Post-authorization safety surveillance of Ad.26.COV2.S vaccine: Reports to the Vaccine Adverse Event Reporting System and v-safe, February 2021-February 2022.

BACKGROUND: On 2/27/2021, FDA authorized Janssen COVID-19 Vaccine (Ad.26.COV2.S) for use in individuals 18 years of age and older. Vaccine safety was monitored using the Vaccine Adverse Event Reporting System (VAERS), a national passive surveillance system, and v-safe, a smartphone-based surveillance system. METHODS: VAERS and v-safe data from 2/27/2021 to 2/28/2022 were analyzed. Descriptive analyses included sex, age, race/ethnicity, seriousness, AEs of special interest (AESIs), and cause of death. For prespecified AESIs, reporting rates were calculated using the total number of doses of Ad26.COV2.S administered. For myopericarditis, observed-to-expected (O/E) analysis was performed based on the number verified cases, vaccine administration data, and published background rates. Proportions of v-safe participants reporting local and systemic reactions, as well as health impacts, were calculated. RESULTS: During the analytic period, 17,018,042 doses of Ad26.COV2.S were administered in the United States, and VAERS received 67,995 reports of AEs after Ad26.COV2.S vaccination. Most AEs (59,750; 87.9 %) were non-serious and were similar to those observed during clinical trials. Serious AEs included COVID-19 disease, coagulopathy (including thrombosis with thrombocytopenia syndrome; TTS), myocardial infarction, Bell's Palsy, and Guillain-Barré syndrome (GBS). Among AESIs, reporting rates per million doses of Ad26.COV2.S administered ranged from 0.06 for multisystem inflammatory syndrome in children to 263.43 for COVID-19 disease. O/E analysis revealed elevated reporting rate ratios (RRs) for myopericarditis; among adults ages 18-64 years, the RR was 3.19 (95 % CI 2.00, 4.83) within 7 days and 1.79 (95 % CI 1.26, 2.46) within 21 days of vaccination. Of 416,384 Ad26.COV2.S recipients enrolled into v-safe, 60.9 % reported local symptoms (e.g. injection site pain) and 75.9 % reported systemic symptoms (e.g., fatigue, headache). One-third of participants (141,334; 33.9 %) reported a health impact, but only 1.4 % sought medical care. CONCLUSION: Our review confirmed previously established safety risks for TTS and GBS and identified a potential safety concern for myocarditis.

Safety Monitoring of mRNA COVID-19 Vaccine Third Doses Among Children Aged 6 Months-5 Years - United States, June 17, 2022-May 7, 2023.

As of May 7, 2023, CDC's Advisory Committee on Immunization Practices (ACIP) recommends that all children aged 6 months-5 years receive at least 1 age-appropriate bivalent mRNA COVID-19 vaccine dose. Depending on their COVID-19 vaccination history and history of immunocompromise, these children might also need additional doses* (1-3). Initial vaccine safety findings after primary series vaccination among children aged 6 months-5 years showed that transient local and systemic reactions were common whereas serious adverse events were rare (4). To characterize the safety of a third mRNA COVID-19 vaccine dose among children aged 6 months-5 years, CDC reviewed adverse events and health surveys reported to v-safe, a voluntary smartphone-based U.S. safety surveillance system established by CDC to monitor health after COVID-19 vaccination (https://vsafe.cdc.gov/en/) and the Vaccine Adverse Event Reporting System (VAERS), a U.S. passive vaccine safety surveillance system co-managed by CDC and the Food and Drug Administration (FDA) (https://vaers.hhs.gov/) (5). During June 17, 2022-May 7, 2023, approximately 495,576 children aged 6 months-4 years received a third dose (monovalent or bivalent) of Pfizer-BioNTech vaccine and 63,919 children aged 6 months-5 years received a third dose of Moderna vaccine.† A third mRNA COVID-19 vaccination was recorded for 2,969 children in v-safe; approximately 37.7% had no reported reactions, and among those for whom reactions were reported, most reactions were mild and transient. VAERS received 536 reports after a third dose of mRNA COVID-19 vaccine for children in these age groups; 98.5% of reports were nonserious and most (78.4%) were classified as a vaccination error.§ No new safety concerns were identified. Preliminary safety findings after a third dose of COVID-19 vaccine for children aged 6 months-5 years are similar to those after other doses. Health care providers can counsel parents and guardians of young children that most reactions reported after vaccination with Pfizer-BioNTech or Moderna vaccine were mild and transient and that serious adverse events are rare.

COVID-19 Vaccine Safety First Year Findings in Adolescents.

