vaccines

A Critical Federal Vaccine Mandate

In response to the viral pandemic, the military ordered all service personnel to receive a controversial vaccine against the virus. The edict also prohibits military families and other civilians who live in high virus transmission areas from entering military bases. Furthermore, military personnel suspected of having contact with infected people are ordered to quarantine. All this was met with stiff opposition from many troops, from certain States, and even from Congress.

COVID-19 in 2021? 

No. Smallpox in 1777.

In 1777 facing an outbreak of smallpox that threatened his troops’ combat readiness, General George Washington ordered that all troops in the Continental Army be inoculated against smallpox. At the time, vaccination against smallpox was quite rare and not widely known. It involved a procedure known as variolation, where a small amount of pus from an active smallpox blister was scratched into the arm of a recipient. The low dose of the smallpox “pathogen” (the world did not know about viruses at that time) would, hopefully, just make the person sick and not kill him while conferring resistance to future smallpox exposure. Variolation was quite controversial and was even prohibited in Washington’s home state, Virginia. Variolation, in fact, did kill a relative of the King George of England. The relative was given too high a dose of pus and developed a full blown case of lethal smallpox. Many others also died from the procedure, hence the controversy.

When the revolution began, the Continentals faced not only the British military, but also the highly contagious smallpox virus carried by European troops coming from England and Germany. Europeans were well exposed to the disease where many survived and had protective immunity. Smallpox was relatively unknown in the Colonies so the colonists did not have that level of protection, and part of Washington’s genius was to realize that. As European troops arrived in Boston and New York, the virus spread through those cities and as the troops deployed, the disease threatened to run rampant through the colonies, potentially decimating the country and the Continental Army.

Washington, who survived smallpox as a child, was somewhat familiar with the rare practice of variolation, which was brought to England from Constantinople in 1721 by Lady Mary Wortley Montagu. By ordering it for his troops, despite stiff opposition from the Continental Congress, he acted as perhaps the country’s first public health advocate and averted a potentially disastrous epidemic among his troops.

After the battles of Lexington and Concord, the Continental Army encamped across the Charles River from Boston, which was stricken with smallpox from the arriving British soldiers. Washington prohibited anyone from Boston from entering his camps. He also swiftly quarantined anyone suspected of being infected, which was perhaps the first example of contact tracing. Washington’s actions were very heady stuff for the pre-epidemiology, pre-infectious disease era.

Washington did not immediately order variolation since he knew that the significant side effects of the procedure would temporarily incapacitate the troops who would take a few weeks to recover. Instead, he waited until the fighting subsided and both sides took a breather. Then he ordered the vaccinations against the wishes of the Continental Congress which initially forbade army surgeons from performing variolation.  Washington first ordered that all new recruits undergo the procedure believing that they would be healthy by the time they were battle ready and when the war was battle was ready for them.

Washington’s prescience was soon proven. Several thousand Continental troops marched on Quebec under Major General John Thomas who refused to follow Washington’s vaccination orders. He, and one-third of his 10,000 soldiers died from the pox and the force was soundly defeated.

Washington then moved to inoculate his main army and by 1777, 40,000 soldiers had been vaccinated in defiance of Congress. Infection rates in the Continental Army dropped from 20% to 1% and, after seeing these results, lawmakers soon repealed bans on variolation across the Colonies. One historian claims that Washington’s decision to inoculate his troops “…was the most important strategic decision of his military career.”

That radical decision could be a big reason why we do not today have the Union Jack flying over these 50 colonies. I find all of this to be an amazing, but little known fact about the American Revolution. Variolation might have been as important to the Colonists’ victory as was the French Navy finally showing up at Yorktown.

Immunology rocks as much as French naval cannons!

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Average US Life Expectancy Drops In 2020

There remain people who try to explain away COVID-19 mortality as due to underlying conditions like diabetes or asthma. This is like claiming that someone with diabetes who was run over by a bus was felled by the diabetes, not the bus. I continue to point these skeptics to two actuarial studies done in the US and UK that showed that COVID-19 was causing much earlier than expected deaths in patients with these and other comorbid conditions. All of this was later confirmed in another report published in the Journal of the American Medical Association. In other words, research has well established COVID-19 as the cause of death in most patients with comorbid conditions.

If something causes the death rate to increase, it is reasonable to expect life expectancy to decrease. This is what has happened in the US during the pandemic. Two recent studies reveal just how much of a toll COVID-19 has taken on life expectancy in the US in 2020.

