Equivalency of Protection From Natural Immunity in COVID-19 Recovered Versus Fully Vaccinated Persons: A Systematic Review and Pooled Analysis

“Our systematic review showed no clear evidence that vaccinated COVID-naïve individuals enjoyed greater protection than unvaccinated COVID-recovered counterparts. Four observational studies [20,24,25] and one RCT [19] found that natural immunity provided superior protection to vaccination in the COVID-naive. None of the identified studies, or pooled groups, found a statistically significant advantage to vaccination in the COVID-naïve population, although the RCTs favoured vaccination. There was solid internal consistency between the conclusions of our pooled analysis and the conclusions of the studies’ authors, taken individually.

While RCTs are more methodologically sound, observational studies yield a more practically realizable result. In our study, pooled RCTs favoured vaccination, while the pooled observational studies more strongly supported natural immunity. This disparity can be partially explained by the difference in timing of the studies, as the RCTs were performed in an earlier phase of the pandemic compared to the observational trials which occurred during the emergence of variants. For example, Satwik et al. (India) and Gazit et al. (Israel), which occurred during the mid-2021 Delta phases of the pandemic, found stronger and statistically significant natural immunity benefits than vaccination alone. Gazit et al. found 13-fold increased odds of all infection in the vaccinated COVID-naive compared to unvaccinated COVID-recovered individuals and a 27-fold increase in symptomatic infection. These more recent and stronger findings of stronger natural immunity highlight the time-dependent sensitivity of this analysis due to variants of concern and potential waning vaccination efficacy. This observation is in line with other recent studies by Keehner et al. [29] and Goldberg et al. [30], demonstrating a time-dependent decline in vaccine efficacy during the pandemic’s Delta phase of the pandemic.

In total, the evidence points quite convincingly to at least the equivalency between the protection of natural versus vaccinated immunity, with the possibility of enhanced durability of protection from natural immunity in non-controlled settings and later phases of the pandemic.

Does vaccination in the previously infected provide a reduction in risk of reinfection?

Regarding this question, the vaccination RCTs did not find a significant benefit to vaccination in the previously infected, either individually or in pooled RCT analysis. This conclusion is reflected in the official briefing narratives, which explicitly stated an absence of observed benefit of vaccination in recovered individuals, due primarily to the limitation of study power. However, in the pooled observational trials, the stronger relative effect was seen favouring vaccination, but the absolute effect was still small.”

Source: Equivalency of Protection From Natural Immunity in COVID-19 Recovered Versus Fully Vaccinated Persons: A Systematic Review and Pooled Analysis

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