9 things to know about COVID-19 two years on

HEALTH AFFAIRS: A useful guide to put things in order as the world continues to grapple with the pandemic.

 A PHARMACY in Jerusalem sells a quick COVID test. (photo credit: MARC ISRAEL SELLEM/THE JERUSALEM POST)
A PHARMACY in Jerusalem sells a quick COVID test.

The pandemic has turned even the most science-phobic person into an amateur doctor.

In December 2019, when the novel virus was lurking among the stalls of a seafood market in Wuhan, few could have imagined what would eventually emerge: a global pandemic that infected more than 260 million people and killed more than five million men, women and children, wreaking havoc on our lives and traumatizing us all.

But it has also educated people.

The coronavirus crisis and the race for a COVID vaccine has made formerly obscure terms like reproduction rate, PCR, messenger RNA and antibodies commonplace in the public’s vocabulary.

Two years on, with the help of Prof. Jonathan Gershoni, The Jerusalem Post offers a “virus and vaccination manual.”

What is a virus?

“Viruses are just USB flash drives, protein-coded RNA or DNA memory chips,” Gershoni of the Shmunis School of Biomedicine and Cancer Research explained. “Viruses are not living organisms, just like flash drives are not computers. It is only when the USB is inserted into its corresponding port that information can be transported from the flash drive to instruct the computer how to behave.”

Viruses also have USBs – proteins that are inserted into receptors on our cells, and only when they are connected can the RNA transfer into the cell and orchestrate the production of new viruses.

These new viruses infect other cells and produce more and more viruses, ultimately causing more damage and sometimes developing into a life-threatening disease.

Can we stop a virus once it enters our cells?

The body’s immune system is responsible for fighting the virus.

“Specialized white blood cells, known as B cells, encounter and intercept the viruses,” Gershoni said. “They study them and, in response, produce antibodies” that then bind to the spike protein and block access to the receptor so that the cells can no longer be infected.

Each time the B cells interact with the virus, they improve and produce more and better antibodies. Some of these B cells soon become stored as memory cells, so that if the virus comes again, the cells will recognize it and start high production of antibodies.

“The intruders are knocked out” by the antibodies, Gershoni said, and the individual does not experience any disease at all.

What’s the role of the vaccine?

The vaccines pretrain our immune system to prevent disease, even if we were never actually infected.

“Vaccines are basically boot camp training of our immune system,” Gershoni said. “Vaccines contain the hardware of the virus – the protein. When we vaccinate, the B cells have the opportunity to interrogate and understand the virus and store memory.

“All the vaccines we know that we give our kids are what we can call hardware vaccines – vaccines that all contain inactive, safe viral protein in some form or another.”

Until recently, developing vaccines for various life-threatening diseases has taken years of research and development. But in times of emergency, like in the COVID crisis, scientists asked themselves: Could it be done differently, safer, quicker, cheaper – and still without compromise?

The answer, said Gershoni, was the mRNA vaccine. These vaccines, although new to most of us, are actually the product of extensive work and perseverance over decades of research.

Where have we seen RNA before?

RNA is a tricky substance because it breaks down easily. At the same time, it raises a “red flag” for our immune system, causing a dramatic inflammatory response when it is introduced into our body. These challenges made it difficult for scientists to use RNA that codes for proteins (known as messenger RNA or mRNA) to produce vaccines.

The breakthrough for using mRNA came some 30 years ago by Hungarian biochemist Katalin Karikó and her colleague Drew Weissman, who worked together in a lab at the University of Pennsylvania trying to figure out what made RNA so inflammatory.

“When we started this, we were not thinking about curing pandemics,” Weissman said in a video published by Penn Medicine. “We were thinking about making new vaccines. We have five phase 1 trials of different mRNA vaccines that we were working on before COVID-19 ever hit. And we knew at that time that this had the potential to be an incredible vaccine.”

In 2005, the team discovered that by encapsulating the mRNA in a certain lipid and tweaking its chemistry a bit, it prevented breakdown and inflammation and allowed mRNA to go to work without interference – this is how the Pfizer and Moderna vaccines are both made.

How can we be sure that injecting RNA is safe?

Actually, RNA is part of seven of the nine mainstream childhood vaccines that are targeting viruses, Gershoni said: Rotavirus, polio, influenza, measles, mumps, rubella and hepatitis A. These vaccines have been approved decades ago and have protected billions of babies since. Thus, the proof of time has demonstrated that RNA containing vaccines are safe and do not cause long-term side effects.

“All of these vaccines can be considered ‘RNA vaccines’ that are not fundamentally different from the RNA contained in the coronavirus vaccine,” Gershoni explained.

These traditional RNA vaccines each contain multiple viral genes.

