Several weeks following the publication of the large real-world COVID-19 vaccine effectiveness study by the Clalit Research Institute in Collaboration with Harvard University in the New England Journal of Medicine (NEJM), additional results focusing on vaccine effectiveness in specific sub-populations have now been published.

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While the original publication demonstrated the effectiveness of the Pfizer-BioNTech mRNA vaccine in the general population, outstanding questions remained regarding vaccine effectiveness in specific sub-populations of interest, including the elderly, multi-morbid individuals, and individuals with specific prevalent chronic conditions.

The new study also took place in Israel and evaluated data on approximately 1,400,000 Clalit members, with extended follow-up time compared to the previous study, and additional subpopulations. The advanced methodologies employed meticulous individual matching techniques to enable an as-clean-as-possible analysis of vaccine effectiveness, comparing vaccinated to unvaccinated (control) individuals. The increased sample size and increased follow up time enabled the assessment of vaccine effectiveness in additional sub-populations, which the original vaccine effectiveness study was unable to assess.

The results of the new study make clear that the vaccine is exceedingly effective, with 96% of symptomatic cases and 95% of severe cases prevented (compared with point estimates of 94% and 92% in the previous study). The results also demonstrate that the vaccine is highly effective across all age ranges, with 92% effectiveness in preventing symptomatic disease in individuals 70 years and older.

It is important to note that vaccine effectiveness in prevention of symptomatic disease is slightly lower amongst the multi-morbid population of all ages (88% effective amongst individuals with three or more chronic illnesses or risk factors). Specifically, the effectiveness in preventing symptomatic illness varied in patients with different chronic illnesses: the vaccine was highly effective (96% and 93%) in overweight and obese patients, but slightly less effective in immunosuppressed individuals (84%), patients with heart disease (80%), chronic kidney disease (80%) and diabetes (86%). Effectiveness against severe disease was generally higher.

According to Professor Ran Balicer, Chief Innovation Officer for Clalit and Director of the Clalit Research Institute, "This publication is a direct continuation of the large study published in the New England Journal of Medicine several weeks ago. The updated results based on a larger population with extended follow-up period show that the vaccine is even more effective than previously estimated, preventing 96% of cases and 95% of severe cases of covid-19 in all age groups - a 20 to 25-fold reduction of risk compared to the unvaccinated. Severe disease is dramatically reduced even among patients with some specific chronic conditions, but as suggested in the original study, this protection is mildly reduced among patients with several co-morbidities. These results are very encouraging, as they suggest that most COVID-19 cases will be prevented by vaccination even in the elderly and chronically ill, though there should be expected a somewhat higher rate of infection and severe illness in vaccinated individuals with several comorbidities or immune suppression, compared to the healthy fully vaccinated population.

The main conclusions as we see them: The study further supports the immediate need to vaccinate at any eligible age and especially among those suffering from chronic conditions that are most vulnerable to covid-19 compilations if not vaccinated. But we also note that these chronically ill vaccinated patients should continue to practice caution in circumstances where a significant risk of infection exists, as they still have somewhat higher residual vulnerability after being vaccinated. We are relieved to note that the risk for such circumstances has been consistently falling in Israel over the last few months, to unprecedented low rates of daily cases - a 50-fold decrease in cases to as low as 10 cases per million per day and less than 1 severe case per million per day - and the numbers are still dropping."