Coronavirus news & views

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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Vaccine Disinformation Moves To Congress

 “War is peace.
Freedom is slavery.
Ignorance is strength.”
―George Orwell, in 1984

“Anecdote is science.”

That silly notion can now be added to the Orwellian Newspeak Catechism thanks to those who prefer confirmation bias over empirical data to determine their “alternative facts.” This seems to include several  members of Congress.

The war on objective science recently spilled over to Congress where a group of anti-vaccine Congressmen and women and one Senator held an impromptu meeting to confirm their disinformation about so-called injuries caused by the COVID mRNA vaccines (note: the technology just won the Nobel Prize for Medicine). This was not a meeting called by a regular committee but an ad hoc gathering of some committed anti-vaccine rogues. It was held in a tiny back room in the Capitol and was poorly attended, poorly staffed, poorly equipped, and, thankfully, poorly publicized. It was described as a meeting of the “shadow Congress;” accurately named as it dabbled in the penumbra of truth.

Leading this November 13 meeting was Congresswoman Marjorie Taylor Greene (R, Georgia). Greene, no stranger to fantasy, has previously claimed that Jewish space lasers caused recent wildfires in California, that the shootings in Parkland, Sandy Hook and Las Vegas were staged, and that 9/11 was an inside job. Because of these and other extremist reflections, the House sensibly stripped Greene of several committee assignments.

Others on the “committee” included Congressmen Clay Higgins (R, Louisiana), Thomas Massie (R, Kentucky), Warren Davidson (R, Ohio), and Andy Biggs (R, Arizona). Also attending was Senator Ron Johnson (R) from my own State of Wisconsin who has been a vaccine dissembler for a while, claiming, for instance, that the vaccines have killed many people. I recently contacted the Senator’s office and asked why he believed that. They quickly responded and sent me to a web site that was very professional looking and had very many graphs and tables claiming to show that the vaccines caused hundreds of thousands of deaths. The problem is that the data they used to put said graphs and tables together were bogus. The statistics were fraudulent (for example to test the site, an MD submitted a claim saying that the vax turned him into the Incredible Hulk. His claim was accepted!). Anti-vaccine crusaders with radio and blog platforms have urged their audiences to post false information on the site, and the website itself had been debunked numerous times by the investigative press and in science journals for incorrectly reporting the data. I pointed this out to Sen. Johnson’s office and never heard back, in contrast to their earlier quick response. Go figure.

Back to the Shadow Congress Committee meeting: Three people testified: A lawyer, an obstetrician-gynecologist, and a scientist. A summary of the testimony of each, with my comments follows.  

The lawyer. Forty-six-year-old Thomas Renz, went first. He passed the Ohio bar exam in 2019 after five tries and since has made a name for himself, along with the MyPillow guy, Mike Lindell and others, as a COVID conspiracy buff. Renz made three unsupported claims enumerated below: 

1. First, Renz declared without any evidence, that it is vaccinated people who are dying. However, a study published in the Journal of the American Medical Association showed that in 2021, unvaccinated adults were 12 times more likely to be hospitalized and in 2022, that they were 6 times more likely to die after infection. Science shows that COVID vaccines have been estimated to have saved the lives of more than 3 million Americans. Renz’s says otherwise. Who are you going to believe, science or the lawyer, Renz?
2. The lawyer also claimed, again without proof (a lawyer without evidence?), that “COVID is not as bad as SARS or MERS but about as dangerous as a bad flu season.” Well. The first human coronavirus outbreak, SARS-1, was identified in Asia in February 2003. It infected a tad more than 8,000 people, killing ~800. By July 2003, the outbreak was contained without a vaccine. The second coronavirus outbreak, called MERS (Middle East Respiratory Syndrome), appeared in June 2012, in Saudi Arabia. That virus infected >2,500 people, killed about 900 and also was contained in a short while without a vaccine. Compare those numbers to SARS-CoV-2, which so far has killed almost 2 million people in the United States and 7 million people in the world. And four years later it continues; it is not contained even though we have several vaccines. Except for the 1918 flu pandemic, which killed more than 50 million people worldwide (that was before flu vaccines) COVID is worse than any other flu in history and much worse than SARS or MERS. Renz’s lawyerly opinion is bunk. Why is he even testifying on a medical matter?
3. Renz saved the best for last. With the help of an “unnamed whistleblower,” Renz claimed, without proof, of course, that "something suspicious" happened in November 2014 at Fort Riley, Kansas, when the Department of Defense (DOD) and the CIA, in collaboration with the Wuhan Institute of Virology, created SARS-CoV-2 virus. Not in the Wuhan lab mind you, but in Kansas in 2014! To support his claim, Renz offered nothing! It was just his opinion. Renz also asserted that Tony Fauci, the CDC, FDA, and the DOD played a part in a massive cover-up of all this (so how in the world does HE know?). He unbelievably stated that Hunter Biden was also involved (why not?). Funny how the FBI hasn’t picked up on any of that. Renz knows because he says he does. Trust him, he’s a lawyer without evidence. But that is good enough for the Shadow Congress.
   

The Ob/Gyn. Next up was Kimberly Biss, MD, a well credentialed obstetrician and gynecologist practicing in Tampa Bay and St. Petersburg, Florida, which makes her testimony all-the-more-difficult to understand.

She claimed that after receiving COVID vaccines, an unspecified number of women in her practice suffered unsubstantiated menstrual cycle irregularities including severe, persistent bleeding. However, the only way to reliably determine whether COVID vaccines caused these  changes in menstruation is to compare the symptoms in women who got the vaccine to women who did not. She didn’t do this. Anecdotal observations like these offered by Biss usually don’t include both groups, which is why medical science considers anecdotes to be unreliable and instead rely on controlled clinical trials to base medical science opinions.

Furthermore, real scientific comparisons between vaccinated and unvaccinated women have been done but these were not entered into evidence at the Shadow Congress Hearing. A study of more than 1,100 women performed by the Boston School of Public Health found that there was no association between COVID-19 vaccination and cycle irregularity, bleed length, heaviness of bleed, or menstrual pain. So, which is more credible, Biss’s personal uncontrolled anecdote on an unknown number of patients whose medical history is unknown vs a controlled scientific study on over 1000 patients with carefully documented medical histories and compared to a comparable cohort of unvaccinated menstruating women?  

