Israeli Study Finds - Natural immunity is longer lasting and stronger against infection than two-dose vaccine-induced immunity

Spoiler Alert: Natural Immunity is way better (like 13X better) than vaccinated immunity based on this study out of Israel. Second spoiler alert: there appears to be a marginal increase in immunity for people who have natural immunity, and get a single dose of the vaccine. Last Spoiler Alert: I talk a little bit about God. 🙂

How current was the study?

The study was published on August 25, 2021 on the medRxiv website.

Is there a source?

This study was conducted in late July or early August, 2021, and published by medRxiv.org. As of this blog-post publication, it has not yet been peer reviewed.

Citation

Gazit S, Shlezinger R, Perez G, et al. Comparing SARS-CoV-2 natural immunity to vaccine-induced immunity: reinfections versus breakthrough infections, August 2021. medRxiv, doi: https://doi.org/10.1101/2021.08.24.21262415

Primary or Secondary Dataset?

This study was based on a single Secondary Datasets, specifically Electronic Medical Records system database of Maccabi Healthcare Services (MHS), which is Israel’s second largest Health Maintenance Organization. Basically MHS is a healthcare delivery system and a healthcare insurance company all in one.

How was the sample collected?

The researchers were given anonymized electronical medical records from MHS’ database for a study period of March 1, 2020 to August 14, 2021.

The sample included:

MHS members aged 16 and older
- Group 1: Who were vaccinated with two doses of the Pfizer vaccine before February 28,2021, or
- Group 2: Who had a documented COVID infection by February 28, 2021, or
- Group 3: Who had a documented COVID infection and received one dose of the vaccine by May 25,2021, which was 7 days before the study period.

These three groups of people (1. vaccinated persons, 2. person who had a COVID infection, and 3. persons who had a COVID infection and a single dose of vaccination) are the 3 groups of people this study compares.

Some additional information about the MHS that’s listed in the article. MHS is a 2.5 million-member, state-mandated non-profit, and the second largest in Israel covering 26% of the Israeli population. Citizens of Israel are required to become members of one of four of the national health organizations.

The article breaks down some of the variables for the study. The researchers pulled various data points from the EMR including vaccine dates, results of a polymerase chain reaction (PCR) tests, reported hospitalizations, mortality information, and related symptoms.

The vaccinated group was used as the reference point, to compare group 2 (prior COVID) and group 3 (prior COVID and a single dose) against. Group 2 and 3 were matched with Group 1 with a 1-to-1 ratio using age, sex, and residential socio-economic status.

There were 4 outcomes that were evaluated as part of the comparison of these three groups. 1. documented confirmed case of SARS-CoV-2 infection, COVID-19, COVID-19 related hospitalization and COVID-19 related death. These outcomes were evaluated based on the period of June 1st to August 14, 2021.

In addition to these 4 outcomes, there were a number of other variables that were included: age, sex, socioeconomic status, geographic area, BMI, chronic diseases, etc..

The statistical analysis was broken down into 3 logistic regression models. Basically what that means is they ran 3 processes or “models” to determine:

Were there differences in reinfection rates based on the length of time of immunity conferred by prior vaccination vs previous COVID infection.
Were there differences in reinfection rates between previously infected individuals and vaccinated individuals regardless of the length of time of immunity.
Were there differences in reinfection rates between previously infected individuals and previously infected and single-dose vaccinated individuals, again, regardless of the length of time of immunity.

In all three cases the comparisons factored in age, sex, geographic location, etc.. and compared the 4 outcomes (SARS-CoV-2 infection, COVID-19, Hospitalization and death). In addition they adjusted or compensated for underlying comorbidities which are common for severe COVID cases: obesity, cardiovascular disease, diabetes, etc…

For the technical folks, they used Python version 3.73 for their analysis.

What were the findings?

This is self-reported as the largest real-world observation study on COVID to-date. There were 673,676 fully vaccinated persons, 62,883 unvaccinated but previously infected persons, and 42,099 previously infected and single-dose vaccinated. Also keep in mind that Israel is likely the most vaccinated nation in the world.

There are tables to reference in the article. I’m not going to copy them here, because although they are helpful to know some of the detailed comparisons between the groups, they don’t add additional value, in my opinion, to my review of the study.

So here are the results:

Model 1

Were there differences in reinfection rates based on the length of time of immunity conferred by prior vaccination vs previous COVID infection.

There were 16,215 people in each of the groups for Model 1. There demographics were similar, although there were some differences in the comorbidities of each person/group.

