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Risk of Reinfection, Vaccine Protection, and Severity of Infection with the BA.5 Omicron Subvariant: A Danish Nation-Wide Population-Based Study

21 Pages Posted: 18 Jul 2022

See all articles by Christian Holm Hansen

Christian Holm Hansen

Statens Serum Institut - Infectious Disease Epidemiology & Prevention

Nikolaj Ulrik Friis

Statens Serum Institut - Infectious Disease Epidemiology & Prevention

Peter Bager

Statens Serum Institut - Department of Epidemiology Research

Marc Stegger

Statens Serum Institut - Department of Bacteria, Parasites and Fungi

Jannik Fonager

Statens Serum Institut - Virus Research & Development Laboratory

Anders Fomsgaard

Statens Serum Institut - Department of Virus and Microbiological Special Diagnostics

Mie Agermose Gram

Statens Serum Institut - Infectious Disease Epidemiology & Prevention

Lasse Engbo Christiansen

Statens Serum Institut - Department of Epidemiology Research

Steen Ethelberg

Statens Serum Institut - Infectious Disease Epidemiology & Prevention

Rebecca Legarth

Statens Serum Institut

Tyra Grove Krause

Statens Serum Institut

Henrik Ullum

Statens Serum Institut

Palle Valentiner-Branth

Statens Serum Institut - Infectious Disease Epidemiology & Prevention

More...

Abstract

Background: Estimates of immunity and severity for the SARS-CoV-2 omicron subvariant BA.5 are important to assess the public health impact associated with its rapid global spread despite vaccination. We estimated natural and vaccine immunity and severity of BA.5 relative to BA.2 in Denmark, a country with high mRNA vaccination coverage and free-of-charge RT-PCR testing.

Methods: This was an observational cohort study including residents 18 years or older with an RT-PCR test between 10 April and 20 June, 2022, identified in the national COVID-19 surveillance system database with information since February, 2020, on RT-PCR tests, wholegenome sequencing, vaccinations and hospitalisations with a positive test and COVID-19 as main diagnosis. We calculated the effect of prior omicron infection on the odds ratio (OR) of BA.5 infection among triple-vaccinated individuals (%protection=1-OR). For BA.5 relative to BA.2 we also calculated the OR of triple-vaccination vs none (ie. vaccine effectiveness) and the OR of hospitalisation. ORs were calculated in logistic regression models adjusted for age, time, sex, region, and comorbidities.

Findings: Among 4,809 BA.5 cases and 164,369 test-negative individuals, a prior omicron infection was highly protective against BA.5 (93.6%, 95%CI92.1-94.8; 96 BA.5 and 29,832 test-negative with prior omicron). Among 4,913 BA.5 and 31,874 BA.2 cases, the OR of triple-vaccination was not different (OR1.02, 95%CI0.83-1.26). Although the overall number of hospitalisations due to COVID-19 diagnosis was low and stable during the study period, the proportion of individuals infected with BA.5 increased. In the crude analysis BA.5 was not associated with hospitalisation (OR 1.04 (0.83-1.31) whereas the adjusted OR was 1.65 (1.16-2.34). The adjusted OR was increased in strata of age and calendar period – the two covariates with the largest contribution to confounding of the crude OR.

Interpretation: We found a high protection against BA.5 from prior omicron infection in triple-vaccinated individuals, and similar vaccine effectiveness for BA.5 infection as currently for BA.2. In an analysis adjusted for covariates, BA.5 infection was associated with an increased risk of hospitalisation which needs confirmation and continued surveillance as hospitalisations were low and stable during the study period.

Funding Statement: None.

Declaration of Interests: None.

Ethics Approval Statement: This study was performed under the authority task of the Danish national infectious disease control institute, which allows Statens Serum Institut to perform analyses on data from existing national COVID-19 surveillance systems. According to Danish law, ethical approval or individual consent is not required for anonymized aggregated register-based studies.

Keywords: Infectious diseases, covid-19, vaccine effectiveness, SARS-CoV-2, epidemiology, risk factors

Suggested Citation

Hansen, Christian Holm and Friis, Nikolaj Ulrik and Bager, Peter and Stegger, Marc and Fonager, Jannik and Fomsgaard, Anders and Gram, Mie Agermose and Engbo Christiansen, Lasse and Ethelberg, Steen and Legarth, Rebecca and Grove Krause, Tyra and Ullum, Henrik and Valentiner-Branth, Palle, Risk of Reinfection, Vaccine Protection, and Severity of Infection with the BA.5 Omicron Subvariant: A Danish Nation-Wide Population-Based Study. Available at SSRN: https://ssrn.com/abstract=4165630 or http://dx.doi.org/10.2139/ssrn.4165630

Christian Holm Hansen

Statens Serum Institut - Infectious Disease Epidemiology & Prevention

Nikolaj Ulrik Friis

Statens Serum Institut - Infectious Disease Epidemiology & Prevention ( email )

Peter Bager (Contact Author)

Statens Serum Institut - Department of Epidemiology Research

Marc Stegger

Statens Serum Institut - Department of Bacteria, Parasites and Fungi ( email )

Jannik Fonager

Statens Serum Institut - Virus Research & Development Laboratory ( email )

Copenhagen
Denmark

Anders Fomsgaard

Statens Serum Institut - Department of Virus and Microbiological Special Diagnostics

Mie Agermose Gram

Statens Serum Institut - Infectious Disease Epidemiology & Prevention

Lasse Engbo Christiansen

Statens Serum Institut - Department of Epidemiology Research ( email )

Steen Ethelberg

Statens Serum Institut - Infectious Disease Epidemiology & Prevention ( email )

Rebecca Legarth

Statens Serum Institut

Denmark

Tyra Grove Krause

Statens Serum Institut

Denmark

Henrik Ullum

Statens Serum Institut ( email )

Palle Valentiner-Branth

Statens Serum Institut - Infectious Disease Epidemiology & Prevention