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.

Reactions following Pfizer-BioNTech COVID-19 mRNA vaccination and related healthcare encounters among 7,077 children aged 5-11 years within an integrated healthcare system.

BACKGROUND: Studies combining data from digital surveys and electronic health records (EHR) can be used to conduct comprehensive assessments on COVID-19 vaccine safety. METHODS: We conducted an observational study using data from a digital survey and EHR of children aged 5-11 years vaccinated with Pfizer-BioNTech COVID-19 mRNA vaccine across Kaiser Permanente Southern California during November 4, 2021-February 28, 2022. Parents/guardians who enrolled their children were sent a 14-day survey on reactions. Survey results were combined with EHR, and medical encounters were described for children whose parents or guardians indicated seeking medical care for vaccine-related symptoms. This study describes self-reported reactions (local and systemic) and additional symptoms (chest pain, tachycardia, and pre-syncope). RESULTS: The study recruited 7,077 participants aged 5-11 years who received the Pfizer-BioNTech COVID-19 mRNA vaccine. Of 6,247 participants with survey responses after dose 1, 2,176 (35 %) reported at least one systemic reaction, and 1,076 (32 %) of 3,401 respondents following dose 2 reported at least one systemic reaction. Local reactions were reported less frequently following dose 2 (1,113, 33 %) than dose 1 (3,140, 50 %). The most frequently reported reactions after dose 1 were pain at the injection site (48 %), fatigue (20 %), headache (12 %), myalgia (9 %) and fever (5 %). The most frequently reported symptoms after dose 2 were also pain at the injection site (30 %), fatigue (19 %), headache (13 %), myalgia (10 %) and fever (9 %). Post-vaccination reactions occurred most frequently-one day following vaccination. Chest pain or tachycardia were reported infrequently (1 %). EHR demonstrated that parents rarely sought care for post-vaccination symptoms, and among those seeking care, the most common symptoms documented in EHR were fever and nausea, comprising<0.5 % of children. No encounters were related to myocarditis. CONCLUSION: While post-vaccination reactions to the Pfizer-BioNTech COVID-19 mRNA vaccine were common in children aged 5-11 years, our data showed that in most cases they were transient and did not require medical care.

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.

Dashboard development for near real-time visualization of COVID-19 vaccine safety surveillance data in the vaccine safety datalink.

The Vaccine Safety Datalink (VSD) conducts active surveillance and vaccine safety research studies. Since the start of the U.S. COVID-19 vaccination program, the VSD has conducted near real-time safety surveillance of COVID-19 vaccines using Rapid Cycle Analysis. VSD investigators developed an internal dashboard to facilitate visualization and rapid reviews of large weekly automated vaccine safety surveillance data. Dashboard development and maintenance was informed by vaccine surveillance data users and vaccine safety partners. Key metrics include population demographics, vaccine uptake, pre-specified safety outcomes, sequential analyses results, and descriptive data on potential vaccine safety signals. Dashboard visualizations are used to provide situational awareness on dynamic vaccination coverage and the status of multiple safety analyses conducted among the VSD population. This report describes the development and implementation of the internal VSD COVID-19 Vaccine Dashboard, including metrics used to develop the dashboard, which may have application across various other public health settings.

Safety of mRNA vaccines administered during the initial 6 months of the US COVID-19 vaccination programme: an observational study of reports to the Vaccine Adverse Event Reporting System and v-safe.

BACKGROUND: In December, 2020, two mRNA-based COVID-19 vaccines were authorised for use in the USA. We aimed to describe US surveillance data collected through the Vaccine Adverse Event Reporting System (VAERS), a passive system, and v-safe, a new active system, during the first 6 months of the US COVID-19 vaccination programme. METHODS: In this observational study, we analysed data reported to VAERS and v-safe during Dec 14, 2020, to June 14, 2021. VAERS reports were categorised as non-serious, serious, or death. Reporting rates were calculated using numbers of COVID-19 doses administered as the denominator. We analysed v-safe survey reports from days 0-7 after vaccination for reactogenicity, severity (mild, moderate, or severe), and health impacts (ie, unable to perform normal daily activities, unable to work, or received care from a medical professional). FINDINGS: During the study period, 298 792 852 doses of mRNA vaccines were administered in the USA. VAERS processed 340 522 reports: 313 499 (92·1%) were non-serious, 22 527 (6·6%) were serious (non-death), and 4496 (1·3%) were deaths. Over half of 7 914 583 v-safe participants self-reported local and systemic reactogenicity, more frequently after dose two (4 068 447 [71·7%] of 5 674 420 participants for local reactogenicity and 4 018 920 [70·8%] for systemic) than after dose one (4 644 989 [68·6%] of 6 775 515 participants for local reactogenicity and 3 573 429 [52·7%] for systemic). Injection-site pain (4 488 402 [66·2%] of 6 775 515 participants after dose one and 3 890 848 [68·6%] of 5 674 420 participants after dose two), fatigue (2 295 205 [33·9%] participants after dose one and 3 158 299 participants [55·7%] after dose two), and headache (1 831 471 [27·0%] participants after dose one and 2 623 721 [46·2%] participants after dose two) were commonly reported during days 0-7 following vaccination. Reactogenicity was reported most frequently the day after vaccination; most reactions were mild. More reports of being unable to work, do normal activities, or of seeking medical care occurred after dose two (1 821 421 [32·1%]) than after dose one (808 963 [11·9%]); less than 1% of participants reported seeking medical care after vaccination (56 647 [0·8%] after dose one and 53 077 [0·9%] after dose two). INTERPRETATION: Safety data from more than 298 million doses of mRNA COVID-19 vaccine administered in the first 6 months of the US vaccination programme show that most reported adverse events were mild and short in duration. FUNDING: US Centers for Disease Control and Prevention.