An updated study published in mid-June (originally published in January) in the Journal of the American Medical Association by researchers from the USC School of Gerontology and from Princeton University reported that in 2020, the average US life expectancy dropped by 1.3 years (from 78.74 to 77.43 years). It also reported that compared to white people, the reduction in life expectancy was three times as large for Latinos and twice as large for blacks. The research was based on data obtained from the CDC, the Census Bureau, and the US Vital Statistics System. The study warned to expect a continued decline in life expectancy in 2021.

A separate study published around the same time in the British Medical Journal, confirmed the racial disparity in life expectancy due to COVID-19, and indicated that the pandemic took a much greater toll on life expectancy in the US than in other high-income nations.

The effects of the coronavirus pandemic on life expectancy include deaths directly attributed to COVID-19, as well as those due to pandemic-related reduced access to health care. It is important to understand that these factors are partly offset by a simultaneous reduction in deaths from other causes such as other infectious diseases and accidents as Americans sanitized more and traveled less. In other words, we saw a reduction in deaths due to common causes, which should improve life expectancy. Therefore, the fact that life expectancy dropped, rather than improved, makes the overall decline in longevity more alarming.

Increased mortality represents only part of the burden of COVID-19; for every death, a much larger number of infected individuals experience serious acute illness that requires hospitalization, many more face long term health and life complications that drain personal finances, stress health resources, and affect ability to work at jobs.

Greater than 95% of hospitalizations and >99% of COVID-19 deaths now occur in unvaccinated people. Almost all of this is preventable with vaccination.


Vaccines And Myocarditis In Young People

Rare cases of inflammation of the heart muscle, or myocarditis, have been found in 1,200 younger people (16-24) after receiving an mRNA vaccine, and this has been used by anti-vaxers to further the hysteria around the vaccine. But, if you talk to a pediatric cardiologist you will learn that we should be much more worried about the disease than the vaccine. There simply is no comparison.

The post-vaccine myocarditis is very mild, has caused no deaths, is easily treated with anti-inflammatory drugs, and quickly goes away without lasting problems. On the other hand, COVID-19 can linger for months, and, as of June 9, has caused ~3000 deaths in young people. Because of this, the American Heart Association and American Academy of Pediatrics continue to strongly recommend vaccination for young people.

Myocarditis in young people is not a new thing, and is usually associated with a viral or bacterial infection. One vaccine against small pox has also been weakly linked to myocarditis. People from puberty through their early 30s are at higher risk for myocarditis, according to the Myocarditis Foundation. Males are affected twice as often as females. Most of these cases are very mild and many times people with myocarditis do not even know they have the problem. The incidence of myocarditis in young people peaks this time of year when the coxsackie virus, which can infect the heart, is more common. This means that an undetermined fraction of post-vaccine myocarditis is likely due to concomitant infection with coxsakie virus and not due to the vaccine.

Bottom line: Post-vaccine myocarditis is much ado about next to nothing. This should not cause one to hesitate getting the vaccine, unless the person has another underlying cardiac problem. The mildness of this rare side effect contrasts with the thousands of young people who have contracted serious COVID-19 and have even succumbed to the infection. While severe morbidity and mortality from COVID-19 is rarer in children and adolescents than in older adults, the number of cases in young people has been steadily rising on a weekly basis according to the CDC. This trend will likely accelerate as the more infectious, and possibly more lethal Delta variant becomes dominant in the US. Since most older adults have been vaccinated, that leaves younger people as available targets for the new virus surge. There is no rational reason for 99.9% of people to not be vaccinated.

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Almost All US COVID-19 Deaths Occur In Un-Vaccinated People

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As the anti-CoV-2 vaccines roll out in the US, COVID-19 infections and hospitalizations have plummeted. Deaths, too, have plummeted from a peak of 3,400 a day in mid-January to fewer than 300 today. About 63% of vaccine-eligible Americans (those 12 and older) have received at least one vaccine dose, and 53% are fully vaccinated. All this demonstrates the efficacy of the vaccines.

