pandemic

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.


Three Years Ago Today

Yup. This is the three year anniversary of the COVID pandemic. On December 31 2019, the health commission of the city of Wuhan announced that they were investigating an outbreak of an unusual respiratory illness. The statement said that most of the afflicted had visited a food market in the city and that 27 people had contracted an unusual viral pneumonia. Seven were in serious condition. Things went down hill from there. China shut down and the rest of the world vaccinated.

I posted in these pages on those early days of the pandemic here if you want to revisit the beginning of this strange time.

At least I can say, all this has kept me occupied. My blog, going on 160 posts now, has earned me some new friends (I got a very nice message last week from someone in the Phillipines thanking me for "helping humanity." It made my day.) And it has earned me enemies from people who want to believe that Trump botched his response. He didn't. He launched Operation Warp Speed that gave us the vaccine and respirators in record time. On the other side of the political spectrum, I get vitriol from those who think that Tony Fauci is Satan incarnate for shutting down schools. He didn't, since NIH has no authority to do so.But that fact doesn't change anyone's mind.

So, among that cognitive dissonance, I thank my friend in the Phllipines and other readers who fined use in my blog.  I write it for you.

 


Pandemic History: Long COVID

"We learn from history that we learn nothing from history."
--George Bernard Shaw

Let’s hope GBS is wrong about what we learn from the recent pandemic. As it recedes in our rear view mirrors, scientists are looking to all the data and information collected to retrospectively see what we learned about this new virus and disease. This is especially true for that totally unexpected disease phenomenon called “long-COVID.” As we became aware that some COVID survivors continued to suffer from a strange constellation of symptoms, referred to as long COVID, I wrote in these pages about what that affliction entailed, and what we were seeing and discovering about it. You can find several other blog posts on that topic by looking under “long COVID” in the "Categories" listed to the side of this post.

Long COVID was particularly difficult to study since, by definition, it lasts months, maybe even years in some people. That means that discerning how it manifests itself, and how to effectively treat it would take months to flesh out. We have gleaned a bit about that and also have identified areas we need to look at more closely in order to fully understand this part of the disease.

A Scottish study of about 100,000 participants began while the pandemic fulminated, and the results of that study are just being released. The study helps clarify how to diagnose long COVID, which earlier had vexed physicians who had no idea what they were looking at. Long COVID presented doctors with a hodge-podge of seemingly unrelated symptoms—was it a single disease? Different disease manifestations? Psychosomatic? What it then was was a head scratcher. The Scottish study helps confirm that it is a real COVID-associated problem, and the most common symptoms include breathlessness, palpitations, chest pain and “brain fog” or reduced mental acuity. We also learn from the study that the risks of acquiring long COVID is greater in women, older people and economically disadvantaged people. Also, people already dealing with other physical and mental health problems, such as respiratory problems or, surprisingly, depression, are more prone to long COVID. Why is that? The study also found that 1 in 20 people had not recovered up to 18 months after coming down with COVID. It also reported that people with asymptomatic infections were unlikely to suffer long-term effects, which helped confirm what we expected, that it probably is not the virus that causes long COVID, but the culprit is some people’s immune response to the virus. Who are those people susceptible to long COVID, and what is different about their immune response? It also seems that vaccination protects a bit against long COVID, but not as much as previously thought. But, this observation complicates things. The vaccine is designed to stimulate an anti-virus immune response without the risk attendant to an infection. Why doesn't this immune response cause long COVID symptoms like the immune response to the actual infection? Basically, how it all works still is not well known, but that bit of new information scientists are gleaming from the data moves us gradually closer to finding out.

Looking at other data collected since the pandemic reared its ugly head, the WHO estimates that about 10-20% of COVID survivors have lasting symptoms that reduce their quality of life to varying degrees.

The Washington Post reports that somewhere between 7-23 million Americans currently suffer from long COVID. One million of these are unable to work. People are not dying from long COVID, but they often are considerably impaired and that makes them heavy consumers of expensive medical care, and often unable to work at full capacity, which adds to the personal and social costs of the chronic complication.

Anthony Fauci, in an interview with The Guardian, cautions that even though COVID deaths and hospitalizations are declining, it is premature to declare victory over COVID since we continue to deal with the insidious chronic sequelae of the disease. Furthermore, all indications suggest that COVID will be a recurring problem for the world and as it regularly sweeps across the globe, it will continue to create new cases of long COVID. This means that we still need to remain vigilant to avoid the virus when possible, and to make sure that vaccinations are effective and available to the population. Other therapies continue to be explored, but, unlike, antibiotics that fight bacteria, safe anti-viral drugs are very hard to develop because they often come with too extreme side effects.

