Common and Uncommon Side Effects of mRNA Vaccines
mRNA COVID-19 vaccines commonly cause mild to moderate side effects that typically resolve within a few days, with injection site reactions and fatigue being the most frequently reported effects. The safety profile of these vaccines shows a favorable benefit-to-risk ratio across all age groups, with serious adverse events being rare.
Common Side Effects
Local Reactions
- Injection site reactions (84.1%) - most common local side effect 1, 2
- Pain at injection site (66.2% after dose 1,68.6% after dose 2) 3
- Local swelling or redness
Systemic Reactions
- Fatigue (62.9%) - second most common side effect 1, 2, 3
- Headache (55.1%) 1, 2, 3
- Muscle pain/myalgia (38.3%) 1, 2
- Chills (31.9%) 1, 2
- Joint pain (23.6%) 1, 2
- Fever (14.2%) 1, 2
Timing and Severity
- Side effects are generally more pronounced after the second dose 2, 3
- Most reactions are mild to moderate in severity 3
- Reactogenicity peaks within 24 hours after vaccination 3
- Most symptoms resolve within 2-3 days 2
- Approximately 32.1% of recipients report being unable to perform normal activities or work after dose 2 (compared to 11.9% after dose 1) 3
- Less than 1% of vaccine recipients seek medical care for side effects 3
Uncommon Side Effects
Rare Cardiovascular Effects
- Myocarditis and pericarditis - primarily in adolescent and young adult males 1
- For every 1 million males aged 12-29 years receiving a second dose, approximately 39-47 cases of myocarditis would be expected 1
- Risk after booster doses appears similar to or lower than after dose 2 1
- The risk may differ between the two mRNA vaccines, with higher rates observed with the Moderna (mRNA-1273) vaccine 1
Neurological Effects
- Bell's palsy - reported in clinical trials at a rate of 4 cases in the Pfizer vaccine group vs. 0 in placebo 1, 4
- Theoretical concerns exist about potential neurological effects in patients with pre-existing conditions 1
Lymphatic System
- Local lymphadenopathy: 1.1% in vaccine recipients vs. 0.63% in placebo 1
Hypersensitivity Reactions
- Hypersensitivity: 1.5% in vaccine recipients vs. 1.1% in placebo 1
Benefit-Risk Assessment
Despite the potential side effects, the benefit-risk ratio strongly favors vaccination. For every 1 million males aged 12-29 years (highest risk group for myocarditis) receiving a second dose:
- 39-47 cases of myocarditis would be expected
- But vaccination would prevent:
Management of Side Effects
For typical post-vaccination symptoms (pain, fever, headache):
- Simple analgesics (acetaminophen, NSAIDs)
- Adequate hydration
- Rest as needed 2
Red flag symptoms requiring immediate medical attention:
- Severe headache with onset 5-30 days after vaccination
- Headache that worsens when lying down
- Visual disturbances, speech difficulties
- Unexplained bruising or bleeding
- Chest pain, shortness of breath 2
Special Populations
- Patients with psychiatric disorders may be at higher risk for COVID-19 complications and should be prioritized for vaccination 1
- Patients with neurological disorders (MS, myasthenia gravis, Guillain-Barré syndrome) can generally receive mRNA vaccines safely 1
- Cancer patients and transplant recipients may have reduced immune response but similar side effect profiles 1, 2
The large-scale surveillance data from over 298 million doses of mRNA COVID-19 vaccines administered in the first 6 months of the US vaccination program confirms that most reported adverse events were mild and short in duration 3, with mRNA-based vaccines showing higher efficacy against SARS-CoV-2 than other vaccine platforms 5.