Coronavirus news & views

Vaccine side effects in a nutshell

From the New England Journal of Medicine, with thanks from the Unbiased Science Podcast

https://www.nejm.org/doi/pdf/10.1056/NEJMoa2110475...

Delta: It is always better to prevent than to treat!

Previously in these pages I wrote that it was important to vaccinate kids as well as all adults, even though kids generally do not get very sick from CoV-2 infection. I also opined that it was important to get vaccines to third-world Asian and African countries that lack them. I further lamented the inability of one of the world’s leading vaccine manufacturing countries, India, to vaccinate its own population. The common reason for these exhortations in separate blog posts was the need to suppress the spread of the virus as much as possible, which I submit is just as important as protecting people from COVID-19 disease. We need to try to suppress the emergence of new viral variants since they could be more deadly and even cause significant disease in younger, healthier people. Such variants could also learn to ignore vaccine immunity and set us back to square one fighting the pandemic. As viruses replicate, they make random genetic mistakes in copying themselves. By chance, some of those mistakes can potentially make the virus more infectious or deadly. It is crucial to slow virus spread as much as possible with vaccines and social distancing measures in order to reduce the chance of such new, more deadly variants developing.

At this juncture, let me introduce the Delta variant and say, “I told you.”

Delta is more infectious. The Delta variant was first detected in October 2020 in India during that country’s long, strict shutdown. As I earlier reported, it then exploded across the country after those restrictions were lifted the following March in time for huge national  election rallies and a major religious holiday that brought hordes of Hindu worshippers to the banks of the Ganges. Delta quickly overtook previous iterations of the virus in India and has now spread to more than 100 countries, meaning that it has a significant advantage over other variants in the race to infect people. Delta was first detected in the U.S. in March and by mid-July accounted for 83% of all U.S. cases. As of the end of July, the Delta variant had caused at least 92% of the new infections in the United States, according to covariants.org, a research firm in Bern, Switzerland. The Johns Hopkins University tracker reported that daily US COVID-19 cases rose from just over 13,000 at the end of June to almost 131,000 in mid-August. almost all of which are due to Delta.

Delta has kept some of the most successful mutations found in earlier variants that first appeared in England and South Africa, but it also contains new genetic changes that, together, enable it to spread faster. In an earlier blog post, I talked about the R₀ value, or the measure of a virus’s ability to spread. For seasonal flu, R₀ is about 2, meaning that on average, an infected person will infect two others. For the original SARS-CoV-2, R₀ was ~4, which means that on average, an infected person infected four others. Now, according to the CDC, the Delta variant has an R₀ of 8-9 meaning that an infected person will, on average, pass the virus to 8-9 others. Therefore, Delta is about 4-times as contagious as the virus first identified in Wuhan. Clearly, viral variants are trending toward increased ability to spread. We can expect that the virus is not finished evolving and could become even more contagious.

How do the mutations make Delta more infectious? Research now shows that Delta has an incubation period of four days, which is the time it takes to begin spreading after infection. The original virus incubated for six days. Thus, people are becoming contagious sooner. Also, people infected with Delta are found to carry >1200-times the viral load compared to prior virus iterations. People carrying more virus pump more virus into their environment making them more infectious. With earlier variants, conventional wisdom held that you needed to be around an infected person for about 15 minutes in order to catch an infectious load of the virus. That wisdom now holds that one only needs to be in the presence of a Delta-infected person for 1-5 minutes before becoming infected. 

Some vaccinated people can also be infected and spread Delta. With any viral vaccine, the hope is that the vax will not only prevent disease, but also retard the spread of the virus, ideally reducing its R₀ value to <1. When an infected person only spreads the virus to fewer than one other person, the epidemic/pandemic would be nipped in the bud. So far, the vaccines have done a pretty good job reducing the spread of the virus; however, the Washington Post recently obtained an internal CDC document  citing a combination of recently obtained data from outbreak investigations and other studies showing that vaccinated individuals can sometimes be infected with Delta and transmit the virus as easily as those who are unvaccinated.

The data showed that vaccinated people infected with Delta sometimes had viral loads similar to infected and unvaccinated people. These data came from a July 4 outbreak in Provincetown, MA where 127 vaccinated people were infected with the Delta variant in the superspreader outbreak and they appeared to carry as much virus as unvaccinated people who also became infected. Vaccinated people with breakthrough infections only showed mild symptoms including cough, headache, sore throat, or fever. Four were hospitalized and no deaths were reported. On July 3, the day before the event, the Massachusetts Department of Public Health reported a two-week average of zero COVID-19 cases per 100,000 residents. By July 17, after the superspreader event, that number rose to 177 daily cases per 100,000. The ability of Delta to infect some vaccinated people and spread from them has been further confirmed by research published by Public Health England.

