Data out of Israel reveals some troubling trends involving this heavily vaccinated population. The daily number of SARS-CoV-2 cases in Israel is increasing, having recorded the highest number on Thursday since March. TrialSite delved into a recent data trove made available by the Israeli government and has found that a majority of those now vaccinated actually, according to the numbers, face as much risk testing positive for the Delta-driven SARS-CoV-2 infection as unvaccinated individuals. Meaning, at this point, the vaccine appears to have a negligible effect on an individual as to whether he/she catches the current strain. Moreover, the data indicates that the current vaccines used (Moderna, Pfizer-BioNTech, AstraZeneca) may have a decreasing effect on reduced hospitalizations and death if one does get infected with the Delta variant. With a majority of vaccinations using the mRNA-based BTN162b2, what are the implications for this trend? What does it mean for the transmission of SARS-CoV-2? Is this a significant trend or can it be explained away? As TrialSite reported recently, Pfizer has moved aggressively to introduce a third booster vaccine for at least the immunocompromised population. The primary regimen actually involved two doses, with one essentially serving as a booster dose. While the Delta variant seems to introduce a considerable challenge, TrialSite asks the question: Is it wise, practical, and scalable to introduce booster doses so soon after a considerably powerful two-dose regimen? Is it wise to consider boosters for a vaccine that is still considered experimental? Will the need for a booster occur each and every time new variants emerge? If so, how can such an approach be scaled around the world—especially in low-and middle-income countries (LIMIC)? Already, the World Health Organization (WHO) issued strong statements about their opposition to a third booster dose given vaccine equity issues—much of the LMIC world isn’t vaccinated. That represents a great majority of people on earth. TrialSite, a media and social network hub dedicated to transparent and accessible research, asks the question: Who among academia, government and industry is monitoring this initiative objectively and candidly with an eye for transparency directed to what should be the correct public health policy and action decisions? Pharmaceutical companies are critically important, but they are also driven by economic considerations—not by choice, but by the very logic of the market system.
First, we start with an introduction to Israel, a nation with just over 9 million people and one of the most vaccinated places on the planet. According to data from Reuters, Israel has administered 10.9 million doses, and given a majority of the population received the two-dose mRNA-based regiment, the estimated total vaccination rate against COVID-19 stands at 60.5% of the country’s total population. According to Fortune, that rate is 65%. These rates would imply that overall infections would wane, particularly in an advanced society driven by stringent public health policy.
Is the Pfizer Vaccine Losing Potency?
Recently in the Jerusalem Post, it was reported that the mRNA-based vaccine was less effective against the SARS-CoV-2 Delta variant than “health officials hoped,” reported Prime Minister Naftali Bennett last Friday. This online media reported that “855 people tested positive for coronavirus and more countries were listed as places of high infection.” The Prime Minister declared, “We do not know exactly to what degree the vaccine helps, but it is significantly less.”
More Concerning Data
An initial review of the data surprised the analysts. A summary follows a review of some examples. The first one reveals the week of June 27th to July 3rd in the age cohort 20-29 years old. According to the data in this cohort, those new COVID-19 cases involving individuals fully vaccinated totaled 79%. How about the percentage of this population that’s fully vaccinated? It turns out to be 78%, indicating that at least for this cohort, the vaccination rate doesn’t seem to impact the infection rate.
In another cohort, aged 30-39 from the week of June 27th to July 3rd, the new COVID-19 cases percentage involving people fully vaccinated came out at 80% while the percentage of the population in that age group fully vaccinated came in at 83%.
In yet another example from the week of July 27th to July 3rd in the 40-49 years old age group, new COVID-19 cases involving fully vaccinated people totaled 84%, and the percentage of the population in this age group that were fully vaccinated stood at 86%.
TrialSite notes that a number of questions needed to be asked involving sample size and whether this data is statistically significant.
But what about hospitalization numbers and deaths? One would expect the hospitalized rate to be significantly higher for the unvaccinated than the vaccinated. According to the data set herein, the total number of hospitalizations is slightly higher in the vaccinated. Is this due to the potency of the Delta variant or waning immunity from the vaccine? Could this be linked to vaccine-induced Antibody-Dependent Enhancement? This is something many vaccine experts wary of fast-tracked mRNA-based vaccines predicted could be a factor. Could this be a small difference now (with smaller numbers) yet lead to worsening numbers in forthcoming seasons?
See the chart based on the links to the data:
Breakthrough Infection Problem?
In a recent study published in the Journal of Clinical Microbiology and Infection, Israel-based scientists and researchers link a growing number of bad SARS-CoV-2 cases, including death, to a minority of fully vaccinated individuals in this eastern Mediterranean nation.
