An Israeli study has looked at how much difference a fourth Covid vaccine dose makes compared with a third dose.
The study was restricted to triple-jabbed healthcare workers, and more specifically to those whose antibody levels were in the bottom 40% of the antibody levels in the cohort (a group comprising around 29% of the cohort). Of the 1,050 eligible healthcare workers, 154 were given a Pfizer fourth dose and 120 Moderna. The rest formed a triple-jabbed control group.
Measuring antibody levels, the researchers found an increase by around 10-fold following the fourth dose, restoring antibodies to the peak levels they hit following the third dose, though no higher.
The study was originally intended just to measure antibody levels and other indicators of immunogenicity. However, the Omicron surge in the country was so large that despite being a small study, enough infections occurred within the study groups to allow an estimate of vaccine effectiveness. The participants were PCR tested each week. The researchers reported that ‘breakthrough’ infections were common and, though mild, had high viral loads. During the study period, 25% of the control groups (triple-dosed) tested positive compared with 18-20% of the four-dose groups. This gave a fourth-dose versus three-dose vaccine effectiveness against PCR-positive infection of just 11-30% – though the small population size led to wide confidence intervals ranging from minus-43% to 55%.
Among the four-dose groups, there were 52 ‘breakthrough’ infections, of which 39 (75%) were classed as symptomatic. The vaccine effectiveness against symptomatic disease was estimated at 31-43%, though again with wide confidence intervals.
The symptoms of all PCR-positive infections were typically “negligible”, the researchers report, and in many cases the infections “would not have been tested or reported, without the active surveillance”. Yet they had relatively high viral loads (Ct around 25), so were presumably infectious. Thus, with a quarter of triple-vaccinated and a fifth of quadruple-vaccinated healthcare workers becoming infected and apparently infectious during the wave, the researchers conclude the vaccine programme is a failure as it is not preventing the spread of Covid: “The major objective for vaccinating [healthcare workers] was not achieved.” However, the apparent efficacy against severe disease and death means older and vulnerable people may benefit from a fourth vaccine dose, they say.
The study also looked at safety. It found that 80% of Pfizer recipients and 40% of Moderna recipients reported some kind of adverse reaction, though none were classed as serious. The adverse reactions are summarised in the chart below.
Larger studies on the efficacy and safety of the fourth dose, which has now been rolled out (having gone ahead without waiting for studies such as this one), are forthcoming, the researchers note.