BACKGROUND AND OBJECTIVES: The Food and Drug Administration expanded Emergency Use Authorization for use of Pfizer-BioNTech (BNT-162b2) coronavirus disease 2019 vaccine to include people ages 12 years and older on May 10, 2021. We describe adverse events observed during the first full year of the US coronavirus disease 2019 vaccination program for adolescents ages 12 to 17 years. METHODS: We conducted descriptive analyses using data from 2 complementary US vaccine safety monitoring systems: v-safe, a voluntary smartphone-based system that monitors reactions and health impacts, and the Vaccine Adverse Event Reporting System (VAERS), the national spontaneous reporting system. We reviewed reports and calculated adverse event reporting rates using vaccine administration data. RESULTS: Among 172 032 adolescents ages 12 to 17 years enrolled in v-safe, most reported reactions following BNT-162b2 were mild to moderate, most frequently reported on the day after vaccination, and more common after dose 2. VAERS received 20 240 adverse event reports; 91.5% were nonserious. Among adverse events of interest, we verified 40 cases of multisystem inflammation syndrome in children (1.2 cases per million vaccinations), 34 (85%) of which had evidence of prior severe acute respiratory syndrome coronavirus 2 infection; and 570 cases of myocarditis (17.7 cases per million vaccinations), most of whom (77%) reported symptom resolution at the time of report. CONCLUSIONS: During the first year BNT-162b2 was administered to adolescents ages 12 to 17 years, most reported adverse events were mild and appeared self-limited. Rates of myocarditis were lower than earlier reports. No new serious safety concerns were identified.

Surveillance for Multisystem Inflammatory Syndrome in US Children Aged 5-11 Years Who Received Pfizer-BioNTech COVID-19 Vaccine, November 2021 through March 2022.

Multisystem inflammatory syndrome in children (MIS-C) is a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; in the United States, reporting of MIS-C after coronavirus disease 2019 (COVID-19) vaccination is required for vaccine safety monitoring. Pfizer-BioNTech COVID-19 vaccine was authorized for children aged 5-11 years on 29 October 2021. Covering a period when approximately 7 million children received vaccine, surveillance for MIS-C ≤ 90 days postvaccination using passive systems identified 58 children with MIS-C and laboratory evidence of past/recent SARS-CoV-2 infection, and 4 without evidence. During a period with extensive SARS-CoV-2 circulation, MIS-C illness in children after COVID-19 vaccination who lacked evidence of SARS-CoV-2 infection was rare (<1 per million vaccinated children).

Reports of Guillain-Barré Syndrome After COVID-19 Vaccination in the United States.

Importance: Because of historical associations between vaccines and Guillain-Barré syndrome (GBS), the condition was a prespecified adverse event of special interest for COVID-19 vaccine monitoring. Objective: To evaluate GBS reports to the Vaccine Adverse Event Reporting System (VAERS) and compare reporting patterns within 21 and 42 days after vaccination with Ad26.COV2.S (Janssen), BNT162b2 (Pfizer-BioNTech), and mRNA-1273 (Moderna) COVID-19 vaccines. Design, Setting, and Participants: This retrospective cohort study was conducted using US VAERS reports submitted during December 2020 to January 2022. GBS case reports verified as meeting the Brighton Collaboration case definition for GBS in US adults after COVID-19 vaccination were included. Exposures: Receipt of the Ad26.COV2.S, BNT162b2, or mRNA-1273 COVID-19 vaccine. Main Outcomes and Measures: Descriptive analyses of GBS case were conducted. GBS reporting rates within 21 and 42 days after Ad26.COV2.S, BNT162b2, or mRNA-1273 vaccination based on doses administered were calculated. Reporting rate ratios (RRRs) after receipt of Ad26.COV2.S vs BNT162b2 or mRNA-1273 within 21- and 42-day postvaccination intervals were calculated. Observed-to-expected (OE) ratios were estimated using published GBS background rates. Results: Among 487 651 785 COVID-19 vaccine doses, 17 944 515 doses (3.7%) were Ad26.COV2.S, 266 859 784 doses (54.7%) were BNT162b2, and 202 847 486 doses (41.6%) were mRNA-1273. Of 295 verified reports of individuals with GBS identified after COVID-19 vaccination (12 Asian [4.1%], 18 Black [6.1%], and 193 White [65.4%]; 17 Hispanic [5.8%]; 169 males [57.3%]; median [IQR] age, 59.0 [46.0-68.0] years), 275 reports (93.2%) documented hospitalization. There were 209 and 253 reports of GBS that occurred within 21 days and 42 days of vaccination, respectively. Within 21 days of vaccination, GBS reporting rates per 1 000 000 doses were 3.29 for Ad26.COV.2, 0.29 for BNT162b2, and 0.35 for mRNA-1273 administered; within 42 days of vaccination, they were 4.07 for Ad26.COV.2, 0.34 for BNT162b2, and 0.44 for mRNA-1273. GBS was more frequently reported within 21 days after Ad26.COV2.S than after BNT162b2 (RRR = 11.40; 95% CI, 8.11-15.99) or mRNA-1273 (RRR = 9.26; 95% CI, 6.57-13.07) vaccination; similar findings were observed within 42 days after vaccination (BNT162b2: RRR = 12.06; 95% CI, 8.86-16.43; mRNA-1273: RRR = 9.27; 95% CI, 6.80-12.63). OE ratios were 3.79 (95% CI, 2.88-4.88) for 21-day and 2.34 (95% CI, 1.83-2.94) for 42-day intervals after Ad26.COV2.S vaccination and less than 1 (not significant) after BNT162b2 and mRNA-1273 vaccination within both postvaccination periods. Conclusions and Relevance: This study found disproportionate reporting and imbalances after Ad26.COV2.S vaccination, suggesting that Ad26.COV2.S vaccination was associated with increased risk for GBS. No associations between mRNA COVID-19 vaccines and risk of GBS were observed.

