risk. However, if the chimeric test virus failed to infect the human tissue culture cells, that meant that the spike protein from the new virus genome would not support infection of human cells and the new virus sequence was not categorized as a concern for human infection.

This is how newly identified coronavirus sequences were categorized as potential human health threats without ever having to grow or isolate each virus itself.

In other words, this test simply expressed the spike protein of each novel coronavirus on the backbone of the safe lab virus genome in order to see if it could infect human cells. This completely negated the need to grow and handle the potentially much more dangerous wild-type virus.

It is important to notice that this strategy eliminated all risk of a lab leak of any dangerous virus since it was not necessary to grow or handle potentially dangerous wild-type viruses using this technique.

Is this gain-of-function-research? Strictly speaking, no. Remember, this sort of coronavirus engineering research had been done years earlier in Baric’s UNC lab, and was being done in other labs around the world, and it was never regarded as GoF research then by NIH.

NIH considers GoF research on pathogens to be research that either: 1) increases the pathogenicity of a microbe (that is, makes its disease worse), 2) improves its transmissibility or its ability to infect hosts, or 3) alters the host range of a pathogen. Therefore, in the WIV experiments to assess the ability of novel virus genome sequences to infect human cells, the chimeric test viruses that simply expressed new spike proteins on a laboratory virus backbone either retained the ability of the original lab virus to infect human cells, or they lost the ability to infect human cells.

Therefore, the chimeric viruses gained no new function that was tested. They either retained or lost the ability to infect human cells. The experiments were not at all designed to give the test virus any new functions. Furthermore, these experiments could not have led to the development of SARS-CoV-2 that caused the COVID pandemic, even by accident, since the laboratory test virus used to create the chimeric viruses in the experiments was not at all related to the SARS-CoV-2 virus.

There is a devil in the details: But. Notice that one of the the NIH definitions of GoF research is research that alters a pathogen’s host range. For example, take a flu virus that only passes between birds; avian flu. If you make changes in its genome so that the birds can also pass it to humans that mutation alters its host range and is a GoF change.

In the WIV lab, viruses with new spike protein gene sequences were only tested for their ability to infect human cells in a petri dish. The ability of these chimeric viruses with new spike proteins to also infect other animals was not tested. Theoretically, the chimeric test viruses could feasibly also infect, say a water buffalo, or a wart hog, or some other animal that the original lab virus might not have been able to. That would be a technical gain-of-function. But, that begs the question; in such an experiment, how would you know whether or not the host range of the chimeric virus had changed until you possibly had tested its ability to infect every known animal? A logistical impossibility.

Therefore, based on this theoretical point, it cannot be definitely stated that the experiments were not GoF experiments. In fact, chances are pretty good that some of the novel spike protein sequences attached to the lab test virus in fact altered its host range and, thus, the experiments would technically be GoF research.

Bottom line: Technically speaking, therefore, these experiments carried out at the WIV probably could be called GoF experiments. By a lawyer. Not by a scientist. That picks the proverbial nit and splits a very fine frog hair, to mix metaphors. The same research had been done ten years earlier in Ralph Baric’s UNC lab and was not considered GoF then. What is important is that the research at the UNC or the WIV never set out to create viruses with enhanced virulence, transmissibility, or altered host range. That was never the intent. The aim of the WIV research was solely to predict the human risk posed by novel coronaviruses without actually having to directly work with the potentially dangerous pathogens. Actually working with the dangerous viruses would have posed a very real risk.

Bottom, bottom line: The research conducted at the WIV was the most safe and responsible way to identify new coronaviruses that could potentially pose future human health risks. It is to the detriment of human health that this research has come under heavy criticism and that such future research has been hampered by criticism from people who fail to understand what the research is about and have, therefore, demonized it and want to prevent it.

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While SARS-CoV-2 And Our Immune Systems Do A Dance, We Get Re-Infected

Note: Artificial intelligence wrote nary a word of the following article, which was fully composed by the natural intelligence of a certain human.

Your sometimes humble blogger remembers how immunology science first beguiled him. It was during senior year in high school in the Virginia suburbs of Washington, DC. More specifically it was during a lunch break while working at a People’s Drug Store that had a lunch counter. Your then nascent blogger grabbed the recent issue of Scientific American from the magazine rack and opened it to an article that was way above his green scientific understanding but, he, nevertheless, gleaned from the article that the immune system could make antibodies to just about any molecule in the universe, even ones newly created in a lab that the universe had never seen. Amazing!

