Effectiveness of mRNA-1273 Variant-Containing Vaccine Formulation Against Severe Outcomes in Adults Aged 50-64 Years Without Risk Factors for Severe COVID-19

The study is a pragmatic, registry-based, open-label, individually randomized trial. The Danish nationwide administrative health registries will be used for data collection including baseline information, follow-up data, and safety monitoring. The study aims to randomize a total of 285,000 participants. Participants will be individually randomized 1:1 to receive either a COVID-19 vaccine or no COVID-19 vaccine. The study is designed to assess the vaccine effectiveness of the COVID-19 vaccine vs. no COVID-19 vaccine on the risk of medically attended COVID-19 infection.

• mRNA-1273 (Moderna COVID-19 vaccine) (Biological): For this arm, the current variant formulation of Spikevax (mRNA-1273) vaccine will be used.

Primary outcomes

• Medically attended COVID-19 [≥14 days after initially booked study visit date until 6 months after initially booked study visit date]: Defined as a positive PCR test for SARS-CoV-2 or hospitalization for COVID-19-related respiratory tract disease

Secondary outcomes

• COVID-19-related hospitalization [≥14 days after initially booked study visit date until 6 months after initially booked study visit date]
• COVID-19-related respiratory tract disease hospitalization [≥14 days after initially booked study visit date until 6 months after initially booked study visit date]
• COVID-19-related cardio-respiratory disease hospitalization [≥14 days after initially booked study visit date until 6 months after initially booked study visit date]
• All-cause respiratory tract disease hospitalization [≥14 days after initially booked study visit date until 6 months after initially booked study visit date]
• All-cause cardio-respiratory hospitalization [≥14 days after initially booked study visit date until 6 months after initially booked study visit date]
• All-cause lower respiratory tract disease hospitalization [≥14 days after initially booked study visit date until 6 months after initially booked study visit date]
• All-cause hospitalization [≥14 days after initially booked study visit date until 6 months after initially booked study visit date]
• COVID-19 death [≥14 days after initially booked study visit date until 6 months after initially booked study visit date]
• All-cause death [≥14 days after initially booked study visit date until 6 months after initially booked study visit date]

Other outcomes

• COVID-19-related hospitalization (alternate definition) [≥14 days after initially booked study visit date until 6 months after initially booked study visit date]
• Laboratory-confirmed COVID-19 [≥14 days after initially booked study visit date until 6 months after initially booked study visit date]
• Total length of hospital stays due to COVID-19-related respiratory tract disease [≥14 days after initially booked study visit date until 6 months after initially booked study visit date]
• Composite of hospitalization for COVID-19 or pneumonia (ICD-10 codes only) [≥14 days after initially booked study visit date until 6 months after initially booked study visit date]
• Hospitalization for any cardiovascular disease [≥14 days after initially booked study visit date until 6 months after initially booked study visit date]
• Hospitalization due to any infectious disease [≥14 days after initially booked study visit date until 6 months after initially booked study visit date]
• Hospitalization requiring mechanical ventilation [≥14 days after initially booked study visit date until 6 months after initially booked study visit date]
• In-hospital mortality [≥14 days after initially booked study visit date until 6 months after initially booked study visit date]
• Cardio-respiratory mortality [≥14 days after initially booked study visit date until 6 months after initially booked study visit date]
• Respiratory mortality [≥14 days after initially booked study visit date until 6 months after initially booked study visit date]
• Cardiovascular mortality [≥14 days after initially booked study visit date until 6 months after initially booked study visit date]
• Intensive care unit admission [≥14 days after initially booked study visit date until 6 months after initially booked study visit date]
• Laboratory-confirmed COVID-19 hospitalization [≥14 days after initially booked study visit date until 6 months after initially booked study visit date]
• Any hospital contact associated with laboratory-confirmed COVID-19 [≥14 days after initially booked study visit date until 6 months after initially booked study visit date]

Sex: All, ages: 50 Years to 64 Years, accepts healthy volunteers

Inclusion Criteria:

* Age 50-64 years
* Informed consent form has been signed and dated

Exclusion Criteria:

* Medical conditions that increase the risk of severe COVID-19, which will be assessed through self-reporting. These medical conditions include:

  1. Asthma
  2. Cancer (excluding non-melanoma skin cancer)
  3. Cardiomyopathies
  4. Cerebrovascular disease
  5. Chronic kidney disease
  6. Chronic lung disease
  7. Cystic Fibrosis
  8. Dementia
  9. Diabetes
  10. Down syndrome
  11. Heart failure
  12. Human Immunodeficiency Virus
  13. Immunosuppressive therapy
  14. Ischemic heart disease
  15. Liver disease
  16. Neurological/neuromuscular disease
  17. Psychiatric disease (psychotic, schizophrenic, schizotypal, depressive, and bipolar (affective) disorders).
  18. Severe obesity (body mass index >35 kg/m2)
  19. Severe substance abuse
  20. Short bowel syndrome
  21. Solid organ transplant or hematological transplant
* Apart from these, there are no specific exclusion criteria for this study

• Tor Biering-Sørensen, MD, MSc, MPH, PhD, Study chair, Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte

NIH grants: 2025