Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Naturally Acquired Immunity versus Vaccine-induced Immunity, Reinfections versus Breakthrough Infections: A Retrospective Cohort Study

Abstract

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.

Protection against Omicron conferred by mRNA primary vaccine series, boosters, and prior infection

“…Compared to prior studies, 8,26–28 our estimates for protection against reinfection were substantially lower than those analyzing infections during pre-Omicron outbreaks; furthermore, we found significant differences in protection conveyed by prior infections before and during the emergence of the Delta variant. Consistent with other studies 11,14 , we found the highest levels of protection among those who had three doses of vaccination and prior infections.…”

Short term, relative effectiveness of four doses versus three doses of BNT162b2 vaccine in people aged 60 years and older in Israel: retrospective, test negative, case-control study

“…For our primary analysis, cases were matched to controls using 1:m matching, with up to five controls per case, based on seven factors: sex, age group (using a binary cut-off age of ≥70 years, because studies 19 have indicated that older age groups are at higher risk, especially for severe disease), city of residence, socioeconomic status, calendar week of first test (to account for potential time-varying risk within the outcome period), the month of receipt of the third dose (to mitigate possible bias related to waning of the third dose), and a categorical variable for the living environment (a medical nursing home, an assisted living facility, or a private residence). The last factor was included because of early pandemic increases in SARS-CoV-2 infection in nursing homes and assisted living facilities, which led to differential regulations in these institutions, mandating staff and residents to be vaccinated and limiting visits from non-residents.…”

The unintended consequences of COVID-19 vaccine policy: why mandates, passports and restrictions may cause more harm than good

“…Vaccine passports risk enshrining discrimination based on perceived health status into law, undermining many rights of healthy individuals: indeed, unvaccinated but previously infected people may generally be at less risk of infection (and severe outcomes) than doubly vaccinated but infection-naïve individuals 80. A weekly negative SARS-CoV-2 test is often seen as a compromise in lieu of full vaccination status, but this places additional burdens (including financial) on the unvaccinated while also risking reputational damage.…”

“…It would violate the proportionality principle to impose significant liberty restrictions (and/or harms) in exchange for trivial public health benefits, particularly when other options are available. Evidence shows that the efficacy of current COVID-19 vaccines on reducing transmission is limited and temporary,7–16 likely lower in younger age groups targeted for vaccine mandates and passports36 and that prior infection provides, roughly speaking, comparable benefit 18 31 80. The effectiveness of vaccine mandates in reducing transmission is likely to be smaller than many might have expected or have hoped for, and decrease over time.…”