Your immune system would also make antibodies against the cells and tissues of your best friend and everyone else in the world, and vice versa, but you and your best friend, et al., would not make antibodies against the same cells and molecules in your own bodies! What?

“Holy cow!” I thought. How in the world can the immune system do all that? How can it respond to something the world had never seen and secern friend from foe? At that moment, at that lunch counter over a burger, Coke and an article I barely understood, an immunologist was made. And I did indeed go on to earn a PhD in immunology and I indeed have studied how the immune system recognizes viruses and have done vaccine research. What a pivotal lunch break that was for me.

The question about antibody discrimination clearly fascinated me. That mystery has been solved and a few Nobel prizes awarded for its elegant solution, but related spin-off questions about how antibodies protect us keep coming up in different ways. It did so most recently during the COVID pandemic. Why weren’t the antibodies we generated via vaccination or via natural infection more protective against subsequent infection? In a twist in the plot of biology, it turns out that we have learned that the answers to these questions center around a complicated dance performed between both the virus and immune biological systems.

Biology is so doggone interesting!!

COVID Vaccine generated immunity: The several vaccines we now have against the SARS-CoV-2 virus are effective and provide examples of how vaccines are very good at getting the immune system to respond to what it detects as foreign invaders. But the vaccines are just designed to tell our immune systems to make antibodies against just a very small fragment of the spike protein. In contrast, the virus is constructed of several large proteins each of which has many different regions that the immune system can separately recognize as foreign. In other words, if the virus is like a brick building, your system theoretically can make a different antibody that specifically recognizes each brick of the building. So, the vaccine is like exposing the immune system to about 2-3 bricks of the whole building and trusting the resulting immune response against those few bricks to bring the whole building down.

The immune system was very good in generating antibodies to a small portion of the virus, yet many vaccinated people still were infected and caught COVID. Does that mean, as many vax naysayers claim that the vaccines were ineffective? Not at all, as I have discussed here before. While the CoV-2 vaccines did a good job at protecting against serious disease and death they were not very good at preventing the spread of the virus. These vaccines effectively generated a systemic immune response, meaning that you had anti-viral antibodies circulating in your blood, which did do a very good job preventing serious disease once the virus got inside you. But, it still got inside. You still got infected and got mildly sick.

We now know that the virus enters via mucous membranes in your nose, sinuses, mouth, throat and eyes. It has to first cross mucous membranes in order to infect you and that is where it needs to be stopped in order to actually prevent infection and further spread to others. The problem is that mucosal immunity is caused by a different type of antibody than what circulates in the blood and by what is generated by a typical vaccine that is given by an injection in the arm. To generate mucosal immunity, you need a vaccine that you spray in your mouth or nose, which then should generate the type of antibodies that provide mucosal protection and better protect you from infection via that route and better prevent the virus from spreading through a population.

At the beginning of the pandemic, we were faced with a brand new pathogen for which we knew nothing about how it behaved or how it infected and spread between people. At that point, we reasonably chose to quickly make the most common type of vaccine--a shot. While it didn’t fully protect against getting infected, it nevertheless was very effective at protecting against serious disease. So, it did a good job. Current efforts are underway to develop a mucosal vaccine. But, we must also deal with other complications we have learned about the dance between the virus and the immune system to make sure that vaccine will be maximally effective at preventing infection. Read on.

“Natural” COVID immunity: As it became clear that vaccinated people were still getting infected, the vaccine dissenters and dissemblers proclaimed loudly, and still do, that the vaxes failed miserably. They ignored the survival data and only focused on the infection data. They then began touting “natural immunity,” which is the immunity one usually gains after being naturally infected. But, that can be uncertain given the fact that the route of infection and the dose of virus can vary wildly and confer different levels of protection, as I reported earlier. Plus, with natural infection, one runs the risk of serious disease and death from the disease.

Then, to the chagrin of the “natural immunity” enthusiasts it turned out that they also were getting re-infected! And this re-infection occurs despite the fact that natural immunity occurs after infection across the mucous membranes that should, as discussed above, generate an immune response that would stop an infection! This is the dance.

