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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 slightly higher after the second dose compared to after the first.[66080] [66120] [66904] [67085] After Pfizer-BioNTech COVID-19 vaccine administration, pain (66.1% to 86.2%), erythema or redness (5% to 18.5%), and swelling (4.9% to 15.3%) at the injection site were reported during clinical trials. About one-third of patients 12 to 55 years (30.9% to 44.7%) who received the vaccine reported pain that either interfered with daily activity or prevented it; the percentage of patients reporting this degree of pain was lower in patients 5 to 11 years (15.2% to 18.1%) and 56 years and older (14.9% to 19.2%). Redness and swelling occurred more frequently in patients 5 to 11 years (14.7% to 18.5% and 10.5% to 15.3%, respectively) compared to patients 12 years and older (5% to 7.2% and 4.9% and 7.8%, respectively). The mean duration of pain at the injection site after dose 2 was 2.3 to 2.5 days (range 1 to 70 days), for redness 2.2 to 3 days (range 1 to 34 days), and for swelling 1.9 to 2.6 days (range 1 to 34 days). After the booster dose, the mean duration of pain at the injection site was 2.6 days (range 1 to 8 days), for redness 2.2 days (range 1 to 15 days), and for swelling 2.2 days (range 1 to 8 days).[66080] [66904] [67085] After Moderna COVID-19 vaccine administration, pain at the injection site was reported in 92% of patients. The highest rates of pain were in patients 18 to 64 years after dose 2, with 89.9% reporting pain and 4.6% reporting that it prevented daily activity and required the use of pain relievers. Erythema or redness (8.9% after dose 2, 3% after dose 1) and swelling or hardness (12.6% after dose 2, 6.7% after dose 1) were reported in patients 18 to 64 years. Similar numbers of erythema or redness (7.5% after dose 2, 2.3% after dose 1) and swelling or hardness (10.8% after dose 2, 4.4% after dose 1) were reported in patients 65 years and older. Axillary swelling or tenderness was more common after the second dose in both age groups (18 to 64 years: 16.2% after dose 2, 11.6% after dose 1 and 65 years and older: 8.5% after dose 2, 6.1% after dose 1). Most local reactions lasted 1 to 3 days. Delayed reactions, occurring 8 or more days after administration, occurred in 0.8% and 0.2% of patients after the first and second dose, respectively, and usually resolved over 4 to 5 days.[66120] [66199] Patients who have received dermal fillers may develop swelling at or near the site of filler injection (usually face or lips) after mRNA COVID-19 vaccine administration. It appears to be temporary and can resolve with medical treatment, including corticosteroid therapy. These patients may receive mRNA COVID-19 vaccines without additional precautions; however, they should be advised to contact their health care provider if they develop swelling at or near the site of dermal filler after vaccination.[66175]

During clinical trials, fatigue (33.6% to 67.6%), headache (22.4% to 64.5%), and malaise (0.1% to 0.5%) 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.[66080] [66120] [66904] [67085] In patients who received the Pfizer-BioNTech COVID-19 vaccine, fatigue was more frequently reported in patients 12 to 55 years (49.4% to 66.2%) compared to patients 5 to 11 years (33.6% to 39.4%) and patients 56 years and older (33.7% to 51%). Mild fatigue (not interfering with activity) was more frequent in patients 5 to 11 years (21.4% to 22% vs. 11.3% to 17.3% moderate) and patients 56 years and older (20.7% to 21% vs. 8.2% to 12.9% moderate). In contrast, patients 12 to 55 years reported moderate fatigue (causing some interference with activity) more frequently (12 to 15 years: 34.1% to 42.7% vs. 21.1% to 24.7% mild; 16 to 55 years: 21.7% to 35.4% vs. 20.8% to 26.2% mild). Headache was also more common in patients 12 to 55 years (43.5% to 64.5%) compared to patients 5 to 11 years (22.4% to 28%) and patients 56 years and older (25% to 39.4%). The incidence of fatigue and headache after a booster dose of the Pfizer-BioNTech COVID-19 vaccine in patients 18 to 55 years (63.7% and 48.4%, respectively) was similar to that seen after the second dose of the primary series.[66080] [66904] [67085] In Moderna COVID-19 vaccine clinical trials, fatigue (70%) was the most frequently reported systemic adverse reaction. The highest incidence of fatigue was reported by patients 18 to 64 years after the second dose, with 67.6% reporting any fatigue, 10.7% reporting fatigue that prevented daily activities, and 1 patient reporting fatigue that required an emergency room visit or hospitalization. Headache was reported by approximately twice as many patients after the second dose in both age groups (18 to 64 years: 62.8% after dose 2, 35.3% after dose 1 and 65 years and older: 46.2% after dose 2, 24.5% after dose 1). The incidence of fatigue and headache after a booster dose of the Moderna COVID-19 vaccine (53.5% to 67.7% and 39.5% to 56.1%, respectively) was similar to that seen after the second dose of the primary series.[66120]