The v-safe after vaccination health checker: Active vaccine safety monitoring during CDC's COVID-19 pandemic response.

The Centers for Disease Control and Prevention (CDC) developed and implemented the v-safe after vaccination health checker (v-safe) to monitor COVID-19 vaccine safety and as an active surveillance supplement to existing CDC vaccine safety monitoring programs. V-safe allows persons who received COVID-19 vaccines to report on post-vaccination experiences and how symptoms affected their health at daily, weekly, and monthly timepoints after vaccination. Text message reminders are sent linking to Internet-based health check-in surveys. Surveys include questions to identify v-safe participants who may be eligible to enroll in a separate pregnancy registry activity that evaluates maternal and infant outcomes in those pregnant at the time of vaccination or receiving vaccine in the periconception period. We describe the development of and enhancements to v-safe, data management, promotion and communication to vaccination sites and partners, publications, strengths and limitations, and implications for future systems. We also describe enrollment in v-safe over time and demographics of persons participating in v-safe during the first year of operation (December 14, 2020 - December 13, 2021). During this time, 9,342,582 persons submitted 131,543,087 v-safe surveys. The majority of participants were female (62.3 %) and non-Hispanic White (61.2 %); median age was 49.0 years. Most participants reported receiving an mRNA COVID-19 vaccine as their first recorded dose (95.0 %). V-safe contributed to CDC's vaccine safety assessments for FDA-authorized COVID-19 vaccines by enabling near real-time reporting of reactogenicity once the COVID-19 vaccination program began in the community, encouraging reports to the Vaccine Adverse Event Reporting System and facilitating enrollment in a large post-vaccination pregnancy registry. Given that v-safe is an integral component of the most comprehensive safety monitoring program in U.S. history, we believe that this approach has promise as a potential application for future pandemic response activities as well as rollout of novel vaccines in a non-pandemic context.

Safety of co-administration of mRNA COVID-19 and seasonal inactivated influenza vaccines in the vaccine adverse event reporting system (VAERS) during July 1, 2021-June 30, 2022.

BACKGROUND: COVID-19 vaccines may be co-administered with other recommended vaccines, including seasonal influenza vaccines. However, few studies have evaluated the safety of co-administration of mRNA COVID-19 and seasonal influenza vaccines. OBJECTIVE: To describe reports to the Vaccine Adverse Event Reporting System (VAERS) after co-administration of mRNA COVID-19 and seasonal influenza vaccines. METHODS: We searched the VAERS database for reports of adverse events (AEs) following co-administration of mRNA COVID-19 and seasonal influenza vaccines and following a first booster dose mRNA COVID-19 vaccine alone, during July 1, 2021-June 30, 2022. We assessed the characteristics of these reports and described the most frequently reported MedDRA preferred terms (PTs). Clinicians reviewed available medical records for serious reports and reports of adverse events of special interest (AESI) and categorized the main diagnosis by system organ class. RESULTS: From July 1, 2021 through June 30, 2022, VAERS received 2,449 reports of adverse events following co-administration of mRNA COVID-19 and seasonal influenza vaccines. Median age of vaccinees was 48 years (IQR: 31, 66); 387 (15.8%) were classified as serious. Most reports (1,713; 69.3%) described co-administration of a first booster dose of an mRNA COVID-19 vaccine with seasonal influenza vaccine. The most common AEs among non-serious reports were injection site reactions (193; 14.5%), headache (181; 13.6%), and pain (171; 12.8%). The most common AEs among reports classified as serious were dyspnea (38; 14.9%), COVID-19 infection (32; 12.6%), and chest pain (27; 10.6%). DISCUSSION: This review of reports to VAERS following co-administration of mRNA COVID-19 and seasonal influenza vaccines did not reveal any unusual or unexpected patterns of AEs. Increased reporting of certain events (e.g., COVID-19 disease) was expected. CDC will continue to monitor the safety of co-administration of mRNA COVID-19 and seasonal influenza vaccines, including co-administration involving bivalent mRNA COVID-19 booster vaccines that have been recommended for people ages ≥ 6 months in the United States.

Safety Monitoring of Bivalent COVID-19 mRNA Vaccine Booster Doses Among Children Aged 5-11 Years - United States, October 12-January 1, 2023.

