Coronavirus news & views

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.

A Single Gene Doubles Risk Of COVID Death

“Nothing shocks me. I’m a scientist.” —Indiana Jones

British scientists recently identified an allele, or a version of a gene, that portends lung failure and death in COVID-19 patients. Research recently published in the journal Nature Genetics, found that a poorly studied gene expressed in lungs, designated LZTFL1, has a variant form that does not differ in its coding sequence. That is, the different alleles of the gene express the same protein sequence. They do differ, however, in their non-coding sequences that regulate expression of the gene. When expressed, the gene product prevents cells lining airways and the lungs from responding properly to the CoV-2 virus. The lining of the lung essentially transforms into less specialized cells which affects their normal function.

Previous work had identified a stretch of DNA on human chromosome 3 that doubled the risk of death from COVID. Using an artificial intelligence algorithm to analyze millions of genetic sequences from hundreds of cell types from all parts of the body, the Oxford University Howard Hughes research team honed in on the lung-specific genetic off-on switch. This is another example of what I previously labeled "BioX," the new frontier of bioscience, or post-molecular biology science.

Importantly, the variant allele that augurs a worse lung response to infection does not affect the immune system. Therefore, the it is probable that vaccination remains the best way to protect these at-risk patients. Finding this new allele could also lead to novel therapies to target the pathway affected by this genetic variant to provide targeted treatment for at-risk populations.

The troublesome variant is mostly found in people of South Asian ancestry—some 60% of whom carry the allele—which partly explains the severe devastation from COVID seen in the Indian subcontinent. In contrast, 15% of those with European ancestry and 2% of Afro-Caribbean people carry the risky allele.

It will be interesting to see if this lung-specific gene also affects the course of other respiratory infectious diseases.

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COVID-Diabetes Link Confirmed

As I penned in these virtual pages almost a year ago, COVID survivors have a high risk for developing diabetes. Early on, diabetes was identified as a risk factor for severe COVID illness, but two years later, scientists were surprised by the unforseen reverse correlation between COVID and the metabolic condition. The increased risk for diabetes in COVID survivors was recently confirmed by US and German scientists.

A study of more than 180,000 American veterans done at the St. Louis VA Health Care System found that COVID survivors were 40% more likely to get a new diagnosis of diabetes within a year of their COVID diagnosis than a control group of veterans who avoided the virus. That works out to about 13.5 extra cases of diabetes per 1,000 COVID patients.

The increased risk for diabetes was evident even in people who had a low risk of diabetes before COVID, and the likelihood of newly diagnosed diabetes increased with the level of care patients received for COVID. In other words, the sicker the patients were with COVID, the more likely they were to develop diabetes.

The other study from Germany found that people who had mild COVID cases were 28% more likely to be diagnosed with type 2 diabetes compared to a control group consisting of patients who had an upper respiratory tract infection caused by a different bug. That study was based on an analysis of electronic records from a nationwide primary care database that followed patients, including almost 36,000 COVID cases, for 3-5 months. This means that these newly diagnosed cases of diabetes arose quickly after COVID infection, and were not a result of general respiratory infection, but were a specific consequence of CoV-2 infection.

Questions remain about whether diabetes that follows COVID is just temporary and reversible after patients fully recover, or whether it leads to chronic disease. In other words, if you had even mild COVID, you should ask your doctor to screen you for diabetes, which simply entails a fasting blood draw to test for glucose and hemoglobin A1c levels, which are elevated in diabetic patients.

A lingering question is how COVID leads to diabetes. Does the virus directly affect the insulin-secreting beta cells in the islets of the pancreas, or is new-onset diabetes caused by metabolic changes in fat cells which we know are readily infected by the virus. It is also possible that insulin production is perturbed by viral damage to the cells that line vessels supplying blood to the pancreas, indirectly causing death of insulin producing cells. A more trivial cause for post-COVID diabetes could simply be an unveiling of incipient diabetes that might have gone undiagnosed because people have been away from the health-care system during the pandemic. It is also possible that steroid medications prescribed to tame the COVID inflammatory response could elevate glucose levels in the blood, leading to a diabetes diagnosis.

Research into the cause of the COVID-diabetes link continues apace—stay tuned.

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Updated: Over 65? Roll Up Your Sleeve Again

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The Washington Post just reported that Pfizer and its partner-in-vax, BioNTech, plan to seek emergency authorization for a second CoV-2 booster for those of us 65 and older (you know who you are). It is intended to beef up immunity that wanes a bit a few months following the previous booster.