The coronavirus vaccine is a much more simplified version of these, using only highly purified mRNA molecules of just one viral gene, coated with lipid, that when injected into our muscle teaches our cells how to make the protein that will trigger an immune response and produce protective antibodies.

The new COVID-19 Pfizer and Moderna RNA vaccines disappear within days after they have done their job.

The production line of these new RNA vaccines is one of its breakthrough novel advantages.

“It is far more efficient and easier to produce the mRNA vaccine and the doses required than manufacturing the traditional vaccines, which would take years and years to make enough,” Gershoni said. “One of the reasons the mRNA vaccine has been embraced is because we can make enough of it. Our biggest problem now is convincing the ‘vaccine hesitants’ to take it.”

But mRNA vaccines seem to have limitations, too

When the world first started vaccinating against COVID, there was a hope that vaccines would eradicate the disease. However, one year on, it has become clear that the vaccines will not completely stop infection. Rather, their main purpose is to prevent serious disease.

“Many of us are a bit disappointed that the vaccine has not proved to be a shield that blocks infection,” Gershoni said.

But he added that this does not make the vaccines any less important.

“The fact is that by being vaccinated, and should you get infected, you most likely will only be casually ill with corona, with a few sniffles and staying at home with a good cup of tea, recovering and then going back to work. This may be unpleasant, but it is not life-threatening, and it does not have a profound impact on our economy, society or health system.”

Could we ever have a corona vaccine that prevents infection?

To understand, one can look at polio and the vaccines that prevent it.

The first polio vaccine developed in 1955 was an inactivated “killed virus” vaccine administered by injection. The vaccine worked well to prevent severe disease, and children were no longer at risk of becoming paralyzed. However, vaccinated individuals could still contract polio in their gut.

However, about six years later, an oral polio vaccine (OPV) containing live attenuated virus, given as liquid drops, was invented that actually protects the digestive tract and induces antibodies in the intestines, providing protection against disease-causing polio virus, should it be encountered in the future.

Because OPV in about one in more than 2 million people would revert to its natural form, it could not be used on its own. Today, most children living in Western states combine the two vaccines and first take two shots of the “killed” polio vaccine followed by two doses of the oral one. This system eliminated polio in the US in 1979 and from the western hemisphere by the early 1990s.

The coronavirus infects a person’s respiratory tract, so a vaccine that is injected into one’s arm does not necessarily stop the virus from entering the body. To do that, one would likely need a nasal vaccine.

Indeed, this is a hot topic of development for a next-generation COVID-19 vaccine.

Laboratories around the world are producing and testing nasal sprays that deliver coronavirus vaccines and are already finding promising results. Here, once again, Israel is contributing to this new approach.

Hebrew University scientist Dr. Gilly Regev and her company SaNotize have developed Enovid, a Nitric Oxide Nasal Spray that protects from viruses and was shown to reduce the corona viral load in a phase 2 trial.

The spray received emergency use authorization as a medical device by the Health Ministry and has been in the country since July.

A trial conducted earlier this year in the United Kingdom showed that it was 16 times more effective than saline control at reducing viral load. Late-stage trials are now under way in India, Bahrain and Canada.

The American company now working to develop Israel’s BriLife vaccine has said that it hopes to provide such an option as well.

Why does vaccine protection wane?

Israelis took their third shots only a few months ago, and already there is talk of a fourth dose. That’s because the best protection against the virus is a high level of antibodies, and in the case of the Pfizer and other mRNA coronavirus vaccines, these antibodies wane over time.

“There are two reasons why the immune protection afforded by vaccination might gradually lose its activity,” Gershoni explained. “Antibody molecules have a limited ‘shelf life’” – meaning that they simply dwindle.

“The other reason is that the virus can accumulate mutations and produce variants that are less sensitive to the antibodies generated against the ancestral virus strain,” he said.

The result would be that the vaccines could need to be updated periodically to ensure maximum protection. The latest Omicron variant has raised concerns of being vaccine-resistant. However, a release by Pfizer on Wednesday showed that, in preliminary neutralizing antibody tests in the lab, three shots of the vaccine appear sufficiently effective.

In addition, research in South Africa showed that while two shots might not afford the same level of protection against Omicron as previous variants, they are likely to protect against severe disease.

When does coronavirus go away?

The novel coronavirus will likely never go away, experts believe. However, we might be able to learn to live with it better. For that to happen, Gershoni said, the world needs to get vaccinated.

Unfortunately, vaccine distribution has not been equal worldwide. The richest countries are getting jabbed an average of 10 times quicker than the poorest nations, which leads to new variants and puts everyone at continued risk.

“Corona knows no borders, and until the rest of the world is protected, we are likely to have to manage corona in Israel as best we can,” Gershoni concluded.