On October 12, 2022, the Food and Drug Administration (FDA) issued Emergency Use Authorizations (EUAs) for bivalent (mRNA encoding the spike protein from the SARS-CoV-2 ancestral strain and BA.4/BA.5 Omicron variants) formulations of Pfizer-BioNTech and Moderna mRNA COVID-19 vaccines for use as a single booster dose ≥2 months after completion of primary series or monovalent booster vaccination for children aged 5-11 years (Pfizer-BioNTech) and 6-17 years (Moderna); on December 8, 2022, FDA amended the EUAs to include children aged ≥6 months (1,2). The Advisory Committee on Immunization Practices (ACIP) recommends that all persons aged ≥6 months receive an age-appropriate bivalent mRNA booster dose (3). The safety of bivalent mRNA booster doses among persons aged ≥12 years has previously been described (4). To characterize the safety of bivalent mRNA booster doses among children aged 5-11 years after receipt of bivalent Pfizer-BioNTech and Moderna booster doses, CDC reviewed adverse events and health impacts reported to v-safe,* a voluntary, smartphone-based U.S. safety surveillance system established by CDC to monitor adverse events after COVID-19 vaccination, and to the Vaccine Adverse Event Reporting System (VAERS), a U.S. passive vaccine safety surveillance system co-managed by CDC and FDA† (5). During October 12-January 1, 2023, a total of 861,251 children aged 5-11 years received a bivalent Pfizer-BioNTech booster, and 92,108 children aged 6-11 years received a bivalent Moderna booster.§ Among 3,259 children aged 5-11 years registered in v-safe who received a bivalent booster dose, local (68.7%) and systemic reactions (49.5%) were commonly reported in the week after vaccination. Approximately 99.8% of reports to VAERS for children aged 5-11 years after bivalent booster vaccination were nonserious. There were no reports of myocarditis or death after bivalent booster vaccination. Eighty-four percent of VAERS reports were related to vaccination errors, 90.5% of which did not list an adverse health event. Local and systemic reactions reported after receipt of a bivalent booster dose are consistent with those reported after a monovalent booster dose; serious adverse events are rare. Vaccine providers should provide this information when counseling parents or guardians about bivalent booster vaccination. Preliminary safety findings from the first 11 weeks of bivalent booster vaccination among children aged 5-11 years are reassuring. Compared with the low risk of serious health effects after mRNA COVID-19 vaccination, the health effects of SARS-CoV-2 infection include death and serious long-term sequalae (6). ACIP recommends that all persons aged ≥6 months receive an age-appropriate bivalent mRNA booster dose ≥2 months after completion of a COVID-19 primary series or receipt of a monovalent booster dose.¶.

Safety Monitoring of Bivalent COVID-19 mRNA Vaccine Booster Doses Among Persons Aged ≥12 Years - United States, August 31-October 23, 2022.

On August 31, 2022, the Food and Drug Administration (FDA) authorized bivalent formulations of BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccines; these vaccines include mRNA encoding the spike protein from the original (ancestral) strain of SARS-CoV-2 (the virus that causes COVID-19) and from the B.1.1.529 (Omicron) variants BA.4 and BA.5 (BA.4/BA.5). These bivalent mRNA vaccines were authorized for use as a single booster dose ≥2 months after completion of primary series or monovalent booster vaccination; Pfizer-BioNTech bivalent booster was authorized for persons aged ≥12 years and Moderna for adults aged ≥18 years.*,† On September 1, 2022, the Advisory Committee on Immunization Practices (ACIP) recommended that all persons aged ≥12 years receive an age-appropriate bivalent mRNA booster dose.§ To characterize the safety of bivalent mRNA booster doses, CDC reviewed adverse events and health impacts reported after receipt of bivalent Pfizer-BioNTech and Moderna booster doses during August 31-October 23, 2022, to v-safe,¶ a voluntary smartphone-based U.S. safety surveillance system established by CDC to monitor adverse events after COVID-19 vaccination, and the Vaccine Adverse Event Reporting System (VAERS),** a U.S. passive vaccine safety surveillance system managed by CDC and FDA (1). During August 31-October 23, 2022, approximately 14.4 million persons aged ≥12 years received a bivalent Pfizer-BioNTech booster dose, and 8.2 million adults aged ≥18 years received a bivalent Moderna booster dose.†† Among the 211,959 registrants aged ≥12 years who reported receiving a bivalent booster dose to v-safe, injection site and systemic reactions were frequently reported in the week after vaccination (60.8% and 54.8%, respectively); fewer than 1% of v-safe registrants reported receiving medical care. VAERS received 5,542 reports of adverse events after bivalent booster vaccination among persons aged ≥12 years; 95.5% of reports were nonserious and 4.5% were serious events. Health care providers and patients can be reassured that adverse events reported after a bivalent booster dose are consistent with those reported after monovalent doses. Health impacts after COVID-19 vaccination are less frequent and less severe than those associated with COVID-19 illness (2).

Outcomes at least 90 days since onset of myocarditis after mRNA COVID-19 vaccination in adolescents and young adults in the USA: a follow-up surveillance study.

