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Background Waning of protection against infection with SARS-CoV-2 conferred by 2 doses of the BNT162b2 vaccine begins shortly after inoculation and becomes substantial within four 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 two groups: (1) SARS-CoV-2-naïve individuals who received a two-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 (COVID-19), hospitalization and death – between June 1 to August 14, 2021, when the Delta variant was dominant in Israel. Results SARS-CoV-2-naïve vaccinees had a 13.06-fold (95% 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 to February 2021, evidence of waning naturally acquired immunity was demonstrated, though SARS-CoV-2 naïve 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 two-dose vaccine-induced immunity.

Using a national database in Israel, the incidence rates of SARS-CoV-2 reinfection in persons who were previously infected with SARS-CoV-2 but did not receive subsequent vaccination were compared with the incidence rates of SARS-CoV-2 reinfection in previously infected persons who received a single dose of the BNT162b2 messenger RNA vaccine.

The BNT162b2 COVID-19 vaccine has been shown to reduce viral load of breakthrough infections (BTIs), an important factor affecting infectiousness. This viral-load protective effect has been waning with time post the second vaccine and later restored with a booster shot. It is currently unclear though for how long this regained effectiveness lasts. Analyzing Ct values of SARS-CoV-2 qRT-PCR tests of over 22,000 infections during a Delta-variant-dominant period in Israel, we find that this viral-load reduction effectiveness significantly declines within months post the booster dose. Adjusting for age, sex and calendric date, Ct values of RdRp gene initially increases by 2.7 [CI: 2.3-3.0] relative to unvaccinated in the first month post the booster dose, yet then decays to a difference of 1.3 [CI: 0.7-1.9] in the second month and becomes small and insignificant in the third to fourth months. The rate and magnitude of this post-booster decline in viral-load reduction effectiveness mirror those observed post the second vaccine. These results suggest rapid waning of the booster’s effectiveness in reducing infectiousness, possibly affecting community-level spread of the virus.

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