Positive SARS-Cov-2 Test

There were 257 cases of a SARS-CoV-2 infection recorded.
238 (92.6%) of those infections were vaccinated persons – considered “breakthrough infections”. (vaccinated immunity)
19 (7.4%) of those infections were previously infected people. (natural immunity)

That’s a statistically significant finding which researchers stated as a 13.06-fold increased risk people who are vaccinated to get re-infected, vs people who have natural immunity from prior COVID infection. You read that right. Their study found that, based on their sample, people who are vaccinated, are 13 times more likely to get reinfected with COVID, then people who had a prior infection and are not vaccinated. In addition, they didn’t find statistical evidence that differences in reinfection had anything to do with comorbidities.

Symptomatic COVID-19 Cases

There were 199 cases recorded where the person exhibited COVID-19 symptoms such as fever, cough, difficulty breathing, diarrhea, loss of taste and smell, etc…
191 (95.9%) of those 199 were vaccinated individuals. (vaccinated immunity)
8 (4%) of those 199 were unvaccinated, previously infected individuals. (natural immunity)

Another statistically significant finding, which researchers stated as a 27.02-fold risk for symptomatic breakthrough infection vs symptomatic reinfection. That means people who are vaccinated, 27.02 times more likely to have symptoms when infected with COVID, than previously infected, unvaccinated individuals.

My opinion – the immune system in the human body God designed is amazing, and far better than anything man-made in defending against viruses and disease. People who say otherwise are likely selling something.

COVID-19 Cases Requiring Hospitalization

There were 9 cases of hospitalization recorded.
8 of those hospitalized were previously vaccinated (vaccinated immunity)
1 of those hospitalized were unvaccinated and previously infected (natural immunity)

COVID-19 Cases Resulting in Death

There were no deaths recorded in vaccinated or unvaccinated individuals.

Model 2

Comparing previously infected vs vaccinated individuals, without comparing the length of time of immunity.

In this case, there were 46,035 people in each group (vaccinated, and previously infected).

Positive SARS-Cov-2 Test

There were 748 cases of a SARS-CoV-2 infection recorded.
640 (85.6%) of those infections were vaccinated persons – considered “breakthrough infections”. (vaccinated immunity)
108 (14.4%) of those infections were previously infected people. (natural immunity)

In this model, they found that people who are vaccinated are 5.96 times more likely to get infected with COVID than people who have natural immunity through prior infection.

Symptomatic COVID-19 Cases

There were 552 cases recorded where the person exhibited COVID-19 symptoms such as fever, cough, difficulty breathing, diarrhea, loss of taste and smell, etc…
484 (87.7%) of those 552 were vaccinated individuals. (vaccinated immunity)
68 (12.3%) of those 552 were unvaccinated, previously infected individuals. (natural immunity)

Vaccinated individuals were 7.13 times more likely to get COVID than unvaccinated individuals who had natural immunity through prior infection.

COVID-19 Cases Requiring Hospitalization

There were 25 cases of hospitalization recorded.
21 of those hospitalized were previously vaccinated (vaccinated immunity)
4 of those hospitalized were unvaccinated and previously infected (natural immunity)

Vaccinated individuals were 6.7 times more likely to be hospitalized than unvaccinated individuals who had natural immunity through prior infection.

COVID-19 Cases Resulting in Death

There were no deaths recorded in vaccinated or unvaccinated individuals.

Model 3

Comparing previously infected vs previously infected and single-dose vaccinated individuals

In this model, there were 14,029 individuals in each group.

Positive SARS-Cov-2 Test

There were 57 cases of a SARS-CoV-2 infection recorded.
20 (35.1%) of those infections were previously infected and single-dose vaccinated individuals (natural immunity + 1-vaccine dose)
37 (64.9%) of those infections were previously infected people with no vaccination. (natural immunity)

In this model, they found that people who have just natural immunity are 0.53 times more likely to get infected with COVID than people who have natural immunity and a single dose of a vaccine.

Symptomatic COVID-19 Cases

There were 39 cases recorded where the person exhibited COVID-19 symptoms such as fever, cough, difficulty breathing, diarrhea, loss of taste and smell, etc…
16 (41%) of those infections were previously infected and single-dose vaccinated individuals (natural immunity + 1-vaccine dose)
23 (59%) of those infections were previously infected people with no vaccination. (natural immunity)

That’s an observable, but not significant difference between natural immunity and natural immunity + 1-vaccine dose.

COVID-19 Cases Requiring Hospitalization

There was a single case of a person who had natural immunity and no vaccine dose that required hospitalization.

COVID-19 Cases Resulting in Death

There were no deaths recorded in natural immunity or natural immunity + 1-vaccine dose individuals.