Musculoskeletal adverse reactions reported during COVID-19 vaccine clinical trials include muscle pain or myalgia (9.1% to 61.6%) and/or joint pain or arthralgia (3.3% to 45.5%).[66080] [66120] [66904] [67085] New or worsened muscle pain (9.1% to 11.7%) and joint pain (3.3% to 5.2%) were reported less frequently in patients 5 to 11 years compared to patients 16 years and older. In patients 12 to 15 years of age, new or worsened muscle pain was reported in about one-third of patients (32.4%) after the second Pfizer-BioNTech COVID-19 vaccine dose compared to 24.1% after the first dose. A similar number of patients 16 to 55 years (39.3% after dose 2, 22.9% after dose 1) and 56 years or older (28.9% after dose 2, 13.6% after dose 1) reported new or worsened muscle pain. Moderate to severe muscle pain (causing some interference with daily activities or preventing activities) was reported after dose 2 in 18.5% of patients 12 to 15 years, 22.9% of patients 16 to 55 years, and 16.6% of patients 56 years and older. New or worsened joint pain was reported in approximately twice as many patients after the second dose compared to the first dose in patients 12 years and older (12 to 15 years: 15.8% after dose 2, 9.7% after dose 1; 16 to 55 years: 23.8% after dose 2, 11.8% after dose 1; and 56 years and older: 19% after dose 2, 8.7% after dose 1). The incidence of myalgia and arthralgia after a booster dose of the Pfizer-BioNTech COVID-19 vaccine in patients 18 to 55 years (39.1% and 25.3%, respectively) was similar to that seen after the second dose of the primary series.[66080] [66904] [67085] During Moderna COVID-19 clinical trials, myalgia was more common after the second dose in both age groups (18 to 64 years: 61.6% after dose 2, 23.7% after dose 1 and 65 years and older: 47.1% after dose 2, 19.7% after dose 1). Myalgia that prevented daily activity was reported in significantly more patients after the second dose (18 to 64 years: 10.1% after dose 2, 0.6% after dose 1 and 65 years and older: 5.6% after dose 2, 0.5% after dose 1). Similar to myalgia, arthralgia was more common after the second dose in both age groups (18 to 64 years: 45.5% after dose 2, 16.6% after dose 1 and 65 years and older: 35% after dose 2, 16.4% after dose 1). Arthralgia that prevented daily activity was reported in significantly more patients after the second dose (18 to 64 years: 5.9% after dose 2, 0.4% after dose 1 and 65 years and older: 3.3% after dose 2, 0.3% after dose 1). One case of arthralgia requiring an emergency room visit or hospitalization was reported in the vaccine group. The incidence of myalgia and arthralgia after a booster dose of the Moderna COVID-19 vaccine (39.5% to 41.9% and 47.4% to 49.6%, respectively) was similar to that seen after the second dose of the primary series.[66120]