This study was led by corresponding authors Tal Brosh-Nissimov, Head of Infectious Diseases Unit, Samson Assuta Ashdod University, Israel; and Efrat Orenbuch-Harroch affiliated with Hadassah Hebrew University Medical Center, Jerusalem, Israel; and a team of other investigators. Of course, during Phase 3 clinical trials, the mRNA-based products exhibited compelling efficacy rates in protecting subjects from more severe forms of the pathogen. This efficacy was generally noted across all age groups, including the elderly and those with compromised immune systems and the like.
Israel earned the status as one of the highest vaccinated nations worldwide. It was able to marshal its government and private sector resources across a population of just over 9 million. A great amount of collaboration across societal sectors helped, which hasn’t necessarily been the case in some other advanced nations.
But now, approximately just 6 months out from the start of an aggressive vaccination campaign, a disturbing set of data points emerge with breakthrough infections across the majority of vaccinated populations. There still isn’t sufficient data to determine the true nature of these observations. The tendency on one side is to declare that these products may not be working optimally while, on the other side, the data points are minimized with an emphasis on overall trends. But there isn’t sufficient data to declare that these vaccines are an overwhelming success. This takes time and observation, and that leads to a discussion below on third booster shots.
The Recent Israeli Study
The multi-site-based study team organized the research endeavor to better understand the nature and trends associated with those who are vaccinated and hospitalized due to breakthrough SARS-CoV-2 infection while seeking to isolate actual risk factors that could inform care and public health policy moving forward.
Thus, analyzing 17 Israeli hospitals in various segments, the investigators targeted subjects who not only received two doses of BNT162b2—the Pfizer-BioNTech vaccine but also were infected with SARS-CoV-2, but also hospitalized in one of the hospitals’ units set up for the novel coronavirus.
Seeking more data in a quest to better understand risk factors, the investigators also included in the study record not only a review of electronic medical records but also viral genomic sequencing to assess which particular SARS-CoV-2 variants were involved with the breakthrough infections. Ultimately seeking to understand if these breakthrough infections were leading to poor outcomes, such as hospitalization with a need for mechanical ventilation or death or, hopefully, positive outcomes associated with no need for assisted ventilation and, of course, hospital discharge.
As TrialSite reported recently, Israel was seeking a third booster shot for those vaccinated individuals who have comorbidities, such as individuals who are immunocompromised. Undoubtedly, this study influenced that movement, as in this study involving 152 subjects, the number of poor outcomes equated to 22% of the study population, or 38 patients. A majority of these subjects fell into the elderly category while also facing a number of other health challenges categorized as comorbidities.
The team discovered that those study subjects with comorbidities (e.g. immunocompromised, etc.) faced a higher risk of breakthrough infection than those who were not. This analysis was based on an assessment associated with a large group of unvaccinated patients who were also hospitalized a range of conditions from central nervous system-based conditions to cardiovascular challenges to cancer, etc.
The Israeli study conclusion was tempered and careful, denoting that only “a small minority of fully-vaccinated BNT162b2 recipients might still develop severe SARS-CoV-2 infection despite the vaccine’s high effectiveness, with need for in-patient care.” Of course, the authors noted the risk cohort associated with these findings: those with a “high rate of comorbidities predisposing for progression to severe COVID-19, and a high rate of immunosuppression.”
That is, in this class of patients receiving the Pfizer BNT162b2 two-dose regimen (that already includes a booster), the outcomes are similar in that it makes no difference whether the subject was vaccinated or not. This Israeli study team recommended that “additional prospective longitudinal studies are urgently needed to identify predictors for vaccine breakthrough infection and simple correlates of vaccine protection” in a bid to find more granular ways to identify those with higher risk. The authors suggest that these individuals be included in a more protected regimen, from “strict precautions” to “repeated active vaccination or other prophylactic measures such as passive vaccination.” They argue for a “mass vaccination” approach to lead to “herd immunity.”
TrialSite finds the data a bit concerning and suggests it justifies a close watch. No severe conclusions can be drawn at this point. Some items that should be considered with the data is the relatively small sample size since Israel still has a low case count, an even lower hospitalization count, with an almost non-existent death rate. The cases are growing though, so this could change in the forthcoming weeks.
The other element here is that Israel experienced a high infection rate before their mass vaccine rollout. Here, it is possible that a sizable percentage of the unvaccinated cohort is protected by natural immunity. Thus, many of the recovered COVID-19 patients may not feel a need to take a vaccine since they already have natural protection. If that is indeed occurring, the comparable numbers of vaccinated and unvaccinated cases could perhaps just confirm that natural immunity and vaccine-derived immunity provide similar levels of protection. The key is to remain open-minded to the myriad scenarios. But regardless, the data points coming out of Israel should prompt concern with more intensified monitoring of what unfolds over the next weeks.
Call to Action: TrialSite asks the community to review the Israel data shared herein. Do you agree with the findings? Disagree? Let us know in the comments, or submit a response in our OpEd feature. TrialSite is a place for dynamic scientific discussion, debate, and even dissension. Only with that do you have true advancement of science and health.