Essentially, there is a slight advantage for people who have natural immunity from prior infection, to get a single dose of the vaccine.

Additional Findings

The outcome differences between model 1 and model 2 suggest that there could be waning natural immunity against the Delta variant, but it’s still significantly better than vaccinated immunity.

Vaccinated individuals were also at greater risk for hospitalization across both models.

What were the limitations?

The study listed a few limitations.

By the way, a note on limitations. Research will always have limitations and/or biases. So limitations are expected. What would be concerning would be research studies that don’t state their limitations, or do a poor job of listing obvious limitations. It’s not necessarily a matter of how many limitations are listed, but rather that they are listed.

The Delta variant was dominant in Israel during the outcome period, so they just called out that the research findings may not necessarily extend to other strains.
The research only looked at the Pfizer BioNTech vaccine, so the study wouldn’t necessarily represent breakthrough infection rates based on the Moderna or Johnson & Johnson vaccine. Or protection provided by a booster dose.
Screening for COVID wasn’t done on a specific protocol for all members, so it’s possible there were asymptomatic infections that were undetected.
This is the first study I’ve seen that listed health behaviors as a limitation, so I’m happy to see that. They mention that they looked at demographics like age, sex, and geographic location, but they didn’t look at social distancing or mask-wearing behaviours, which could have a confounding impact on the results.

“This analysis demonstrated that natural immunity affords longer lasting and stronger protection against infection, symptomatic disease and hospitalization due to the Delta variant of SARS-CoV-2 compared to the BNT162b2 two-dose vaccine-induced immunity”
Discussion Section, Para 8.

What you should consider

Did they cite a source and can you navigate to it? 10/10. Requests can be made to get access to the dataset.
Did the source clearly describe how the data was acquired. 8/10. They could have been more specific with the query and filter logic, but overall, they summarized it well.
Did the source cite potential biases or limitations to the study? 10/10. I liked the call out for behavioral variables, which I’ve not seen called out in the studies I’ve looked at. That’s one of the biggest variables that I think is missing from most studies.
Is the source reputable? 10/10. Israel was one of the first nations to get the vaccine to their population, and they have, I think, the highest national vaccination rate. The Israeli healthcare system is one of the best in the world and the sample population was very large.
We’re there enough participants in the sample? 10/10. This was self-reported as the largest real-world observational study. It is an Israeli population, so there may be aspects of their healthcare system, their geography, the demographics of their population, etc.. that likely limit the representation of this sample.
Did the study or news article focus on one finding and not talk about other findings that are obviously visible in the study? 10/10. I didn’t notice anything obviously missing. They did a nice job explaining the models and results of the study.
Are all the variables included that you think are necessary to arrive at the same conclusion, or at least identified as limitations? 10/10. They cited a limitation of their study being that of behavioral factors like mask-wearing and social distancing. However, that would be incredibly difficult and likely very intrusive on the population to really track these types of variables.
Is the study clearly described to the point that it could be reproduced by someone else given the same data and research background? 8/10. There would need to be more specifics, I think, around the way they queried the data. It looks simple enough, but without looking at the actual data-set to see how simple it really is I’d hesitate to give this more than an 8 out of 10.

My Conclusion

This is probably my favorite study to-date, because I think it showcases well the differences between natural immunity and vaccinated/man-made immunity. There are a lot of organizations today that are mandating the COVID-19 vaccines for employees, yet completely ignoring the fact that in healthcare (and many other industries for that matter), many of those employees have already had COVID resulting in natural immunity.

While my opinion is that we shouldn’t have to validate natural immunity to the extent of studies like this, this one does a nice job of making a really simple case for unvaccinated, previously infected individuals to forego the vaccine. I’m not saying people shouldn’t get the vaccine, but I know a lot of people who do not want the vaccine for very complex and varied reasons. Prior infection should be sufficient for exemption from vaccine mandates based on this study.

If you are an employer requiring the vaccine for your employees, take into consideration natural immunity from prior infection. Based on this study, it’s likely as good and perhaps significantly superior to vaccinated immunity in terms of preventing reinfection, COVID-19 symptoms, and hospitalization. For healthcare workers, especially those who have been on the front-lines of COVID for the last 18 months, they likely already have natural immunity. Don’t discount that.

Lastly, it’s hard to ignore the Designer of the human body. God designed the immune system to do exactly what this study shows – to learn about and fight new infections and viruses that the body comes into contact with. He is an amazing God, and if you don’t know Him, I’d love to make introductions.

Stay safe, and be kind.

-Josh