Covid-19 vaccines and boosters are transiently effective against the Omicron

1. Two doses of BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccine provided good protection against the Omicron (B.1.1.529) variant but rapidly waned after 10 or more weeks which was restored after a booster.

2. Patients only receiving two doses of the ChAdOx1 nCoV-19 (AstraZeneca) had no protection against the Omicron variant but gained protection after a booster with an mRNA-based vaccine.

Evidence Rating Level: 3 (Average)

Study Rundown: Vaccines are among the first-line tools available to combat the Covid-19 pandemic, particularly against the potentially more infectious and resistant Omicron (B.1.1.529) variant which has quickly become the dominant strain internationally. To assess the effectiveness of our currently employed Covid-19 vaccines: BNT162b2 (Pfizer-BioNTech), ChAdOx1 nCoV-19 (AstraZeneca), and mRNA-1273 (Moderna), a test-negative, case-control study was performed. Patient data on vaccination status including the type of primary vaccination and booster, Covid-19 infection, and the variant of infection were identified. Using logistic regression, vaccine effectiveness against the symptomatic disease was determined. The study found that two doses of the ChAdOx1 nCoV-19 offered no protection against the omicron variant, but vaccine effectiveness was gained after a booster with an mRNA vaccine which waned after 10 weeks. Patients receiving two doses of BNT162b2 had good protection against omicron within 4 weeks of inoculation but significantly waned after 25 or more weeks. A booster with BNT162b2 or mRNA-1273 restored protection against omicron within 4 weeks in these patients, which waned again after 10 or more weeks. Overall, vaccine effectiveness against symptomatic disease caused by the omicron variant is lower than against the delta variant with protection waning rapidly. Two doses are inadequate in protecting against the omicron variant; however, booster vaccinations transiently restored this protection.

Click to read the study in NEJM 

Relevant Reading: Reduced Neutralization of SARS-CoV-2 Omicron Variant by Vaccine Sera and monoclonal antibodies

In-Depth [case-control study]: In this large, test-negative, case-control design study, the primary objective was to evaluate vaccine effectiveness against symptomatic disease caused by the Covid-19 omicron (B.1.1.529) variant. Patient data were extracted and analyzed to identify 866,774 persons infected with omicron, 204,154 persons infected with delta, and 1,572,621 test-negative controls, along with their corresponding vaccine status and type of vaccine received between BNT162b2 (Pfizer-BioNTech), ChAdOx1 nCoV-19 (AstraZeneca), and mRNA-1273 (Moderna). Variants were identified by sequencing PCR-positive samples. Logistic regression was used to determine vaccine effectiveness controlled for demographic factors, and stratified by primary immunization course and booster type. The study found that vaccine effectiveness was overall lower for the Omicron variant compared to Delta. Two doses of the ChAdOx1 nCoV-19 vaccine offered almost no protective effect against omicron disease while two doses of BNT162b2 offered 65.5% vaccine effectiveness (95% Confidence Interval [CI], 63.9-67.0), which dropped to 8.8% (95% CI, 7.0-10.5) after 25 or more weeks. In patients receiving ChAdOx1 nCoV-19 primary course, a BNT162b2 booster dose increased protection to 62.4% (95% CI, 61.8-63.0) within 4 weeks, then waned down to 39.6% after 10 or more weeks. The mRNA-1273 booster found similar results in these patients, with 70.1% vaccine effectiveness (95% CI, 69.5 – 70.7) within 4 weeks, which wanted to 46.7% (95% CI, 34.4-56.7) after 9 weeks. Those receiving a primary course with the BNT162b2 vaccine showed improvements in vaccine effectiveness which waned slightly after 10 weeks with either mRNA vaccine. Altogether, this study demonstrates that vaccine effectiveness against the omicron variant is non-existent after two doses of ChAdOx1 nCoV-19 and limited after two doses of BNT162b2 which wanes after time. After a booster with either mRNA vaccine, vaccine effectiveness is restored within 4 weeks before waning beyond 10 weeks from inoculation.

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