US data show protection against severe COVID illness is robust after the first booster, but falls somewhat from 91 percent effective in preventing severe illness to 78 percent effective over several months. Still, 78% protection is very good, but given how transmissible Omicron is, and the possible emergence of the Son-of-Omicron, which might be even more infectious and virulent, the idea behind a second booster is to offer people the chance to acquire the greatest level of protection possible. Not a bad idea.

The data that will be submitted to the FDA in support of the 2^nd booster probably will include real-world data collected in Israel, which has already rolled out the second shot, and has reduced infections and serious illness in people older than 60. This will likely not be the last CoV-2 vax we will see. Pfizer and BioNTech are also working on a vaccine more effective against all variants and provide more lasting protection. That remains on the horizon, so stay tuned.

For those of us 65 and older, we (at least the males in that demographic) remember draft cards. As we entered our later years, the draft card, if unburned, was replaced in our wallets with our AARP cards, and then accompanied with our Medicare cards. Now we need a new wallet pocket to accommodate our vax card.

On a personal note about cards, your maturing and slowing bloggeur admits favoring a certain grocery store in town because they still card him when he buys his bottles of 80 proof anti-vax remedies.

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Update: Three days after this was first posted, Moderna announced that it also has asked for FDA approval for a second booster. However, they ask that the booster be approved for all adults over 18, and not just for those over 65 as Pfizer/BioNTech have done. This request, like the one submitted by Pfizer/BioNTech is largely based on recent data from Israel. 

Moderna made a strategic decision to request approval for all adults in order to give the FDA flexibility in deciding which patients would be good candidates for the booster. In other words, they could decide that it also would benefit under 65 and so recommend.

 

 

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.

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?

Harry Became Severely Disabled After The Vaccine

Does the crowing of a rooster cause the sun to rise?

Harry: A follower of this blog, recently wrote to me about the experience of his senior friend, Harry. With permission, I relay the story here and add some thoughts.

Harry was 80 years old and living a healthy, robust life. He did his own home improvement projects, he was mobile and drove everywhere--he lived an active life. His only health concern was a bit of a problem with high blood pressure (who doesn’t at his age?) that was well controlled with a statin drug.

But, soon after his third shot (booster), his shoulder in the non-injection arm began stiffening. After that, one side of his groin became very painful and the pain migrated to the other side and then began shooting into his legs. Within weeks, he was unable to walk, relying on a walker or wheelchair. He became home-bound. His painful arm is now useless—he needs to hoist it with his other hand to get dressed. Same with both legs. Harry gets by each day on pain meds, but he is reluctant to take a higher dosage to fully control the pain as it makes him too groggy, so he only sleeps an hour or two at night due to the pain, then catnaps in his recliner throughout the day.

This sudden and quick decline began about a month after his booster shot so he was convinced his new maladies were a consequence of the vaccine.

VAERS: Harry’s case is the sort of case that is reported to the CDC’s Vaccine Adverse Effects Reporting Site or VAERS. When someone begins experiencing untoward health problems soon after vaccination they or their doc can easily report it on the VAERS site, which has served as an early warning system for identifying rare side effects of vaccines since 1990. Thousands of people have reported post-vaccination symptoms, and the site is accessible to anyone. Hence, there is a CDC database listing thousands of reports of health problems following COVID vaccination that you can pull up after a few clicks.

The CDC uses this uncorroborated raw anecdotal information to look for patterns that could point to previously unknown side effects of vaccines. This is common practice for all medicines after they have been approved for use. Data from clinical trials that form the basis for approval or rejection of a new medicine or vaccine only include results from ~40,000 test subjects. That is enough to discover very significant and fairly common side effects. But, after the medicine gets on the market, patient data still are collected in order to see if there are serious side effects that only appear in, say, one out of 250,000 people and that would not be found during the clinical trial on just 40,000 subjects. Remember the COX-2 anti-inflammatory drugs that were widely used in the 90s but were pulled because they were found to cause rare, but serious cardiovascular problems? This was found by collecting post-approval data from a few million people who had taken the drugs. Evaluating data collected after a medicine is on the market is referred to as post-market or Phase IV research. This is what the CDC uses the VAERS database for.