During clinical trials, chills (4.6% to 48.6%) and fever (1.3% to 19.6%) 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.[66080] [66120] [66904] [67085] In patients 5 to 15 years, fever of 101.2 degrees F (38.4 degrees C) or higher was reported in 3 times more patients after the second Pfizer-BioNTech COVID-19 vaccine dose (5 to 11 years: 3.1% after dose 2, 1% after dose 1; 12 to 15 years: 9.9% after dose 2, 3.6% after dose 1). In patients 16 to 55 years, fever of 101.2 degrees F (38.4 degrees C) or higher was reported in 6 times more patients after the second Pfizer-BioNTech COVID-19 vaccine dose (6.9% after dose 2, 1.2% after dose 1). In patients 56 years and older, fever of 101.2 degrees F (38.4 degrees C) or higher was reported in 3.3% of patients after dose 2 compared to 0.1% of patients after dose 1. In patients who received the Pfizer-BioNTech COVID-19 vaccine, chills were more frequently reported in patients 12 to 55 years (16.5% to 41.5%) compared to patients 5 to 11 years (4.6% to 9.8%) and patients 56 years and older (6.5% to 23.4%).[66080] [66904] [67085] After Moderna COVID-19 vaccine administration, fever was reported in more patients 18 to 64 years after dose 2 (17.4%) compared to dose 1 (0.9%). A fever of 102.1 degrees F (38.9 degrees C) or higher was reported by 1.7% of patients after dose 2 compared to less than 0.1% after dose 1. Significantly more patients 65 years and older also reported fever after the second dose (10% after dose 2, 0.3% after dose 1). A fever of 102.1 degrees F (38.9 degrees C) or higher was reported by 0.5% of patients after dose 2 compared to less than 0.1% after dose 1. The greatest incidence of chills occurred after dose 2 in patients 18 to 64 years (48.6%).[66120] The incidence of chills and fever after a booster dose of the Pfizer-BioNTech COVID-19 vaccine and the Moderna COVID-19 vaccine was similar to that seen after the primary series.[66080] [66120]

Adverse gastrointestinal (GI) reactions have been reported during COVID-19 vaccine trials.[66080] [66120] [66904] [67085] Diarrhea (5.3% to 10.7%), nausea (0.4% to 1.2%), and vomiting (0.5% to 2.8%) were reported during Pfizer-BioNTech COVID-19 vaccine clinical trials. Anorexia (decreased appetite) was reported by 0.1% of patients 5 to 11 years old.[66080] [66904] [67085] During Moderna COVID-19 vaccine clinical trials, nausea and/or vomiting was reported in twice as many patients 18 to 64 years after dose 2 (21.4%) compared to dose 1 (9.4%). A similar difference was seen in patients 65 years and older (11.8% after dose 2; 5.2% after dose 1). One case of intractable nausea and vomiting requiring hospitalization was reported as a serious adverse reaction in the vaccine group.[66120] The incidence of GI adverse reactions after a booster dose of the Pfizer-BioNTech COVID-19 vaccine and the Moderna COVID-19 vaccine was similar to that seen after the primary series.[66080] [66120]