Continued research into the virus and disease by medical scientists, and further examination of the pandemic history by epidemiologists hopefully will lead to a better understanding of the causes of long COVID, how to more definitively diagnose it, and ultimately how to effectively treat, or even prevent it. Toward these ends, Fauci’s National Institute of Allergy and Infectious Diseases recently launched a $1.15 billion initiative to achieve these goals. The CDC also recently began its own major study of the problem.

Stay tuned for changes in how we deal with the virus and with long COVID as we learn more about it. That is how science works.


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.

Development of bact resistance

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.

Time to resistance

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.


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.


Still More Evidence For An Animal Origin Of The Virus

Conspiracy buffs won’t like this, but compelling new evidence presented in three papers, which include photographic and DNA data, has pretty much nailed down the origin of the SARS-CoV-2 virus. It began in a wet market animal not in the lab eight miles away as the conspiracists have conjectured. This new data comes from an international team of scientists which concluded that the coronavirus twice jumped from  caged wild animals into people at the Huanan Seafood Wholesale Market in Wuhan. These data correlate nicely with previous geo-epidemiological data showing the market, not the lab, to be the infection nidus with later infections radiating out from there.

Despite the Chinese’s government denial that live animals were sold in the Wuhan market, the new studies provide photographic evidence of wild animals sitting in stacked cages in the market in late 2019, in or near stalls where scientists found SARS-CoV-2 virus on a number of surfaces, including on cages, carts and machines that process animals after they are slaughtered at the market. This, along with a new genetic analysis pinpoints a specific stall at the market where the virus passed from an animal into people. These data also estimate the time when not just one but two zoonotic spillovers occurred, once in late November or early December and then again few weeks later. This coincides almost exactly with the timing of the outbreak of disease at and around the market.

The two initial infection events involved slightly different versions of the SARS-CoV-2 virus. The fact that they were related is evidence that the virus had spread and mutated in animals in the market before it infected humans.

A leader of two of the studies was U of Arizona professor, Michael Worobey, a viral pandemic sleuth who has been at the forefront of the search for the origins of the bug responsible for the current pandemic. His lead in the research is significant since, back in May, 2021, Worobey, along with 17 other scientists, called for investigation into the lab-leak theory. His latest research overturned that conjecture. This new evidence adds to previous evidence for an animal/market origin of the virus presented earlier in these pages here and here.

Final thought. It is sobering to think how these two simple infection events that occurred in November and December of 2019 in a Chinese market triggered something that has now caused six million deaths and untold misery around the world. And it is not finished with us.

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Another Unexpected Pandemic Consequence: Undiagnosed Cancer

In these pages, your humble bloggeur (that would be me) has written about several unusual consequences of the COVID-19 pandemic. Most of these were on the ironically funny side, such as farmed fish being too large for restaurant plates, rattlesnakes climbing in plane landing gears, and the ketchup packet shortage. But, not all of these odd aftermaths of the pandemic are humorous. The topic of this post is very unfunny.

Lungs

It seems that as healthcare providers were swamped with COVID cases, or were at reduced capacity because staff became ill, or because service slowed in order to prevent CoV-2 spread, many people have missed routine medical care for non-COVID problems. It is feared that this will create a crisis in coming years involving increased diagnosis of cancers that were caught later than usual. As we deal with the fourth wave of COVID-19 caused by the Omicron variant, we are learning that the pandemic dramatically disrupted routine health screenings for cancer and other chronic diseases. Some now predict that the next crisis that could overwhelm the US health system will be a surge in advanced chronic diseases like cancer that went undiagnosed and untreated for too long.

Screenings for several major cancers and new cancer diagnoses fell significantly during 2020, according to a study published in December 2021 in the journal Cancer. This was not because there was less cancer in the world. It was because fewer patients were seeing their doctors.

A co-author of the Cancer study, and who is a professor at the University of Maryland School of Medicine, said that we have never before seen screening rates drop so dramatically in such a short time.

In one case, a Hispanic man in his 40s first noticed rectal bleeding in early 2020 that his doctor said was probably due to hemorrhoids. The man was unable to get a timely colonoscopy to rule out cancer because the local hospitals were overwhelmed with COVID-19 patients, and he also feared catching COVID if he went to a hospital swamped with COVID patients. Eighteen months later, he finally got a colonoscopy, which revealed advanced rectal cancer. Those 18 months likely were the difference between being cured by a simple polyp removal vs dealing with a cancer that had metastasized throughout his body.

At this point, nobody knows how many cases like this are out there. We will find out.  

This patient, as thousands of others like him, had the misfortune to notice symptoms that needed followup amid the biggest disruption of medical care in US history. In 2020, while hospitals curtailed services in order to prepare for the COVID surge, the number of colonoscopies plummeted 93 percent. By the end of the year, there had been 133,231 fewer colonoscopies performed compared to 2019. There also were 62,793 fewer chest CT scans, 49,334 fewer fecal blood tests, and prostate biopsies dropped 25%.