The CDC then digs into the raw VAERS reports to make sense of them. They first confirm the reports and then to see if they are just correlations or causative. Scientists look at further health data on the patients, and look for similar recurring problems in other patients. This also means that the raw data reported on the VAERS site are just that—raw. The raw data you can see on the site have not been confirmed or determined to have actually arisen from a vaccine side effect. In fact, the VAERS web site carries this clear disclaimer:

“VAERS reports alone cannot be used to determine if a vaccine caused or contributed to an adverse event or illness. The reports may contain information that is incomplete, inaccurate, coincidental, or unverifiable. In large part, reports to VAERS are voluntary, which means they are subject to biases. This creates specific limitations on how the data can be used scientifically. Data from VAERS reports should always be interpreted with these limitations in mind.”

The task for the CDC then is to separate health complaints that are just coincidental (i.e., that would have happened anyway without the vaccine) from those that are causal (i.e., that were caused by the vaccine). The fact alone that someone vomited a day after being vaccinated cannot be taken as proof that the vaccine caused the vomiting. There is a big difference between correlation, i.e., when two unrelated things happen together, vs causation when one thing leads to the other thing.

But, this is what the vaccine naysayers are doing—they look at the VAERS site and believe that all those raw reports are causative reports showing that the vaccines harm people. In other words, they completely ignore (or do not even read) the CDC disclaimer that the VAERS data are very incomplete and require further investigation before any conclusions can be drawn. When you hear someone on social media, TV, or the radio claim that tens of thousands of people have been seriously hurt by the vaccines, they are basing that claim on an incompetent (and possibly dishonest) use of the raw, uncorroborated VAERS data. I know this because every time I ask someone to back up their claim that the vaccines have injured tens of thousands of people, they eventually cite the VAERS database. When I quiz them further, most clearly have not even looked at the complicated VAERS web site, but are reporting second hand what they have heard elsewhere.

The truth is that few of the VAERS reports have been confirmed to be related to vaccination. Furthermore, the side effects mostly are of the “sore arm” variety, while serious health effects are vanishingly rare. Only about 200 people have actually died from the vaccines. All this compares to the almost 900,000 deaths (and counting) from COVID, and the ~20 million (and counting) cases of long term debilitation from long COVID. Remember, both the deaths and long COVID are prevented by the vaccines.

Back to Harry: Harry developed his debilitating conditions shortly after his third shot and attributed his woes to the vaccine. That is a temporal correlation—the debilitation happened shortly after the vaccine. But, is there anything that proves the vaccine caused Harry’s debilitation?  Well, a deep dive into Harry’s medical condition, like the CDC does into the data in its VAERS data, proves the vaccine did not cause Harry’s condition.

Sadly, a couple of days ago my blog friend told me that recent scans showed a mass on Harry’s lung. He has end-stage lung cancer that has spread to his pelvic bones and shoulder causing severe bone lesions and the pain. He will soon die from untreatable advanced cancer. It seems that Harry has a 50+ history as a smoker. But, he, as well as folks who abuse the VAERS system, totally ignore that kind of history and jump on the less-likely correlation between vaccination and diminishing health as proving a cause and effect relationship between the two. In doing this, people must assume that there could be no other causative factor for any malady that appears shortly after vaccination. Harry himself, ignored his long history of smoking, which is, by far, the leading cause of lung cancer, while the vaccines have been associated with zero cases of cancer.

This is a sad example of the mental gymnastics anti-vaxers resort to in order to confirm their bias against the vaccine. Real data be damned once they see a simple correlation that fits their bias.

Bottom line: Just as the vaccine did not cause Harry’s cancer, the crowing of the rooster does not cause the sun to rise. Both are correlations of events only temporally, not causally related.

Do not buy into the claims that the VAERS shows that people are suffering by the thousands from the vaccines. It is not true.

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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The History Of Vaccine Mandates In The US

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As employers and the President are pushing vaccine mandates because too many have refused them, voices are crying out for their perceived rights saying “my body my choice.” They do not like their bosses or the government telling them to get vaccinated. This is a clash between individual rights and public health measures designed to save lives and to protect the larger community. Who gets to make the key decisions? How far can the government and employers go? Do individual rights trump community safety?

On Sept. 9, Biden announced the most sweeping vaccine requirements in American history, ordering that businesses with 100 or more employees ensure that all their workers are either vaccinated or get tested weekly for the coronavirus. The new rules also require vaccinations for federal workers and for federal contractors, as well as for workers at healthcare facilities that receive funding from Medicare and Medicaid. This will affect about 100 million people.