Rare cases of myocarditis and pericarditis have been reported after mRNA COVID-19 vaccination, particularly in adolescents and young adults. The observed risk is greater for males younger than 40 years of age than for females and older males and the risk is highest in males 12 to 17 years of age (Pfizer-BioNTech COVID-19 vaccine) and in males 18 to 24 years of age (Moderna COVID-19 vaccine). Onset typically has been within 7 days after vaccination, occurring more often after the second dose. From May 1 through June 11, 2021, there were 40.6 cases of myocarditis per million second doses of mRNA COVID-19 vaccines administered to males aged 12 to 29 years and 2.4 cases per million second doses administered to males aged 30 years and older; reporting rates among females were 4.2 and 1 cases per million second doses, respectively. Although postmarketing data is limited, available evidence suggests a lower risk after administration of a mRNA booster dose compared to the risk after the second dose in the primary series. No cases of myocarditis were reported in patients aged 5 to 11 years (n = 3,082) in Pfizer-BioNTech COVID-19 trials with at least 7 days of follow-up after dose 2, although the study was not powered to assess the risk for myocarditis. Consider myocarditis and pericarditis in adolescents and young adults with acute chest pain, shortness of breath, or palpitations. Most patients require hospitalization, but have experienced resolution of acute symptoms. Although data from short-term follow-up suggests that most patients have resolution of symptoms, information is not yet available about long-term sequelae. It is unclear if patients who develop myocarditis or pericarditis after a first dose of mRNA COVID-19 vaccine are at an increased risk of further adverse cardiac effects after a subsequent dose of vaccine; until additional information is available, defer subsequent doses. A subsequent dose may be considered in certain circumstances that include personal risk of severe acute COVID-19 (e.g., age, underlying conditions), level of COVID-19 community transmission and personal risk of infection, additional data on the risk of myocarditis or pericarditis after the first dose of mRNA vaccine, or timing of any immunomodulatory therapies. Patients with a history of myocarditis or pericarditis prior to COVID-19 vaccination or after the first dose should not receive a mRNA vaccine dose until their episode of myocarditis or pericarditis has completely resolved, which incudes no evidence of ongoing heart inflammation or sequelae. For men 18 years and older who develop myocarditis or pericarditis after a dose of mRNA COVID-19 vaccine and chose to receive a subsequent dose of COVID-19 vaccine, consider administration of the Janssen COVID-19 vaccine instead of a mRNA COVID-19 vaccine, taking into account the risk of thrombosis with thrombocytopenia syndrome. In a retrospective study of 139 patients (mostly white male; median age of 15.8 years), suspected myocarditis was reported in 131 (94.2%) patients receiving the Pfizer-BioNTech vaccine, with the majority of cases occurring after the second dose 128 (91.4%). Five cases (3.6%) were reported after the Moderna COVID-19 vaccine, 1 case (0.7%) occurred after the Janssen COVID-19 vaccine, and the brand was unknown in 2 patients. Median onset of symptoms was 2 days after vaccination and the most common symptom was chest pain (99.3%). Patients were treated with nonsteroidal anti-inflammatory drugs (81.3%), intravenous immunoglobulin (21.6%), glucocorticoids (21.6%), colchicine (7.9%), or no anti-inflammatory therapies (8.6%). Twenty-six patients (18.7%) were in the ICU, but only 2 patients were treated with inotropic/vasoactive support, and none required ECMO or died. The median hospital stay was 2 days (0 to 10 days).[66080] [66120] [66175] [66698] [66770] [66904] [67172]