Biss further testified that in her practice miscarriage rates went up in vaccinated women, again without indicating the number of patients she saw and without providing any medical documentation. She again failed to note the miscarriage rates in unvaccinated women (why does she always leave out the data from unvaxed women?). Another scientific study of 40,000 pregnant women showed that vaccination was not at all associated with an increased risk of premature births. And other controlled studies have shown that COVID vaccination during pregnancy does not increase the risk of birth defects. Again, what would you believe, Biss’s anecdotes or several well controlled peer-reviewed and published science studies?

Biss continued her misleading anecdotal testimony by claiming that it was unsafe for vaccinated women to breastfeed because she "heard" it caused myocarditis in babies in Scotland. She failed to provide any substantiation for her wild claim that no one else seems to have heard. Not only has breastfeeding proven to be safe in women who have received COVID vaccines, newborn infants benefit from vaccine-induced antibodies in breast milk. This provides newborns with their initial protection against COVID as they develop their own immune system. That is a normal part of the maternal-fetal immune system that newborns immensely benefit from. That is basic immunology.  

Finally, and most outrageous was Biss’s stance on vaccinating children. She advised against vaccinating kids falsely claiming that only “three in one million children will die from COVID.” One wonders where she gets her facts like this and like those about myocarditis in breast fed babies in Scotland. As of January 2023, COVID was the leading cause of infectious disease deaths in children. Contrary to Biss’s claims, the COVID death rate for children less than one year of age was 43 per million. Hundreds of young children have died from COVID and many, many more have been hospitalized long term with the very serious condition called multisystem inflammatory syndrome, or MIS, which I have written about in these pages. COVID is much more serious than the flu for kids. None of those deaths or serious illnesses in kids are acceptable. Her claims to the contrary are simply irresponsible for a physician to make.

Finally, the scientist. Perhaps the silliest testimony in front of MTG’s “shadow” committee came from a scientist and physician named Robert Malone who recently has gone around claiming he “invented” the mRNA vaccine. He did not. In the late 1980s and early 90s, labs around the world were fixated with the idea of trying to express genes in cells via transferring DNA into cell cultures. The technique was called “transfection.” It promised to be a powerful tool for studying the function of genes in cells, but proved enormously difficult as I wrote about earlier. My own lab considered trying it, but discarded the idea in favor of another approach, viral-based gene transfer, which we often used to study gene function, and which some might call routine gain-of-function research as I also described earlier in these pages.

Meanwhile, Malone was a small part of the “transfection” bandwagon and in the late 80s published two papers showing it was possible to transfect fragile mRNA protected by a lipid micro-bubble into cells (most labs transfected DNA, which was easier to work with than mRNA). Undoubtedly, his research represented a stepping stone on the path to developing the vaccines, but he had no role in vaccine development. He was one of very many scientists who contributed incremental advances that ultimately made the vaccines possible. He is now way overselling his role. The technology that produced the mRNA COVID vaccines recently won a Nobel Prize and Malone was never mentioned in the invention. He is only a giant in his own mind.

More to the point, Malone testified that the vaccines are contaminated with fragments of DNA and dangerous. He argued, without evidence and contrary to all other science, that these DNA fragments alter cellular DNA of vaccine recipients, causing cancers, autoimmune diseases, and a variety of other disorders. For pregnant women, Malone further opined, again without a shred of proof and contrary to common science, that these DNA fragments could cross the placenta and cause birth defects. Furthermore, according to Malone, the FDA, the CIA, and other government agencies know about this DNA contamination but are covering it up (is Hunter involved in this too??). Again, he offered no evidence at all for this allegation. But, maybe we can excuse him, because there is no evidence to offer.

The idea that the vaccines are contaminated with DNA detritus is old news. All vaccines contain DNA of different sorts, which has never caused any harm as long as vaccines have been given. In fact it is biologically impossible that miniscule amounts of DNA detritus could mess up our cellular DNA. It is irresponsible, and scientifically ignorant of Malone to simply throw this out without elaborating. He didn’t elaborate because to do so would have ruined his “Frankenscience” innuendo that seemed to duly impress the scientifically naïve Shadow Congressional audience he spoke to.

The mRNA used in the vaccine is produced from a DNA strand. The DNA strand is then digested with an enzyme called DNase which chews up all DNA strands, leaving only the DNA building blocks, or remnants of it behind; DNA detritus. It is like taking a large building and demolishing it into its bricks. The large mRNA molecules are then easily biochemically separated from most of the DNA detritus. Even if there were miniscule traces of DNA detritus left over, it is biologically impossible for it to damage cellular DNA. It simply is recycled and reused by our cells. Our cells do that all the time.

But, maybe larger, intact DNA fragments could mess up our cellular DNA? We are exposed to large fragments of DNA all the time with no adverse effects. Consider the following two points: 1) we eat foreign DNA from plants and animals all the time and that DNA enters our blood stream in intact pieces much larger than the digested detritus we have been talking about. Yet, we are totally unaffected by this. 2) We also get vaccinated with whole DNA virus vaccines and have no concern that they affect our cellular DNA. Studies have shown that there is NO genotoxic effect of any of the vaccines.

Finally, consider the inherent conflict in Malone’s position. On the one hand he goes around promoting himself as the inventor of the vaccine technology. He even laments that he has not been given his due credit for the invention. Then he tries to discredit the same invention as something very dangerous and that should not be given to people because it causes enormous harm.

Which is it? Do we laud Malone as he would like for discovering a lifesaving vaccine, or pillory him for creating the dangerous vaccine he says it is? The man is as confused as his testimony.

This is what some of our Congress people spent their time doing last November. The Congressional Flake Caucus wasting their time and our money on a "hearing" without a single reputable testimony. At least it received the very little attention it deserved.

Last word. In an earlier post in these pages I asked the question if it was criminal to intentionally mislead people about lifesaving vaccines. That question is worth raising again, now.

‘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.

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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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.

