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Yair Goldberg, Micha Mandel, View ORCID ProfileYinon M. Bar-On, Omri Bodenheimer, Laurence S Freedman, Eric Haas, View ORCID ProfileRon Milo, Sharon Alroy-Preis, Nachman Ash, Amit Huppert


This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.


Background: Starting December 2020, Israel began a mass vaccination campaign against coronavirus administering the Pfizer BNT162b2 vaccine, which led to a sharp curtailing of the outbreak. After a period with almost no SARS-CoV-2 infections, a resurgent COVID-19 outbreak initiated mid June 2021. Possible reasons for the breakthrough were reduced vaccine effectiveness against the Delta variant, and waning immunity. The aim of this study was to quantify the extent of waning immunity using Israel national-database. Methods: Data on all PCR positive test results between July 11-31, 2021 of Israeli residents who became fully vaccinated before June 2021 were used in this analysis. Infection rates and severe COVID-19 outcomes were compared between individuals who were vaccinated in different time periods using a Poisson regression, stratifying by age group and adjusting for possible confounding factors. Results: The rates of both documented SARS-CoV-2 infections and severe COVID-19 exhibit a statistically significant increase as time from second vaccine dose elapsed. Elderly individuals (60+) who received their second dose in March 2021 were 1.6 (CI: [1.3, 2]) times more protected against infection and 1.7 (CI: [1.0, 2.7]) times more protected against severe COVID-19 compared to those who received their second dose in January 2021. Similar results were found for different age groups. Conclusions: These results indicate a strong effect of waning immunity in all age groups after six months. Quantifying the effect of waning immunity on vaccine effectiveness is critical for policy makers worldwide facing the dilemma of administering booster vaccinations.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

No funding.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.


The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was approved by the Institutional Review Board of the Sheba Medical Center. Helsinki approval number: SMC-8228-21.

All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.


I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).


I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.


Paper in collection COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxiv

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