Therefore, we now know that neither vaccine immunity, nor infection immunity fully protects against future infection with the CoV-2 virus (there is partial protection, but I won’t go into that here).

As we learned as recently as last April, from a Harvard study published in the journal Science, despite the fact that a natural infection presents the immune system with the full viral “building and all its bricks” potentially recognizable by antibodies, it turns out that only a few of the “bricks” are in fact actively “seen” at any time by the immune system.

This immuno-dominance of a small part of a larger pathogen that has thousands of sites or bricks the immune system can recognize is not unusual. It is like a large building consisting of thousands of bricks, but having a very attractive window that draws your attention. While you know an entire building is there, your attention is mostly drawn to the window. So can the focus of the immune system be preferentially drawn to a small part of a larger edifice. The immune system is perfectly capable of seeing the rest of the “building,” but it prefers to direct its attention to a small part of it. However, if you take away the part it prefers to focus on, the immune system will easily recognize something else. This immuno-dominance in what the immune system “sees” has several causes that are way too complicated to go into here without writing a textbook (an interested reader might try Paul’s Fundamental Immunology. My rather old edition of that book runs about 1500 pages!). Suffice it to just know that this sort of immuno-dominance often happens where only a small part of a large pathogen is preferentially recognized by the immune system.

Thus, the immunity developed after a natural infection is mostly only directed at a small portion of the virus, much like the antibody response after vaccination with just a small part of the virus. The natural immune response, like the vaccine immune response, is robust and effective, yet both are only directed against a very small portion of a big pathogen, and both are very leaky in that one can still get infected again! What gives?

Mutation gives.

How the virus escapes immunity: The SARS-CoV-2 virus is highly mutable unlike the other viruses like polio and small pox we vaccinate against and maintain long term immunity against. Thus, the virus quickly mutated, or changed, the “bricks” against which the vaccines were made rendering the immune response less and less effective over time as new viral iterations appeared. That is why the many boosters we got were necessary to keep vaccination immunity up with viral changes.

And that also is how someone who became immune after natural infection also became re-infected. The virus did a two-step and mutated the small region recognized by the immune system. It was pretty easy for the virus to do since it only had to change a couple of “bricks” in its facade that the antibodies were mostly attacking. That means that upon re-infection with a slightly mutated virus, the immune systems have to be re-educated to recognize a new intruder, and that takes time, which allows a new infection to settle in. Thus, in this dance, the gentleman virus leads and the dame immune system follows.

New vaccines continue to be developed that scientists hope will solve these problems unique to SARS-CoV-2. Most of the new vaccines are being built on the mRNA platform, but using novel approaches to 1) develop vaccines that can be given as a nasal spray in order to generate the mucosal immunity that hopefully would be more effective at actually preventing COVID. If this works, it might even be possible to hinder COVID spread. 2) But in order to block CoV-2 spread on a population level, we need to find other regions of the virus that are not so highly mutable. These would conceivably be regions of COVID proteins critical for viral function that tolerate little change in structure because that change would destroy the proteins' critical function and essentially kill the virus. Alternatively, new vaccines could incorporate multiple "bricksl" from different regions of the edifice assuming that it would be nigh impossible for all those sites to simultaneously mutate. If such regions are accessible to the immune system, then the resulting immunity would be expected to be impervious to viral mutation, thus ending the dance on a sour note.

It is even possible that such a vaccine could protect against a wide range of coronaviruses, thereby preventing future health problems arising from new coronaviruses. Remember SARS that also popped up in China a couple of decades ago? That virus has some genome similarity to the virus that caused the COVID pandemic, and both are distantly related to the virus that caused MERS that arose in the Middle East. If a pan-coronavirus vaccine can be developed, it could feasibly prevent many future epidemics and pandemics.

We shall see.

This is all part of a new biology that I earlier dubbed BioX. Biology is so doggone interesting!!

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The Virus Came From Wuhan Lab DOE Now Says…..Sort Of

 Where’s the beef?” Clara Peller in a 1984 Wendy’s commercial

So, the world has been abuzz since the Department of Energy recently reported that it decided, albeit with low confidence, that the SARS-CoV-2 virus might have leaked by accident from the virology lab in Wuhan. Across cable television and the internet, including sources such as Fox, Breitbart, Joe Rogan, gossip lines, et al., are full of “I knew it all along,” and “I told you so’s.” Never have so many virology experts suddenly been spawned on Facebook. And most of them could not tell you whether a coronavirus is an RNA or DNA virus, let alone the difference between RNA and DNA.

