Local injection site reaction was the most commonly reported adverse reaction after COVID-19 vaccine administration during clinical trials. In general, the rates and severity of the reactions were higher after the second dose compared to after the first. In individuals 18 to 64 years, injection site pain (36.3% to 64.3%), injection site tenderness (54.8% to 76.5%), erythema or redness (0.9% to 8.6%), and swelling (0.8% to 7.8%) at the injection site were reported after any Novavax COVID-19 dose administration or booster dose administration. In individuals 65 years and older, the incidence of injection site pain (20.1% to 44.1%), injection site tenderness (33.7% to 57.8%), erythema or redness (0.7% to 6.7%), and swelling (0.7% to 6.6%) was lower compared to younger patients during clinical trials receiving Novavax COVID-19 vaccine or booster dose. Injection site pruritus was also reported in 0.1% of individuals. In pediatric patients 12 to 17 years, injection site pain (44.7% to 67.1%), injection site tenderness (56.6% to 71.3%), erythema or redness (1% to 10.3%), and swelling (1.4% to 9.5%) at the injection site were reported. Cellulitis of the injection site was reported in a 58-year-old individual with the onset of cellulitis occurring 3 days after a booster vaccination. The cellulitis resolved following antibiotic and steroid treatment. Available information about this event is insufficient to determine a casual relationship with the vaccine.[67783] [72242]

During clinical trials, fatigue, malaise, and headache occurred after administration of the COVID-19 vaccine. The rates and severity of the reactions were generally higher after the second dose compared to the first dose. In individuals 18 to 64 years receiving any Novavax COVID-19 vaccine or booster dose, fatigue (27.1% to 56.4%), malaise (15.3% to 43.2%), and headache (26.8% to 54.6%) were reported. In individuals 65 years and older, the incidence of fatigue (18.8% to 36.3%), malaise (10% to 24.3%), and headache (16.7% to 31.3%) was lower than that in younger individuals. In individuals 12 to 17 years, fatigue (24.2% to 57.1%), malaise (14.8% to 45.1%), and headache (30.4% to 63.3%) were reported.[67783] [72242]

Musculoskeletal adverse reactions were reported during COVID-19 vaccine clinical trials. The rates and severity of the reactions were generally higher after the second dose compared to the first dose. In individuals 18 to 64 years receiving any Novavax COVID-19 dose or booster dose during clinical trials, arthralgia (7.9% to 25.7%) and myalgia (24.3% to 57.4%) were reported. In individuals 65 years and older, the incidence of arthralgia (6.1% to 15.5%) and myalgia (14.1% to 33.8%) was lower than that in younger patients. In pediatric patients 12 to 17 years, arthralgia (7% to 21.9%) and myalgia (34% to 60.4%) were reported. Muscle edema was reported 7 days after a booster vaccination in a 51-year-old individual. The muscle edema was not responsive to non-steroidal antiinflammatory agents. The event was reported as not resolved. Available information about this event is insufficient to determine a causal relationship with the vaccine.[67783] [72242]

In individuals 18 to 64 years receiving any Novavax COVID-19 vaccine dose or booster dose during clinical trials, fever was reported in 0.4% to 8.8% of individuals. In individuals 65 years and older, the incidence of fever was 0.4% to 4.2%. In individuals 12 to 17 years, fever was reported in 0.6% to 16.9% of individuals. Chills were also reported in 0.3% of individuals during clinical trials.[67783] [72242]

Nausea and vomiting was reported after any Novavax COVID-19 vaccine administration or after booster dose administration in individuals 18 to 64 years (7% to 16.4%) and in 12 to 17 years (7.8% to 23.6%). In individuals 65 years and older, the incidence of nausea and vomiting (5.2% to 6%) was lower than that in younger patients.[67783] [72242]

Within 7 days of any dose, hypersensitivity reactions (including urticaria, hypersensitivity, angioedema, and swelling of the face, lips, ear and/or eyelids) were reported by 0.11% of individuals receiving the Novavax COVID-19 vaccine and 0.04% of individuals receiving placebo. Of these events, 1 reaction (generalized urticaria and facial angioedema lasting for 2 days) was serious and occurred 2 days after Dose 1 of the vaccine. Anaphylactoid reactions were reported during postmarketing experience.[67783] [72242]

