2021 was the year of the coronavirus vaccine

“I think we are in a revolution that no one believed would happen.”

Prime Minister Benjamin Netanyahu and Health Minister Yuli Edelstein pose for a photograph with Janet Lavi-Azulay, 34, the 5 millionth Israeli to get the Pfize vaccine, in Tel Aviv on March 8 (photo credit: MIRIAM ALSTER/POOL/REUTERS)
Prime Minister Benjamin Netanyahu and Health Minister Yuli Edelstein pose for a photograph with Janet Lavi-Azulay, 34, the 5 millionth Israeli to get the Pfize vaccine, in Tel Aviv on March 8

One year ago, the world’s biggest vaccination drive in history began with the hope and prayer that unexpectedly bold and innovative modern science packaged in a 2-milliliter vial could spell the end of the COVID-19 crisis.

It was December 9, 2020 and former prime minister Benjamin Netanyahu, together with former health minister Yuli Edelstein, traveled to Ben-Gurion Airport to meet the DHL delivery airplane on the tarmac and touch the country’s first shipment of vaccines.

“I believe in this vaccine,” Netanyahu said, it is the “light at the end of the tunnel.”

If the majority of Israelis get inoculated, he instructed, then the economy will open, and life will soon return to the way it once was.

“This is one of the most moving moments that I have worked on very hard, for long months, with the health minister and his ministry to bring relief and a solution to the coronavirus pandemic,” Netanyahu said as the forklift lowered the container with the vaccines and he placed his hand on the shipment like a young Jewish boy touching the Western Wall for the first time. “We are here today on a great holiday for the State of Israel. We see the end.”

The vaccine doses were transferred directly to the Teva SLE Logistic Center, where they were stored ahead of countrywide distribution, which began officially on Saturday night, December 19 at Sheba Medical Center at Tel Hashomer, with the inoculation of the prime minister, health minister and Sheba staff. The next day, vaccine complexes opened up across the country and in a record three months, the majority of eligible Israelis had been jabbed.

The rate of infection did not go down overnight, and deaths continued to mount for several months, but ultimately the country’s first phase of its vaccination campaign was a success with around 5 million Israelis getting inoculated in just a few months.

The vaccination campaign in Israel and around the world was in many ways a contradiction. Western countries bought up all the vaccines and were able to help keep their people safe, while poorer countries struggled to treat the sick. At the same time, the protection afforded by the vaccines was found to be exceptional but short-lived, requiring citizens to head to the vaccine complexes multiple times in order to keep infection rates down.

The Pfizer coronavirus vaccine in Israel, and this vaccine as well as vaccines developed by other companies and administered around the world, saved an untold and unprecedented number of lives in 2021 – especially the lives of elderly people who could otherwise have fallen victim to the deadly COVID virus.

“We have saved a lot of lives, a huge number of lives, thanks to the vaccines,” said Prof. Cyrille Cohen, head of the immunology lab at Bar-Ilan University. “I think if you look at the number of infections, for example, in Israel during the third wave and the number of deaths and we compare that to what happened in the fourth wave this summer – we can discover that there is less and less correlation between the number of cases and severe disease and death, so this is a victory.”

Scientists have attempted to calculate the extent of this success.

In Israel, it was estimated that more than 4,750 lives were saved between March 15 and June 26, 2021 due to the country’s mass vaccination campaign, according to a study published this fall on the health research sharing platform MedRxiv by Dr. Ronen Arbel, assistant professor in the Technological Marketing Department and Maximizing Health Outcomes Research Lab at Sapir College.

“The most effective and definitely most cost-effective way to reduce disease and mortality is vaccination,” he said.

Using real-world observational data, Arbel and his team set out to examine the effect of mass vaccination on COVID-19 mortality, comparing projected to actual deaths from the virus during a period when the country went from being largely closed in lockdowns to being open again.

What they found was that there were 370 confirmed deaths from COVID-19 recorded in the over-70 population after mass vaccination versus 5,120 estimated without vaccinations.

“Vaccines against COVID-19 saved more lives than expected by simply applying individual vaccine efficacy to the vaccinated population in Israel, despite a loosening of government stringency,” the report said.

In the United States, a study published in Health Affairs in August estimated that vaccinations against the virus may have averted up to 140,000 deaths in the country and prevented nearly 3 million infections in just the first five months of distribution.

And yet a third report, published in November in the open-access medical journal Eurosurveillance, found that the vaccines saved an estimated 469,186 lives in 33 European countries from December 2020 to November 2021 – 51% of 911,302 expected deaths.

