Vaccine effectiveness against SARS-CoV-2 infection and COVID-19-related hospitalization with the Alpha, Delta and Omicron SARS-CoV-2 variants: a nationwide Danish cohort study
Authors: Gram Mie Agermose , Emborg Hanne-Dorthe , Schelde Astrid Blicher , Friis Nikolaj Ulrik , Nielsen Katrine Finderup , Moustsen-Helms Ida Rask , Legarth Rebecca , Lam Janni Uyen Hoa , Chaine Manon , Malik Aisha Zahoor , Rasmussen Morten , Fonager Jannik , Sieber Raphael Niklaus , Stegger Marc , Ethelberg Steen , Valentiner-Branth Palle , Hansen Christian Holm 
Published: May 2022

Background

The continued occurrence of more contagious SARS-CoV-2 variants and waning immunity over time require ongoing re-evaluation of the vaccine effectiveness (VE). This study aimed to estimate the effectiveness in two age groups (12-59 and 60 years or above) of two and three vaccine doses (BNT162b2 mRNA or mRNA-1273 vaccine) by time since vaccination against SARS-CoV-2 infection and COVID-19-related hospitalization in an Alpha, Delta and Omicron dominated period.

Methods

A Danish nationwide cohort study design was used to estimate VE against SARS-CoV-2 infection and COVID-19-related hospitalization with the Alpha, Delta and Omicron variants. Information was obtained from nationwide registries and linked using a unique personal identification number. The study included all residents in Denmark aged 12 years or above (18 years or above for the analysis of three doses) in the Alpha (February 20 to June 15, 2021), Delta (July 4 to November 20, 2021) and Omicron (December 21, 2021 to January 31, 2022) dominated periods. VE estimates including 95% confidence intervals (CIs) were calculated using Cox proportional hazard regression models with adjustments for age, sex and geographical region. Vaccination status was included as a time-varying exposure.

Findings

In the oldest age group, VE against infection after two doses was 91.0% (95% CI: 88.5; 92.9) for the Alpha variant, 82.2% (95% CI: 75.3; 87.1) for the Delta variant and 39.9% (95% CI: 26.4; 50.9) for the Omicron variant 14-30 days since vaccination. The VE waned over time and was 71.5% (95% CI: 54.7; 82.8), 49.8% (95% CI: 46.5; 52.8) and 4.7% (95% CI: 0.2; 8.9) >120 days since vaccination against the three variants, respectively. Higher estimates were observed after the third dose with VE estimates against infection of 86.0% (Delta, 95% CI: 83.3; 88.3) and 57.6% (Omicron, 95% CI: 55.8; 59.4) 14-30 days since vaccination. Among both age groups, VE against COVID-19-related hospitalization 14-30 days since vaccination with two or three doses was 94.8% or above for the Alpha and Delta variants, whereas among the youngest age group, VE estimates against the Omicron variant after two and three doses were 62.4% (95% CI: 46.3; 73.6) and 89.8% (95% CI: 87.9; 91.3), respectively.

Conclusions

Two vaccine doses provided high protection against SARS-CoV-2 infection and COVID-19-related hospitalization with the Alpha and Delta variants with protection waning over time. Two vaccine doses provided only limited protection against SARS-CoV-2 infection and COVID-19-related hospitalization with the Omicron variant. The third vaccine dose substantially increased the protection against Delta and Omicron.