Lymphadenopathy was reported in 0.2% to 0.7% of individuals receiving the Novavax COVID-19 vaccine during clinical trials.[67783] [72242]

Cases of myocarditis and/or pericarditis were identified in clinical trials of Novavax COVID-19 vaccine and through passive surveillance during postauthorization use outside the United States. The risk of myocarditis may be reduced by extending the interval to 8-weeks between the first and second dose in individuals 12 years and older, especially males 12 to 39 years.[66175] Myocarditis and/or pericarditis were reported by 2 patients after the Novavax COVID-19 vaccine. The first individual was a 67-year-old male reporting the reaction 28 days after Dose 1 and the second individual was a 20-year-old male reporting the reaction 10 days after Dose 1. Additionally, myocarditis was reported in 2 individuals, a 16-year-old patient 2 days after Dose 2 and a 28-year-old male 3 days after a booster dose. The adverse reaction after the booster dose was adjudicated as a non-ST elevation myocardial infarction; however, clinical features were also consistent with myocarditis (chest pain and elevated troponin). No cardiac catheterization or cardiac MRI was performed during the acute presentation. Myocarditis was also reported in a 19-year-old male and pericarditis in a 60-year-old female within 10 days of administration of Dose 2 and Dose 1, respectively.[67783] [72242]

Cardiomyopathy and cardiac failure was reported by 10 individuals (0.04%) after the Novavax COVID-19 primary vaccine series (6 events) or booster dose (4 events) compared to 3 events in 2 individuals (0.01%) after placebo. All events were serious except congestive heart failure (n = 2), cardiomyopathy (n = 2), and congestive cardiomyopathy (n = 1). Atrial fibrillation was reported in 13 (0.07%) individuals who received Novavax COVID-19 vaccine and in 4 individuals (0.04%) who received placebo during clinical trials. The onset of atrial fibrillation occurred within 30 days post vaccination in 6 individuals compared with 2 individuals in the placebo group. Current available information on cardiomyopathy, cardiac failure, or atrial fibrillation is insufficient to determine a causal relationship with the vaccine.[67783] [72242]

Acute cholecystitis was reported by 6 individuals (0.02%) after the Novavax COVID-19 vaccine compared to 2 individuals (0.01%) after placebo. All events were serious. Current available information on acute cholecystitis is insufficient to determine a causal relationship with the vaccine.[72242]

A total of 12 non-cardiac, non-neurovascular thrombotic and embolic events were reported by 11 individuals (0.04%) after the Novavax COVID-19 vaccine and a total of 7 events were reported by 6 individuals (0.02%) after placebo. Events included pulmonary embolism (n = 5), deep vein thrombosis (n = 2), thrombosis (n = 2), and portal vein thrombosis, mesenteric artery thrombosis, and peripheral arterial occlusive disease (n = 1 each). Of the events, 6 were serious, including pulmonary embolism (n = 5) and deep vein thrombosis (n = 1). Events after placebo included pulmonary embolism (n = 3), deep vein thrombosis, and peripheral arterial occlusive disease (n = 2 each). Current available information on non-cardiac, non-neurovascular thrombotic and embolic events is insufficient to determine a causal relationship with the vaccine.[67783] [72242]

Uveitis, including iritis, uveitis, iridocyclitis, was reported by 3 individuals (0.01%) after the Novavax COVID-19 vaccine and 2 individuals (0.01%) after placebo. All events were non-serious. One individual had onset of uveitis after Dose 1 of the vaccine which resolved and then recurred after Dose 2. The 2 placebo patients appeared to have a previous history of uveitis and 1 of the Novavax COVID-19 vaccine patients had a history of iritis. Current available information on uveitis is insufficient to determine a causal relationship with the vaccine.[67783] [72242]

In a study with a recombinant spike protein COVID-19 vaccine manufactured by a different process than the Novavax COVID-19 vaccine, Guillain-Barre syndrome was reported 9 days after administration of Dose 1 of the vaccine. Cranial nerve palsies have also been reported during clinical trials. A serious adverse event of the fourth cranial nerve palsy was reported, with the onset of symptoms 7 days post vaccination, and a serious adverse event of the sixth cranial nerve palsy occurred 14 days post vaccination. Both individuals had risk factors, including diabetes, hypertension, and hypercholesterolemia. Currently available information on oculomotor cranial palsies is insufficient to determine a causal relationship. An individual reported a serious adverse event of vestibular neuronitis (eighth cranial nerve). This occurred twice, on days 11 and 16 post Dose 1 and Dose 2, respectively. This was assessed as related to the vaccine.[72242]

