Two doses of the AstraZeneca/Oxford, Pfizer/BioNTech, or Moderna COVID-19 vaccine offered limited protection against symptomatic infection with the SARS-CoV-2 Omicron variant, and although a third dose with any of the three vaccines boosted effectiveness substantially, it waned a bit over time.
These findings, from a study by UK Health Security Agency researchers, were published yesterday in the New England Journal of Medicine.
The researchers used National Immunization Management System data to estimate vaccine effectiveness (VE) against symptomatic illness caused by infection with the Omicron and Delta variants from Nov 27, 2021, to Jan 12, 2022. They compared the odds of vaccination in symptomatic residents who tested positive for COVID-19 with those who tested negative.
Moderna boosters outperform Pfizer
A total of 886,774 residents of England were diagnosed as having COVID-19 infections caused by Omicron, while 204,154 were infected with Delta, and 1,572,621 were included in the study as test-negative controls.
Throughout the study, VE was higher against Delta than Omicron for all combinations of the primary vaccine series and booster doses. Two doses of the AstraZeneca vaccine became ineffective after 20 weeks, while two doses of the Pfizer vaccine were 65.5% effective (95% confidence interval [CI], 63.9% to 67.0%) at 2 to 4 weeks, falling to 8.8% (95% CI, 7.0% to 10.5%) at 25 weeks.
Of recipients of a primary course of the AstraZeneca vaccine, a Pfizer booster dose increased VE to 62.4% (95% CI, 61.8% to 63.0%) by 2 to 4 weeks, dropping to 39.6% (95% CI, 38.0% to 41.1%) by 10 weeks. VE among Pfizer primary course recipients climbed to 67.2% (95% CI, 66.5% to 67.8%) after a Pfizer booster and then decreased to 45.7% (95% CI, 44.7% to 46.7%) by 10 weeks.
Two to four weeks after a Moderna booster among AstraZeneca primary course recipients, VE increased to 70.1% (95% CI, 69.5% to 70.7%) but slipped to 60.9% (95% CI, 59.7% to 62.1%) at 5 to 9 weeks. A Moderna booster also pushed VE in Pfizer primary course recipients to 73.9% (95% CI, 73.1% to 74.6%) at 2 to 4 weeks, but it fell to 64.4% (95% CI, 62.6% to 66.1%) at 5 to 9 weeks.
Third doses warranted
The researchers said they weren't able to determine VE against severe illness using their test-negative, case-control study design, because the number of severe Omicron cases leading to hospitalization was too small and the natural lag between infections and poor outcomes was too long.
"Our findings indicate that two doses of vaccination with BNT162b2 [Pfizer] or ChAdOx1 nCoV-19 [AstraZeneca] are insufficient to give adequate levels of protection against infection with the omicron variant and mild disease," they authors concluded. "Boosting with BNT162b2 or mRNA-1273 [Moderna] provided a substantial increase in protection against mild disease, although waning occurred over time."
They said that third vaccine doses likely offer greater levels of protection against critical COVID-19 and death. "Our findings support maximizing coverage with third doses of vaccine in highly vaccinated populations such as in the United Kingdom," the researchers concluded. "Further follow-up will be needed to assess protection against severe disease and the duration of protection after booster vaccination."