Will Four Waves, Vaccines – and New COVID Drugs – Be Enough for Israel to End the Pandemic?

Ido Efrati
Ido Efrati
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A coronavirus ward in Shaare Zedek Medical Center, Jerusalem, last month.
A coronavirus ward in Shaare Zedek Medical Center, Jerusalem, last month.Credit: Emil Salman
Ido Efrati
Ido Efrati

In the past year and a half, Israel has fought four waves of COVID-19 and witnessed the death of more than 8,000 people from the virus. It has also vaccinated over 6 million people (4 million of which also received a booster shot). Calling the situation a crisis no longer reflects its reality. The pandemic is not just a momentary event, nor limited in time or space. It’s become an ongoing, fluctuating reality.

Israelis feel a familiar sense of relief at the tail end of the fourth wave, as they did after prior waves ebbed, but they’re less naïve about the future. “We’re not dismantling anything – not the control rooms, not the [nursing home program] or the testing facilities at Ben-Gurion airport, not sampling and tracing capabilities and not other systems,” Health Minister Nitzan Horowitz told Haaretz this week.

Horowitz appeared to be hinting that the prior government prematurely decided to close up shop and scale back on operations involving pandemic-related facilities. “The infection rate is declining, but nothing is over. We are still in a global pandemic,” the health minister explained. “Our effort now is to maintain life as normal and to do everything to prevent it from being disrupted.”

A line to get vaccinated in Jerusalem.Credit: Ohad Zwigenberg

The waning of the virus in Israel has been consistent and clear by every measure. Worldwide, there have been daily reports of half a million cases and about 5,000 deaths. On a global basis, the death toll from COVID-19 has now surpassed 5 million.

The question of where Israel is headed in the coming months is multifaceted and broad. Experts agree that as long as the pandemic rages around the world, Israel will still be facing a threat from the coronavirus and that it will not disappear entirely, but will wax and wane. That understanding prompts new questions: What would the magnitude of another wave be and when it would occur, if at all? There is definitely a chance that we will see a fifth wave, and the health system is taking it into account.

A fifth wave

A scenario presented to senior Health Ministry officials about a week ago speaks of the possibility of a fifth wave within three to six months. It’s based on the assumption that the third dose – the booster shot – that Israelis received will wane in the same manner as the second dose, with a decrease of about 10 percent or more of protection against infection per month.

Under such circumstances, which assumes the prevalence of the delta variant, the protective value of the vaccine would drop to about 30 percent, spurring a new wave with a projected death rate three times that of the fourth wave. Such a wave could cost 5,000 lives without Israel swiftly providing a fourth vaccine dose to the population.

It’s important to stress, however, that this scenario is theoretical scenario, centering around one major unknown factor: whether the booster shot Israelis have received actually does wane in its effectiveness. If it does, at what pace will it wane? Will it leave behind an effective immunological memory compared to the second dose? We don’t have answers yet. Considering a similar scenario at the beginning of the fourth wave led the government to administer the booster shot.

“We assume there won’t be cases in Israel in around another month, so it will be more difficult to spot the immunological waning of the booster compared to the fourth wave. Since [Israelis] got vaccinated before [the rest of the world], we expect a blind spot in the near future,” one expert with whom the Health Ministry consults said.

“We know that the waning of the second dose’s effects took place without any connection to the delta variant’s arrival, but we don’t know what the number of people with COVID-19 would have been without that variant, and to what extent such a waning would have been felt without the variant's spread,” he added.

This in-between situation, characterized by uncertainty regarding vaccine efficacy, raises a crucial question about vaccinating children aged 5 to 11. “Acknowledging the fact that the vaccine’s effects fade over time, it’s possible that given the low numbers of sick people, the right thing would be to postpone the vaccination of children, so we can learn more from other countries. Perhaps we could fully exploit its potential at a more suitable timing, with the advent of the fifth wave,” this expert speculated. Other experts also believe in a more moderate approach, supporting the approval of the vaccine for children and making it available for those interested, but suggesting to wait for a sweeping recommendation and suspending an aggressive vaccination campaign, which may erode public trust.