The number was calculated using weekly reported deaths and vaccination coverage and ranged by country from 6% in Iceland to 93% in Ukraine.

“Countries with high early uptake – Israel, Malta, England and Scotland – have substantially reduced predicted mortality, especially in people 80 years and older,” the study showed. 

“The fact that we vaccinated at all is quite extraordinary,” said Dr. Margaret Ann Harris, a spokesperson for the World Health Organization who specializes in public health emergency risk communication. “This was really about scientific collaboration and sharing data from day one.”

She said that even before SARS-CoV-2, the scientific name used to refer to the coronavirus, there was substantial information about the family of coronaviruses that had been learned from previous, though less widespread, coronavirus pandemics. These included the 2002-2004 SARS outbreak, which also began in China, and the 2012 MERS (Middle East Respiratory Syndrome) outbreak, which was first discovered in Saudi Arabia.

“So, a lot of work had been done on potential vaccines – animal studies, early human studies as well – which led to the development of the vaccine so quickly,” Harris said. “But still it was unprecedented, not just to do it so quickly, but to do it safely and to have such a large number of human volunteers willing to be in the experiment.”

This is especially the case with the Pfizer and Moderna vaccines, the world’s first authorized vaccines that use messenger RNA (mRNA) – tiny snippets of genetic code that serve as an instruction manual for our cells, directing them to make proteins to prevent or fight disease.

 Prepping the vaccine at a Health Ministry center in Jerusalem's Malcha Mall (credit: OLIVIER FITOUSSI/FLASH90) Prepping the vaccine at a Health Ministry center in Jerusalem's Malcha Mall (credit: OLIVIER FITOUSSI/FLASH90)

BUT THE OPTIMISM of a jab that could potentially end the worst of the pandemic was quickly marred by the world’s failure to share these vaccines.

“Early on, we realized that if we got a vaccine, it would work best if it was rolled out to the highest-risk groups first, those like healthcare workers, older people, people with underlying medical conditions and that needed to happen all around the world at the same time so that we did not have the opportunity for the virus to be in people, making them sick for a long time, replicating and producing variants,” Harris said. “Sadly, this has not happened.”

According to WHO data, about 67% of people in high-income countries have had at least one dose, compared to not even 10% in low-income countries.

WHO had set a target of inoculating 40% of the world’s population by the end of the year. But WHO Director-General Dr. Tedros Adhanom said last week that while a sufficient quantity of vaccines was developed in 2021 to have reached the coverage target by September, it did not happen because vaccines were not distributed equitably. 

In countries without vaccines, and in those in which the public has been hesitant to use them, COVID deaths have continued at a steady pace.

To date, more than 5 million people have succumbed to the virus worldwide, including more than 3.4 million this year.

“Vaccine distribution was something that the world needed to do not in a self-interested way. There is a system to make it very possible that has been achieved. It is not a charitable system, but a logical, scientific system,” she said, seemingly referring to the COVAX program.

“Diverting supply to countries that already have high levels of vaccination coverage gives the virus more opportunity to spread and mutate,” Tedros said last week as the Omicron variant spread and some countries, including Israel, started pondering a fourth shot. “It’s important to remember that the vast majority of hospitalizations and deaths are in unvaccinated people, not un-boosted people.”

ISRAEL’S OWN campaign has had its highs and lows.

“Israel started with a very big and energetic vaccination campaign in December to March and this actually created an epidemiological situation where it lowered the number of cases dramatically and it was the main reason for our going out of the third wave that was very dramatic in terms of infection rate, morbidity and mortality,” said Prof. Nadav Davidovitch, director of Ben-Gurion University’s School of Public Health.

But he said that from April to July, the country entered a period of stagnation. Those who wanted to be vaccinated had been jabbed, leaving a million eligible Israelis – mostly younger people – without protection. That number remains at around 700,000.

Among the most hesitant was a large cohort of minorities, especially Bedouin, and those at a lower socioeconomic level.

The Health Ministry approved vaccines for young adults ages 12 to 15 in early June, but only after several outbreaks at schools later in the month did it push to get these youngsters to the vaccine complexes. Vaccine uptake was slow among teens, even as the Delta variant burned across the country. To date, only 59% of kids in this age cohort are fully vaccinated.

At the same time, Israel launched a booster campaign in August, quickly making the third jab available to anyone over 18 for which five months had passed since their second shot. Israelis, especially older ones, whose vaccines were waning and who were getting infected, took advantage of the government’s offer.