The authority for these government mandates, claims Biden, is a 1970 federal statute that gives the Secretary of Labor authority to issue a six month Emergency Temporary Standard (ETS) to protect workers from “grave danger from exposure to substances or agents determined to be toxic or physically harmful.” His move has triggered a political and legal battle, with many Republican governors vowing to fight the mandates in court. The mandates raise several new questions regarding this vague statute: Is a virus a “…toxic or physically harmful substance?” Does COVID-19 present a “grave danger?” Has the executive branch exceeded its authority in offering a solution to a problem previously reserved to the states? Do these mandates violate the 14th Amendment by depriving workers of their personal liberties? It is important to note that Biden’s mandates do not actually make vaccines compulsory: The government may levy a fine or forbid a child from attending school, but no American will be forced to get an unwanted jab. This has not always been the case.

There are historical precedents for vaccine mandates and even for forced vaccination.

In February 1991, five Philadelphia children died from measles, a disease that was mostly eradicated in the US, due to vaccination. Measles once sickened millions of kids, each year hospitalizing ~50,000 and killing close to 500 before a successful vaccine was developed in 1963. After that, cases dropped dramatically as all states mandated measles shots for school children. Vaccine hesitancy and resistance were rare because people saw the tangible success of the measles vaccine.

But, in Philadelphia that winter of 1991, the serious cases of measles came from a single source, a church cult that rejected “…all means of healing apart from God’s way.” Church members took no medicines, owned no thermometers, and saw no doctors. Rejecting all birth control, they raised large families in close quarters, a recipe for the measles epidemic, which they cooked. Trying to contain the threat to the rest of the city, officials worked through the courts to gain access to the homes of the congregants and received the authority to vaccinate the children against the wishes of their parents. In this public health emergency, defending the parents’ anti-vax actions was close to impossible. Even the ACLU took a pass.

Vaccine mandates even appeared during the Revolutionary War. George Washington mandated that all his troops be immunized against smallpox, even against their will. He described smallpox to Virginia’s Governor Patrick Henry as “more destructive to an Army in a Natural Way, than the Enemy’s Sword.” As I wrote earlier in these pages, smallpox had doomed the Colonial Army’s assault on Quebec in 1775, and it threatened Washington’s main force. Washington’s mandate proved a brilliant gambit and smallpox largely disappeared from the ranks. Some historians point to the mandate as a major factor in winning the war against the Brits.

During that war, smallpox vaccination entailed a primitive vaccination procedure known as variolation. That involved opening a lesion from an infected person and scraping its contents into the arm of a recipient. It was effective, but the vaccinated person became quite ill for a couple of weeks, and about 3% of them died from the pox. Later, in 1796, the English scientist Edward Jenner discovered a much safer method of immunization using cowpox, a virus similar to smallpox that did not cause significant disease in people. But the new smallpox vaccine got a mixed reception in the US as some resisted it for reasons of personal safety based on the variolation experience. They rationalized, “what good could possibly come from polluting the body with dangerous foreign matter?” Or, “Why challenge the plans of the Creator?” Still, Jenner’s vaccine was a clear improvement over variolation and drove a steady decline in smallpox outbreaks throughout the 19th century. States began passing laws mandating smallpox vaccinations for school children, and some forcibly vaccinated prisoners, paupers, and orphans.

In 1905, the issue of vaccine mandates reached the Supreme Court in the seminal case of Jacobson v. Massachusetts. Henning Jacobson, a Lutheran pastor in Cambridge had defied a city ordinance requiring smallpox vaccinations during an outbreak. He refused to pay a $5 fine so he was arrested. Jacobson posited that “healthy and law-abiding” people like himself (even though he was disobeying the law at the time) posed a minimal danger to the community. He argued that even if his refusal to be vaccinated led to him spreading the smallpox virus, the only victims would be others “who failed or refused to be vaccinated.” In other words, he reasoned that it would be ok to not get the vax because the vaxed would be safe, but wholly ignored the rights to safety of those who were not vaxed. 

It is an argument that is repeated today about the CoV-2 vax. Using modern science that was not available in the early 20^th century, experts have repeatedly refuted this argument, explaining that many people who want the vax cannot be fully vaccinated because they are immunocompromised, or allergic to the vaccine’s contents, or do not have access to the vaccine. Also, we now know that the more RNA viruses, like the coronavirus, are allowed to spread, the greater the chance more deadly variants can appear. Jacobson’s contention that the decision to vaccinate solely belongs to the individual, not to the state, employers, or to medical authorities remains a central tenant of today's anti-vaxers.

