Study investigates messenger ribonucleic acid-based SARS-CoV-2 vaccine efficacy against SARS-CoV-2 Omicron in Denmark

A recent study posted to the Research Square* preprint server assessed the efficacy of two severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines (Moderna and Pfizer-BioTech) against Omicron infections and disease-related hospitalization in the Denmark population. 

Study: Vaccine effectiveness against infection and COVID-19-associated hospitalisation with the Omicron (B.1.1.529) variant after vaccination with the BNT162b2 or mRNA-1273 vaccine: A nationwide Danish cohort study. Image Credit: oleschwander/Shutterstock


The World Health Organization (WHO) designated the SARS-CoV-2 variant B.1.1.529, called Omicron, as a variant of concern (VOC) on November 26, 2021. Omicron has since spread swiftly around the globe, including in Denmark, despite the country's high SARS-CoV-2 vaccine coverage.

The longevity and levels of protection imparted by existing SARS-CoV-2 vaccines against Omicron infections and infection-associated hospitalizations remain unknown.

SARS-CoV-2 surveillance and mitigation strategies in Denmark mainly included bulk reverse transcription-polymerase chain reaction (RT-PCR) testing since 2020. As a result, the rates of coronavirus disease 2019 (COVID-19) PCR testing in Denmark are among the world's highest, with nearly 25% of the population testing each week in December 2021 and January 2022.

About the study

In the present study, the researchers aimed to determine the protection of two SARS-CoV-2 messenger ribonucleic acid (mRNA) vaccinations against hospitalization or infection with the Omicron VOC by month after the receipt of two or three doses of the vaccine. For this, the researchers combined the COVID-19 PCR screening data in Denmark and data from other national registries to obtain near-complete details on all comorbidities, SARS-CoV-2 vaccinations, and COVID-19-linked hospitalizations at the population level. 

Of note, this nationwide Danish cohort study was conducted between December 28, 2021, and February 12, 2022, a period when the Omicron was the predominant SARS-CoV-2 variant in Denmark. The eligible participants for two and three doses of COVID-19 vaccines’ assessment groups were Danish citizens aged above 12 years and 18 years on December 28, 2021, respectively.

Additionally, these individuals also should not have had a prior SARS-CoV-2-positive RT-PCR result. Cox regression was used to determine trends in vaccine efficacy following two to three doses of COVID-19 mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech) vaccines.

Individual-level data on SARS-CoV-2 vaccinations were gathered from the Danish Vaccination Registry. Person-level RT-PCR-confirmed COVID-19 cases were identified from the Danish Microbiology Database.

Details on comorbidities and COVID-19-associated hospitalizations were procured from the Danish National Patient Registry. Data about gender, vital status, age, and the residential region were gathered from the Danish Civil Registration System, and all datasets were connected via a unique civil registry number granted to all Danish citizens.


The results illustrated that the protection against COVID-19 during the initial timelines following the two doses of mRNA-based SARS-CoV-2 vaccines was approximately 37%, with a drastic decline in the next three months. People who were immunized 121 days earlier demonstrated minimal residual protection against SARS-CoV-2. Of the third mRNA dose vaccinees, vaccine-elicited protection against COVID-19 hiked to about 48% and exhibited minimal waning in the following months.

Although the estimations were relatively inaccurate, vaccination efficacy against COVID-19-associated hospitalization following two doses with the Pfizer-BioNTech vaccine varied from 42.6% to 51.6%. Nevertheless, COVID-19-related hospitalizations dropped from 88.8% to 79.0% for the Pfizer-BioNTech vaccine during the initial four months following the third dose. Similarly, after the third dose of the Moderna vaccine, SARS-CoV-2-associated hospital admissions declined from 90.2% to 83.6%.

The vaccine-induced protection against Omicron infections observed in this investigation was remarkably lower than those against the SARS-CoV-2 Alpha and Delta variants. Nevertheless, the substantial degree of protection against SARS-CoV-2-related hospitalizations, particularly after the third dose, indicates that both the mRNA vaccines evaluated in the present study could protect from severe forms of COVID-19.

Additionally, the two mRNA-based COVID-19 vaccines had surprisingly identical vaccine efficacy estimates in modeling hospitalizations or infections and by time following immunizations.


The present nationwide cohort research from Denmark demonstrated that the mRNA-1273 and BNT162b2 COVID-19 vaccines had poor efficacy in safeguarding from asymptomatic or symptomatic Omicron infections. This observation agreed with prior reports on this topic. However, vaccine efficacy against SARS-CoV-2-linked hospitalizations was significant following the third dose of both the evaluated COVID-19 vaccines.

The estimations of vaccine efficacy following three doses of the two mRNA-based vaccines against SARS-CoV-2-linked hospitalizations reached 90% in the initial timestamps and were maintained at 80-90% during the first four months following immunization and then declined subsequently.

On the whole, the present work states that infection with the SARS-CoV-2 Omicron VOC was substantially less likely than infection with the Delta VOC to result in hospitalizations in three-dose vaccinated people, regardless of the levels of protection imparted by COVID-19 vaccination. Thus, the study emphasizes the need for a third dose of SARS-CoV-2 mRNA-based vaccines to minimize hospitalization rates during the Omicron-dominant period.

*Important notice

Research Square publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
  • Christian Hansen, Astrid Schelde, Ida Moustsen-Helm et al. (2022). Vaccine effectiveness against infection and COVID-19-associated hospitalization with the Omicron (B.1.1.529) variant after vaccination with the BNT162b2 or mRNA-1273 vaccine: A nationwide Danish cohort study. Research Square. doi:

Posted in: Medical Science News | Disease/Infection News | Healthcare News

Tags: Coronavirus, Coronavirus Disease COVID-19, covid-19, Efficacy, Hospital, Immunization, Microbiology, Omicron, Polymerase, Polymerase Chain Reaction, Research, Respiratory, Ribonucleic Acid, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Syndrome, Transcription, Vaccine

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Shanet Susan Alex

Shanet Susan Alex, a medical writer, based in Kerala, India, is a Doctor of Pharmacy graduate from Kerala University of Health Sciences. Her academic background is in clinical pharmacy and research, and she is passionate about medical writing. Shanet has published papers in the International Journal of Medical Science and Current Research (IJMSCR), the International Journal of Pharmacy (IJP), and the International Journal of Medical Science and Applied Research (IJMSAR). Apart from work, she enjoys listening to music and watching movies.

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