herd immunity

‘Tis The Season To…..Mask Up Again??

"It's a bug hunt!"

-Private Hudson, in “Aliens”

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Why risk what can be prevented by a simple vaccination?

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What We Learned From Sweden’s Response To COVID

Sometimes I wonder whether the world is being run by smart people who are putting us on or by imbeciles who really mean it.
― Laurence J. Peter, The Peter Principle

Many people have asked why we didn't let the virus hit us like a big wave and get it over with. The Great Barrington Declaration (GBD), a letter penned by three physicians, favored such an approach and called it “focused protection.” It recommended quarantining the highly vulnerable, i.e., the elderly and those with high risk factors like diabetes, heart and lung disease, etc., and letting the virus run amok through the rest of the population to quickly build natural herd immunity across the country. They said we should do away with non-pharmaceutical interventions that prevent infections, such as masks, sanitation, personal distancing, quarantines, closings, etc. The recommendation was published as a letter on October 5, 2020 because no medical journal would accept it as an article. Vaccines were still considered to be months away at that time, but actually began to roll out in mid-December of that year. Admittedly, the letter’s authors did not have a crystal ball.

We didn’t accept that recommendation, but Sweden did something very similar on their own and kept their country open and had considerably less morbidity and mortality than the US. Armchair health experts who learned their subjects at Google and Facebook Universities have been clucking their tongues and scolding the CDC and public health professionals ever since. Should we have responded like Sweden did? Would it have been better if we had followed the recommendations made in the GBD?

When the declaration came out, it was widely panned as being ridiculous by health experts and organizations around the world. A Yale epidemiologist pointed out that almost half the US population would be considered to have an underlying risk factor for COVID meaning that half the population would have to be quarantined from the other half, not much different from the protective measures already underway at that point. It also would have meant that people at less risk would be exposed to a rather nasty virus. They essentially would be sacrificed to a disease more lethal than any flu we have encountered since 1918. And then there is the problem with long COVID and other morbidities such as an uptick in new onset diabetes in many COVID survivors. Even though kids have a very low level of mortality from COVID, the disease was still much worse than any flu for them and too many of them were hospitalized in serious shape with a malady called multisystem inflammatory syndrome or MIS. This was the sacrifice the folks who proposed the GBD were willing to impose on half the population.

Anyway, this post is supposed to be about Sweden, not the US. Did Sweden’s experiment turn out as positive as many people believe? It depends on which countries you compare it to. Comparing the Swedish experience to that of the US, it seems they did pretty well. They did not shut down and had much less mortality than we did. But is that an accurate apples-to-apples comparison? Sweden is a country of just over 10 million people. Its demographic is much more homogenous than that in the US and it has much less poverty. In the US, COVID hit impoverished and minority populations especially hard. They have fewer medical resources to deal with the disease. In contrast, Sweden does not have such a large minority or poor population and it has cradle to grave social welfare for everyone, including medical care. It does not at all resemble the US.

It is more accurate to compare Sweden to its neighboring Nordic countries with similar populations, demographics, and social welfare, but that also enacted more stringent social controls in response to the pandemic like the US did.

It turns out that compared to other Nordic countries, Sweden fared quite poorly with the highest mortality rate. Sweden had four times the number of COVID deaths compared to many of its neighbors. In particular, it had ten times the COVID death rate of Norway.

What about the economy? Of course the Nordic countries that enforced public and commercial shutdowns suffered significant economic hits like the rest of the world. Importantly, so did Sweden, which kept its economy open. Nevertheless, the country suffered as much economic downturn as its neighboring countries that enforced stricter shutdowns. In fact, the Organization for Economic Cooperation and Development and Development (OECD), of which Sweden is a member, reported that the country actually did markedly worse than Denmark, Norway and Finland. It seems that economic health is not only related to open commerce, but also to the public health of the country. Sick people do not work or venture out to buy things. It seems that public health affects economic health. That was not considered in the GBD, which was concerned about the economic impact of closing down commerce via fiat. They did not consider the economic impact of closing down commerce by hospitalizing so many people.

As these effects of its open policies became clear, Sweden eventually began to enforce greater social restrictions later in the pandemic, but the damage had already been done. The architect behind its initial open policies eventually admitted that things did not work out as planned. And in December 2020, Sweden’s King Gustav publically declared that the government’s approach had failed.

The real lesson from Sweden is that if you keep things open and people get sick, the economy still suffers in a pandemic. As far as the economy goes, it is a case of “damned if you do and damned if you don’t” enforce public restrictions.

And if you don’t, people still get sick and die and dead people stop buying things.

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Lessons for COVID Vaccinations And Herd Immunity From Influenza And Rubella

Note: The following is modified from the blog post, “Rubella: We vaccinate for far less,” by Katelyn Jetelina, MPS, PhD who is an “epidemiologist, biostatistian, professor, researcher, wife, and mom of two little girls.” She writes a blog entitled, “Your Local Epidemiologist.”