Take Your Vaccine Skepticism To A Cemetery

“Still a man hears what he wants to hear and disregards the rest”

            --Paul Simon, in The Boxer

They say you won’t find an atheist in a foxhole. Well, perhaps you shouldn’t find a vaccine skeptic in a cemetery, either. Bear with me and I will explain.

I have been reading about how vaccine skepticism is growing beyond the COVID vaccine to include other common vaccines against flu, measles, chicken pox, polio, etc. Perhaps this all began with parental resistance to Gardasil, a vaccine against human papillomavirus, or HPV, introduced in 2006. HPV is a sexually transmitted virus that causes genital, anal, and oral cancers. It is the most common cause of cervical cancer. In order to confer maximal and lasting protection, it is recommended that children around 11 and 12 years old be vaccinated. Some parents have railed that this promotes promiscuity. They fret that the vax licenses licentiousness in children, akin to giving them condoms with illustrated instructions in their use. Balderdash!  

While that medical insurrection continues to smolder, along came COVID and the anti-COVID mRNA vaccines accompanied by the surprising resistance of many people against the shots. It is a resistance that seems to be growing and spreading to vaccines in general including those listed above that have long been commonly accepted.

This is concerning because it portends that in the near future, kids will begin coming down with diseases that we have pretty well controlled. In fact, in the last year or so, de novo cases of polio have appeared in the US in unvaccinated people. Before this incipient vaccine resistance, polio had been eradicated in North America, thanks to the vaccine.

It is safe to expect that vaccine resistance will persist, and probably increase as new vaccines are developed to treat cancer and better protect against flu. The mRNA vaccine technology is being used to develop new vaccines against the deadly skin cancer melanoma, and research is underway to also develop vaccines to prevent breast, liver, prostate, and other cancers. This use of modern vaccine technology to prevent cancer is a very novel and promising approach to dealing with malignancy. Anti-cancer vaccines are a potentially exciting new weapon in the armamentarium for the war on cancer. Too bad for those who would reject an effective cancer-preventing vaccine. At least they can fall back on the standard harsh radiation and chemo therapies.

mRNA vaccine technology also is being used to try to develop a universal vaccine against the flu. Flu is a highly malleable virus because there are many strains out that that can mix and shuffle their genetic material. This means that every year, it is a guessing game as to which combination of flu we will contend with—hence the changing flu numbers each year-- H1N3, H2N4, H3N1, etc. Since the Southern Hemisphere’s flu season precedes ours in the North, flu sleuths follow what goes on down there and track which strains make their way Northward, often via migrating birds, and try to predict what flu strains will be prevalent here each year. Then flu vaccines are made based on the best predictions. Usually, the annual flu vaccine is a mix of 2-3 of the flu strains that we are most likely thought to encounter. Some years we better predict which flu strains to vaccinate against than in other years, hence the efficacy of the vaccine can vary from year to year. Therefore, the advantage of a universal vaccine effective against all strains would be to remove this uncertainty and variability. That is the goal of using mRNA technology to take genetic material that is common to all flu strains and package it into lipid particles as pseudo-viral particles to trick the immune system to make an immune response to these parts of the viruses. If successful, this would protect against all flu strains and eliminate the need to guess which strains to vaccinate against. Theoretically.

The point is, vaccine science is moving forward and continues to offer great promise to prevent diseases that have proven very difficult to treat. The vaccine naysayers will miss the boat if they continue their misguided dissent. I suggest that they test their skepticism in a cemetery.

Go to an old cemetery and find the graves of people who died in the 1950s and earlier. See how many headstones belong to children.

Then go to the part of the cemetery where the grave stones are for people who died in the 60s and later and see how many graves are occupied by children.

The sharp drop in the number of childhood deaths after the 60s can largely be attributed to vaccines. Vaccines prevent serious disease and death in children who used to die from meningitis, pneumonia, dysentery, small pox, flu, and other diseases, but now do not. And to those who think that the vaccines are killing people, where are their headstones?

It is always better to prevent disease than to treat it. Vaccines prevent disease. Avoid vaccines if you wish. Darwin might approve.

The Next Pandemic Is Here

Who ya gonna call?  --“Ghostbusters”

We seem to have mostly weathered two-plus years of a pandemic like the world has not seen in our lifetimes. It raced across the globe killing and maiming people, and overwhelming health care capabilities. Sure, we have read the history about the black plague, small pox, and the Spanish flu pandemics, but vicarious experience through books and film is no substitute for first-hand experience. We now have that experience. It was sobering to see the novel SARS-CoV-2 virus ravage country after country while medical experts played a desperate game of catch-up to learn how to retard the spread of a brand new virus and how to treat the brand new COVID-19 disease it spawned. It was sobering seeing and hearing about people we know get very ill and sometimes die, and sobering reading the statistics of millions of deaths that occurred worldwide.

While most of us today have not seen such a pandemic wild-fire before, we have seen other, more smoldering pandemics that do not spread as fast. HIV is a good example. It too is a world-wide disease that, for many years was a death sentence for those who were infected. Now it is a well-managed chronic disease, thanks to medical science.

The world was not as frantic over HIV and AIDS as we were over CoV-2 and COVID. The reasons for this are probably two-fold: First, it was quickly recognized that AIDS was largely limited to homosexual men and IV drug users and, therefore, was not an eminent threat to most of us. It was not necessary to quarantine, mask up, and shut down businesses and schools in order to prevent catching the “gay disease.” Second, despite the world-wide spread of AIDS, it is not easy to catch. You must be in very intimate contact with an infected person to catch it—it is not caught by simply breathing the same air as an infected person like COVID is. Clearly, not all pandemics are created equal. Some smolder like AIDS, others fulminate like COVID. What will our next pandemic be like?

As the global population grows, as the climate changes, as humans push into spaces occupied by wild animals, and as we continue enjoying our ever increasing global connectedness, future pandemics become more likely. We are not guaranteed the luxury of facing just one a century, or even one at a time. As greatly encouraging, even exciting as it was to watch the post-molecular BioX science, as I have called it, roar into life to produce several effective and novel anti-CoV-2 vaccines in record time, there is no guarantee BioX can save us next time.

