Local Reactions, Systemic Reactions, Adverse Events, and Serious Adverse Events: Moderna COVID-19 Vaccine

Local Reactions

Local reactions were reported by the majority of vaccine recipients and at higher rates than placebo recipients. Vaccine recipients reported higher rates of local reactions after dose 2 than dose 1. The frequency of local reactions was higher in the younger age group (aged 18 to 64 years) than the older age group (aged ≥65 years) (90.5% vs 83.9% after dose 2). Pain at the injection site was the most frequent and severe reported solicited local reaction among vaccine recipients. After dose 1, the younger age group reported pain more frequently than the older age group (86.9% vs 74.0%); a similar pattern was observed after dose 2 (90.1% vs 83.4%). Axillary swelling or tenderness was the second most frequently reported local reaction. Axillary swelling or tenderness was reported more frequently in the younger age group than the older age group (16.0% vs 8.4% after dose 2). Injection site redness and swelling following either dose were reported less frequently. Redness and swelling were slightly more common after dose 2. No grade 4 local reactions were reported. Overall, the median onset of local reactions in the vaccine group was 1 day after either dose, with a median duration between 2 and 3 days. (Table 1, Table 2)

Table 1. Local reactions in persons aged 18-64 years, Moderna COVID-19 vaccine and placebo

^a Pain grade 3: any use of prescription pain reliever or prevented daily activity; grade 4: required emergency room visit or hospitalization.

^b Swelling grade 3: >100mm/>10cm; grade 4: necrosis/exfoliative dermatitis.

^c Axillary swelling or tenderness was collected as a solicited local adverse reaction (i.e., lymphadenopathy: localized axillary swelling or tenderness ipsilateral to the vaccination arm); grade 3: any use of prescription pain reliever or prevented daily activity; grade 4: required emergency room visit or hospitalization.

Note: No grade 4 local reactions were reported.

Table 2. Local reactions in persons aged ≥65 years, Moderna COVID-19 vaccine and placebo

^a Pain grade 3: any use of prescription pain reliever or prevented daily activity; grade 4: required emergency room visit or hospitalization.

^b Swelling grade 3: >100mm/>10cm; grade 4: necrosis/exfoliative dermatitis.

^c Axillary swelling or tenderness was collected as a solicited local adverse reaction (i.e. lymphadenopathy: localized axillary swelling or tenderness ipsilateral to the vaccination arm); grade 3: any use of prescription pain reliever or prevented daily activity; grade 4: required emergency room visit or hospitalization.

Note: No grade 4 local reactions were reported.

Systemic Reactions

Systemic reactions were reported by the majority of vaccine recipients and at higher rates than placebo recipients. The frequency of systemic reactions was higher in the younger age group than the older age group (81.9% vs 71.9% after dose 2). Within each age group, the frequency and severity of systemic reactions was higher after dose 2 than dose 1. For both age groups, fatigue, headache and myalgia were the most common. The majority of systemic reactions were mild or moderate in severity, after both doses and in both age groups. Fever was more common after the second dose and in the younger group (17.6%) compared to the older group (10.2%). Among vaccine recipients, the median onset of systemic reactions was 1 to 2 days after either dose, with a median duration of 2 days. Grade 4 fever (>40.0°C) was reported by four vaccine recipients after dose 1 and 11 vaccine recipients after dose 2. There was one report of grade 4 fatigue and one report of grade 4 arthralgia, both in the younger age group after dose 1. In the older age group, there was one report of grade 4 nausea or vomiting after dose 2. No other systemic grade 4 reactions were reported. (Table 3, Table 4)

Table 3. Systemic reactions in persons aged 18-64 years, Moderna COVID-19 vaccine and placebo

^a Fever – Grade 3: ≥39.0 – ≤40.0°C or ≥102.1 – ≤104.0°F; Grade 4: >40.0°C or >104.0°F
^b Headache – Grade 3: significant; any use of prescription pain reliever or prevented daily activity; Grade 4: required emergency room visit or hospitalization.
^c Fatigue, Myalgia, Arthralgia – Grade 3: significant; prevented daily activity; Grade 4: required emergency room visit or hospitalization.
^d Nausea/Vomiting – Grade 3: prevented daily activity, required outpatient intravenous hydration; Grade 4: required emergency room visit or hospitalization for hypotensive shock.
^e Chills – Grade 3: prevented daily activity and required medical intervention; Grade 4: required emergency room visit or hospitalization.

Table 4. Systemic reactions in persons aged ≥65 years, Moderna COVID-19 vaccine and placebo

^a Fever – Grade 3: ≥39.0 – ≤40.0°C or ≥102.1 – ≤104.0°F; Grade 4: >40.0°C or >104.0°F
^b Headache – Grade 3: significant; any use of prescription pain reliever or prevented daily activity; Grade 4: requires emergency room visit or hospitalization.
^c Fatigue, Myalgia, Arthralgia – Grade 3: significant; prevented daily activity; Grade 4: required emergency room visit or hospitalization.
^d Nausea/Vomiting – Grade 3: prevented daily activity, required outpatient intravenous hydration; Grade 4: Requires emergency room visit or hospitalization for hypotensive shock.
^e Chills – Grade 3: prevented daily activity and required medical intervention; Grade 4: required emergency room visit or hospitalization.

Unsolicited Adverse Events

A higher frequency of unsolicited adverse events was reported in the vaccine group compared to the placebo group and was primarily attributed to local and systemic reactogenicity following vaccination. Reports of lymphadenopathy were imbalanced with 1.1 % of persons in the vaccine group and 0.6% in the placebo group reporting such events; lymphadenopathy is plausibly related to the vaccine. Lymphadenopathy occurred in the arm and neck region and was reported within 2 to 4 days after vaccination. The median duration of lymphadenopathy was 1 to 2 days. Bell’s palsy was reported by three vaccine recipients and one placebo recipient. One case of Bell’s palsy in the vaccine group was considered a serious adverse event. Currently available information is insufficient to determine a causal relationship with the vaccine.

Serious Adverse Events

Serious adverse events were defined as any untoward medical occurrence that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, or resulted in persistent disability or incapacity. The proportions of participants who reported at least one serious adverse event were 1% in the vaccine group and 1% in the placebo group. The most common serious adverse events occurring at higher rates in the vaccine group than the placebo group were myocardial infarction (5 cases in vaccine group vs. 3 cases in placebo group), cholecystitis (3 vs. 0), and nephrolithiasis (3 vs. 0). Three serious adverse events were considered by the U.S. Food and Drug Administration (FDA) as possibly related to vaccine: the one report of intractable nausea/vomiting and two reports of facial swelling in persons who had a previous history of cosmetic filler injections. The possibility that the vaccine contributed to the serious adverse event reports of rheumatoid arthritis (n=1), peripheral edema/dyspnea with exertion (n=1), and autonomic dysfunction (n=1) cannot be excluded.

Data source: FDA briefing documentexternal icon