The Supreme Court disagreed with Jacobson. The majority opinion, written by Justice John Marshall Harlan, asserted that “the liberty secured by the Constitution does not import an absolute right in each person to be at all times, and in all circumstances, wholly freed from restraint.” Rather, he argued, the Constitution rests upon “the fundamental principle of the social compact…that all shall be governed by certain laws for the protection, safety, prosperity and happiness of the people, and not for the profit, honor or private interests of any one man, family or class of men.” Jacobson had not only broken the law, the court suggested he also had violated the principle upon which a well-ordered society depends. We are not wholly independent the court ruled. The greater good of the community can trump individual rights.

Using Jacobson as precedent, the Supreme Court in 1922, upheld a local ordinance in San Antonio requiring proof of smallpox vaccination for people entering “public schools or other places of education.”  

Later, during World War II, the US military made vaccines mandatory for a host of diseases, such as typhoid, yellow fever and tetanus, and it still mandates certain vaccines for troops in certain deployments. Soon after the war very successful vaccines were developed against several childhood diseases like polio, measles, mumps and chickenpox. Guided by the Supreme Court’s ruling in Jacobson, all 50 states put laws on the books mandating many of these vaccinations for school children. Even today, many school districts and colleges mandate certain vaccines for students and staff. Hospitals, too, often mandate certain vaccines for their staff. Until lately, vaccine mandates have not generated much angst and anger.

Why is this? Perhaps vaccines have done their job too well: Many of them have erased the tragic evidence of why they were needed in the first place. The world no longer deals with small pox, thanks to the vaccine. Almost no one in this country has seen someone ravaged by polio, or a child hospitalized with measles, or who lost his hearing due to chicken pox, all thanks to vaccines. Yet, now with COVID-19, anti-vaccine anxieties have found their way into the political mainstream, especially among conservatives. An estimated 80 million American adults remain unvaccinated against COVID and represent potential factories for producing the next deadly coronavirus variant, which is very preventable.

As I have addressed before in these pages, many factors fuel resistance to the life-saving shots, including doubts about their quick development and their possible long-term effects. But a growing distrust of professional expertise, including medical science, has also played a role, which is unwarranted. Who are you going to believe, a medical scientist like me with nothing to gain in the debate (except the safety of my friends, family, and self), or someone who read a web post from folks who are selling nostrums they claim will protect you, like Dr. Steve Hotze, or from one of America’s Frontline Doctors whose web site claimed that gynecological problems were caused by having sex with demons? Do you jump on the side of those who tout that their individual freedoms have been abridged, but who do not consider the freedoms from disease of the greater community, and whom the courts already have decided against?

Almost 300 years ago, Benjamin Franklin struggled over whether to have his sons variolated against smallpox. In his “Autobiography,” he worried that well-meaning people were tragically misjudging the calculus between the risks and benefits of the procedure, as he had once done, with a tragic result. He wrote, “In 1736, I lost one of my sons, a fine boy of four years old, by the smallpox….I long regretted bitterly and still regret that I had not given it to him by inoculation. This I mention for the sake of the parents who omit that operation, on the supposition that they should never forgive themselves if a child died under it; my example showing that the regret may be the same either way, and that, therefore, the safer should be chosen.”

Unvaccinated People Are 11 Times More Likely To Die Of COVID-19

People who were not fully vaccinated this spring and summer were ~10 times more likely to be hospitalized, and 11 times more likely to die of COVID-19, than those who were fully vaccinated, according to one of three major studies published mid-September by the CDC.

That study did not distinguish between which vaccine the vaccinated cohort received. But, a second study compared the different vaccines and found that the Moderna vax was somewhat more effective in preventing hospitalizations than the Pfizer and J&J vaccines. This assessment was based on the largest US study to date of the real-world effectiveness of all three vaccines, involving about 32,000 patients seen in hospitals, emergency departments and urgent-care clinics across nine states from June through early August. While the three vaccines were collectively 86 percent effective in preventing hospitalization, protection was higher among Moderna vaccine recipients (95 percent) than among those who got the Pfizer (80 percent) or J&J vaccines (60 percent). That finding echoes a smaller study by the Mayo Clinic Health System in August, which showed the Moderna vaccine to be more effective than the Pfizer vax at preventing infections from the Delta variant.

Vaccine effectiveness against infection dropped from 90 percent last Spring, when Delta had not yet gained significant traction, to less than 80 percent from mid-June to mid-July, when Delta began out-competing other viral variants. Importantly, effectiveness against hospitalization and death showed barely any decline during the entire period. Thus, all vaccines remain quite effective and useful in protecting against illness.

Get one!

Why there is a difference in preventing infection between the Pfizer and Moderna mRNA vaccines was discussed earlier in these pages.