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Fourth COVID-19 vaccination effectiveness drops after only 10 weeks

While a fourth COVID-19 vaccination is more effective against infection than three doses, this effectiveness drops after only 10 weeks

A fourth COVID-19 vaccination dose provides better protection against infection than three doses but this protection quickly reduces over a 10 week period but still remains effective against severe disease. This was the conclusion of a retrospective analysis by Israeli researchers.

It has become well established that a third COVID-19 vaccination is more effective at protecting individuals against severe COVID-19-related outcomes in comparison to two doses. However, emerging evidence, particularly in the presence of COVID-19 variants such as Omicron, indicates that this additional level of protection reduces over time. For example, in one study, the effectiveness of a third COVID-19 vaccine, waned from 53.4% a month after vaccination to 16.5% three months later.

Given this evidence, countries are now planning to administer a fourth vaccine dose, although the impact of a fourth COVID-19 vaccination on breakthrough infections and protection against severe infection is largely unknown, particularly among older and more vulnerable patients.

As a result, the Israeli team set out to compare the relative effectiveness of four and three doses against infection and severe disease. They retrospectively analysed information held within a centralised healthcare national database and focused on patients over 60 years of age and examined a 10 week period between January to March 2022, starting 7 days after the date when the fourth COVID-19 vaccination could be administered to eligible patients. The main outcomes of interest were breakthrough infections, defined as occurring 7 or more days after vaccination and breakthrough infections that resulted in either hospitalisation or COVID-19-related death.

Fourth COVID-19 vaccination and breakthrough infections

A total of 97,499 individuals with a mean age of 70.8 years (45.3% male) were included, 69,623 of whom had received only three COVID-19 vaccinations.

The relative vaccine effectiveness of the fourth dose compared to the third dose peaked at 65.1% (95% CI 63 – 67.1%) three weeks after inoculation. However, this waned quickly, so that after 9 weeks, the effectiveness had reduced to 22% (95% CI 4.9 – 36.1%).

With respect to hospitalisation and deaths, the vaccine effectiveness peaked at 86.5% (95% CI 63.4 – 95%) 49 – 69 days after inoculation and was maintained over the 10 week period of analysis

The researchers concluded that a fourth vaccine dose offered a higher level of protection against infection than three doses but that this protect waned over the following10 weeks. Nonetheless, protection against more severe disease was sustained over this period.

Gaxit S et al. 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 BMJ 2022

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