Israel trumped even the US Food and Drug Administration on the decision to give a booster shot – a decision proven right and essential for protecting the most at risk.

But here too, the campaign has struggled. By year’s end, there were still a million Israelis eligible for booster shots that had not gone to get them.

Finally, the country’s children’s vaccination campaign has also been slower than expected. Less than 10% of five-year-old kids and less than 20% of 6- to 11-year-olds have been vaccinated, even as Omicron threatens to shut the country down.

“Around the globe, there is more hesitancy with children,” Davidovitch said. “There is a lot of fake news and false ideas about risks, especially long-term risks.”

He said that in reality, data shows that vaccination side effects are fewer and less severe among the youngest children and that Israel “we need to get children vaccinated to protect them and protect the community.”

Israel was called the “vaccination nation” in March. Today, only around 60% of the total population is fully vaccinated.

 Proffering a vial of the Pfizer/BioNTech vaccine for children, at a Meuhedet vaccination center in Tel Aviv (credit: AVSHALOM SASSONI/FLASH90) Proffering a vial of the Pfizer/BioNTech vaccine for children, at a Meuhedet vaccination center in Tel Aviv (credit: AVSHALOM SASSONI/FLASH90)

MOREOVER, THE vaccines have also offered a sense of false protection in some sense, since they do not protect against infection but rather were developed and tested against serious disease, hospitalization and death.

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.

The Pfizer vaccines also do not seem to be too long-lasting, meaning that protection wanes within three to five months of inoculation.

“We might have won the battle, but we have not won the war,” Cohen said. “We have won the battle in terms of having vaccines. But these are not the best vaccines. These are good vaccines, but we will need something better in the future.”

Cohen recalled the euphoria of spring 2021, when Israel opened up and almost weekly shed another restriction, believing that the country had reached herd immunity and beat the virus. Daily cases were in single digits and there were no deaths.

But it only took a few weeks before Israelis realized they were still at risk. The vaccines were waning, and vaccine inequality had led to new and more infectious mutations, just as WHO had predicted.

Researchers in Israel recently performed a network meta-analysis (NMA) to compare the short-term efficacy of nine vaccines. Their study, published in the peer-reviewed journal Scientific Reports, found that mRNA vaccines, Pfizer and Moderna, were associated with the highest efficacy to prevent symptomatic COVID-19 compared to other vaccines.

The vaccines included in the study were the Pfizer and Moderna jabs, AstraZeneca, Sputnik V, Johnson & Johnson, Novavax, Sinovac and two versions of the Sinopharm vaccine.

Each vaccine was given a “p-score” ranking its efficacy to prevent COVID-19. The p-score represented the probability that each intervention was better than all competing interventions in subjects over 60 years in warding off symptomatic disease. The results were as follows: Pfizer: 0.953, Moderna 0.844, Sputnik 0.782, Novavax 0.701, Sinovac’s CoronaVac 0.570, two vaccines from Sinopharm 0.428 and 0.327, Johnson’s 0.198 and AstraZeneca 0.197.

But the lead researcher, Hebrew University’s Dr. Victoria Rotshild, stressed that this was only referring to the effectiveness of the vaccines within the first few months of inoculation and mostly against the original Wuhan strain. She said a next study needs to look at the long-term effectiveness of these shots.

“If we know mRNA vaccines require a shot every six months, this is not the way we want to deal with this pandemic,” Rotshild said. “We will probably need new vaccines.”

Cohen said that 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.

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.

LOOKING AHEAD to 2022, the first goal should be getting at least a first dose of any vaccine into everyone’s arm who will take one, Harris said.

“The greatest bang for the buck with vaccines is that first and second dose – that is where you make the big difference,” she said. “We need that to happen in all populations.”

The WHO has looked at various scenarios and determined that there are enough vaccines being produced to reach its goal of 40% world vaccination in the first quarter of 2022 and 70% by mid-year, “as long as hoarding does not happen,” Harris said.

Davidovitch said he expects vaccines to expand to younger cohorts in 2022, too – likely even to children six months old.

The success of the Pfizer and Moderna vaccines could also unlock entirely new uses for mRNA this coming year, including a new line of vaccines and treatments for cancer and neurodegenerative, rare genetic and infectious diseases – something that scientists have dreamed of for the past two decades.

“I think we are in a revolution that no one believed would happen,” said Prof. Dan Peer, vice president for R&D and head of the Laboratory of Precision Nanomedicine at the Shmunis School of Biomedicine and Cancer Research at Tel Aviv University. “Basically, everything is open right now.”