This is the reason why the CDC just recommended that all people, including vaccinated people, again don face masks when in public indoor spaces. Fortunately, the virus does not cause significant disease in this population meaning that the vaccines still protect from serious disease.

So far.

Vaccine efficacy. The CDC reports that even though the current vaccines do not fully protect against breakthrough infections, such infections only occur in about 0.1% of the 140 million vaccinated people and they still reduce the risk of severe disease 10-fold and they still reduce the risk of breakthrough infection three-fold. That is the good news.

The disappointing news is that real-world studies of vaccine efficacy indicates that the current vaccines have become somewhat less effective at preventing infection from the Delta variant than they were against earlier versions of the virus. One way to measure a virus’s ability to evade vaccines is to take antibodies from vaccinated patients and combine them with the virus in the lab, then measure how much of the virus is neutralized, or prevented from infecting cultured human cells. Dr. Akiko Iwasaki, an immunologist at Yale University, and colleagues used this technique to compare how well different coronavirus variants can withstand vaccine immunity. Iwasaki found that Delta was better at evading neutralization than earlier versions of the virus. More concerning, however, is that they also found that two other variants, Beta, first found in South Africa, and Gamma, from Brazil, were even more adept at avoiding antibody neutralization. It appears that viral mutations are being gradually selected for their ability to bypass the immunity conferred by the current vaccines. That trend is worrisome.

Other reports coming in now indicate that the early vaccine efficacy of ~95% has dropped to 70-80%. This value represents the protection a vaccinated person can expect when exposed to the virus. The increase in the number of vaccinated people who become infected suggests either that that their immunity is fading over time, or that, as mentioned above, Delta is learning how to avoid vaccine immunity. Or both. As I wrote earlier, the initial antibody response to a vaccine naturally decays over time but immunity is usually sustained via memory immune cells which serve as quick-response sentinels to subsequent exposure to the pathogen. Memory immune cells were found in another study to be robust six months following mRNA vaccination and able to efficiently respond to the known viral variants. This indicates that long-term immunity remains strong and suggests that Delta has begun to learn how to avoid vaccine immunity.

Stay tuned.

Severity of Delta disease. In India, the Delta variant caused more severe and faster illness than earlier variants, and now in the US, Delta also seems to more readily cause significant disease and do so in younger people. Currently, teens 16-17 years old are now seeing the highest rate of COVID-19 cases among all age groups in the US. That is up from a rate of 48 per 100,000 on July 10, to 200 per 100,000 people on August 14. As Delta now accounts for >95% of new COVID-19 infections and hospitalizations in the US, doctors on the front lines are reporting anecdotally that unvaccinated people in their 20s and 30s are becoming more critically ill, and faster than they did before Delta arrived. Studies in a handful of other countries confirm that Delta causes more severe disease in younger people. For example, a study in Scotland reported that patients infected with Delta ran twice the risk of needing hospitalization. Researchers in Canada confirmed this and reported that young people infected with Delta had a 4-fold increased risk of requiring ICU care and double the risk of death. Other studies out of Singapore and India further corroborated these observations.

The emergence and rise of a viral variant with enhanced infectability and increased morbidity in younger, healthier patients is a prediction I and others have made in the face of the continuing global spread of this virus.

I told you so.

What does it all mean? Breakthrough infections we are now seeing in vaccinated people could be especially worrisome. The immunity conferred by vaccination usually retards viral spread and reduced viral replication scales down the development of new, more virulent viral variants. But, when immunized people do get infected and the virus grows in their bodies, the virus has to fight the vaccine immunity to eventually develop new mutations that allow the virus to simply brush off vaccine immunity. With Delta, we might be seeing the early stage of this viral evolution in vaxed people.

Vaccine resistance by the virus can be prevented by a rapid and robust vaccination effort as a team of European scientists recently reported in the journal Nature. It is imperative to get vaccines to countries that remain largely unvaccinated, and we need to get the naysayers in countries with more robust vaccine efforts to understand how their actions perpetuate the pandemic and promote the development of dangerous variants. There is no rational reason for the vast majority of people to refuse vaccination. The ongoing pandemic is totally preventable.

Vaccines have eradicated small pox in the world and polio from most developed countries. Measles is now extremely rare in the US thanks to vaccines. Go to an old cemetery and count the number of headstones belonging to children who died before 1950, then compare that to the number of kids who died after 1950. That striking difference is a powerful testimony to the effectiveness of vaccines as preventive medicine.

It is always better to prevent than to treat!

Note: In order to have blog updates delivered to your email, see the simple Subscription Instructions here. Remember, you can easily unsubscribe when you want.

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!

Note: In order to have blog updates delivered to your email, see the simple Subscription Instructions here. Remember, you can easily unsubscribe when you want.