Also showing how effective the vaccines are, almost all new infections, hospitalizations, and deaths now occur in unvaccinated people. An Associated Press analysis of CDC data since May reveals that fewer than 1,200 vaccinated people, out of a total of 853,000, were hospitalized for COVID-19. Furthermore, in May there were 18,000 COVID-19 deaths in the US, of which only 150 were fully vaccinated. The vaccines are so successful that the CDC director was quoted as saying, “…nearly every death…due to COVID-19 is, at this point, is entirely preventable.” Let me repeat that, COVID-19 deaths are almost 100% preventable now because of the vaccines. Let that sink in, anti-vaxers.

These observations are especially relevant in the face of the Delta, or double mutant virus variant that has taken over India, the UK, Israel, and is rapidly spreading in the US. As I reported earlier, this double mutant variant first appeared in India and carried the same mutations as two earlier variants first identified in the UK and in South Africa. Individually, these mutations made the variants either more virulent, or able to spread faster than the parent virus. Together, they create a more dangerous, faster spreading virus. The good news was that the current vaccines are pretty effective against the Delta variant.

However, there are two concerning things about the Delta variant that raise alarms. First, in Israel, about half of adults infected with the variant were fully vaccinated with the Pfizer vaccine. 90% of new infections in that country are now caused by the Delta variant and children under 16 account for about half of those new infections. So-called “break-through infections” can occur in fully vaccinated people, but have been, so far, rare. This makes the high level of break-through infections in Israel worrisome. Breakthrough infections in previously vaccinated people are especially worrisome--how is the virus avoiding vaccine immunity? These kind of infections are what most concerns this writer, since a virus that can replicate in a fully infected person suggests we could have a new variant that resists vaccine immunity. We do not yet know why break-through infections appear with greater frequency in that country. However, when vaccinated people are infected, they almost always avoid severe symptoms. Hopefully, this will continue to be the case in Israel. We will see.

The second concerning thing is something I have earlier warned anti-vaxers about—the emergence of further variants that could be even more virulent or able to avoid vaccine immunity. India has just reported a new Delta variant, referred to as “Delta Plus.” It also has been detected in 11 countries including the UK, Japan, and the US. Little is known about this variant, but it has been declared a “variant of concern” and is being closely watched. Again, we will see.

Delta Plus arose in people who have not been vaccinated. As I have strongly argued in these pages, each anti-vaxer represents a potential incubator for a new variant for which current vaccines are ineffective and/or is much more lethal. And as I also pleaded in a previous blog post, “get over yourselves; it is not all about you!” Get the shots.


Anti-vaxers, Get Over Yourselves--The Vaccine Is Not All About You

As predicted, viral variants are now causing most of the new cases of COVID-19 disease around the world. The Delta variant, formerly known as the “double mutant,” which first arose in India and as earlier discussed in these pages, is extremely transmissible and seems to cause more severe illness. It arose in India because the country was way under-vaccinated and, therefore, a prime incubator for producing more lethal viral variants. As the virus replicates in a person’s cells, then spreads to another person, it accumulates small mutations that, by chance, can make a significant difference in its virulence. The virus replicated over and over and over in unvaccinated India and a more potent strain evolved. It is a matter of time before an even more potent virus emerges that resists the current vaccines, thanks to people who refuse to be vaccinated. That refusal potentially affects all of us, not just the vaccine recipient.

It is one thing to not be vaccinated because of vaccine supply and delivery problems. India, and countries in Africa and South America fall into this category. It is another thing to willfully refuse to be vaccinated when the vax is readily available. The latter is just wrong and inexcusable. There is no rational reason to not be vaccinated!

Anti-vaxers cite a litany of false claims about how the vaccine might be dangerous for them (the evidence refutes that). They say it is experimental (it has been well proven and uses technologies that are decades old!), or that it is not FDA approved (it is!), or that it is ‘gene therapy’ (it is NOT!), or that people have died or become sterile from it (flat wrong!). Anti-vaxers also complain that we do not know the long term effects of the vax (name ONE vax that had long term effects!). After millions have been infected with the virus or have been vaccinated, the evidence clearly shows that the worst thing that can happen to someone is to be infected with the virus, and that the safest thing is to get the shot. Follow the science, not your emotions.

Note that the objections to the vaccine are all self-focused. No thought is given to the reality that if an unvaccinated person is infected and does not practice caution, he will be responsible for spreading the virus to his family, friends and strangers. And, he might very well be the source of the next, more deadly variant. As I wrote earlier, a great example of how vaccines protect others is the Japanese experience with flu vaccines. After Japan mandated that school kids be vaccinated against the flu, elderly flu deaths plummeted. The vaccine clearly did not just benefit the kids, it benefited others with whom they had contact. The same holds true with the coronavirus vaccine.