But let’s slow down a bit. Have you even wondered why the Department of Energy is releasing an assessment about a virus? And did you wonder what data they based their assessment on? I did and I explain it here. What I learned tells a much more complete, and less compelling story than what most of the priests of the press, Junior virologists, and other rumor mongers have reported. What has been reported has been woefully inadequate and vastly misleading.

The DOE report was based on intelligence data that remains classified, and is not a science report. Apparently intel spooks weigh science information much differently than scientists do, and often put less credibility in published science because the information usually does not come from “trusted” sources that an spook has history with (their version of "peer review" I guess). The US intelligence community is distributed between 18 agencies, including Energy, State, Treasury, and others including, of course, the CIA, FBI, and DOD. Eight of these entities have been involved in reviewing the COVID-origins issue.

In 2121, the Energy Department, which oversees 17 national laboratories, several of which study SARS-CoV-2 and its origins, reported it was undecided on how the virus emerged. What caused DOE to recently change their assessment is not known. They are not releasing the classified data. Therefore, their information appears not to be scientific data, which is usually published. Four other unnamed agencies, along with a national intelligence panel, still judge that the virus was likely the result of a natural transmission from an animal to humans, and two other agencies are undecided. Only the FBI agrees with DOE in thinking that the virus leaked from the lab. Notably, the CIA also remains undecided. In other words, the DOE’s opinion is a minority opinion of low confidence in the intel community. It is hardly worth all the breathless excitement it elicited from Tucker Carlson and other bloviators who now dishonestly insinuate that it has now been proven the virus came from the lab. That is far from decided.  

The intel community’s definition of low confidence intelligence is “that the information’s credibility and/or plausibility is uncertain, that the information is too fragmented or poorly corroborated to make solid analytical inferences, or that reliability of the sources is questionable.”  Someone should send that to Tucker.

The origin of the virus has been actively investigated over the last couple of years and your sometimes humble correspondent has reported previously on those investigations in these pages (it is worth reading for background). These blog posts have favored the natural origin of the virus, because that is what the preponderance of data have suggested. There have been no published data supporting a lab leak hypothesis. None. Also, recent science reports in top-flight science journals continue to conclude that the virus had a natural origin. A paper just published in 2023 in Cell reported that SARS-CoV-2 is the ninth known coronavirus to have jumped from an animal into humans. Two earlier reports in Science, and also summarized in these pages last March, agreed that the virus originated in the Wuhan wet market not just once, but twice. These studies included genetic evidence and epidemiological tracing showing that the early cases of COVID all centered around the Wuhan wet market and not around the lab eight miles away.

Furthermore, back in 2020, I also wrote a summary of how the earliest events of the pandemic unfolded. Here is a synopsis of the first few days: On December 31, 2019, Chinese officials informed the WHO about a cluster of 41 patients with a mysterious pneumonia in the city of Wuhan associated with a new coronavirus. Then, in the middle of that night a Chinese CDC team from Beijing arrived and collected 585 “environment” samples from a garbage truck, drains and sewers in the wet market. Thirty-three of the samples tested positive for the new coronavirus. Fourteen of the positive samples were from the area of the market where wildlife was traded. At the same time, Wuhan officials quietly began disinfecting the market, and it was closed.

It is interesting that the immediate focus was on the market and not the lab.

Keep in mind that we have very many examples of viruses, including several other coronaviruses similar to SARS-CoV-2, spontaneously passing from animals to cause disease in humans. This includes the first example of SARS-CoV-1 that came from a food market in China in 2002, and then MERS, which passed from a camel to humans. It was natural for medical scientists to first think that SARS-CoV-2 arose similarly. So far, the evidence is not convincing that it did not. The fact that we have not yet convincingly identified an animal source for the virus is not surprising. It took 30 years to establish the source of the HIV virus, and we still do not know the source of the Ebola virus.