BACKGROUND: Data on medium-term outcomes in indivduals with myocarditis after mRNA COVID-19 vaccination are scarce. We aimed to assess clinical outcomes and quality of life at least 90 days since onset of myocarditis after mRNA COVID-19 vaccination in adolescents and young adults. METHODS: In this follow-up surveillance study, we conducted surveys in US individuals aged 12-29 years with myocarditis after mRNA COVID-19 vaccination, for whom a report had been filed to the Vaccine Adverse Event Reporting System between Jan 12 and Nov 5, 2021. A two-component survey was administered, one component to patients (or parents or guardians) and one component to health-care providers, to assess patient outcomes at least 90 days since myocarditis onset. Data collected were recovery status, cardiac testing, and functional status, and EuroQol health-related quality-of-life measures (dichotomised as no problems or any problems), and a weighted quality-of-life measure, ranging from 0 to 1 (full health). The EuroQol results were compared with published results in US populations (aged 18-24 years) from before and early on in the COVID-19 pandemic. FINDINGS: Between Aug 24, 2021, and Jan 12, 2022, we collected data for 519 (62%) of 836 eligible patients who were at least 90 days post-myocarditis onset: 126 patients via patient survey only, 162 patients via health-care provider survey only, and 231 patients via both surveys. Median patient age was 17 years (IQR 15-22); 457 (88%) patients were male and 61 (12%) were female. 320 (81%) of 393 patients with a health-care provider assessment were considered recovered from myocarditis by their health-care provider, although at the last health-care provider follow-up, 104 (26%) of 393 patients were prescribed daily medication related to myocarditis. Of 249 individuals who completed the quality-of-life portion of the patient survey, four (2%) reported problems with self-care, 13 (5%) with mobility, 49 (20%) with performing usual activities, 74 (30%) with pain, and 114 (46%) with depression. Mean weighted quality-of-life measure (0·91 [SD 0·13]) was similar to a pre-pandemic US population value (0·92 [0·13]) and significantly higher than an early pandemic US population value (0·75 [0·28]; p<0·0001). Most patients had improvements in cardiac diagnostic marker and testing data at follow-up, including normal or back-to-baseline troponin concentrations (181 [91%] of 200 patients with available data), echocardiograms (262 [94%] of 279 patients), electrocardiograms (240 [77%] of 311 patients), exercise stress testing (94 [90%] of 104 patients), and ambulatory rhythm monitoring (86 [90%] of 96 patients). An abnormality was noted among 81 (54%) of 151 patients with follow-up cardiac MRI; however, evidence of myocarditis suggested by the presence of both late gadolinium enhancement and oedema on cardiac MRI was uncommon (20 [13%] of 151 patients). At follow-up, most patients were cleared for all physical activity (268 [68%] of 393 patients). INTERPRETATION: After at least 90 days since onset of myocarditis after mRNA COVID-19 vaccination, most individuals in our cohort were considered recovered by health-care providers, and quality of life measures were comparable to those in pre-pandemic and early pandemic populations of a similar age. These findings might not be generalisable given the small sample size and further follow-up is needed for the subset of patients with atypical test results or not considered recovered. FUNDING: US Centers for Disease Control and Prevention.

Association between history of SARS-CoV-2 infection and severe systemic adverse events after mRNA COVID-19 vaccination among U.S. adults.

BACKGROUND: Risk of experiencing a systemic adverse event (AE) after mRNA coronavirus disease 2019 (COVID-19) vaccination may be greater among persons with a history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; data on serious events are limited. We assessed if adults reporting systemic AEs resulting in emergency department visits or hospitalizations during days 0-7 after mRNA COVID-19 vaccine dose 1 were more likely to have a history of prior SARS-CoV-2 infection compared with persons who reported no or non-severe systemic AEs. METHODS: We conducted a nested case-control study using v-safe surveillance data. Participants were ≥ 18 years and received dose 1 during December 14, 2020─May 9, 2021. Cases reported severe systemic AEs 0-7 days after vaccination. Three controls were frequency matched per case by age, vaccination date, and days since vaccination. Follow-up surveys collected SARS-CoV-2 histories. RESULTS: Follow-up survey response rates were 38.6 % (potential cases) and 56.8 % (potential controls). In multivariable analyses including 3,862 case-patients and 11,586 controls, the odds of experiencing a severe systemic AE were 2.4 (Moderna, mRNA-1273; 95 % confidence interval [CI]: 1.89, 3.09) and 1.5 (Pfizer-BioNTech, BNT162b2; 95 % CI: 1.17, 2.02) times higher among participants with pre-vaccination SARS-CoV-2 histories compared with those without. Medical attention of any kind for symptoms during days 0-7 following dose 2 was not common among case-patients or controls. CONCLUSIONS: History of SARS-CoV-2 infection was significantly associated with severe systemic AEs following dose 1 of mRNA COVID-19 vaccine; the effect varied by vaccine received. Most participants who experienced severe systemic AEs following dose 1 did not require medical attention of any kind for symptoms following dose 2. Vaccine providers can use these findings to counsel patients who had pre-vaccination SARS-CoV-2 infection histories, experienced severe systemic AEs following dose 1, and are considering not receiving additional mRNA COVID-19 vaccine doses.

Safety of Booster Doses of Coronavirus Disease 2019 (COVID-19) Vaccine in Pregnancy in the Vaccine Adverse Event Reporting System.