This drop in screenings has created a huge backlog that will take months to clear. A gastroenterologist at a small community hospital in the Middle-of-No-Where, Kansas was recruited by a larger hospital in Kansas City to do nothing but colonoscopies from 7 in the morning to “whenever at night.” They had a backlog of 1000 patients—a certain percentage of whom have cancer already growing in their colons while waiting to be told they had colon cancer. And that backlog begets a fresh one of new patients who also need to be scoped because they just noticed something like rectal bleeding, but will have to wait for those who have already been waiting.

This backlog creates a subtle form of medical rationing. It forces doctors to make hard choices about which patients to prioritize. "Lucky" are the serious patients who are moved to the head of the line. Not so lucky are those whose colonoscopies or mammograms or biopsies are then further delayed.

I would rather deal with rattlesnakes in my plane's landing gear or forgo mustard on my brat (which would be pushing the limit) than delay a needed medical test or procedure. It seems that your humble bloggeur (me again) has been caught in the backlog. I am scheduled to have an enlarged parathyroid gland removed next week, but COVID can still derail that. I won’t be certain that the surgery will happen until the day before I am to be operated on and that depends, in part, on everyone, including me, being COVID-free, and the OR not being diverted for use as a COVID ICU. If it proceeds as scheduled, I will have waited several months since the initial diagnosis for the surgery. An additional routine diagnostic test I need in order to determine how the fractious organ might have affected my bone health was scheduled six months out. Six months for a routine scan?


File This Under ‘Weird Pandemic Effects’: Decreased Incidence Of Lightning

If lightning is the anger of the gods, then the gods are concerned mostly about trees.”

- Lao Tzu

Yup, since the pandemic began, it appears that trees are safer. Thanks to the lockdowns, there is less lightning to strike them.

A study presented at the fall meeting of the American Geophysical Union (AGU) analyzed atmospheric factors that may have contributed to lightning reductions of 10-20%. 

It seems that atmospheric aerosols produced by burning fossil fuels were reduced because of pandemic lockdowns. Particles in these aerosols enhance the collection of water vapor, which causes clouds to form. And the more these particles absorb water they also reduce rain and, therefore, the creation of small ice crystals that collide in the clouds and build electrostatic charges that create lightning. So, fewer aerosol particles, less bumping and rubbing, less static and fewer zaps.

I have previously noted other weird effects of the pandemic such as farmed fish being too large for restaurant plates, rattle snakes in plane landing gears, and a dearth of ketchup and mustard condiment packages to go along with less lightning. What crazy thing will happen next—the Cincinnati Bengals win a playoff game?

Oh….wait a minute……..

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The Long Haul, Part 4: The Cost of Long COVID In Terms Of Individual Health And Quality Of Life

Surviving COVID-19 is one thing, recovering is another.

My frustration with those who would minimize the impact of COVID-19 is reaching an apex. I constantly have to deal with their baseless rationalizations that “it is just a cold,” or “it only kills 0.01% of people” (actually the number is 2% around the world), etc. And I constantly reply to these iconoclasts that COVID has become, by far, the leading killer in the US. I also explain over and over that treating simple mortality percentage as the only relevant statistic to consider is falderal. For example, the Spanish flu also killed “only” 2% of those infected, but in just 24 weeks, that virus killed more people around the world than were killed in WWI AND WWII together! The percent figure is meaningless without considering the percent of what. Why do they continue to ignore the devisor and, hence, the total number of deaths?

A small percentage of a very large number is, in fact, another large number.

Those who wish to downplay the significance of the pandemic only focus on this mortality percent, but mortality is NEVER the whole story for any pandemic. A serious person will also consider the morbidity caused by the disease. In fact, the major CDC publication on health in the US is called the Morbidity and Mortality Weekly Report. Notice that it considers both morbidity and mortality, and further notice that morbidity is listed first in the title. I have made three prior posts in this series on Long COVID, about the significant lasting morbidity of COVID-19. You can see these posts here, here, and here. In those posts, I shared data showing that some ~10-30% of COVID survivors suffer serious health problems that last months.

In those posts, I mentioned the cases of a young, healthy MD, and of a young, healthy journalist, both of whom struggled with long COVID, and how it affected their careers and cost them thousands of dollars in out-of-pocket expenses for the dozens of tests and doctors they needed. In an article in Maclean’s magazine, a reporter interviewed many Canadian long COVID patients and heard how their lives have been turned upside down. They reported that they are unable to live like they used to and care for their families, do anything mildly strenuous, or even cook their meals. They spend long stretches of time in bed. Many of those interviewed had not returned to work several weeks after recovering from the acute disease.

