Effectiveness of COVID-19 Vaccines Over 13 Months Covering the Period of the Emergence of the Omicron Variant in the Swedish Population

Background: True population-based estimates of vaccine effectiveness (VE) against COVID-19 remain scarce, and VE against the SARS-CoV-2 Omicron variant is not well characterized. In this study, we estimated real-world VE against infection, hospitalization, and more severe outcomes (ICU admission and death) up to 13 months after vaccination among individuals without prior COVID-19. VE before and after the emergence of the Omicron was investigated.Methods: We used data from the entire Swedish population above age 12 (n=9,153,456) from multiple national registers. Cox regression with time-varying exposure was used to estimate weekly/monthly VE against COVID-19 outcomes from December 27, 2020, to January 31, 2022. The analyses were stratified by age, sex, and vaccine type (BNT162b2, mRNA-1273 and AZD1222).Findings: Two vaccine doses showed long-lasting good protection against infection before Omicron (VE were above 85% for all time intervals), but less protection against Omicron infection (dropped to 43% by week four and no protection by week 14). Similarly, VE against hospitalization was high and stable before Omicron, but showed clear waning during the Omicron period, although VE estimates were substantially higher (above 80% to week 25, dropping to 40% by week 40) than against infection. For severe COVID-19 outcomes, higher VE were observed during the entire follow-up period. The mRNA vaccines showed better VE against infection than AZD1222 among individuals above age 65 but similar high VE against hospitalization. The vaccines were generally equally effective regardless of age and sex.Interpretation: Two vaccine doses offered long-lasting protection against infection before Omicron but waned rapidly during Omicron period. Regarding severe COVID-19 outcomes, good long-term protection during a 13-month follow-up was observed.Funding Information: SciLifeLab / Knut & Alice Wallenberg Foundation, Swedish Research Council, Swedish government ALF-agreement, FORMAS.Declaration of Interests: Dr. Gisslén reports personal fees (DSMB) from AstraZeneca, Gilead, GSK/ViiV, MSD, Biogen, Novocure, Amgen, Novo Nordisk, outside the submitted work. Dr Leach reports consulting for Scandinavian Biopharma. Dr. Vanfleteren has received grants and personal fees from AstraZeneca and personal fees from GSK, Novartis, Boehringer-Ingelheim, Menarini, Resmed, Chiesi, AGA Linde, Zambon and Pulmonx. Dr. Nyberg reports prior employment at AstraZeneca until 2019, and ownership of some AstraZeneca shares. Mr. Kirui, Dr. Wettermark, Dr. Santosa, Dr. Li, and Dr. Xu have nothing to disclose. Ethics Approval Statement: This study extends previous vaccine investigations by modelling exposure over time with high granularity (first weekly, then monthly after vaccination) and was approved by the Swedish Ethical Review Authority.