OBJECTIVE: To evaluate and summarize reports to the Vaccine Adverse Event Reporting System (VAERS), a national spontaneous reporting system, in pregnant people who received a booster dose of mRNA coronavirus disease 2019 (COVID-19) vaccine. METHODS: We searched VAERS for U.S. reports of adverse events in pregnant people who received a booster dose of an mRNA COVID-19 vaccine from September 22, 2021, to March 24, 2022. Clinicians reviewed reports and available medical records. RESULTS: The Vaccine Adverse Event Reporting System received 323 reports of adverse events in pregnant people who received a booster dose of COVID-19 vaccine; 178 (55.1%) after BNT162b2 from Pfizer-BioNTech and 145 (44.9%) after mRNA-1273 from Moderna. Seventy-two (22.3%) reports were coded as serious. One neonatal death was reported, but no maternal deaths occurred. Pregnancy-specific outcomes included 56 (17.3%) spontaneous abortions (before 20 weeks of gestation), eight (2.5%) episodes of vaginal bleeding, five (1.5%) stillbirths (at or after 20 weeks of gestation), four (1.2%) episodes of preeclampsia, and two (0.6%) preterm deliveries. Reporting rates for stillbirth and preterm delivery were below background rates. Ten instances of adverse events in neonates were reported, which included two reports of birth defects. Non-pregnancy-specific adverse events (n=207; 64.1%) were mostly systemic (eg, headache, fatigue) and local reactions and occurred in proportions comparable with those seen in pregnant people who received the primary COVID-19 vaccination series and reported to VAERS during the same period. CONCLUSION: Review of reports after a booster dose of mRNA COVID-19 vaccine in pregnant people in VAERS found their safety profile was comparable with that of published reports after primary COVID-19 vaccination in pregnant people.

Multisystem Inflammatory Syndrome in Adults After Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection and Coronavirus Disease 2019 (COVID-19) Vaccination.

BACKGROUND: Multisystem inflammatory syndrome in adults (MIS-A) was reported in association with the coronavirus disease 2019 (COVID-19) pandemic. MIS-A was included in the list of adverse events to be monitored as part of the emergency use authorizations issued for COVID-19 vaccines. METHODS: Reports of MIS-A patients received by the Centers for Disease Control and Prevention (CDC) after COVID-19 vaccines became available were assessed. Data collected on the patients included clinical and demographic characteristics and their vaccine status. The Vaccine Adverse Events Reporting System (VAERS) was also reviewed for possible cases of MIS-A. RESULTS: From 14 December 2020 to 30 April 2021, 20 patients who met the case definition for MIS-A were reported to CDC. Their median age was 35 years (range, 21-66 years), and 13 (65%) were male. Overall, 16 (80%) patients had a preceding COVID-19-like illness a median of 26 days (range 11-78 days) before MIS-A onset. All 20 patients had laboratory evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Seven MIS-A patients (35%) received COVID-19 vaccine a median of 10 days (range, 6-45 days) before MIS-A onset; 3 patients received a second dose of COVID-19 vaccine 4, 17, and 22 days before MIS-A onset. Patients with MIS-A predominantly had gastrointestinal and cardiac manifestations and hypotension or shock. CONCLUSIONS: Although 7 patients were reported to have received COVID-19 vaccine, all had evidence of prior SARS-CoV-2 infection. Given the widespread use of COVID-19 vaccines, the lack of reporting of MIS-A associated with vaccination alone, without evidence of underlying SARS-CoV-2 infection, is reassuring.

Safety Monitoring of Pfizer-BioNTech COVID-19 Vaccine Booster Doses Among Children Aged 5-11 Years - United States, May 17-July 31, 2022.

On May 17, 2022, the Food and Drug Administration (FDA) amended the Emergency Use Authorization (EUA) for BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine to authorize a homologous* booster dose for children aged 5-11 years ≥5 months after receipt of the second primary series dose† (1) based on findings from a clinical trial conducted among 401 children aged 5-11 years (2). To further characterize the safety of booster vaccination in this age group, CDC reviewed adverse events and health impact assessments after receipt of a Pfizer-BioNTech third dose reported to v-safe, a voluntary smartphone-based safety surveillance system for adverse events occurring after COVID-19 vaccination, and adverse events reported to the Vaccine Adverse Event Reporting System (VAERS), a passive vaccine safety surveillance system comanaged by CDC and FDA. During May 17-July 31, 2022, approximately 657,302 U.S. children aged 5-11 years received a third Pfizer-BioNTech dose (either a third primary series dose administered to immunocompromised children or a booster dose administered to immunocompetent children)§; 3,249 Pfizer-BioNTech third doses were reported to v-safe for children in this age group. Local and systemic reactions were reported to v-safe after a second dose and a third dose with similar frequency; some reactions (e.g., pain) were reported to be moderate or severe more frequently after a third dose. VAERS received 581 reports of adverse events after receipt of a Pfizer-BioNTech third dose by children aged 5-11 years; 578 (99.5%) reports were considered nonserious, and the most common events reported were vaccine administration errors. Three (0.5%) reports were considered serious; no reports of myocarditis or death were received. Local and systemic reactions were common among children after Pfizer-BioNTech third dose vaccination, but reports of serious adverse events were rare. Initial safety findings are consistent with those of the clinical trial (2).

Menstrual irregularities and vaginal bleeding after COVID-19 vaccination reported to v-safe active surveillance, USA in December, 2020-January, 2022: an observational cohort study.