Unvaccinated people in India led to the emergence of the Delta virus variant that has overwhelmed health care systems in India. Even younger, healthier people are getting sick. Delta is now spreading in unvaccinated people in at least 62 countries, including the US where it now accounts for 20 percent of new cases, up from just 2 percent a couple of weeks ago. You do not have to be a scientist to see where that trend is leading.

Delta also is now the dominant strain in the UK accounting for three quarters of new cases there. It has forced a four-week pause in the UK’s reopening plans. The variant could also affect reopening in the US as well, thanks to the anti-vaxers.

The good news is that people who are fully vaccinated are well-protected against the Delta and other variants—so far. Again, it is just a matter of time that a vaccine-resistant variant emerges. Again, there is no rational reason to not be vaccinated, but there are billions of reasons to get vaccinated. It is not all about you, but also about your fellow humans on the planet. Get the shot!

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Why It Is Necessary To Vaccinate Kids

Vaccine makers are applying to the FDA for approval to give the COVID-19 vaccines to children. Some people have questioned the need for this since kids seldom get sick, let alone die from COVID-19. But, there is a very good reason to vaccinate them, which is to protect them, as well as the rest of us from the emerging new viral variants that are more infectious and more potent and that I discussed earlier.

Vaccines do two things; 1) they protect the vaccinated from the disease, and 2) they prevent the further spread of the pathogen and disease. A good example of the latter point is Japan and flu vaccines. A number of years ago, Japan mandated that all school kids be vaccinated against the flu. A major result was a sharp drop in flu deaths in the elderly. Kids are walking incubators for respiratory viruses and carry them home for their families to enjoy. Thus, Japan's flu vaccination program meant that fewer kids were catching the flu and carrying it home to infect their parents and grandparents. Hence, flu mortality dropped.

That is why we need to vaccinate kids against CoV-2 even though they seldom get seriously ill from it. Related to that point is the fact that the more CoV-2 spreads, the greater the chance that the virus will mutate into variants that are increasingly infectious, more deadly, and that can evade the immune response to the current vaccines. If that happened, we would be starting all over again. Hundreds of thousands, if not millions around the world would die, countless more would suffer long term consequences from COVID-19, and the disease could very well become more serious in young people. We already are seeing increases in infections and hospitalizations in younger, healthier people from the viral variants that already have arisen in the UK, South Africa, Brazil, and India.

We need to vaccinate kids in order to slow as much as possible transmission of this virus in order to minimize the development of potentially more deadly variants.


What Caused India’s Devastating Second Wave?

Understanding what contributed to a second, more intense COVID-19 surge in India can inform the rest of the world on how to avoid a similar surge for this and future pathogens. This outbreak threatens to extend the pandemic itself and drive world-wide infections to new highs, creating an enormous a breeding ground for new and potentially more dangerous viral variants. If variants emerge that are not touched by the current vaccines, the world will be at square one with the pandemic. What a depressing thought.

It appears that the second wave arose due to a combination of three things: 1) India’s relaxing quarantine measures back in January, 2) the emergence of more rapidly spreading viral variants, including one that first appeared in India, and 3) a very poor rollout of vaccines to protect India’s population from spread of the virus. These are further discussed below.

  1. Relaxed safety measures. India’s second surge came after loosening restrictions, which let public complacency set in, which, in turn, was exacerbated by government officials like Prime Minister Modi and Health Minister Harsh Vardhan declaring that the pandemic was defeated. Life returned to normal. Masks went away, as did social-distancing. Weddings and parties resumed, which usually are large events in India. A new season of state-level elections ushered in big political rallies and street parades. A massive religious festival known as the Kumbh Mela took place, bringing an estimated 5 million Hindu pilgrims to the banks of the river Ganges in April. By mid-March, cases started gradually climbing again—then suddenly accelerated, becoming a vertical line rather than an upward sloping curve. The government was slow to respond. It was not until late April that Modi finally acknowledged the urgency of the situation. Local containment measures are beginning to be enacted, including shutting down the capitol of Dehli, and a few Indian states. However, Modi remains reluctant to enact country-wide restrictions like he did during the first wave. Without a more aggressive vaccine campaign, that could be a bad decision.

