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Five Critical Questions Will Determine if the Vaccine or the Virus Wins in Israel

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People wearing face masks wait to receive a coronavirus vaccine at a COVID-19 vaccination center in Jerusalem, Monday, Jan. 4, 2021
People wearing face masks wait to receive a coronavirus vaccine at a COVID-19 vaccination center in Jerusalem, Monday, Jan. 4, 2021Credit: Oded Balilty,AP
רן בליצר
Ran Balicer

The State of Israel made history this month when it launched a highly complex campaign at top speed and vaccinated 1 million people within two weeks. It is also exceptional that less than one in 1,000 vaccinations here were destroyed, despite the strict rules for maintaining the cold chain; Pfizer’s vaccine must be kept at minus 70 degrees C (minus 94 degrees F). There are many worthy people responsible for this success, but we must not get carried away and forget that we’re in the heat of a race whose results have yet to be determined: a local race between the spread of the pandemic and the effect of the mass-vaccination campaign.

Israel is in the midst of a third wave of the disease, which threatens to be more aggressive than its predecessors, both because of the winter season, when people tend to spend more time in closed unventilated settings, and, to a yet-unknown extent, because of the spread of the UK variant in Israel.

Although this variant is not more pathogenic, experts believe it is more infective – perhaps 1.5 times more than the viral strains circulating thus far – and could therefore significantly change the transmission dynamics. And Israel’s current state of affairs is fragile and risky: In recent weeks the incidence rates have gradually increased to one of the highest rates per capita globally.

Direct protection vs. indirect protectionCredit: Ran Balicer

To date, the early winter wave has led to a sharp increase in illness and death in almost all European countries, including the Czech Republic, Belgium, Sweden, Switzerland and Greece. All these countries are similar in size to Israel and they have seen weeks of 80 to 200 deaths per day attributed to Covid. Israel, which already sees ~20 deaths a day from the coronavirus, watches these countries with concern, trying to tackle the impending impact by two means of intervention: limiting the spread of the virus through the currently enforced partial lockdown, and through an expedited mass-vaccination campaign.

Direct vs indirect effect

The vaccination campaign could change the consequences of the winter wave of infections in two key ways: by affecting serious illness among those vaccinated (“direct protection”) and interrupting virus spread at the population level (“indirect protection”). We will try to assess and quantify the impact of each of these arms:

The large-scale Pfizer and Moderna studies clearly demonstrated the vaccines' direct protective effect. In the Moderna study published last week in The New England Journal of Medicine, one of the world’s leading medical journals, 30 cases of serious illness were registered in the placebo group, and zero (!) in the vaccinated group. It is difficult to recall such impressive results in a vaccine efficacy study.

Still, on the level of the population as a whole, the overall impact of the direct effect of vaccinating the elderly is limited. According to Clalit Health Services data, about 80 percent of severe illness occurs in those aged 60 and older. A simple calculation would show that vaccinating 70 percent of the elderly expected by the end of this week – 85 to 90 percent of whom will develop immunity within a few weeks – will lead to a 50% reduction in the severe illness rates among those infected.

Credit: Ran Balicer

That is undoubtedly a dramatic improvement, but in itself does not change the rules of the game – because a doubling of the daily number of new cases, which currently happens every two weeks, will completely negate this beneficial effect.

Even greater hope lies in the potential of indirect protective effects, which maintains that the steadily increasing proportion of vaccinated individuals interrupts the virus spread. Thus, if the average patient was expected to infect four people (the ‘R’ factor), but encounters a population in which a quarter of the people are immune, he will infect only three people. The fourth person, who, thanks to the vaccine was not infected, thereby “saves” the four people whom he himself was expected to infect, although three of those four were never vaccinated themselves.

And that is the indirect effect, which protects the unvaccinated. This effect was demonstrated to protect more lives among unvaccinated elderly than among children, when vaccinating children against pneumococcal disease.

Does the coronavirus vaccination really reduce infection and asymptomatic disease and thus confer indirect protective effects? The answer is not as self-evident as one might think. Administering a vaccine to the muscle, which leads to both cellular immunity and formation of antibodies of the type that spreads in the bloodstream, does not guarantee the formation of antibodies in the mucous membranes of the nose and mouth, which are required to protect the person from a mild upper respiratory infection and potential spread to other people. To date there has been no properly designed study to determine whether this is true and to what extent, but the Clalit Research Institute has a relevant large-scale prospective study ongoing.

The extent of indirect protective effect depends not only on how many get vaccinated, but also on who gets vaccinated. For example, inoculating adults who are socially isolated will have less effect than inoculating young people who are at the center of the social network, as we demonstrated in past studies on influenza. Non-homogenous mixing of the vaccines in the population further complicates the assessment of this indirect protective effect.

