• Nick Andrews, Julia Stowe, Freja Kirsebom, Samuel Toffa, Tim Rickeard, Eileen Gallagher, Charlotte Gower, Meaghan Kall, Natalie Groves, Anne-Marie O'Connell, David Simons, Paula B Blomquist, Asad Zaidi, Sophie Nash, Nurin Iwani Binti Abdul Aziz, Simon Thelwall, Gavin Dabrera, Richard Myers, Gayatri Amirthalingam, Saheer Gharbia, Jeffrey C Barrett, Richard Elson, Shamez N Ladhani, Neil Ferguson, Maria Zambon, Colin N J Campbell, Kevin Brown, Susan Hopkins, Meera Chand, Mary Ramsay, and Jamie Lopez Bernal.
• From the U.K. Health Security Agency (N.A., J.S., F.K., S. Toffa, T.R., E.G., C.G., M.K., N.G., A.-M.O., D.S., P.B.B., A.Z., S.N., N.I.B.A.A., S. Thelwall, G.D., R.M., G.A., S.G., R.E., S.N.L., M.Z., C.N.J.C., K.B., S.H., M.C., M.R., J.L.B.), the National Institute for Health Research (NIHR) Health Protection Research Unit in Vaccines and Immunisation, London School of Hygiene and Tropical Medicine (N.A., G.A., C.N.J.C., K.B., M.R., J.L.B.), the Paediatric Infectious Diseases Research Group, St. George's University of London (R.M., S.N.L.), the Medical Research Council Centre for Global Infectious Disease Analysis (N.F.) and the NIHR Health Protection Research Unit in Respiratory Infections (N.F., M.Z., J.L.B.), Imperial College London, and Guy's and St. Thomas's Hospital NHS Trust (M.C.), London, Wellcome Sanger Institute, Hinxton (J.C.B.), and Healthcare Associated Infections and Antimicrobial Resistance, University of Oxford, Oxford (S.H.) - all in the United Kingdom.
• N. Engl. J. Med. 2022 Apr 21; 386 (16): 153215461532-1546.

BackgroundA rapid increase in coronavirus disease 2019 (Covid-19) cases due to the omicron (B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 in highly vaccinated populations has aroused concerns about the effectiveness of current vaccines.MethodsWe used a test-negative case-control design to estimate vaccine effectiveness against symptomatic disease caused by the omicron and delta (B.1.617.2) variants in England. Vaccine effectiveness was calculated after primary immunization with two doses of BNT162b2 (Pfizer-BioNTech), ChAdOx1 nCoV-19 (AstraZeneca), or mRNA-1273 (Moderna) vaccine and after a booster dose of BNT162b2, ChAdOx1 nCoV-19, or mRNA-1273.ResultsBetween November 27, 2021, and January 12, 2022, a total of 886,774 eligible persons infected with the omicron variant, 204,154 eligible persons infected with the delta variant, and 1,572,621 eligible test-negative controls were identified. At all time points investigated and for all combinations of primary course and booster vaccines, vaccine effectiveness against symptomatic disease was higher for the delta variant than for the omicron variant. No effect against the omicron variant was noted from 20 weeks after two ChAdOx1 nCoV-19 doses, whereas vaccine effectiveness after two BNT162b2 doses was 65.5% (95% confidence interval [CI], 63.9 to 67.0) at 2 to 4 weeks, dropping to 8.8% (95% CI, 7.0 to 10.5) at 25 or more weeks. Among ChAdOx1 nCoV-19 primary course recipients, vaccine effectiveness increased to 62.4% (95% CI, 61.8 to 63.0) at 2 to 4 weeks after a BNT162b2 booster before decreasing to 39.6% (95% CI, 38.0 to 41.1) at 10 or more weeks. Among BNT162b2 primary course recipients, vaccine effectiveness increased to 67.2% (95% CI, 66.5 to 67.8) at 2 to 4 weeks after a BNT162b2 booster before declining to 45.7% (95% CI, 44.7 to 46.7) at 10 or more weeks. Vaccine effectiveness after a ChAdOx1 nCoV-19 primary course increased to 70.1% (95% CI, 69.5 to 70.7) at 2 to 4 weeks after an mRNA-1273 booster and decreased to 60.9% (95% CI, 59.7 to 62.1) at 5 to 9 weeks. After a BNT162b2 primary course, the mRNA-1273 booster increased vaccine effectiveness to 73.9% (95% CI, 73.1 to 74.6) at 2 to 4 weeks; vaccine effectiveness fell to 64.4% (95% CI, 62.6 to 66.1) at 5 to 9 weeks.ConclusionsPrimary immunization with two doses of ChAdOx1 nCoV-19 or BNT162b2 vaccine provided limited protection against symptomatic disease caused by the omicron variant. A BNT162b2 or mRNA-1273 booster after either the ChAdOx1 nCoV-19 or BNT162b2 primary course substantially increased protection, but that protection waned over time. (Funded by the U.K. Health Security Agency.).Copyright © 2022 Massachusetts Medical Society.

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