So far, despite the very weak statement from the DOE, the preponderance of data still favors a natural origin of the virus, not a lab origin. But, that still is far from definitive. That “preponderance” of evidence, can change in a hurry with new data. Therefore, it remains worth further investigation. But until the Chinese government allows outside scientists to review lab data books and interview scientists from the Wuhan labs, the investigation will proceed with one hand tied behind its back. It remains remotely possible that an animal carrying the ancestral coronavirus will be caught confirming that it did come from an animal. Yet, even if we did find an animal source for the virus, it may not tell us about the path it took to get into humans. We might never know that to the delight of the conspiracy nuts and fabulists out there who have never weaned off the teat of fantasy.

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The Latest On Long COVID (So Far)

“After all, tomorrow is another day.” Gone With the Wind

In these pages, your humble bloggeur (me) has followed the evolution of what we know about the odd condition known as long COVID. You can find seven previous blog posts on the topic here. Because we were just learning what long COVID was all about, many of those posts ended with the disclaimer, “we will see.”

Well, we have seen and continue to see. Here is what we now know after over 2 years of experience with this complication. But, tomorrow is indeed another day.

The risk of death from COVID is now about the same as the risk of death from flu, which can vary from year to year, thanks to vaccines, natural exposure, and developing therapies. One study in Lancet found that people with COVID had a 3-fold greater chance than uninfected people of dying each year. But, as I explained before, mortality is only part of the story. There also is morbidity. Long COVID is "the rest of the story" as Paul Harvey used to drone. Some 54 studies on long COVID, involving 1.2 million people, have been reviewed and it was reported that about 6% of people with symptomatic COVID infection wind up with long COVID. This agreed with a massive Swedish study of COVID patients done between 2020-21. According to the new Census Bureau Household Pulse Survey, some 16 million working age Americans now suffer from long COVID, which creates a huge burden on our health system. Up to 4 million of these are unable to work, which is a major drain on a labor market already short of workers. The annual cost in lost wages is up to $230 billion! The total economic cost of long COVID in the US so far has been an astounding $3.7 trillion!!

And as the virus evolves, reinfections with new CoV-2 variants are becoming more and more common. Unfortunately, a large VA study on reinfections suggests that you want to avoid them. A second or third infection is associated with worse disease and increased chance for long COVID. And a large German study including nearly 12,000 children with COVID concluded that long COVID “cannot be dismissed among children and adolescents.”

A sobering study of medical records from millions of US military veterans in the VA medical system published in Nature Medicine found that 7% more COVID patients (compared to uninfected veterans) had lasting brain or neurological disorders. This extrapolates into about 6.6 million Americans with long-term brain impairments linked to COVID. Memory impairment was the most common brain malady. But those with a history of COVID also were at greater risk of ischemic stroke, seizures, anxiety and depression, and movement disorders.

The good news is that vaccines reduce the risk of long COVID—how much is still debatable at this point. The anti-COVID medicine, Paxlovid, reduces long COVID risk by 25% according to one study. And the Omicron CoV-2 variant shows a reduced risk of long COVID compared to the more pathogenic Delta variant.

Assessing the risk: How much should the risk of catching long COVID affect one’s daily decisions? Should I go to the concert? Graduation? Grocery store? Wear a mask everywhere? That is hard to say definitively. Perhaps it would help to compare COVID risk to other risks we face every day.

  • The annual risk of getting in a car accident is about 1 in 30 per year. Of those, ~43% involved injuries and ~10% of those cause permanent impairment. This makes the annual risk of permanent injury from an auto accident about 1 in 700.
  • The annual risk of serious injury in a house fire is ~1 in 20,000.
  • The risk of needing reconstructive surgery after a dog bite is 1 in 400 annually.
  • The risk of catching the Omicron variant (symptomatic or asymptomatic disease) is ~1 in 2 annually (it was 1 in 4 before Omicron). Say 3% of those get long COVID, and ~18% of them are so sick they are unable to work for an extended period. This makes the annual risk of severe long COVID about 1 in 370.

So, the risk of debilitating long COVID is about twice the risk of serious injury from driving and about the same as getting a serious dog bite. The risk of severe long COVID is much higher than being injured in a house fire. Of course, all of these risks are affected by our personal behaviors. We don’t drive drunk and wear seat belts (hopefully). We replace the batteries in home smoke detectors every year and avoid growling curs. And if we are smart, we vaccinate and stay home when we are not feeling well.

At least those are things that responsible people do to reduce the risks of life.