Serious allergic reactions or anaphylactoid reactions have been reported in patients outside of clinical trials during mass vaccination. During phase 2/3 Pfizer-BioNTech COVID-19 vaccine clinical trials, a subset of patients in the vaccinated group had hypersensitivity-related adverse reactions, possibly representing allergic reactions (0.63% vs. 0.51%, placebo).[66080] [66175] During mass vaccination with the Pfizer-BioNTech COVID-19 vaccine outside of clinical trials, severe allergic reactions, including anaphylaxis and other hypersensitivity reactions (e.g., rash, pruritus, urticaria, angioedema), have been reported.[66080] During this time, 21 cases of anaphylaxis were identified (a rate of 11.1 anaphylaxis cases per million doses administered). Of those, 17 patients had a documented history of allergies or allergic reaction and 7 patients had a history of anaphylaxis. Median time to symptom onset was 13 minutes (range = 2 to 150 minutes). Twenty patients were available for follow-up and all had recovered or been discharged home. An additional 83 nonanaphylaxis allergic reactions were reported; symptoms included pruritus, rash, itchy and scratchy sensation in the throat, and mild respiratory symptoms. Median time to symptom onset was 12 minutes (range = less than 1 minute to 20 hours). In most patients (85%), symptoms occurred within 30 minutes. For 67% of patients, a past history of allergies or allergic reactions was documented. Rash was reported in patients 5 to 11 years old (0.3%) and in patients after administration of the booster dose (0.3%).[66397] [67085] During Moderna COVID-19 clinical trials, hypersensitivity related adverse reactions were reported in 1.5% of vaccine recipients compared to 1.1% of placebo recipients. Hypersensitivity reactions included injection site rash and injection site urticaria. Rash was also reported in 1.8% of patients after administration of the booster dose.[66120] During mass vaccination with the Moderna vaccine, 10 cases of anaphylaxis were identified (a rate of 2.5 anaphylaxis cases per million doses administered). Of those, 9 patients had a documented history of allergies or allergic reaction and 5 patients had a history of anaphylaxis. Median time to symptom onset was 7.5 minutes (range = 1 to 45 minutes). Eight patients were available for follow-up and all had recovered or been discharged home. An additional 43 nonanaphylaxis allergic reactions were reported; symptoms included pruritus, rash, itchy and scratchy sensation in the throat, sensations of throat closure, and mild respiratory symptoms. Median time to symptom onset was 15 minutes (range = less than 1 minute to 24 hours). In most patients (73%), symptoms occurred within 30 minutes. For 60% of patients, a past history of allergies or allergic reactions was documented.[66398]

Lymphadenopathy was reported in 0.3% to 0.9% of patients 5 years and older during Pfizer-BioNTech COVID-19 vaccine clinical trials and 5.2% of patients 18 to 55 years after the booster dose. From dose 1 through 30 days after dose 2, lymphadenopathy was reported in more patients in the vaccine group than in the placebo group (5 to 11 years: 13 vs. 1; 12 to 15 years: 7 vs. 1; 16 years and older: 64 vs. 6).[66080] [66904] [67085] During Moderna COVID-19 vaccine clinical trials, lymphadenopathy-related events were reported in 1.1% of patients who received the vaccine compared to 0.6% of patients who received placebo. These events included lymphadenopathy, lymphadenitis, lymph node pain, vaccination-site lymphadenopathy, injection-site lymphadenopathy, and axillary mass.[66120]

During Pfizer-BioNTech COVID-19 vaccine clinical trials, appendicitis was reported as a serious adverse reaction in 8 patients receiving vaccine (n = 18,801) vs. 4 receiving placebo (n = 18,785). Bell's palsy (facial paralysis) was reported by 4 patients in the Pfizer-BioNTech COVID-19 vaccine group (n = 18,801) compared to none of the patients in the placebo group. Onset of facial paralysis occurred on day 37 after dose 1 (patient did not receive dose 2) and days 3, 9, and 48 after dose 2. During Moderna COVID-19 vaccine clinical trials, there were 3 reports of Bell's palsy in the vaccine group (n = 15,185) compared to 1 patient in the placebo group (n = 15,166). Onset of facial paralysis occurred 22, 28, and 32 days after vaccination in the vaccine group and 17 days after vaccination in the placebo group. In the United States, it is estimated that between 25 and 35 in 100,000 people are affected with Bell's palsy. Currently available information is insufficient to determine a causal relationship between appendicitis or Bell's palsy with the vaccine.[66080] [66120] [66184]