Well, the “next pandemic” already is upon us and BioX is struggling to deal with it. This pandemic is not as volatile as COVID or the Spanish flu. In fact, compared to COVID, it is a “slow mo’” pandemic, more like AIDS. But, it promises to be more difficult than COVID, even for BioX, to mitigate. It currently kills about 700,000 people annually around the world, but threatens to kill 10 million people a year by 2050 (in contrast, COVID killed ~6 million around the world in 2.5 years).

The problem

 In March 1942, Anne Miller of New Haven, Connecticut, was near death. A bacterial infection had made its way into her bloodstream, which was a death sentence at that time. Desperate to save her, doctors administered an experimental drug called penicillin, which Alexander Fleming accidentally discovered 14 years earlier. In just hours, she recovered, becoming the first person to ever be saved by an antibiotic. Rather than dying in her thirties, Mrs. Miller lived to be 90 years old and Fleming went on to win the Nobel Prize for his inadvertent discovery.

Today, decades later, germs like the one that infected Mrs. Miller, but easily eradicated with antibiotics, are increasingly becoming resistant to penicillin and the many other antibiotics that have since been developed. There is a very good chance that right now, you have such a “superbug” in or on your body—a resistant germ that, given the opportunity could enthusiastically sicken you leaving medical people at a loss on how to treat you. You would be at the mercy of the bug just as all patients with a microbial infection were before Mrs. Miller.

We are not talking about a new, exotic germ like CoV-2 suddenly appearing and ravishing the world. The antimicrobial resistance crisis stems from the simple fact that new antibiotic development cannot keep pace with the rate that common microbes become resistant to antibiotics. This very slowly growing pandemic we are now in involves run-of-the-mill pathogens, bacteria and fungi that have caused disease since humans first dragged their knuckles on the earth. These are bugs which we had well controlled with antibacterial and antifungal drugs, but there is a very definite trend toward these germs becoming resistant to ALL known antimicrobial medicines we have. Infection with multidrug resistant pathogens is the slow moving pandemic that already is among us but that is growing at a logarithmic rate.

Since multi-drug-resistant infections do not respond to our antibiotics, treatment increasingly involves surgically removing an infected organ. For example, in the case of drug-resistant Clostridioides difficile (aka, “C-diff”) colitis, an emergency colectomy is performed when patients no longer respond to antibiotic therapy. CDC data show C-diff infections occur in half a million patients each year, and at least 29,000 die within one month of initial diagnosis. Up to 30% of patients with severe C-diff colitis develop sepsis require emergency surgery, and still their mortality remains high.

As of 2019, about 18 drug resistant pathogens affected >3 million people in the US, causing 48,000 deaths. These bugs cause pneumonia, septic shock, various GI problems, STDs, urinary tract infections, typhoid fever, TB, and infection with the so-called “flesh eating bacteria.” Compared to COVID, this has received relatively little attention in the popular press, but has been a frequent topic in medical lectures and conferences for the last 20 or more years. These infectious disease lectures tend to scare the bejeebers out my colleagues and me. This smoldering pandemic is that serious.

And it is not just antibiotic-resistant bacteria we have to worry about. Certain fungi, especially of the Candida genus, cause various serious ailments in people. Recently, for the first time, the CDC reported five unrelated cases (two in DC and three in Texas) of people infected with fungi that showed “de novo” resistance to all drugs. Usually, drug resistant fungi only appear after infected patients have been treated with antifungals. But, the patients in these five de novo cases had no prior exposure to antifungal drugs. The fungi were already drug-resistant when they infected the patients; they were picked up from the environment already resistant to our medicines.

Antibiotic resistance is now one of the biggest threats to global health. It occurs naturally in naturally occurring pathogens, but is accelerated by overuse of antibiotics in humans and animals, especially farm animals. What happens is that upon treatment with an antibiotic, a single infectious bug out of a population of millions or billions fortuitously mutates and becomes resistant to the antibiotic. The antibiotic then kills off all the non-resistant population, including beneficial bacteria, opening the door for the drug-resistant pathogen to take over. This resistance can occur via many different mechanisms. The bacteria or fungal cell can stop taking up the drug, it can spit out the drug if it is taken up, it can neutralize the drug once it takes it up, or it can change its internal machinery so that it no longer responds to the drug. This problem can be further exacerbated since bacteria and fungi can pass along their mutations by sharing mobile genetic material with their progeny and even with other bugs in their immediate environment that have never been exposed to the antibiotic. They can even pass along this DNA to microbes of different species. Bacteria can also pick up DNA remnants left over from dead germs. Thus, DNA that confers resistance to anti-microbial drugs can spread to the environment even in treated human and animal waste contaminating lakes and streams and ground water.

Currently, the major problem with drug resistant infections occurs in in-patient clinical settings—perhaps you have seen the heightened infection control efforts (gowns, gloves, masks, and isolation) in hospitals designed to prevent the spread of untreatable pathogens. People receiving health care, especially those with weakened immune systems, are at higher risk for getting an infection. Routine procedures, such as bladder catheterization or kidney dialysis are common ways to introduce drug resistant germs into clinical patients. But, infection can happen in any surgical or invasive procedure. Treatment of diabetes, cancer, and organ transplantation can weaken a person’s immune system making them even more susceptible for infections that either are, or that can become drug resistant.

But, antibiotic infections can also occur in the community outside of clinical settings. There is the case of Mike who needed a month long hospital stay for kidney failure after bringing home a new puppy from which he caught a multidrug-resistant Campylobacter infection. He was one of 113 people across 17 states who was part of an outbreak linked to pet store puppies. He recovered after surgery to remove a dead section of his stomach.

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The NIH Hospital Experience. About 10 years ago, the NIH Clinical Center in Bethesda was hit with an epidemic of drug resistant infections that killed a number of patients in just a few months. It was such an intractable problem that NIH finally had to gas rooms with a disinfectant, rip out plumbing, and build a wall to isolate infected patients. Still, over a period of six months it reached 17 patients, 11 of whom died. In this case, the bug was Klebsiella pneumoniae, which arrived in June 2011 with a 43-year-old female lung transplant patient who had just transferred from New York City. NIH nurses noted something startling in her chart: She was carrying an antibiotic-resistant infection.