 “Those who cannot learn from history are doomed to repeat it.”

 George Santayana

 

In the US, more than 300,000 kids aged 5-11 have been vaccinated with the Pfizer COVID-19 vaccine, which has proven that the vaccine is safe and can benefit some kids. It prevents infection, COVID-19 disease, death, long COVID-19, and keeps kids in school. Admittedly, only a few kids develop serious COVID disease and fewer have died from it. Most infected kids only have mild, if any, symptoms. Vaccine skeptics use this fact to stridently argue against childhood COVID vaccines. So, why are we pushing to vaccinate children who rarely get seriously ill?

There are two reasons why we vaccinate anyone. The first reason is to protect the vax recipient from the disease; this is an individual-level benefit of the vaccine. The second is to protect a larger population by trying to retard disease spread; this is a population-level benefit of vaccines that is better known as herd immunity.

But, anti-vaxers only focus on the fact that childhood vaccines provide little individual-level benefit to children and wholly ignore the larger population-level benefit of the vaccines. As I have written before, vaccinating children who are at low risk for serious disease is still very important for reducing viral spread in order to  prevent more dangerous viral mutants from emerging. It also is important for reducing infection and disease in more vulnerable people in the population. It is these population-level benefits that are the most important reason to vaccinate low-risk children. Vaccinating children for a population-level benefit, rather than for individual-level benefit, is not at all new and is a very acceptable practice. Here are a couple of examples.

Influenza: A few decades ago, Japan mandated flu vaccines for all school kids. That vaccine slowed the spread of flu in schools leading to many fewer student illnesses and absences. More significantly, vaccinating all school kids also caused a sharp drop in flu deaths in older people like school teachers and staff, parents, and grandparents who have close contact with the kids.

Kids are walking incubators for respiratory viruses and readily spread their germs to others. Infected children essentially are virus vectors much like mosquitoes are vectors for malaria and yellow fever. Therefore, in Japan, the flu vaccine effectively shut down a major vector of influenza infection for at-risk older people. That is an undeniable and important population-level benefit of vaccinating school kids against the flu.

Rubella: Now, let us take a deeper dive into rubella, or German measles, and its vaccine, which is the “R” in the MMR shot. It is especially enlightening to compare the natural history of rubella to what we are learning about COVID-19.

Both COVID and rubella are caused by airborne viruses that spread when infected people cough, sneeze, or even talk. As with COVID, rubella symptoms in children are quite mild. They include its tell-tale measles-like rash, sore throat, low grade fever, mild pink eye, and general discomfort. But, about 25 to 50% of infected children will not experience any symptoms. Likewise, many CoV-2 infected kids also do not develop symptoms. But, asymptomatic kids infected with either rubella or CoV-2 readily spread their viruses to friends and family; hence, they can be significant vectors delivering both viruses to people at-risk for serious disease.

Over the last two years, we have learned that COVID mostly (with significant exceptions) causes serious illness and death in older people or for those with certain other health conditions. Similarly, while rubella only causes mild disease in most children, it is incredibly dangerous for developing fetuses. A woman infected with rubella during the first 3 months of pregnancy has a 90% chance that the fetus either will not survive or will develop Congenital Rubella Syndrome (CRS), characterized by deafness, blindness, heart defects, and/or severe brain damage. In the early 1960s, a rubella outbreak began in Europe and spread to the US. In 1964-65 ~12.5 million total cases were reported in America affecting nearly 50,000 pregnancies. More than 11,000 of the infected mothers miscarried, or delivered still-born babies. Of the >20,000 infants born alive to infected mothers, the majority had severe illnesses: 2,100 died shortly after birth, 12,000 were deaf, 3,580 were blind, and 1,800 had permanent mental disabilities.

The rubella outbreak proved hard to contain because, as with COVID, infected asymptomatic people make it hard to know when someone is spreading the virus. Rubella also is just as contagious as COVID. Both viruses have an R0 = 6-7 meaning that each infected person will infect, on average, 6-7 other people. For comparison, flu’s R0 = 2-3, which means it is about half as contagious as the other two viruses. It, therefore, is not surprising that like rubella, the COVID outbreak is proving hard to contain.

Soon after the 1960s rubella pandemic began, a safe and effective vaccine was quickly developed and approved for use in Europe and North America (this is reminiscent of the quick development of the COVID vaccines). Early on, there was a robust international debate on who should get the rubella vaccine. There were two schools of thought:

  1. Despite the fact that rubella only caused mild problems in kids, some proposed vaccinating all children hoping to provide indirect population-level protection for pregnant women and their at-risk fetuses.
  2. Others argued that because children were only minimally affected they should not be subjected to the vaccine and that only women of childbearing age should be vaccinated. This, proponents argued, would more specifically protect those most at risk.

