When making health decisions, it’s important to look at the best available evidence. A large, real-world study of more than 28 million adults aged 18–59 examined long-term outcomes after receiving an mRNA COVID-19 vaccine.

What the Study Found

In this research published in JAMA Network Open, investigators followed vaccinated and unvaccinated adults for up to four years after their first dose of an mRNA COVID-19 vaccine. 

Here’s what they observed:

• Lower overall mortality: Adults who received at least one mRNA shot had a 25% lower risk of death from any cause compared with unvaccinated peers, even after adjusting for health conditions and demographics. 
• Significantly fewer COVID-related deaths: Vaccinated individuals were 74% less likely to die from severe COVID-19 in the hospital. 
• Consistent results over time: The reduced risk of death held across different causes of death and in additional analyses, indicating no increase in long-term mortality linked to vaccination.

Understanding Risk and Benefit

Every medical choice carries some risk, whether someone chooses to get vaccinated or not. The goal is to choose the option associated with the lowest overall risk for each person.

Across large studies like this one, there is currently no evidence that mRNA COVID-19 vaccines increase the risk of death compared with remaining unvaccinated. In fact, vaccinated individuals in this analysis had lower all-cause mortality over four years.

Addressing Specific Risk Groups

Some rare side effects have been documented with mRNA vaccines, including myocarditis (inflammation of the heart muscle). For example, young males (<40 years) may have a slightly increased short-term risk of myocarditis after a second mRNA vaccine dose compared with their risk from COVID-19 infection itself. However, when weighing overall outcomes, vaccination still prevents many more serious health events.

For every one million males ages 12–29 receiving a second mRNA dose:

• ~39–47 cases of myocarditis may occur
• But ~560 hospitalizations, ~138 ICU admissions, and ~6 deaths are prevented thanks to vaccination

Latest Vaccine Formulations

Newer vaccine doses,  such as the updated Moderna “Nextspike” formulation, use lower doses than the original vaccines, which may further reduce side-effect risks while maintaining strong immune protection.

Bottom Line

This study supports what other evidence has shown:

• mRNA COVID-19 vaccines reduce the risk of serious illness and death
• They are associated with lower overall mortality over several years
• They remain a safe and effective tool, especially when paired with individualized medical advice

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