We must now first and foremost complete vaccination of vulnerable subgroups as soon as possible, as the direct effect is clear and not dependent on the ever-changing public behavior.

Vaccinating the 20% most vulnerable segments will not allow us to return to the “pre-coronavirus” routine – this will likely be considered when we reach immunity of 70 to 90 percent of the entire population (some through natural infection, and most by the safer route of the vaccine), the indirect protection will allow for a built-in reduction of R below 1, without dependence on social distancing. At this point, which is called “herd immunity,” we can hope to return to routine life almost as it was before the virus.

An Israeli health worker is vaccinating a man against the coronavirus in Jerusalem, January 2021.Credit: Ohad Zwigenberg

The questions that will determine how the story will unfold:

There are five open-ended questions that will determine who will win the 2021 ‘race’ between the vaccination campaign and the virus spread in Israel. Mathematical models have produced various outcomes depending on the following attributes in question.

1. The real-life vaccine effectiveness among the elderly

In the recently published Moderna study, the efficacy was 94 percent among young people, compared with 86 percent among those 65 and older. These results indicate the need for conservative assumptions of real-life vaccine effectiveness in a campaign that focused on the sickest most immune-compromised subgroups, in logistical conditions cold chain that may not be as perfect as in the clinical trials. This focus on this subgroup also serves to suggest against considering the British model of deferring the second vaccine dose.

2. The vaccine effectiveness in reducing infection and infectivity to others, thus lowering the R factor

Prime Minister Benjamin Netanyahu poses with the millionth recipient of the COVID-19 vaccine in Umm-al Fahm, on his first visit to an Arab town in over a year, January 1, 2021. Credit: Sharon Tzur

The Moderna vaccine study hints at ~60 percent effectiveness in reducing infection – which is a reasonable working assumption, in my opinion, and very good news.

3. The effectiveness of the present containment efforts imposed by the government

The partial lockdown plan lacks coherence (shutdown of street commerce and prohibiting take-away from businesses, while meetings of up to 10 people in a closed spaces and open high-school classes in face of clear risk of infection). We will begin to see measurable effects later this week, and there is genuine concern that the outcomes will be limited, despite the grave impact on the economy.

4. The rate of spread of the U.K. variant in Israel

The new variant is potentially a game changer, and if and when it becomes the dominant strain in Israel, it is likely to increase the R factor significantly, regardless of government efforts to check the virus. Our mission is to protect the at-risk population before that happens and to improve the national containment mechanisms before we confront the full force of this challenge.

5. Perhaps the most important unknown: the rate of the arrival of vaccines to Israel

Israel received a relatively large initial shipment of vaccines, which enables it, with judicious use, to cover its entire at-risk population. There is no way of knowing now for certain when we will receive additional shipments, and where we will stand at that stage in terms of the virus spread. Therefore we must be very meticulous about earmarking the vaccine for its target population – older people and a small group of younger patients with multiple chronic illnesses, which places them at particularly high risk. We should do that and ignore the background noise urging us to maintain vaccination centers active in full capacity at all costs, wrongly focusing on the overall daily number of vaccinations performed.

In the choice between a dizzying rate of vaccination and a precise choice of the target populations, we must now choose precision. Because if vaccinating young populations causes us to get “stuck” for weeks without the ability to vaccinate high percentages of the at-risk populations, the potential of the vaccination campaign to stop serious damage from a continued spread of the virus is likely to sustain a mortal blow.

Hope mingled with fear

This is a tricky and unstable period, in which hope and fear are often intermingled. We have a unique opportunity to avoid most of the severe consequences of the winter wave now being seen in Europe and the United States, despite an increasing spread of the virus and more contagious variants already spreading in Israel as well.

The achievements of the Israeli health care system in this herculean mass-vaccination campaign to date should be greeted with gratitude, but the battle is far from over. There is a complex risky period before us, with heavy burdens on the health care system and a prolonged period of dealing with the serious consequences of the prolonged damage to our economy.

The vaccination of the older population is not in itself a flak jacket of total protection, one that frees us from the need to control the viral spread. We won’t be able to properly assess the extent of the impending risk we are facing in the coming months, until the above open-ended questions are answered.

Therefore, even during this vaccination campaign we must be vigilant and adhere to the basic rules of personal responsibility: wear a mask, maintain social distancing, reduce out-of-household contacts, and be sure to self-isolate whenever there is a sign of illness. Covid continues to spread at a fast pace and endanger those who have not yet been vaccinated or have not developed immunity.

The eyes of the many countries are now on Israel to see how the story unfolds here and how the vaccination will change the disease course. We must hope that during this last chapter of the crisis we will once again be a role model, as happened during the first wave, and not a warning light to the world, as we were in the second wave, when we hastily declared victory before the final whistle.

Prof. Ran Balicer is chief innovation officer at Clalit Health Service and head of the cabinet of coronavirus experts in Israel.

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