Desperately trying to contain the superbug before it could spread, the NIH staff quickly isolated the woman in the ICU. Staff members donned disposable gowns and gloves before entering her room and her nurses cared for no other patients. After a month, the patient was discharged and the staff believed that their containment measures had worked. There were no signs that the bacteria had spread. But a few weeks later, they were shocked when a second patient tested positive for resistant Klebsiella. A third and fourth soon followed and all these patients died.

This pattern was baffling since, if the bug had not been cleared, it should have reappeared sooner. Even though it was the same type of bacteria, K. pneumoniae, perhaps it had spontaneously arisen anew in the other three patients. But by reading the genomes of the bacteria isolated from each patient, including the NYC transfer, scientists at NIH’s National Human Genome Research Institute saw that the bacteria in the subsequent patients came from the New York patient.

That meant two unsettling things: The bacteria lingered for weeks unnoticed in the hospital environment; and the hospital’s infection control measures for the New York patient failed. A further search for the bacteria found it on a ventilator that had been bleached twice. They also found it in a sink drain in a patient’s room, so they tore out all the plumbing. Yet, it began popping up it in more patients, at a rate of about one per week.

As hospital staff desperately raced to stanch the outbreak, they also struggled to treat the infected patients. Out of desperation, doctors battling the deadly, drug-resistant superbug turned to colistin, an antibiotic of last resort. It is not a new drug, having been discovered in 1949 in a beaker of fermenting bacteria in Japan. It had quickly fallen out of favor then since it causes significant kidney damage. The fact that the doctors resorted to such an old, dangerous drug highlights the lack of new antibiotics coming out of the pharmaceutical pipeline even in the face of a global epidemic of hospital-acquired bugs that quickly grow resistant to our toughest drugs.

While colistin defeated the superbug in a few patients, in at least four, the bacteria evolved so rapidly it outran colistin, too. Those four died. This was when the wall was built and all new Klebsiella-positive patients were moved into a new isolation unit behind the wall. Blood pressure cuffs and other normally reusable gear were tossed after one use. Clinical monitors were hired to follow doctors and nurses around to ensure that they were donning gowns, gloves and masks, and scrubbing their hands after seeing each patient.

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Among the most concerning mutating bacteria are carbapenem-resistant Enterobacteriaceae (CRE). Enterobacteriaceae are a large family of more than 70 bacteria that includes the common E. coli, that normally live in the digestive system and help digest food. But, if conditions allow the bacteria to leave the digestive system, they can cause serious disease that needs to be treated with antibiotics. They too can quickly develop resistance to front-line drugs and become a serious problem.  Carbapenem is an antibiotic "drug of last resort" used to treat disease caused by bacteria resistant to other front line antibiotics. Therefore, CRE are resistant to all or nearly all antibiotics and kill up to half the >13,000 patients who get bloodstream infections from them. The CDC first detected this type of antibiotic-resistant bacteria in 2000. Since then, it has been reported in 41 states. In the 10 years between 2001 and 2011, the percentage of Enterobacteriaceae resistant to antibiotics increased almost fourfold according to the CDC. Recently, the CDC tracked one type of CRE from a single health-care facility to facilities in at least 42 states.

The cause

The antimicrobial resistance crisis stems from the simple fact that new antibiotic development cannot keep pace with the rate that bacteria become resistant to antibiotics. Between 1945 and 1968, drug companies invented 13 new categories of antibiotics. Between 1968 and today, just two new categories of antibiotics have arrived. In 1980, the FDA approved 4-5 new antibiotics a year, but now only about 1-2 new drugs are submitted annually for approval. Hence, the solution appears quite simple: Develop more novel antibiotics. However, this is quite complicated since BioX science, which led to the rapid development of the novel mRNA anti-COVID vaccines, has not quite caught up to novel antibiotic development. There are two general reasons for this. First, finding a drug that disrupts the metabolism of bacteria or fungi, but that does not interfere with mammalian biochemical pathways is a difficult and narrow path. Second, so far, the market for novel antibiotics has been comparatively small, meaning that the profit incentive for pharma companies has not been large compared to that for so-called lifestyle medications. While a new antibiotic may bring in a billion dollars over its lifetime, a drug for heart disease may net $10 billion. Drugs to treat depression and erectile dysfunction are typically taken for years making them much more profitable than antibiotics that are used short-term.

Even if we could develop new antibiotics faster, their overuse is the primary driver of antibiotic resistance. According to the CDC, in 2018 seven antibiotic prescriptions were written for every 10 Americans. Of these, one-third were unnecessary, and very often were prescribed for viral illnesses that do not respond to antibiotics. Clinicians writing these prescriptions argue that the antibiotic can help prevent the primary viral infection from leading to a secondary bacterial infection. In other words, many antibiotics are prescribed for prophylaxis rather than treatment.

The number of new antibiotics that the FDA approves annually has slowed to a trickle, while the rate of bacterial mutation has grown exponentially. It used to take 21 years on average for bacteria to become resistant when antibiotics were first used. Now it takes just 1 year for bacteria to develop drug resistance because antibiotics are so readily prescribed and used. Today, the CDC lists 18 different types of antibiotic-resistant bacteria, five of which are classified as urgent threats to human health.

Physician-prescribed antibiotics, however, are not the only, or even main, source of our antibiotic resistance crisis. In the U.S., 70%-80% of all antibiotics are given to animals, especially farm animals destined for human consumption.  Drug-resistant pathogens from farm animals can spread to the environment providing a gateway through which drug resistant germs can quickly spread across our communities, food supply, and even our soil and water around the world.

Surprisingly, antibiotic use is even rampant in salmon and other fish farms, which is especially concerning, considering that 90% of fresh salmon eaten in the U.S. comes from such farms. Antibiotic-resistant infections also affect petting zoo animals, which can then transfer the germs to people.