Immunocompromised patients, including patients with immunosuppression or receiving immunosuppressive therapy, may not have an adequate immune response to the COVID-19 vaccine. An additional third dose of the same mRNA vaccine administered at least 28 days after the 2-dose regimen has been authorized for individuals who have undergone solid organ transplantation (e.g., heart transplant, kidney transplant, liver transplant, lung transplant, or other organ transplant), or are diagnosed with a condition that is considered to have an equivalent level of immunocompromise. Patients at increased risk include, but are not limited to, those who have received a solid-organ transplant and are taking immunosuppressive therapy, those who are receiving active treatment with high-dose corticosteroids (i.e., 20 mg or more of prednisone or equivalent per day when administered for 2 weeks or more), transplant-related immunosuppressive drugs, and other biologic agents that are immunosuppressive or immunomodulatory, and patients with moderate or severe primary immunodeficiency (e.g., DiGeorge syndrome, Wiskott-Aldrich syndrome). Administration of a third dose appears to be only moderately effective in increasing antibody titers; counsel patients to maintain physical precautions to avoid exposure to the SARS-CoV-2 virus.[66080] [66120] [66175] [66904] Immunosuppressed persons may also include patients with severe combined immunodeficiency (SCID), hypogammaglobulinemia, or agammaglobulinemia. Short-term (less than 2 weeks) corticosteroid therapy or intra-articular, bursal, or tendon injections with corticosteroids should not be immunosuppressive.[65107] [66175] Ideally, complete COVID-19 vaccination (including the primary series and an additional dose) 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 patient'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. Re-vaccination after immune competence is regained in patients who received mRNA COVID-19 vaccines during treatment with immunosuppressive drugs is not recommended. For patients receiving antibody therapies not specific to COVID-19 treatment (e.g., intravenous immunoglobulin, RhoGAM), there is no recommended minimum interval between these therapies and administration of mRNA COVID-19 vaccines. Administration of mRNA COVID-19 vaccines either together or at any interval before or after receipt of an antibody-containing product is unlikely to substantially impair the development of a protective antibody response. During clinical trials, no imbalances were noted in the occurrence of symptoms consistent with autoimmune conditions or inflammatory disorders in patients who received the COVID-19 vaccine compared to placebo. Patients with autoimmune conditions may receive the COVID-19 vaccine.[66175]

Patients with altered immune states due to generalized neoplastic disease or an immune system compromised by radiation therapy or chemotherapy may not have an adequate immune response to the COVID-19 vaccine. An additional third dose of the same mRNA vaccine administered at least 28 days after the 2-dose regimen has been authorized for individuals who have undergone solid organ transplantation, or are diagnosed with a condition that is considered to have an equivalent level of immunocompromise. Patients at increased risk include, but are not limited to, those receiving active treatment for solid tumor and hematologic malignancies, receipt of chimeric antigen receptor (CAR) T-cell or hematopoietic stem cell transplant (within 2 years of transplantation or taking immunosuppression therapy), and active treatment with alkylating agents, antimetabolites, transplant-related immunosuppressive drugs, cancer chemotherapeutic agents classified as severely immunosuppressive, tumor-necrosis (TNF) blockers, and other biologic agents that are immunosuppressive or immunomodulatory. Administration of a third dose appears to be only moderately effective in increasing antibody titers; counsel patients to maintain physical precautions to avoid exposure to the SARS-CoV-2 virus.[65107] [66080] [66120] [66175] [66904] Ideally, complete COVID-19 vaccination (including the primary series and an additional dose) 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 patient'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] Delay vaccination for at least 3 months after hematopoietic cell transplantation (HCT) or engineered cellular therapy (e.g. CAR-T cells) to maximize vaccine efficacy.[66335] Revaccinate patients who received the COVID-19 vaccine series prior to receiving a HCT or CAR-T-cell therapy with a primary vaccine series at least 3 months after transplant or CAR-T-cell therapy. An additional primary dose of an mRNA COVID-19 vaccine (if revaccinated with a 2-dose mRNA COVID-19 vaccine primary series) is recommended in patients who continue to have moderate or severe immune compromise.[66175] For patients with hematologic malignancies receiving intensive cytotoxic chemotherapy (e.g., cytarabine/anthracycline-based induction regimens for AML), delay vaccination until absolute neutrophile count (ANC) recovery. For patients with solid tumor malignancies undergoing major surgery, separate date of surgery from vaccination by at least a few days to allow symptoms (e.g. fever) to be correctly attributed to surgery vs. vaccination. For more complex surgeries (e.g. splenectomy or surgery that may lead to an immunosuppressive state) surgeons may recommend a wider window (+/- 2 weeks) from the time of surgery.[66335]

