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Fourth COVID-19 vaccination effectiveness drops after 10 weeks

30th May 2022

A fourth COVID-19 vaccination’s effectiveness against infection drops after only 10 weeks but remains high against severe disease

A fourth COVID-19 vaccination dose offers greater protection against infection than three doses but this effectiveness quickly wanes within 10 weeks but is maintained against more severe disease. This was the key finding of a retrospective analysis by Israeli researchers.

The use of a third COVID-19 vaccination is more effective at protecting individuals against severe COVID-19-related outcomes in comparison to only two doses. Nevertheless, it is also becoming clear that in the presence of COVID-19 variants such as Omicron, the relative protection against infection even from three doses wanes over time.

For instance, 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.

As a result, many countries are considering the use of a fourth dose although currently, the impact of a fourth COVID-19 vaccination on breakthrough infections and protection against severe infection is largely unknown, especially among the older and more vulnerable patients.

Due to this uncertainty, the Israeli team set out to compare the effectiveness of a fourth and third dose 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