The solution

Antibiotics clearly have been miracle medicines, saving countless lives; however, anytime they are used, they drive the development of antibiotic resistant pathogens that ultimately defeat their purpose.  Developing new antimicrobial drugs to counter the growing resistance to current drugs is not working; it is not keeping pace with the appearance of new antibiotic resistant germs. Without drastic changes in the science and economics behind antibiotic development and business, this will only be a partial solution to the growing pandemic. However, what we can do now is resort to low-tech, less expensive, and more innovative mitigation measures. These include alternative prevention steps such as more judicious use of antibiotics and increased use of isolation and sanitation measures (where have we heard this before?). Isolation and sanitation defenses against infectious diseases have been part of our disease fighting repertoire since the earliest awareness that contagions can spread through communities. It is an ancient remedy, but still the most effective way to protect ourselves against contagious diseases worldwide. Between 2013-2019, these mitigation measures led to an 18% reduction in US deaths from drug resistant infections. It always is better to prevent than treat.

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Alternative medical treatment and prevention options.  Besides the obvious masks, gloves, sanitation, and quarantine measures, there are other alternative medical (i.e., non-antibiotic) options that can be used to prevent and control drug resistant infection. In fact, these methods are often preferable to using antibiotics, which also deplete the microbiome of “good bacteria” that are critical for good health. These options include vaccines, therapeutic antibodies, and bacteriophages.

From 2000 to 2016, members of the WHO increased the use of the pneumococcal vaccine around the world, thereby decreasing antibiotic use which slowed the development of antibiotic resistant S. pneumoniae saving ~250,000 children from death. Pneumonia caused by secondary infection with other bacteria is a leading cause of complications and death in patients who get the flu. Therefore, the influenza vaccines also are effective tools to decrease the risk of drug-resistant bacterial pneumonias by preventing viral influenza. Since patients with COVID can also develop secondary complications from bacterial pneumonia, COVID vaccination now is another important weapon in the arsenal to prevent the development of antibiotic resistant bacterial lung infection.  

In recent years, healthcare providers also have been increasingly using therapeutic antibodies to treat viral and bacterial infection. For example, antibody therapy is often used to treat recurrent C-diff GI infections, and antibodies to prevent and treat bacterial associated pneumonia also are being developed. So far, we have not seen bacteria develop resistance to antibodies.

Finally, a different and very novel approach to dealing with untreatable bacterial infection has recently taken advantage of bacteriophages, which are viruses that can specifically infect and kill bacteria. There are a few cases in which phage therapy has been used to cure people dying of multidrug-resistant bacterial infections.  According to Pew Charitable Trusts, as of June 2019, 29 non-antibiotic products like therapeutic antibodies and phages were in clinical development and seven were in Phase 3 clinical trials. 

Perhaps BioX is indeed coming to rescue us from the growing pandemic of drug-resistant pathogens.

Notes: 1) By way of disclaimer, your correspondent has consulted for a biotech company that engages in “big genome” research to search for novel antibiotic molecules produced by everyday bacteria and fungi that grow in the soil under your feet. Something like this could be part of the future of novel antibiotic development. 2) In order to have blog updates delivered to your email, see the simple Subscription Instructions here. Remember, you can easily unsubscribe when you want. But, you can’t beat the price.

COVID More Deadly Than Flu For Kids

In the US, nearly six times more kids and teens died from COVID in one year than did from the flu, according to a new analysis of pediatric mortality data. According to CDC data, childhood flu deaths have ranged from 39 to 199 per year since 2004. Meanwhile, in 2021 alone, more than 600 children died from Covid-19, according to an analysis done by researchers at the Harvard University Medical School and at Brigham and Women’s Hospital in Boston.  The analysis used data from the CDC to compare COVID deaths during the pandemic to flu deaths over the last decade (see figure below).

Of the known respiratory viruses, only CoV-2 has ever killed more than 100 US kids in a single month since the middle of the 20^th century. Much of that is because we have long had vaccines for other viruses that cause human respiratory disease, but have yet to widely vaccinate children against COVID-19. Hopefully, new vaccines will also render COVID less deadly for kids like vaccines have done for several other respiratory diseases.

Throughout the pandemic, some have argued that COVID poses little health risk to kids aside from a few days of sniffles. Though kids often experience less-severe symptoms than adults, COVID is still a very real risk. An estimated half a million kids now deal with long COVID, a number that experts say is likely an undercount because its myriad symptoms make it tricky to diagnose.

What Happened To The Flu And Other Respiratory Diseases?

A NYC based travel blogger who travels a lot used to get a respiratory infection whenever she flew. That stopped when the airline mask mandates went into effect. The mandates, of course, were designed to hinder the spread of the CoV-2 virus that causes COVID, but it makes sense that if masks and other physical (that is, non-medical) mandates worked to mitigate COVID, then we would see a decrease in other contagious respiratory diseases after the mandates were, well…mandated.

We did.

The mandates worked, despite persistent claims of some to the contrary. This particular blog subject was stimulated by a radio talk show where a couple of nonscientist talking heads announced that there was no scientific proof that the masks or other mandates prevented disease. I previously posted in these pages evidence that masks, in particular, do indeed work to retard the spread of disease (see here, here, here, and here). In this post, I present further data on how the mandates significantly reduced the incidence of other infectious respiratory diseases around the world. If the measures can reduce flu, then you can bet that they also reduced COVID-19.

Note, however, that this is not necessarily an endorsement for returning to the measures. Your humble scribe didn’t much like his glasses fogging up, or having to make two trips from the car to the store because he forgot his mask. But, let’s argue the issue based on its merits and not from false premises based on incorrect claims.

After South Korea implemented various hygiene and social distancing measures in response to COVID, they saw the 2019-20 flu season end an astounding 12 weeks earlier than the previous year. Epidemiological surveillance data bolstered by clinical diagnostic testing showed that infection from several different pathogenic respiratory viruses (including adenovirus, bocavirus, metapneumovirus, rhinovirus, flu, parainfluenza, and respiratory syncytial virus) dropped to nearly 0% just five weeks into 2020!

In the United States, the incidence of infection by influenza, respiratory adenovirus, rhinovirus, enterovirus, RSV, non-COVID coronaviruses, metapneumovirus, and parainfluenza viruses all decreased in March 2020, soon after implementation of mandates. Similar results were seen in Japan.