Postponing vaccination with the COVID-19 vaccine is recommended in patients with an acute moderate to severe illness or infection, both before the first vaccine or before the second vaccine if infection develops after the first vaccine administration. Patients who have active tuberculosis (TB) disease or an illness that is being evaluated as active TB disease can receive an mRNA COVID-19 vaccine. If vaccination is not deferred, observe the patient for 15 minutes after vaccine administration.[66175]

Clinical trials for the vaccine were expanded to include patients with chronic, stable human immunodeficiency virus (HIV) infection. Efficacy information for the COVID-19 vaccine is not yet available in this patient population and although patients with HIV infection or acquired immunodeficiency syndrome (AIDS) could have a diminished response, the COVID-19 vaccine should be offered to patients with chronic, stable HIV.[65107] [66080] [66086] [66120] [66904] An additional third dose of the same mRNA vaccine administered at least 28 days after the 2-dose regimen has been authorized for individuals who have undergone solid organ transplantation, or are diagnosed with a condition that is considered to have an equivalent level of immunocompromise. Patients at increased risk include, but are not limited to, those with advanced or untreated HIV infection (people with HIV and CD4 counts less than 200/mm³, history of AIDS-defining illness without immune reconstitution, or clinical manifestations of symptomatic HIV infection). Administration of a third dose appears to be only moderately effective in increasing antibody titers; counsel patients to maintain physical precautions to avoid exposure to the SARS-CoV-2 virus.[66080] [66120] [66175]

The COVID-19 vaccine is administered by intramuscular (IM) injection only. Carefully consider the risks and benefits in patients at increased risk for bleeding after an intramuscular injection, such as thrombocytopenia, bleeding disorders (e.g., hemophilia), coagulopathy, vitamin K deficiency, and those receiving anticoagulant therapy. Caution and appropriate precautions to minimize the risk of bleeding or hematoma formation are advised.[65107] [66080] [66120] [66904]

COVID-19 vaccination is recommended in all eligible women regardless of pregnancy status (including those who are pregnant, trying to get pregnant, or may become pregnant in the future). Pregnant and recently pregnant patients (for at least 42 days after the end of pregnancy) with COVID-19 are at increased risk for severe illness compared to patients who are not pregnant.[66175] [66179] [66863] If a woman becomes pregnant after the first dose, administer the second dose as indicated. Manage potential post vaccination fever with acetaminophen.[66863] [66864] A growing body of evidence suggests that benefits of COVID-19 vaccination outweigh any known or potential risk of vaccination during pregnancy. Data analyzed from 3 vaccine safety-related databases (VAERS, the v-safe active surveillance system, and the v-safe pregnancy registry) did not identify safety concerns for pregnant patients who were vaccinated late in their pregnancy or their infants. Analysis of current data from the V-SAFE pregnancy registry did not find an increased risk of miscarriage among approximately 2,500 pregnant women who received an mRNA COVID-19 vaccine before 20 weeks of pregnancy. Miscarriage rates in this population were 13%, compared to 11% to 16% of pregnancies in the general population. There is no current evidence that COVID-19 vaccines cause fertility problems in woman or men.[66175] [66863] [66864] In a prospective cohort study of 131 mRNA COVID-19 vaccine recipients (84 pregnant, 31 lactating, and 16 non-pregnant), vaccine-induced antibody titers were equivalent in pregnant and lactating women compared to non-pregnant women. All titers were significantly higher than those induced during SARS-CoV-2 infection during pregnancy. Vaccine-generated antibodies were present in all umbilical cord blood samples; neutralizing antibody titers were lower in umbilical cord compared to maternal sera, although statistical significance was not reached. No differences in reactogenicity were noted between the groups.[66558] A pregnancy exposure registry is available that monitors pregnancy outcomes in women exposed to Comirnaty (Pfizer-BioNTech COVID-19 vaccine) during pregnancy. Encourage women vaccinated during pregnancy to enroll in the registry by going to https://mothertobaby.org/ongoing-study/covid19-vaccines/.[66904] A pregnancy exposure registry is available that monitors pregnancy outcomes in women exposed to Moderna COVID-19 vaccine during pregnancy. Encourage women vaccinated with Moderna COVID-19 vaccine to enroll in the registry by calling 1-866-663-3762. Additionally, encourage pregnant women to enroll in the CDC's V-SAFE program by going to vsafe.cdc.gov.[66120] [66864]