The more the virus spreads throughout India, and even into its neighboring countries of Nepal, Pakistan, and Bangladesh, the greater the risk that it will generate more infectious and dangerous viral variants that will not be affected by the current vaccines. If that happens, well vaccinated countries will have to start over. That is not a pleasant prospect, and is further discussed below.

  1. More infectious viral variants. India’s more deadly second wave of the CoV-2 virus can also be attributed to more infectious and more persistent viral variants. In this second wave, India, like many other countries, has been inundated with viral variants first identified in the UK and South Africa that were recently discussed in these pages. The UK variant has a mutation in its spike protein that makes it more infectious than its parent virus. The South African variant has a different mutation in its spike protein that makes the virus more resistant to some vaccines.

India’s second surge also has introduced the world to a unique viral variant dubbed the "double mutant," which was first identified in October. It is now the dominant strain in the state of Maharashtra, home to India’s financial center, Mumbai.

“Double mutant” is actually a misnomer for this variant since it has 13 mutations throughout its genome. However, it acquired that sobriquet because it has joined the UK and South African spike protein mutations in the same virus. It is a double whammy.

While scientists are still learning about the double mutant variant, India is seeing people who were previously infected become re-infected with this new variant. Also, younger and healthier people are being hospitalized in greater numbers. These observations are concerning. Similar observations of re-infection have also been seen in Brazil with yet another viral variant that was first identified there (more about Brazil in a future post). The ability of viral variants to re-infect people can be an important driver of future pandemic waves even in countries where the population is well vaccinated, but where isolation measures have been lifted or ignored.

For the country overall, the double mutant virus made up 70.4% of the samples collected during the week ending March 25, and that is compared with 16.1% just three weeks earlier, according to Covid CG, a tracking tool from the Broad Institute of MIT and Harvard. The tool mines data from the GISAID Initiative, a global database for coronavirus genomes. These data also show that the double mutant virus has already hopped to at least 21 countries including the US. In Australia viral genome sequencing showed that the double mutant made up 40% of the samples collected over the week ending April 15, compared with 16.7% a month earlier. It accounted for 66.7% of samples from New Zealand for the week that ended April 8, up from 20% a month ago. It also has been detected in California, according to Dr. Benjamin Pinsky, director of the Clinical Virology Laboratory at Stanford University. Clearly, where the double mutant virus appears, it quickly achieves dominance.

  1. Poor vaccine distribution. As of 4/30, India had only administered 15 million vaccinations, a tiny proportion of its population of 1.4 billion people. The country is the primary producer of the AstraZeneca vaccine that has run into supply chain problems causing delays in vaccine delivery. In February, Biden signed the Defense Production Act to boost U.S. COVID-19 vaccine production but that decision cut off US exports of raw materials that India needs in order to maintain its vaccine production capabilities. Thus, vaccine makers around the world, including the Serum Institute of India (SII), the largest vaccine manufacturer in the world, face a shortage of materials to make COVID-19 vaccines. The ban has garnered much criticism as resource hoarding that threatens global vaccine production. On April 16, SII appealed directly to Biden to lift the embargo of raw material exports so that vaccine production could continue. Several days later, the White House announced it would partially lift the ban for materials the Indian company needed to manufacture the AstraZeneca vaccine, specifically.

The US also inexplicably has a large stockpile of millions of doses of the AstraZeneca vaccine, that were made here, even though it is not approved for use in the US. If we are not using it, why not release the stores to the world? The Biden administration also has faced criticism for hoarding these doses that could help India and other countries around the world that also are experiencing a new surge in infections. On Friday, April 30th, the U.S. Chamber of Commerce called on Biden release the AstraZeneca vaccines to India and other hard-hit countries.

There is some irony in all of this since India is a huge manufacturer of vaccines and pharmaceuticals for the world, and likes to bill itself as the “pharmacy of the world.” India produces 60 percent of the world’s vaccines, but cannot supply its own country, partly because of reduced production due to the supply chain problems, but also because it failed to order sufficient vaccine doses. India almost completely halted vaccine exports last month in order to divert supplies to its domestic population, which is affecting supply in the rest of the world. Rather than rely on its own manufacturers for vaccines, India approved Russia’s Sputnik vaccine, and has fast-tracked the approval process for other vaccines manufactured in foreign countries. That means that while the industrialized world was being vaccinated with vaccines produced in India, the country was still looking at approving foreign-made vaccines for use in its country.