Receipt of COVID-19 Vaccine During Pregnancy and Preterm or Small-for-Gestational-Age at Birth - Eight Integrated Health Care Organizations, United States, December 15, 2020-July 22, 2021.

COVID-19 vaccines are recommended during pregnancy to prevent severe maternal morbidity and adverse birth outcomes; however, vaccination coverage among pregnant women has been low (1). Concerns among pregnant women regarding vaccine safety are a persistent barrier to vaccine acceptance during pregnancy. Previous studies of maternal COVID-19 vaccination and birth outcomes have been limited by small sample size (2) or lack of an unvaccinated comparison group (3). In this retrospective cohort study of live births from eight Vaccine Safety Datalink (VSD) health care organizations, risks for preterm birth (<37 weeks' gestation) and small-for-gestational-age (SGA) at birth (birthweight <10th percentile for gestational age) after COVID-19 vaccination (receipt of ≥1 COVID-19 vaccine doses) during pregnancy were evaluated. Risks for preterm and SGA at birth among vaccinated and unvaccinated pregnant women were compared, accounting for time-dependent vaccine exposures and propensity to be vaccinated. Single-gestation pregnancies with estimated start or last menstrual period during May 17-October 24, 2020, were eligible for inclusion. Among 46,079 pregnant women with live births and gestational age available, 10,064 (21.8%) received ≥1 COVID-19 vaccine doses during pregnancy and during December 15, 2020-July 22, 2021; nearly all (9,892; 98.3%) were vaccinated during the second or third trimester. COVID-19 vaccination during pregnancy was not associated with preterm birth (adjusted hazard ratio [aHR] = 0.91; 95% CI = 0.82-1.01). Among 40,627 live births with birthweight available, COVID-19 vaccination in pregnancy was not associated with SGA at birth (aHR = 0.95; 95% CI = 0.87-1.03). Results consistently showed no increased risk when stratified by mRNA COVID-19 vaccine dose, or by second or third trimester vaccination, compared with risk among unvaccinated pregnant women. Because of the small number of first-trimester exposures, aHRs for first-trimester vaccination could not be calculated. These data add to the evidence supporting the safety of COVID-19 vaccination during pregnancy. To reduce the risk for severe COVID-19-associated illness, CDC recommends COVID-19 vaccination for women who are pregnant, recently pregnant (including those who are lactating), who are trying to become pregnant now, or who might become pregnant in the future (4).

U.S. Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines.

The Coronavirus Disease 2019 (COVID-19) pandemic has had a devastating impact on global health, and has resulted in an unprecedented, international collaborative effort to develop vaccines to control the outbreak, protect human lives, and avoid further social and economic disruption. Mass vaccination campaigns are underway in multiple countries and are expected worldwide once more vaccine becomes available. Some early candidate vaccines use novel platforms, such as mRNA encapsulated in lipid nanoparticles, and relatively new platforms, such as replication-deficient viral vectors. While these new vaccine platforms hold promise, limited safety data in humans are available. Serious health outcomes linked to vaccinations are rare, and some outcomes may occur incidentally in the vaccinated population. Knowledge of background incidence rates of these medical conditions is a critical component of vaccine safety monitoring to aid in the assessment of adverse events temporally associated with vaccination and to put these events into context with what would be expected due to chance alone. A list of 22 potential adverse events of special interest (AESI), including neurologic, autoimmune, and cardiovascular disorders, was compiled by subject matter experts at the U.S. Food and Drug Administration and the Centers for Disease Control and Prevention. The most recently available U.S. background rates for these medical conditions, overall and by age, sex, and race/ethnicity (when available), were sourced from reported statistics (data published by medical panels/ associations or federal government reports), and literature reviews in PubMed. This review provides estimates of background incidence rates for medical conditions that may be monitored or studied as AESI during safety surveillance and research for COVID-19 vaccines and other new vaccines.