COVID-19 vaccination is recommended in all eligible women, including those who are breast-feeding.[66179] [66864] There are limited data regarding use of the COVID-19 vaccine during breast-feeding, its effect on milk production, and its excretion in human breast milk. However, the COVID-19 vaccines cannot cause infection in either the lactating patient or the infant.[66175] Recent reports suggest mothers who have received mRNA COVID-19 vaccines have antibodies in their breast milk, which may help protect their babies.[66864] In a prospective cohort study of 131 mRNA COVID-19 vaccine recipients (84 pregnant, 31 lactating, and 16 non-pregnant), vaccine-induced antibody titers were equivalent in pregnant and lactating women compared to non-pregnant women. All titers were significantly higher than those induced during SARS-CoV-2 infection during pregnancy. Vaccine-generated antibodies were present in all breast milk samples. No differences in reactogenicity were noted between the groups.[66558] If a breast-feeding infant experiences an adverse event possibly related to a maternally administered vaccine, health care providers are encouraged to report the adverse event to the FDA.[66080] [66904]

Injectable vaccines, including the Pfizer-BioNTech COVID-19 vaccine, have been associated with episodes of syncope and fainting, especially in adolescents. Prior to administration, ensure procedures are in place to prevent falls and manage syncopal reactions. Patients should remain seated or lying down during the observation period to decrease the risk for injury. If syncope develops, observe patients until symptoms resolve.[66080] [66175] [66904]

Data suggest immune response to COVID-19 vaccination may be reduced in patients with renal failure receiving hemodialysis. Counsel hemodialysis patients about the potential for reduced immune responses and the need to continue following precautions to avoid exposure to the SARS-CoV-2 virus.[66175]

The Pfizer-BioNTech COVID-19 vaccine (Comirnaty) is FDA-approved in patients 16 years and older; use in patients 5 to 15 years is covered under an Emergency Use Authorization (EUA). The safety and effectiveness of the COVID-19 vaccine have not been established in children 4 years and younger, infants, or neonates.[66080] [66904] [67085]

The use of the COVID-19 vaccine has resulted in laboratory test interference with the Bio-Rad Laboratories BioPlex 2200 Syphilis Total and Rapid Plasma Reagin (RPR) kit. False reactivity may occur for at least 5 months after COVID-19 vaccination. It is unknown if other RPR tests may also be affected. Treponemal testing for syphilis such as Treponema pallidum particle agglutination (TP-PA) and treponemal immunoassays do not appear to be impacted. Retest patients who receive a positive result using the Bio-Rad BioPlex 2200 Syphilis Total and RPR kit for syphilis with another test to confirm results. For patients with a negative treponemal test, but reactive RPR result using the Bio-Rad BioPlex 2200 Syphilis Total and RPR kit, repeat RPR testing is not necessary unless otherwise clinically indicated. For patients previously treated for syphilis, whose treponemal testing will remain persistently positive, and are being evaluated for a possible new syphilis infection, interpret a reactive RPR in the context of the patient's medical history, risk factors, and clinical presentation. If the Bio-Rad BioPlex 2200 Syphilis Total and RPR kit was used and the clinical presentation does not support syphilis reinfection, then confirm reactive results with a RPR test from another manufacturer.[67201]