More dramatically, since pandemic mitigation measures were put in place, there has been a 99% global reduction of infections from both influenza types A and B compared to prior years. In particular, one of two flu B substrains has not been isolated in the world since August 2021 suggesting that this variant is now extinct. The overall genetic diversity of influenza viruses has also dramatically diminished indicating that other flu sub-types (or clades) have disappeared around the world since the pandemic mandates were put in place.

And this reduction of respiratory infectious disease does not only hold for those caused by viruses. Another study looked at surveillance data from 26 countries across 6 continents for several bacterial diseases caused by Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, which are typically transmitted via respiratory droplets. Numbers of weekly cases in 2020 were compared with corresponding data for 2018 and 2019. Data for disease due to Streptococcus agalactiae, a non-respiratory pathogen, were also collected from nine laboratories for comparison. All countries experienced a significant and sustained reduction in respiratory bacterial diseases in early 2020 (Jan 1 to May 31), coinciding with the introduction of non-medical COVID containment measures in each country. By contrast, the incidence of disease due to S agalactiae (which is not transmitted by the respiratory route) did not differ significantly from the 2 previous years.

Clearly, the mandates significantly reduced the incidence of respiratory infections by non-COVID viruses and bacteria. They worked. So, why did we still have COVID infections after the mandates went into place? The mandates reduced, not eliminated these diseases, so infections still happened. Since we did not have historical COVID infection data from previous years to compare with, the effects of the current mandates on the incidence of COVID are not as clear cut as they are with other diseases for which we do have historical data for comparison. But, as I wrote before (see above), it is clear that places in the US and around the world that used masks and other protective measures saw reduced incidence of COVID compared to similar places that did not.

Bottom line: The studies mentioned here regarding non-COVID infectious diseases fully support data previously posted in these pages that the mandates, including masks, are effective non-medical tools for controlling infectious respiratory diseases.

Don’t let anyone tell you differently.

Gain-Of-Function Viral Research: What’s The Big Deal?

Senator Rand Paul and many others have raked Dr. Anthony Fauci, long-time director of the National Institute for Allergy and Infectious Diseases (NIAID), over the coals for supporting research at the Wuhan Institute of Virology, and especially for supporting “gain-of-function” (GoF) research at that facility.

This needs some ‘splaining.

First, Senator Paul and the anti-Fauci crowd need to give us their definition of GoF research and then explain why it is bad. If they mean research that gives viruses new capabilities, then most labs seeking to learn how a virus functions is guilty. For example, University of Wisconsin flu researcher, Yoshi Kawaoka, did research that exchanged genes from the 1918 H1N1 Spanish flu virus with less virulent H1N1 viruses in order to learn why the Spanish flu caused so much death back then. That is classical gain-of-function research and it was done under strict quarantine and safety conditions (disclaimer, your blogger was on the safety review committee that vetted and approved Kawaoka’s Spanish flu research). It is legitimate and important research.

The Wuhan Institute of Virology had a small bit of indirect funding from Fauci’s NIAID to support a genetic registry of coronavirus sequences that is freely available to all researchers around the world. As new coronaviruses were discovered and their genomes sequenced, the lab investigators cataloged them. They also inserted the new spike protein genetic sequences into incipient, harmless viruses to see how well the new spike proteins allowed a virus to infect mammalian cells in tissue culture. This was done to help assess how much of a risk a new coronavirus was for spreading among mammals. Strictly defined, this research gave the engineered test viruses new capabilities—they acquired new spike proteins and gained the new functions that came with that. This is legitimate research and not some nefarious plot to weaponize coronaviruses that Rand Paul, et al., dishonestly allude to in their allegations.

Furthermore, there are the thousands of other labs around the world, including mine at UCLA and the University of Wisconsin that use viruses as tools for gene transfer in order to study the activity of newly discovered genes. For example, my lab discovered an aberrant gene that was associated with a particular human leukemia that used to be untreatable. We wanted to learn how the abnormal gene affected blood cells, so we cloned it and inserted it into a virus that could infect mouse cells. We then gave mice leukemia by infecting them with a virus that expressed a human cancer gene. That recombinant virus gained the function of the human cancer gene. Rand Paul, et al., would call that sinister gain-of-function virus research. However, from that and other research, that incurable leukemia now is 95% curable. Sinister?

Sure, using modern molecular technology, a minacious actor could help a pathogen gain super-lethal function and develop a super-pathogen, or a weaponized bug, like antibiotic resistant anthrax or super-spreading Ebola virus. It would be pretty easy to do. But, by far, the GoF research routinely done in labs around the world is done for learning not for killing.

When Paul accuses Fauci of supporting GoF research, that accusation is attached, without evidence, to an implicit accusation that the Wuhan labs are creating more virulent pathogens for nefarious reasons. So, why does Paul not go after Kawaoka or me for using NIH money to create viruses that might be able to kill people (Kawaoka’s flu construct) or that could cause cancer (my virus expressing a human cancer gene)?  

Could it be for political reasons?

Lions And Tigers And…Deer? Oh My!

First it was bats and humans, then domestic cats and dogs, farmed mink, and big zoo cats; now gorillas, hippos, and wild deer that have been infected by the SARS-CoV-2 (CoV-2 for short) virus. Many of these animals have become ill and several have died of COVID-19, most recently three snow leopards in South Dakota and Nebraska zoos. This is quite a wanton virus.

Of course, before CoV-2 and COVID-19 were known to the world, we knew that bats, humans and a few other animals, notably civets and even camels, were ready hosts of several different strains of “‘rona” viruses. We also knew that domesticated animals are also susceptible to their own coronavirus diseases—in fact veterinary coronavirus vaccines have been in use for years. Humans are known hosts for several coronaviruses, including those that cause the common cold, as well as the viruses that cause SARS, MERS, and now COVID-19. And we know that humans often catch these germs from bats and other intermediate hosts as diverse as civets and camels. After we genetically identified CoV-2 and were able to follow its spread, we quickly noticed that domestic pets also could be infected. This was closely followed with news that seven big cats at the Bronx zoo had become infected, and that mink farms across Europe were hotbeds for CoV-2 spread between humans and the animals and back. In fact, mink farms became such a hotbed of CoV-2 zoonotic spread that a couple of European countries completely shut down mink farming and culled all their animals. Several US states have also sharply curtailed mink farming. PETA probably applauds.