Bottom line. The combination of relaxed safety protocols, the appearance of deadlier viral variants, and poor distribution of vaccines to its people has left the country as the world’s epicenter for the pandemic. As the virus races through its huge population, all of this provides an enormous breeding ground for new variants to arise, which is worrisome even for countries that have had successful vaccine rollouts and have begun to see reduced viral spread. Let us hope this is not a perfect storm for restarting the pandemic with vaccine-resistant variants.

And India is not the only problem. In Africa, vaccination is also off to a slow start. Just 6m doses have been administered in sub-Saharan Africa, fewer than in New Jersey. Just 1% of African adults have received a first jab, versus a global average of 13%. Prepare for Africa to become the next hot-spot and breeding ground for troublesome variants, if Brazil and South America do not beat them to the punch.

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COVID-19 mRNA Vaccines Safe For Pregnant Women

I have received a few questions about the safety of the coronavirus vaccines for pregnant and lactating women. I discussed toward the end of one blog post about how maternal immunity can benefit the baby by passing the mother’s antibodies across the placenta and given in mother’s milk, thereby protecting neonates whose immune systems are still developing.

Now, an analysis of the CDC’s Vaccine Adverse Event Reporting System, and the “v-safe after vaccination health checker," and its associated v-safe pregnancy registry, shows that the Pfizer and Moderna mRNA vaccines appear to be safe for mothers and babies. The analysis examined almost 36,000 pregnant women who received one of the mRNA vaccines, and was reported in the New England Journal of Medicine.

Compared to non-pregnant women, pregnant women who were vaccinated reported more injection-site pain, but fewer incidents of headaches, myalgia (muscle pain), chills, and fever. About 14% of vaccinated pregnant women suffered pregnancy loss while about 9% of neonates born to vaccinated women suffered adverse events, and 3% of them were undersized. No neonatal deaths were reported. The important thing is that the incidence of these outcomes was similar to the incidence observed in pregnant women before the pandemic arose. Most of the pregnant women who were evaluated were vaccinated in the third trimester.

The study concluded that the data revealed no obvious warning signals for pregnant women who receive the mRNA vaccines. But, it also advised that followup with women vaccinated earlier in pregnancy is warranted.

Stay tuned.


Vying With Viral Variants

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The back story: There are four known CoV-2 variants in the US that are more transmissible than the parent strain. They are the UK variant, which is 70% more infectious and 60% more deadly than the original strain. There also are Californian and Brazilian variants that are more transmissible, but it is not yet known if they are more deadly. However, in Brazil, their variant is associated with a significant increase in infections and ICU stays for young, healthy, unvaccinated people. Fortunately, the current vaccines seem to be effective at preventing infection with these strains.

More worrisome is the South African variant that is 50% more transmissible. It is worrisome because the AstraZeneca vaccine is not very effective against this variant, and a very recent, but a small study out of Israel suggests that the Pfizer vax might have reduced efficacy against the S. African variant. It is not yet known if this strain causes more serious disease. These findings provide evidence that mutation can produce new viral strains that can evade the immune response to the viral spike protein.

Two other variants, the so-called New York variant, and a second Brazilian variant have early signs of being more infectious or even being able to reinfect people who previously had COVID-19. Data are still being collected in order to better understand the risk that these variants pose. Stay tuned.

You can follow the variants in the US here.

The bottom line is that the world is in a race to roll out vaccines faster than troubling virus variants can arise. The UK is expected to reach herd immunity​ early next week. Infections there dropped by 60% during March, with deaths dropping more rapidly, indicating that the vaccines are helping prevent severe illness and viral spread. Meanwhile, the US leads the world in total vaccines administered (175 million), with 43% of the adult population having received at least one shot. More than 700 million doses have been administered world-wide.

The major concern is that a too-slow vaccine distribution, such as what has happened in Brazil, will encourage more virulent variants to arise. If we don’t quickly achieve herd immunity across the world, it probably will just be a matter of time before a variant arose that renders the current vaccines useless, and we would have to start over.

What is a world to do? Besides increasing surveillance of viral variants, a couple more prevention initiatives are in the works. One is economic and the other scientific.

Economics of viral mitigation: The economic approach is detailed in an article by the Associated Press Economics Writer, Martin Crutsinger. Basically, the International Monetary Fund (IMF) proposes giving $650 million to support vulnerable countries struggling to deal with a global pandemic. Along with that, the Group of 20 major industrial countries issued a joint statement that announced a six-month moratorium on debt payments by 73 of the world’s poorest countries.