A health care worker prepares a Pfizer-BioNTech COVID vaccine in Jerusalem, in August. Credit: Emil Salman

There is broad consensus among experts that the Israel of November 2021 is not the Israel of March 2020. The vaccine, effective medications such as Regeneron’s antibody cocktail, as well as 1.3 million confirmed cases of infection (beyond an unknown number of undiagnosed cases), gives Israel much more leeway for taking risks and responding quickly when needed. And yet, as experience shows, there are flaws, missteps and surprises. The arrival of the delta variant, and the fourth wave that took place amid the vaccination campaign, cost 1,600 Israeli lives. Health services should exploit the lull in order to draw lessons for the future. There is no shortage of such lessons.

Vaccination policy

Vaccines have undoubtedly had the most dramatic impact in combating the coronavirus. Ten months after Israel started administering them, their high efficacy has been proven in endless studies, whether they examine antibody levels, virus transmission, symptoms, serious illnesses or mortality. And yet, this picture is incomplete. The waning of the vaccine’s effectiveness after several months, discovered during the fourth wave, and the need for a booster shot, leave some unresolved questions for the future.

“I think the most significant lesson from the fourth wave is the extent to which the vaccines are effective. We possess a very effective vaccine, good in preventing not just serious illness but also transmission,” said Prof. Eyal Leshem, an expert on infectious diseases and the director of the Center for Travel Medicine and Tropical Diseases at Sheba Medical Center. “The use of vaccines to prevent virus (and not just illness) transmission is an innovative approach that Israel implemented. Most public health experts worldwide believe that using the vaccine for preventing infections should not be the vaccination’s primary aim.” He noted that while the vaccine is less effective at preventing infections, “most of the population is protected” thanks to it. Accordingly, Leshem said, the lesson learned is to adhere to vaccinations while intensively monitoring outbreaks, new variants, and the vaccines’ long-term safety and effectiveness.

However, vaccine effectiveness is not the only factor having an impact. The timing of decisions on vaccine policy and the allocation of resources to the right locations are of critical importance. Thus, for example, “a major error we made about vaccination was that we left a too-large group of people, around 1.4 million Israelis, unvaccinated during the previous wave. We did vaccinate 750,000 of them during the fourth wave, but it took too much time. The fact that many of these people got vaccinated during this wave shows we didn’t do enough to reach them during the earlier waves.”

Another expert on the Health Ministry’s advisory panel said the decision to give the booster shot was correct, bold and relatively rapid, but should have been made two weeks earlier. “We could have blocked the epidemic with 2,000 confirmed cases a day, not 10,000,” he said. “This would have prevented many unnecessary deaths. People, including professionals, tend to focus on serious illness and at-risk groups, not understanding that transmissions are the most important parameter, and that even with 95 percent effectiveness you can reach huge numbers of seriously ill people, leading to deaths, when the number of confirmed cases is very large.”

Treating patients

The way to treat people with COVID-19 in its different stages has been learned on the go. Different medications were tried, as well as different approaches regarding ventilation. Professional discourse among doctors treating COVID-19 in Israel usually took place informally, often through WhatsApp groups, revealing varied approaches and treatments.

Until recently, there has been a lack of medication treatment for COVID-19 patients. While Israel and the world at large already began vaccinating against the virus, doctors in coronavirus wards and community physicians were left without the means to treat those infected. Accordingly, when tending to infected patients – including those experiencing increasingly severe symptoms – doctors could only treat different symptoms brought on by the disease, and were unable to counter the activity of the virus itself. Some of these treatments included anti-coagulants, or steroids to reduce the inflammation caused by the immune system.

The Regeneron drug recently put into use was the first significant designated drug for COVID-19. It is intended for patients in at-risk groups and can reduce the need for hospitalization significantly – by up to 70 percent. But its main drawbacks are that it must be used within 72 hours of the appearance of symptoms, and that it is administered intravenously – which makes the whole process more cumbersome and less appealing.

But the two new drugs – Molnupiravir by Merck (operating under “MSD” in Israel) which reduces the chance of severe illness by 89 percent – may significantly ease the fight against COVID-19. It is likely also to impact the way the next outbreak looks – if it does indeed come – throughout the healthcare system and inpatient wards. The great advantage of these drugs, beyond their efficacy, is that they are taken in pill form and not via IV or some other cumbersome mechanism.