BACKGROUND: Anecdotal reports of menstrual irregularities after receiving COVID-19 vaccines have been observed in post-authorisation and post-licensure monitoring. We aimed to identify and classify reports of menstrual irregularities and vaginal bleeding after COVID-19 vaccination submitted to a voluntary active surveillance system. METHODS: This observational cohort study included recipients of a COVID-19 vaccine who were aged 18 years and older and reported their health experiences to v-safe, a voluntary smartphone-based active surveillance system for monitoring COVID-19 vaccine safety in the USA, from Dec 14, 2020, to Jan 9, 2022. Responses to survey questions on reactions after vaccination were extracted, and a pre-trained natural language inference model was used to identify and classify free-text comments related to menstruation and vaginal bleeding in response to an open-ended prompt about any symptoms at intervals after vaccination. Related responses were further categorised into themes of timing, severity, perimenopausal and postmenopausal bleeding, resumption of menses, and other responses. We examined associations between symptom theme and respondent characteristics, including vaccine type and dose number received, solicited local and systemic reactions reported, and health care sought. FINDINGS: 63 815 respondents reported on menstrual irregularities or vaginal bleeding, which included 62 679 female respondents (1·0% of 5 975 363 female respondents aged ≥18 years). Common themes identified included timing of menstruation (70 981 [83·6%] responses) and severity of menstrual symptoms (56 890 [67·0%] responses). Other themes included menopausal bleeding (3439 [4·0%] responses) and resumption of menses (2378 [2·8%] responses). Respondents submitting reports related to menopausal bleeding were more likely to seek health care than were those submitting reports related to other menstruation and vaginal bleeding themes. INTERPRETATION: Reports of heterogeneous symptoms related to menstruation or vaginal bleeding after COVID-19 vaccination are being submitted to v-safe, although this study is unable to characterise the relationship of these symptoms to COVID-19 vaccination. Methods that leverage pretrained models to interpret and classify unsolicited signs and symptoms in free-text reports offer promise in the initial evaluation of unexpected adverse events potentially associated with use of newly authorised or licensed vaccines. FUNDING: Centers for Disease Control and Prevention.

Safety of COVID-19 Vaccination in United States Children Ages 5 to 11 Years.

BACKGROUND AND OBJECTIVES: Limited postauthorization safety data for the Pfizer-BioNTech coronavirus disease 2019 vaccination among children ages 5 to 11 years are available, particularly for the adverse event myocarditis, which has been detected in adolescents and young adults. We describe adverse events observed during the first 4 months of the United States coronavirus disease 2019 vaccination program in this age group. METHODS: We analyzed data from 3 United States safety monitoring systems: v-safe, a voluntary smartphone-based system that monitors reactions and health effects; the Vaccine Adverse Events Reporting System (VAERS), the national spontaneous reporting system comanaged by the Centers for Disease Control and Prevention and Food and Drug Administration; and the Vaccine Safety Datalink, an active surveillance system that monitors electronic health records for prespecified events, including myocarditis. RESULTS: Among 48 795 children ages 5 to 11 years enrolled in v-safe, most reported reactions were mild-to-moderate, most frequently reported the day after vaccination, and were more common after dose 2. VAERS received 7578 adverse event reports; 97% were nonserious. On review of 194 serious VAERS reports, 15 myocarditis cases were verified; 8 occurred in boys after dose 2 (reporting rate 2.2 per million doses). In the Vaccine Safety Datalink, no safety signals were detected in weekly sequential monitoring after administration of 726 820 doses. CONCLUSIONS: Safety findings for Pfizer-BioNTech vaccine from 3 United States monitoring systems in children ages 5 to 11 years show that most reported adverse events were mild and no safety signals were observed in active surveillance. VAERS reporting rates of myocarditis after dose 2 in this age group were substantially lower than those observed among adolescents ages 12 to 15 years.

Safety Monitoring of COVID-19 mRNA Vaccine Second Booster Doses Among Adults Aged ≥50 Years - United States, March 29, 2022-July 10, 2022.

The Advisory Committee on Immunization Practices (ACIP) recommends that all persons aged ≥5 years receive 1 booster dose of a COVID-19 vaccine after completion of their primary series.* On March 29, 2022, the Food and Drug Administration (FDA) authorized a second mRNA booster dose ≥4 months after receipt of a first booster dose for adults aged ≥50 years and persons aged ≥12 years with moderate to severe immunocompromise (1,2). To characterize the safety of a second mRNA booster dose among persons aged ≥50 years, CDC reviewed adverse events and health impact assessments reported to v-safe and the Vaccine Adverse Event Reporting System (VAERS) after receipt of a second mRNA booster dose during March 29-July 10, 2022. V-safe is a voluntary smartphone-based U.S. active surveillance system that monitors adverse events occurring after COVID-19 vaccination. VAERS is a U.S. passive surveillance system for monitoring adverse events after vaccination, managed by CDC and FDA (3). During March 29-July 10, 2022, approximately 16.8 million persons in the United States aged ≥50 years received a fourth dose.† Among 286,380 v-safe registrants aged ≥50 years who reported receiving a second booster of an mRNA vaccine, 86.9% received vaccines from the same manufacturer for all 4 doses (i.e., homologous vaccination). Among registrants who reported homologous vaccination, injection site and systemic reactions were less frequent after the second booster dose than after the first booster dose. VAERS received 8,515 reports of adverse events after second mRNA booster doses among adults aged ≥50 years, including 8,073 (94.8%) nonserious and 442 (5.1%) serious events. CDC recommends that health care providers and patients be advised that local and systemic reactions are expected after a second booster dose, and that serious adverse events are uncommon.