The rationale behind these actions is to ensure that poor countries, where vaccinations are lagging due to lack of resources and infrastructure, can pick up the pace of vaccination. Their lag in rolling out shots is a threat to the whole world, even while wealthy countries are approaching herd immunity. In order to beat the variants, vaccines are needed to quickly create herd immunity and stop viral spread before a variant that can avoid vaccine immunity appears. When countries lag in vaccinations, the virus continues to spread increasing the chance for an immune-avoiding variant to pop up. Such a variant can then spread to countries that are highly vaccinated, starting the pandemic over again because the current vaccines would be ineffective. We would be back at square one.

Science to the rescue: So far, all the vaccines, except one from China, which uses the whole virus, direct the immune response to the viral spike protein that is used to attach to receptors on the surface of cells in your body. The viral variants we are concerned about show mutations in the spike protein that allow them to become more infectious, and in one case, to be less affected by some of the vaccines. In addition to trying to  nip the virus in the bud by quickly building world-wide herd immunity, new vaccine strategies are being developed to quickly respond to newly arising CoV-2 variants, and even to respond to entirely new strains of viruses that will arise in the future.

  • One way to do this is to begin developing booster shots as soon as a coronavirus variant becomes a significant concern. With the new mRNA, and adenovirus vaccine delivery technology, this is eminently possible. It just requires scientists around the world being vigilant for new variants. Pfizer, Moderna, AstraZeneca, and Johnson & Johnson have all said they’re starting work on developing booster shots to the known variants.
  • Last week, the US government announced a pact with CureVac to tackle variants, pairing artificial intelligence to predict future mutations that can be quickly addressed with modern vaccine technology. London-based GlaxoSmithKline is also working with CureVac on mutant-quelling vaccines.
  • Another strategy is to identify viral molecules other than the spike protein that the immune system can recognize. Efforts are underway to test the immunogenicity of what is called the CoV-2 nucleocapsid, or N protein, which wraps itself around the viral RNA. If successful, future vaccines could incorporate both the N and S (or spike) proteins, which would require the virus to mutate both of those genes in order to avoid vaccine-induced immunity, a greatly tougher task for the virus.
  • Researchers at Moderna, Novavax, and the University of Oxford are designing multivalent vaccine strategies to protect against multiple CoV-2 variants with a single shot, and even against new viruses that might emerge in the future. A similar strategy is used with the annual flu vaccine, which usually incorporates four different influenza strains in one shot. It is also used with measles, mumps, and rubella vaccines. Some vaccines against pneumonia target as many as 23 variants of that pathogen.
  • Finally, a wholly new vaccine technology has shown recent success in animal studies. It works by chemically attaching many short viral protein sequences from different CoV-2 variants, and even from completely different coronaviruses, to engineered nanoparticles that are then injected. In mice, this single vaccine induced an antibody response capable of neutralizing many different coronavirus strains. If successful, this could represent a universal vaccine capable of neutralizing CoV-2 and its variants, as well as other coronaviruses such as SARS and MERS with a single vaccine. And it can be easily modified to quickly respond to future viral epidemics caused by novel coronaviruses or other viruses that will certainly arise. The technology is being developed at Cal Tech using technology developed by collaborators at Oxford University. The nanoparticle platform is a “cage” made from 60 identical proteins. Each of those proteins has a small protein tag that functions like a piece of Velcro to which the viral protein sequences stick resulting in a vaccine nanoparticle with short protein sequences from four to eight distinct coronavirus strains on its surface. If successful, this could prevent infection and disease for several different viruses with a single shot.

 We are in a revolutionary era of vaccinology. BioX marches on.


Paying The Piper

In the face of a pandemic caused by a new and deadly virus, states and local governments enact social-distancing measures, bans on crowds, closure orders, and mask mandates in an effort to flatten the curve and prevent health care systems from being overwhelmed with critically infected people. Initially, people are fairly compliant with the order, but, as the days of restriction turn into weeks, then months, compliance wanes. Theater owners complain about financial losses. Clergy bemoan church closures. People argue whether children are safer in classrooms or at home, and many rebel at having to wear face masks in public, complaining that the government has no right to infringe on their civil liberties. Sound familiar?