More recently two snow leopards at the Lincoln, NE children’s zoo and one in a zoo in South Dakota died from COVID. The Lincoln zoo also had two infected Sumatran tigers who recovered after being treated with steroids and antibiotics to prevent secondary infections and pneumonia. How the animals were infected is uncertain, but the most likely scenario is that they caught the virus from a caretaker. The problem is, none of the caretakers tested positive for the virus. Bats? Something else?

Since April 2020, when a tiger tested positive at the Bronx Zoo, dozens of other animals in zoos around the world have caught COVID. This month, the Denver Zoo reported the first coronavirus cases in hyenas, and the St. Louis Zoo found eight positive cases among its big cats, including two snow leopards. Abroad, the virus has killed a lion in India and two tiger cubs in Pakistan. Big cats seem especially susceptible since three other snow leopards at the Louisville Zoo were infected last December, and another snow leopard tested positive at the San Diego Zoo in July. The virus doesn’t just infect our fuzzy friends either; two hippos, named Imani and Hermien, at a zoo in Antwerp recently tested positive for COVID-19. Zoo keepers were first alerted to a potential problem when they noticed that the colossi had “runny noses.”  One reckons that a runny nose for a hippo is a big deal. One also wonders who gets to dab that nasal maw in order to test for the virus.

In fact, zoo and domestic animal infections have become so prevalent that an animal COVID vaccine developed by Zoetis, a NJ-based veterinary pharma company and former Pfizer subsidiary, has been authorized by the USDA for experimental use. The Cincinnati Zoo, for one, has vaccinated  80 animals, from giraffes to apes, against COVID.

Deer too. Oh my! It is one thing for zoo animals to acquire COVID—their captivity makes it easy to limit their interaction with other animals and humans to prevent spread of contagions, and they seldom complain that their rights are being infringed when they are quarantined. However, COVID in wild animals is a different story, as we have seen with bats and how easily they transmit the virus to humans. Scientists now have evidence that CoV-2 also readily propagates in white-tailed deer. In fact, the virus is already widespread in cervids across the US, which likely has significant implications for the long-term course of this pandemic.

In September of last year, genetic analysis of the gene that encodes the ACE2 protein (i.e., the viral receptors expressed on many cells in the body) in many different animal species suggested that CoV-2 could easily infect deer (and several other animals too). A survey of white-tailed deer in the Northeast and Midwest found that 40% had antibodies against the CoV-2 virus, indicating prior exposure. Between April and December 2020, veterinarians at Penn State found active CoV-2 infections in ~30% of deer tested across Iowa. Then during the winter COVID surge in humans from Nov. 23, 2020, to Jan. 10 of this year, ~80% of the tested deer were infected. The prevalence of the virus in deer was 50 to 100 times greater than in Iowa residents at the time (and the deer reportedly did not wear face masks). The study, published about two months ago, indicates that white-tailed deer have become a permanent reservoir for CoV-2. While it is not fully understood how the virus entered the deer population, genetic sequence analysis of nearly 100 viral samples found that the variants circulating in deer matched the variants circulating in people. This suggests that deer caught the virus from people multiple times in Iowa alone. How that happens is not known since people usually do not have close contact with live deer. More concerning is whether viral variants arising in deer readily pass back to people.

Bottom line. Clearly, a lot of different animal species can catch Cov-2 and spread it. It is clear that people can spread coronaviruses to pets and other animals, but the FDA says that the reverse, animal-to-human virus transmission, is not common. But, it clearly happens as we have seen with this pandemic, and with many other viruses that cause SARS, MERS, AIDS, Ebola, flu, etc., that spread from animals to humans. The prevalence of CoV-2 infection in so many species of mammals, especially in animals that have close contact with humans, suggests that several animal species, not just bats, can serve as permanent reservoirs for the virus and the jump to humans is something that can happen over and over. This is not unprecedented. It is what we see with influenza, which is carried back and forth between the Northern and Southern hemispheres with migratory birds, in which different flu viruses shuffle their genomes to create the new strains of flu for which we have to vaccinate against each year. This animal reservoir for flu makes it next to impossible to eliminate influenza, and similar animal hosts for CoV-2 likely would make it nigh impossible to eliminate COVID too. I raised this specter some months ago in these pages when reporting that pet dogs and cats can carry the virus. Our furry friends represent a viral reservoir that is in even closer contact with people than bats, deer, and fortunately, hippos and leopards.

We also have to be worried about the CoV-2 virus mutating in the different animal species that harbor and spread it. We know that happens in bats, which makes it almost certain that new strains of the virus will arise in deer and dogs too. We have already seen this on mink farms in the Netherlands and Poland. Farmworkers passed the virus to captive animals where it spread, mutated, and then spilled back into humans. In fact, zoonotic transmission from animals to humans probably happens thousands of times a year. Researchers from the EcoHealth Alliance and from Duke-NUS Medical School in Singapore, estimate that each year many people are newly infected with SARS-related coronaviruses. Many may get sick, but there are many reasons why most of these infections never grow into noticeable outbreaks (for example see my earlier blog post about unusual respiratory infection clusters in China and Los Angeles just before COVID). The researchers also created a detailed map of Asian habitats of 23 bat species known to harbor SARS-related coronaviruses then overlaid it with data on where humans live to create a map of potential infection hot spots. They found that close to 500 million people live in areas where bat-to-human transfer is likely, and this risk is highest in southern China, Vietnam, Cambodia, and Indonesia. Other surveys done before COVID-19 showed that many people in Southeast Asia harbor antibodies against other SARS-related coronaviruses. Blending these data with data on how often people encounter bats and how long antibodies remain in the blood, the researchers calculated that ~400,000 undetected human infections with these viruses occur each year across the region.

That is just for bat-to-human transfer in Southern Asia. It now looks like we will have to also concern ourselves with zoonotic coronavirus transfer from Buddy and Bambi too.

For this reason, researchers are working to develop a universal coronavirus vaccine that will be effective against most viral strains and variants. I will write about this soon. Stay tuned.

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