From the Journals

Double-dose COVID-19 vaccines showed limited effectiveness against Omicron


 

FROM NEW ENGLAND JOURNAL OF MEDICINE

The currently available two-dose COVID-19 vaccines were not effective in preventing symptomatic disease caused by the Omicron variant, as determined on the basis of data from more than 800,000 Omicron-infected individuals.

Early laboratory data suggested a substantially lower neutralizing antibody response to the Omicron variant, compared with both the original COVID-19 strain and the Delta variant, write Nick Andrews, PhD, of the United Kingdom Health Security Agency, London, and colleagues.

Vaccines have shown high levels of effectiveness against symptomatic disease and severe disease and death resulting from the original COVID-19 virus and the Alpha variant and modest effectiveness against the Beta and Delta variants, they say.

“Neutralizing antibodies correlate with protection against reinfection and vaccine effectiveness against infection; therefore, reduced vaccine effectiveness against the omicron variant is anticipated on the basis of these early laboratory findings,” they explain.

In a study published in the New England Journal of Medicine, the researchers identified 886,774 adults aged 18 years and older who had been infected with the Omicron variant, 204,154 who had been infected with the Delta variant, and 1,572,621 symptomatic control patients who tested negative for COVID-19 between Nov. 27, 2021, and Jan. 12, 2022. The participants had been vaccinated with two doses of BNT162b2 (Pfizer–BioNTech), ChAdOx1 nCoV-19 (AstraZeneca), or mRNA-1273 (Moderna) vaccine, plus a booster given at least 175 days after a second dose, after Sept. 13, 2021.

Vaccine effectiveness was calculated after primary immunization at weeks 2-4, 5-9, 10-14, 15-19, 20-24, and 25 or longer after the second dose, and at 2-4, 5-9, and 10 or more weeks after boosters.

Omicron infections that occurred starting 14 or more days after a booster occurred a median of 39 days after the booster.

“Vaccine effectiveness was lower for the Omicron variant than for the Delta variant at all intervals after vaccination and for all combinations of primary courses and booster doses investigated,” the researchers write.

Individuals who received two doses of ChAdOx1 nCoV-19 had almost no protection against symptomatic disease caused by Omicron from 20-24 weeks after the second dose. For individuals who received two doses of BNT162b2, effectiveness was 65.5% 2-4 weeks after the second dose, but effectiveness declined to 15.4% after 15-19 weeks and to 8.8% after 25 or more weeks. For individuals who received two doses of mRNA-1273, vaccine effectiveness was 75.1% after 2-4 weeks, but effectiveness declined to 14.9% after 25 or more weeks.

Boosters created a short-term improvement in vaccine effectiveness against the Omicron variant, but this effect also declined over time.

Among individuals who received primary doses of ChAdOx1 nCoV-19, vaccine effectiveness increased to 62.4% 2-4 weeks after a BNT162b2 booster, then declined to 39.6% after 10 or more weeks. After an mRNA-1273 booster, vaccine effectiveness increased to 70.1% at 2-4 weeks and decreased to 60.9% at 5-9 weeks.

Among individuals who received primary doses of BNT162b2, vaccine effectiveness increased to 67.2% 2-4 weeks after a BNT162b2 booster, then declined to 45.7% at 10 or more weeks. After an mRNA-1273 booster, vaccine effectiveness increased to 73.9% at 2-4 weeks, then declined to 64.4% at 5-9 weeks.

Among individuals who received primary doses of mRNA-1273, vaccine effectiveness increased to 64.9% 2-4 weeks after a BNT162b2 booster and 66.3% 2-4 weeks after an mRNA-1273 booster.

The study findings were limited by potential confounding from study participants who had traveled and may have had different levels of vaccine coverage and by the inability to break down estimates on the basis of age and clinical risk that might affect vaccine effectiveness, the researchers note. Other limitations include a lack of data on vaccine effectiveness for a longer period after boosters, they say.

However, the results are consistent with neutralization data for the Omicron variant in studies from the United Kingdom, South Africa, and Germany, they write. “Our findings support maximizing coverage with third doses of vaccine in highly vaccinated populations such as in the United Kingdom. Further follow-up will be needed to assess protection against severe disease and the duration of protection after booster vaccination,” they conclude.

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