But this is not about the 2020-21 coronavirus pandemic; these are descriptions of the US response to the deadly Spanish flu pandemic between 1918 and 1920. In many ways our current pandemic mirrors the one that occurred a century ago, and that is presciently described in the book, The Great Influenza, by John M. Barry. Like CoV-2, the H1N1 “Spanish” flu killed less than 1% of the people it infected, but during a third wave of infection with a more virulent strain, that flu killed more people around the world in just 24 weeks than were killed in the 10 years of WWI and WWII combined! In remote areas with little access to health care, the flu wiped out entire villages.

Like COVID-19, the Spanish flu pandemic hit hard and fast, going from a handful of reported cases in a few cities to a nationwide outbreak within a few weeks, then with increased mobility due to WWI, it quickly spread around the world, from America to Europe and back. Many communities, responding to the ebbs and flows of the epidemic waves, issued several rounds of closure in an attempt to keep the disease in check. These social-distancing orders worked to reduce cases and deaths. However, just as today, they often proved difficult to maintain. By the late autumn of 1918, just weeks after wide-spread social-distancing orders went into effect, the pandemic seemed to be coming to an end as the number of new infections declined. People clamored to return to their normal lives. Businesses pressed officials to be allowed to reopen. Believing the pandemic was waning, some state and local authorities began rescinding public health edicts. Sound familiar?

Americans hurried to return to their pre-pandemic routines. In some cities, they packed into movie theaters and dance halls, crowded into stores and shops, and gathered with friends and family for holidays and celebrations. Meanwhile, officials warned the nation that cases and deaths likely would continue for months to come, but the warnings fell on increasingly deaf ears, as people enjoyed a return to normalcy. The nation carried on, inured to the toll the pandemic was taking. But as health officials warned, the pandemic wore on, stretching into a third deadly wave that lasted through the spring of 1919, with a fourth wave hitting in the winter of 1920. Some blamed those world-wide resurgences on careless Americans.

The different responses and experiences of two large American cities are noteworthy here. In Denver, local business interests lobbied heavily to get rid of the quarantine measures that had shut down schools, churches, libraries, pool halls, businesses, and theaters. The city capitulated. The city opened up and was hammered by the deadly third wave of the flu. On Armistice Day, November 11, 1918, residents poured out of their homes to celebrate the end of World War I. A few days later, many were dead, victims of the pandemic flu. Two weeks later, a headline in the Denver Post captured the devastation: “All Flu Records Smashed in Denver in Last 24 Hours.”  An editorial in the Denver Monthly Magazine said, “For some reason, even the most enlightened citizens will not take the influenza epidemic seriously. They know that it is the most widespread epidemic that has ever visited America. They know the disease is a deadly menace and snuffs out life almost before the victim realizes he is ill. Yet when health officers try to impress upon people the necessity of following essential rules and regulations, the average citizen simply refuses to heed these admonitions.”

In contrast to Denver, St. Louis enacted and maintained strong social distancing measures, including in-home quarantines for infected people. They experienced a fraction of the deaths that Denver saw. The quarantine measures worked there.

The similarities in our responses to the 1919-20 flu and 2020-? coronavirus pandemics are noteworthy. But, there is one big, hopefully defining difference between the two pandemics that might make the outcomes quite different. Vaccines. There were no flu vaccines to rescue the world from the ravages of the Spanish flu. In fact, the influenza virus would not even be discovered for another 15 years, and a vaccine was not available until 1945. For the first 12 or so months of the current coronavirus pandemic, we were in the same boat—we faced a novel virus with no vaccine or effective medicine. When there is no available medical response to a pathogen, we must rely on protective public health measures to provide a buffer against the pathogen while we learn how to respond to it.

Today, we have significant advantages with a much better understanding of virology and epidemiology then we did in 1918. We know that both social distancing and masking work to help save lives. Most critically, we now have multiple safe and effective anti-CoV-2 vaccines that are being deployed, with the pace of vaccinations increasingly weekly.

Still, the deadly third wave of influenza shows what can happen when people prematurely relax their guard against viruses that can mutate and become more deadly. That is why we must remain vigilant while the coronavirus vaccines roll out. We are still learning about this virus and are only beginning to learn about the variants spawned by the virus. We still need a public health buffer from the virus to keep us safe until we better understand its full capabilities and can vaccinate more people.

Be smart. Stay safe. Get the vaccine.