Ultimately, it was found that countries that chose #2 were not able to sufficiently reduce the virus, because it still spread unfettered among children. This strategy did not reduce the rates of CRS. Eventually, option #1, vaccinating low-risk children (like what we are moving toward with the COVID vaccine) was adopted world-wide. Vaccination rates of school kids reached ~85% in the US, which last experienced a serious rubella outbreak in 1995. In 2004, transmission of rubella was eliminated in the United States and in 2015, it was eliminated in all the countries of North and South America.

Soon, the MMR vaccination was mandated for children in all 50 states. It is important to realize that these mandates were not to protect kids from the mild disease but to protect the at-risk population, or fetuses. In other words, we vaccinate kids against rubella not so much to protect them, but to provide a significant population-level benefit to others.

Today, because of broad rubella vaccination of low-risk children, we see an annual average of just 10-15 cases of CRS in the US that are traced back to international travel to countries with poor rubella vaccination rates. In contrast, in countries with low vaccination rates, about 120,000 children are born each year with severe CRS birth defects and even more die in utero.

Bottom Line: This country, and indeed all of the Americas and most of Europe came together to eliminate endemic rubella through broad population-level vaccination programs targeting low-risk groups responsible for spreading the virus to the high risk population. Japan saw the same effect with influenza. They focused on broadly vaccinating a low-risk population (school kids) and saw great benefits in the high-risk older population. As we approach a broad COVID vaccination strategy that includes giving the shot to low-risk children, it very likely will have a population-level benefit and help protect those most at-risk for serious disease.

It is important to note that the population-benefit conferred by the COVID vaccine also applies to all of us and not just to children. When we are vaccinated, not only does it protect us, it also provides significant protection to at-risk people around us. That, in fact, is called “herd immunity.”

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Evidence That Facemasks Prevent COVID-19

As Delta proliferates while the world tries to get back to normal, requirements to wear facemasks in public are also proliferating. The mask mandates are causing no end of consternation in certain segments of the population, which like to claim that there is no evidence that they prevent disease. Their evidence behind this claim is weak and usually boils down to claiming that the virus is similarly prevalent in states with and without mask requirements. For instance, they like to point out that California, with strict mask mandates, has about the same rate of COVID-19 as Florida, which does not have widespread mask mandates.

But, this is not a strong argument. In research, we carefully design studies to compare experimental vs control groups that are as similar as possible in every way except for the variable we wish to test. In other words, we try to isolate the test variable by making all else as equal as possible. This goal for a well-controlled experiment falls apart when comparing California to Florida—they are very different. Differences include age, population and housing density, reliance on public transportation, climate, humidity, and demographics. All of these variables, if not controlled for, will confound the relationship between mask policies and COVID-19 outcomes because each of these variables also affects the spread of disease.

However, comparing counties within a state helps address at least some of these confounding factors since counties within the same state are generally more similar than two different states at opposite ends of the country. Researchers have done just this in Kansas where 21 counties implemented a mask mandate while the others did not. Counties with a mask mandate saw a significant drop in COVID-19 while counties without a mandate saw a 100% increase in new cases during the period of evaluation.

More recently, the ABC Science Collaboration, a partnership between health scientists, K-12 schools and community leaders, in North Carolina collected infection data from >1 million students and staff members between March-June 2021. More than 7000 students and staff caught COVID-19 during that period and contact tracing showed that >40,000 people had close contact with the infected ones. Very few of these close contacts caught the virus and all of them, the infected cases and their close contacts, wore masks. In other words, in schools with mask mandates, there were no outbreaks despite initial COVID infections. And schools are ripe for creating super-spreader outbreaks.

A systematic review and meta-analysis published in The Lancet, examined the efficacy of face masks in reducing the transmission of different coronaviruses (SARS, MERS, and COVID-19). The authors evaluated 39 studies and found that face masks significantly reduced the risk of coronavirus infection compared to no mask wearing.

An article published in the Proceedings of the National Academy of Sciences in January 2021 also reviewed the evidence supporting the use of face masks and similarly concluded that near-universal adoption of non-medical (i.e., cloth) face masks in public could significantly reduce the R0 value of the virus, which is a measure of how well it spreads. In fact, I earlier discussed in these pages a similar finding by British researchers who concluded that widespread mask-wearing could substitute for herd immunity.

There are several other published studies that reach similar conclusions about facemasks. But, perhaps the most comprehensive study was just reported by researchers at Stanford and Yale. It involved a method called cluster randomization where villages in Bangladesh were randomized to get facemasks or not. It involved some 340,000 people in 600 villages. 100 villages received cloth masks and 200 villages received surgical masks. The remaining 300 villages did not receive any intervention to increase mask wearing. The results showed that increased community masking decreased COVID-19 disease in these real-world settings. Surgical masks performed better than cloth masks at reducing COVID-19 disease, though cloth masks were definitely better than no masks.

On a final note, let me reissue my earlier challenge to anti-maskers: If you really think they do not prevent infection, then next time you have surgery, invite the surgical team to throw the masks out when they open you up.

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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.