A nurse from the ICU at Beilinson Hospital in the coronavirus ward, Wednesday. Credit: Hadas Parush

According to Prof. Dror Mevurach, head of the COVID-19 unit at Hadassah Ein Kerem, “the new drugs are definitely revolutionary. Molnupiravir, already approved in the UK, reduces hospitalization of medium condition patients with a risk factor by 50 percent, and the Pfizer drug, which belongs to the “protease inhibitor” type of drug (drugs that inhibit enzymes and prevent the virus from effectively replicating) reduces such hospitalizations by 90 percent. This will undoubtedly reduce hospitalizations in the next wave.”

According to Dr. Tal Brosh, head of the viral infections unit at the public hospital Assuta Ashdod: “These drugs are very important in my view. This is the first time you can intervene at the very beginning of the disease, and not with a drug that’s hard to administer like Regeneron, but rather a simple pill.” 

In preparing for another potential wave, Dr. Noa Eliakim-Raz, director of Beilinson Hospital’s coronavirus ward said Israel "should exploit the lull in order to bolster health services, with an emphasis on intensive care and internal medicine departments, which bear most of the burden.” She added that in view of the literature that keeps growing at a dizzying pace, the Health Ministry should establish a professional body to keep abreast of articles on COVID-19 treatments and to inform coronavrius wards regularly regarding treatment protocols.

She also noted lessons about the touchy issue of family visits. “One should allow relatives with Green Passes who understand the risks of exposure in a coronavirus ward to be beside their loved ones for as long as they wish. Implementing this requires resources, both personnel and equipment.” She stressed that uniformity is needed in issuing safety rules for coronavirus wards. “Mounting evidence shows some of these measures can be significantly relaxed,” she claimed. Furthermore, she added, one should reconsider the approach to patients too. “During lulls between infection waves, one could place these patients in regular wards, carefully ensuring their isolation, instead of concentrating them in designated wards,” she asserted.

Another issue requiring urgent attention during the lull is the physical and mental exhaustion of medical teams. “There is no doubt the mental fortitude of these coronavirus ward teams has been eroded, Eliakam-Raz said. “These teams remain scarred and traumatized.”

Children and the education system

The operation of schools and the population of unvaccinated children exposed to the virus remain one of the key issues in Israel’s battle with the epidemic. Behind the decision to embrace the “Green Classroom” program lies the great importance attributed to maintaining frontal teaching, after such a long absence, something which was very harmful to not only children but also parents, families and the economy. The decision was taken despite a failed pilot. Experts say the sole reason for adopting this program is that there was a general decline in the number of COVID-19 cases. If the contagion factor were on the rise, the results would have been different. This policy may be put to the test in a fifth wave, unless it is decided to vaccinate the 5-11 age group soon. A large proportion of vaccinated people could change the picture. But vaccinating children at this point, even after its approval in the United States, could lead to more mistrust by parents, school-parents squabbles, and a sense of wasted time by which the vaccine is effective during a period of insignificant infection rates.

A first grade class in Jerusalem in September.Credit: Ohad Zwigenberg

“The issue of schools and coronavirus was very politicized throughout this crisis, characterized by a lack of cooperation with the Education Ministry. In fact, no serious analysis of this topic seeking effective solutions has been done so far. The most meaningful thing that could bring about a change ahead of the next wave is apparently vaccination, but when infection rates are waning, it’s not clear that vaccinations should take place immediately,” said another advisory panel member.

“What is happening in the school system is a demonstration of a wider problem, showing the need to invest much more in an epidemiological database enabling better decision making, argued Prof. Hagai Levine, the head of the Association of Public Health Physicians. “Even after the pilot study, we don’t know if the ‘Green Classroom’ program is a good one. The way to handle this is through utilizing good, secure data.”

Vaccination has added another significant layer of defense, alongside testing and sequencing, but all professionals realize there is no hermetic way to keep out variants. “There is much investment in testing and expensive genetic sequencing, but there is no smart operational plan that matches responses to different risk levels,” said an advisory panel member.

Levine believes the ad hoc responding to each wave must change. “We have to break loose of thinking in terms of waves,” he said. “We’re in a global pandemic that may be with us for a long time, and we need to constantly look a few steps ahead, seeing how we can create long-term solutions, not just apply band-aids. The epidemic should be leveraged for bolstering health services and their preparedness not only for epidemics but also for events such as heart waves, flooding or other large-scale events.”

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