Ravindra K Gupta & Eric J Topol –

The pivotal phase 3 clinical trials of the two-dose messenger RNA (mRNA) vaccines, among the largest ever conducted, led to the notable finding of ∼95% efficacy for prevention of symptomatic COVID-19 2 months after the second dose. Adenovirus vectored vaccines showed lower protection against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) but achieved >90% protection against severe disease. No vaccines protect against all infections, and very few achieve such a high level of protection as that of the COVID-19 vaccines. In the early months after vaccinations at scale began, around January 2021, post-vaccination infections (or breakthrough infections) were rare, accounting for <1% of COVID-19 cases, and only ∼0.1% resulted in hospitalization or death in high-income countries. However, by 5 to 6 months after vaccinations began, this pattern changed. Even before vaccine introduction, it was anticipated that a third, booster dose would be necessary to preserve efficacy, but when that would be needed was uncertain.

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