Reactogenicity of Simultaneous COVID-19 mRNA Booster and Influenza Vaccination in the US.

Importance: COVID-19 and seasonal influenza vaccines are essential in preventing respiratory infections and their potentially severe complications. Simultaneous administration of vaccines is efficient and may improve coverage with each vaccine. However, the safety of simultaneous administration of COVID-19 and influenza vaccines has not been well described. Objective: To evaluate adverse events and health impacts associated with simultaneously administered COVID-19 mRNA booster and seasonal influenza vaccines in the US population. Design, Setting, and Participants: In this retrospective cohort study, self-reported vaccine data were collected on days 0 to 7 after vaccination from September 22, 2021, through May 1, 2022, through v-safe, a voluntary smartphone-based monitoring system established by the Centers for Disease Control and Prevention. Participants were persons who voluntarily registered in v-safe following COVID-19 vaccination. Exposure: Receipt of simultaneously administered COVID-19 mRNA booster and seasonal influenza vaccines or COVID-19 mRNA booster alone. Main Outcomes and Measures: Local injection site and systemic reactions (eg, fatigue, headache, and myalgia) and health impacts reported by v-safe respondents in the week following COVID-19 mRNA booster vaccination. Adjusted odds ratios (aORs) were estimated for simultaneous administration compared with booster dose alone, controlling for sex, age, and week of vaccination. Results: Of a total of 981 099 persons aged 12 years or older registered with v-safe, simultaneous administration of COVID-19 mRNA booster and seasonal influenza vaccines was reported by 92 023 (9.4%) v-safe respondents; of these respondents, 54 926 (59.7%) were female, 36 234 (39.4%) were male, and sex was unknown for 863 (0.9%). In the week following vaccination, any systemic reactions were reported by 36 144 (58.9%) of 61 390 respondents who simultaneously received Pfizer-BioNTech booster and influenza vaccines and 21 027 (68.6%) of 30633 respondents who simultaneously received Moderna booster and influenza vaccines. Respondents who simultaneously received influenza and Pfizer-BioNTech booster vaccines (aOR, 1.08; 95% CI, 1.06-1.10) or influenza and Moderna booster vaccines (aOR, 1.11; 95% CI, 1.08-1.14) were slightly more likely to report any systemic reaction in the week following simultaneous vaccination than respondents who received only a COVID-19 mRNA vaccine booster. Conclusions and Relevance: In this study, compared with administration of COVID-19 mRNA booster vaccines alone, simultaneous administration of COVID-19 mRNA booster and seasonal influenza vaccines was associated with significant increases in reports of systemic reactions during days 0 to 7 following vaccination. These results may help better characterize the outcomes associated with simultaneously administered COVID-19 booster and influenza vaccines in the US population.

Safety Monitoring of COVID-19 mRNA Vaccine First Booster Doses Among Persons Aged ≥12 Years with Presumed Immunocompromise Status - United States, January 12, 2022-March 28, 2022.

Persons with moderate to severe immunocompromising conditions are at risk for severe COVID-19, and their immune response to COVID-19 vaccination might not be as robust as the response in persons who are not immunocompromised* (1). The Advisory Committee on Immunization Practices (ACIP) recommends that immunocompromised persons aged ≥12 years complete a 3-dose primary mRNA COVID-19 vaccination series followed by a first booster dose (dose 4) ≥3 months after dose 3 and a second booster dose (dose 5) ≥4 months after dose 4.† To characterize the safety of first booster doses among immunocompromised persons aged ≥12 years during January 12, 2022-March 28, 2022, CDC reviewed adverse events and health impact assessments reported to v-safe and the Vaccine Adverse Event Reporting System (VAERS) during the week after receipt of an mRNA COVID-19 first booster dose. V-safe is a voluntary smartphone-based safety surveillance system for adverse events after COVID-19 vaccination. VAERS is a passive surveillance system for all vaccine-associated adverse events co-managed by CDC and the Food and Drug Administration (FDA). A fourth mRNA dose reported to v-safe or VAERS during January 12, 2022-March 28, 2022, was presumed to be an mRNA COVID-19 vaccine booster dose administered to an immunocompromised person because no other population was authorized to receive a fourth dose during that period (2,3). In the United States, during January 12, 2022-March 28, 2022, approximately 518,113 persons aged ≥12 years received a fourth dose. Among 4,015 v-safe registrants who received a fourth dose, local and systemic reactions were less frequently reported than were those following dose 3 of their primary series. VAERS received 145 reports after fourth doses; 128 (88.3%) were nonserious and 17 (11.7%) were serious. Health care providers, immunocompromised persons, and parents of immunocompromised children should be aware that local and systemic reactions are expected after a first booster mRNA COVID-19 vaccine dose, serious adverse events are rare, and safety findings were consistent with those previously described among nonimmunocompromised persons (4,5).