Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Naturally Acquired Immunity versus Vaccine-induced Immunity, Reinfections versus Breakthrough Infections: A Retrospective Cohort Study
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Abstract
Background: Waning of protection against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) conferred by 2 doses of the BNT162b2 vaccine begins shortly after inoculation and becomes substantial within 4 months. With that, the impact of prior infection on incident SARS-CoV-2 reinfection is unclear. Therefore, we examined the long-term protection of naturally acquired immunity (protection conferred by previous infection) compared to vaccine-induced immunity. Methods: A retrospective observational study of 124 500 persons, compared 2 groups: (1) SARS-CoV-2-naive individuals who received a 2-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 vaccine, and (2) previously infected individuals who have not been vaccinated. Two multivariate logistic regression models were applied, evaluating four SARS-CoV-2-related outcomes—infection, symptomatic disease (coronavirus disease 2019 [COVID-19]), hospitalization, and death—between 1 June and 14 August 2021, when the Delta variant was dominant in Israel. Results: SARS-CoV-2-naive vaccinees had a 13.06-fold (95% confidence interval [CI], 8.08–21.11) increased risk for breakthrough infection with the Delta variant compared to unvaccinated-previously-infected individuals, when the first event (infection or vaccination) occurred during January and February of 2021. The increased risk was significant for symptomatic disease as well. When allowing the infection to occur at any time between March 2020 and February 2021, evidence of waning naturally acquired immunity was demonstrated, although SARS-CoV-2 naive vaccinees still had a 5.96-fold (95% CI: 4.85–7.33) increased risk for breakthrough infection and a 7.13-fold (95% CI: 5.51–9.21) increased risk for symptomatic disease. Conclusions: Naturally acquired immunity confers stronger protection against infection and symptomatic disease caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 2-dose vaccine-indued immunity.
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Are COVID-19 Vaccine Boosters Needed? The Science behind Boosters
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“Receipt of 2 vaccine doses was associated with significantly lower adjusted estimated protection (95% CI) than 3 doses among both individuals with (68% [67%-70%] vs 83% [81%-84%]) and without (42% [41%-44%] vs 73% [72%-73%]) prior infection, recognizing longer median follow-up time (IQR) since the second vs third dose…”
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“Studies show that natural immunity is more potent in protecting against SARS-CoV-2 infections than vaccination is in SARS-CoV-2 naïve individuals [4,5], and waning is seen for both types of immunity but less so for the naturally induced [5].”
COVID‐19 vaccination in children and university students
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“This protection against infection was higher than vaccination for all variants (up to 7 times higher for Omicron, in agreement with recent estimate of Gazit and co-authors 17 ).”
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Coronavirus Disease 2019 Vaccine Boosting in Previously Infected or Vaccinated Individuals
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The impact of sphingosine-1-phosphate receptor modulators on COVID-19 and SARS-CoV-2 vaccination
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“From SARS-CoV-2 vaccination have the potential to provide protection from infection and disease-related morbidity, but it is not infallible (Sormani et al., 2021b; Tuekprakhon et al., 2022; Peng et al., 2022; Cho et al., 2021; Gazit et al., 2022; Antonelli et al., 2022).”
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Epidemiological assessment of SARS-CoV-2 reinfection
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“It is also possible that naturally acquired immunity provides more robust protection than vaccination.(24) Our VE/rVE estimates were lower than estimates of vaccine efficacy seen in clinical trials.”
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“These modelling results are supported by retrospective observational studies reporting that previous infection with SARS-CoV-2 provides stronger and longer protection than vaccine-induced protection in naive individuals [66].”
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“Procrustean policies such as universal mandates that do not take into account one’s individual risk, including age [130], prior infection [131], and pre-existing conditions or a lack thereof [132,133], reduced trust between the general public and the biomedical community.”
BackgroundAssessing the risk of vaccine-driven virulence evolution in SARS-CoV-2
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The Evolving Faces of the SARS-CoV-2 Genome
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Measurement of IFN-γ and IL-2 for the assessment of the cellular immunity against SARS-CoV-2
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SARS-CoV-2 herd immunity of the Kyrgyz population in 2021
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Protection Associated with Previous SARS-CoV-2 Infection in Nicaragua
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Natural and vaccine-induced immunity are equivalent for the protection against SARS-CoV-2 infection
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“Conversely, a retrospective cohort study conducted in Israel showed that vaccinees with PfizerBioNTech had a 13-fold increased risk of infection with the Delta variant, as compared to unvaccinated previously infected individuals [7].”
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Can the SARS-CoV-2 Omicron Variant Confer Natural Immunity against COVID-19?
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An immune correlate of SARS-CoV-2 infection and severity of reinfectionsPreprint
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Can live-attenuated SARS-CoV-2 vaccine contribute to stopping the pandemic?
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Elevated BMI reduces the humoral response to SARS‐CoV‐2 infection
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“8 This humoral response is generated from both SARS-CoV-2 infection and vaccination, with conflicting reports as to whether infection 9 or vaccination 10 elicits a stronger immune response.”
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“Some studies, however, have reported that fully vaccinated individuals may carry the same amount of virus as unvaccinated individuals and naturally acquired immunity was more protective against infection and severity of disease in the case of Delta variant [42, 43].”
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“68 We also planned to study VE against severe COVID-19 outcomes.”
- Authors
- Gazit, S., Shlezinger, R., Perez, G., Lotan, R., Peretz, A., Ben-Tov, A., Herzel, E., Alapi, H., Cohen, D., Muhsen, K., Chodick, G., & Patalon, T.
- Affiliations
- Maccabi Healthcare Services (IL)
- Kahn Sagol Maccabi (KSM) Research & Innovation Center, Maccabi Healthcare Services , Tel Aviv , Israel
- Tel Aviv University (IL)
- Corresponding author
- Gazit, Sivan
- ORCID
- Venue
- Clinical Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2022-04-05
- Volume
- 75
- Issue
- 1
- Pages
- e545-e551
- ISSN
- 1058-4838 (ISSN-L)
- 1537-6591
- PMC
- PMC9047157
- OpenAlex
- W4225130422
- Cited by
- 283
- References
- 40
- Citations by year
- 2026: 5 · 2025: 19 · 2024: 29 · 2023: 61 · 2022: 127 · 2021: 42
- FWCI
- 28.97
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Clinical Infectious Diseases (publishedVersion)
- medRxiv (acceptedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Physical Sciences › Mathematics › Modeling and Simulation › COVID-19 epidemiological studies
- Keywords
- SARS-CoV-2, COVID-19 pandemic, BNT162b2, naturally acquired immunity, vaccine-induced immunity, breakthrough infection, reinfection, waning immunity, Delta variant, prior infection, symptomatic disease, hospitalization, mortality
- MeSH terms
- Reinfection, COVID-19, SARS-CoV-2, BNT162 Vaccine, Humans, Retrospective Studies, Viral Vaccines, Adaptive Immunity
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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