Anecdotes like these have been repeated millions of times around a world that, according to the Johns Hopkins University COVID tracker, has seen more than 330 million cases of COVID (and this is a significant undercount since many countries do not record these data well). Research has corroborated these anecdotes.

+++

Common long-term symptoms include debilitating fatigue; respiratory problems; and “brain fog.”  Other common symptoms include compromised function of the heart, and kidneys, which sometimes require transplantation. Wide-spread clotting problems can cause significant illness and even limb amputation. There also are frequent neurological and neuropsychiatric symptoms as highlighted in Part 3 of this series. Surprising manifestations continue to emerge, such as new-onset diabetes.

Lung scarring often occurs in patients who experienced COVID-caused acute respiratory distress syndrome (ARDS), a common problem seen in acute COVID patients who required ICU care. ARDS is a serious respiratory problem that can be caused by different respiratory viruses and other things. About a third of patients with ARDS arising from any cause were unemployed 5-years later because of their lung damage. It is fully expected that patients with COVID-related ARDS will be found to fare similarly.

There also is the dysfunctional immune response common in many moderate to severe COVID cases that can cause long-term multi-organ damage, particularly in the liver and kidneys. It can also disrupt coagulation control of the blood, sometimes leading to amputations, mostly in patients in their 30s and 40s. It was reported that amputations due to vascular problems have doubled since the CoV-2 virus arrived. Compromised coagulation control in COVID patients can also precipitate adverse cardiovascular events such as heart failure, or hemiplegia due to strokes. Data from the COVID Infection Survey on long-COVID suggest that the risk of major adverse cardiovascular events and long-term illness is about ten times higher in COVID patients (even after mild COVID) compared to non-COVID matched controls. A Dutch study found that 31% of COVID ICU patients suffered thrombotic complications. These problems can unexpectedly pop up in people who had completely recovered from COVID.

A global survey tallied 205 different symptoms across 10 different organ systems that can persist after COVID infection has cleared. Typically, these manifold long COVID symptoms do not appear in isolation, but in multi-symptom clusters. A long hauler typically has several of these problems at a time.

While it is estimated that overall, 10-30% of COVID patients become long haulers, reports on the number of people suffering long COVID vary widely. Depending on the report, anywhere from 30-90% of COVID survivors suffer long term health problems. And even at the lower end of that range, 30% of over 330 million people world-wide who have been infected is a very large number. It represents an enormous personal toll in terms of lost health and diminished quality of life. Some of these reports are summarized below.

  • Half of 70,000 hospitalized UK COVID-19 patients experienced long-term complications, according to a study published in July. Complications occurred regardless of age group: For instance, 25% of adults aged 19-29 developed complications, as did 33% of those aged 30-39. Complications affecting the kidneys and respiratory system, liver injury, anemia, and arrhythmia were the most common.
  • Many COVID-19 survivors require extensive and prolonged rehabilitation. An European study found about one-third of 1,837 non-hospitalized COVID patients (i.e., those with mild disease) needed a caregiver three months after their symptoms started.
  • In April the CDC reported in its Morbidity and Mortality Weekly Report that 69 percent of nonhospitalized adult COVID patients in Georgia required
  • one or more outpatient visits 28 to 180 days after their diagnosis.
  • A study published last February in the Journal of the American Medical Association found that roughly one-third of 177 people who had mild COVID disease not requiring hospitalization reported persistent symptoms and a decline in quality of life up to nine months after illness.
  • 70% of people hospitalized for COVID-19 in the UK had not fully recovered five months after hospital discharge. They averaged nine long COVID symptoms requiring continued medical care.
  • A study in South Korea found that 90% of patients who recovered from acute COVID experienced long-term side effects.
  • According to a report in the journal, Lancet, 75% of people hospitalized with COVID-19 in Wuhan early in the pandemic, reported continued problems with fatigue, weakness, sleep problems, anxiety and depression six months after being diagnosed with the disease. More than half also had persistent lung abnormalities.

Data like these have been commonly reported around the world, pointing to a more chronic and expensive health problem than seen with the flu or common cold, which often is caused by different coronaviruses. A July 2021 article in Scientific American talked about how all of this indicates that long COVID will cause a “tsunami of disability” that will affect individual lives as well as create enormous strain on the health system. Consider the numbers: More than 60 million Americans (this is an underestimate since many COVID cases are not reported) have been infected with the CoV-2 virus. Therefore, if only 30% of these suffer long COVID, we are talking about 20 million long haulers and counting.

The related health care and disability costs of all of this are also still being calculated. How many “long haulers” will not be able to return to work for months, or at all? How many will need short-term disability payments, and how many will become permanently dependent on disability programs? As increasing numbers of younger people become infected, will we see a generation of chronically ill? This then moves us to consider the economic and financial cost of long COVID, which will be the topic of the next installation in this series.

Stay tuned.

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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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