Paresthesias and hypoesthesia were reported during postmarketing use of the Novavax COVID-19 vaccine.[72242]

Injectable vaccines, including the Novavax COVID-19 vaccine, have been associated with episodes of syncope and fainting. Prior to administration, ensure procedures are in place to prevent falls and manage syncopal reactions. Individuals should remain seated or lying down during the observation period to decrease the risk for injury. If syncope develops, observe patients until symptoms resolve.[66175] [72242]

Heavy menstrual bleeding (menorrhagia) was reported by 1 individual during clinical trials who received a dose of Novavax COVID-19 vaccine and was considered related to the vaccine.[67783] [72242]

Autoimmune hepatitis was reported in a 57-year-old individual approximately 12 days after a booster dose of Novavax COVID-19 vaccine. The individual did have a history of elevated alanine transferase (ALT), up to 3 times the upper limit of normal (ULN), a year prior to vaccination. The baseline ALT was normal prior to the receipt of the first dose of Novavax COVID-19 vaccine. The ALT increased to 4 times the ULN after the second dose of the primary series. After the booster dose, a recurrent and higher ALT increase was observed (7 times ULN). Viral hepatitis tests were negative and no alternative etiology was identified. The event was ongoing for 8 months and was not resolved with azathioprine treatment. Currently, available information for this event is insufficient to determine a causal relationship with the vaccine. Obstructive pancreatitis was reported during a clinical trial and assessed as severe and not related to the vaccination.[67783] [72242]

One severe, related non serious adverse event of diarrhea was reported during clinical trials.[67783] [72242]

Immunocompromised individuals, including individuals with immunosuppression or receiving immunosuppressive therapy, may not have an adequate immune response to the COVID-19 vaccine.[72242] Immunosuppressed persons may include individuals with congential or acquired immunodeficiencies, whether due to concurrent disease (e.g., HIV infection, leukemia, lymphoma), cancer therapy (e.g., cytotoxic drugs, radiation), or immunosupressive therapy (e.g., corticosteroids). Short-term (less than 2 weeks) corticosteroid therapy or intra-articular, bursal, or tendon injections with corticosteroids should not be immunosuppressive. COVID-19 vaccines may be administered without regard to timing of corticosteroid treatment, including topical or intra-articular treatment, bursal, or tendon injection.[65107] [66175] Ideally, complete COVID-19 vaccination at least 2 weeks before initiation or resumption of immunosuppressive therapies, but timing of COVID-19 vaccination should take into consideration current or planned immunosuppressive therapies and optimization of both the individual's medical condition and response to vaccine. Serologic testing or cellular immune testing to assess for immunity after COVID-19 vaccination, outside the context of research studies, is not recommended.[66175]

There are insufficient data to assess the effects of the Novavax COVID-19 vaccine during breast-feeding, on milk production, and excretion in human breast milk.[67669]

COVID-19 vaccination is strongly recommended by the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine. It is recommended as soon as possible, regardless of trimester, to optimize maternal and fetal health. There is no preferential recommendation for the use of any one COVID-19 vaccine over another.[66179] [72307] Currently, the CDC does not have the COVID-19 vaccine listed on its Adult Immunization Schedule for pregnant individuals.[72295] The available data regarding use of the Novavax COVID-19 vaccine during pregnancy is insufficient to inform a vaccine-associated risk. Animal data did not reveal evidence of impaired fertility or harm to the fetus when administered at doses containing the same quantity of SARS-CoV-2 recombinant spike protein (5 mcg), one-fifth the quantity of adjuvant (10 mcg), and inactive ingredients contained in a single dose of the Novavax COVID-19 vaccine. A pregnancy exposure registry is available that monitors pregnancy outcomes in women vaccinated with the Novavax COVID-19 vaccine during pregnancy. Encourage women vaccinated during pregnancy to enroll in the registry by going to https://c-viper.pregistry.com.[67669]