The U.S. COVID-19 vaccination program, which commenced in December 2020, has been instrumental in preventing morbidity and mortality from COVID-19 disease. Safety monitoring has been an essential component of the program. The federal government undertook a comprehensive and coordinated approach to implement complementary safety monitoring systems and to communicate findings in a timely and transparent way to healthcare providers, policymakers, and the public. Monitoring involved both well-established and newly developed systems that relied on both spontaneous (passive) and active surveillance methods. Clinical consultation for individual cases of adverse events following vaccination was performed, and monitoring of special populations, such as pregnant persons, was conducted. This report describes the U.S. government\'s COVID-19 vaccine safety monitoring systems and programs used by the Centers for Disease Control and Prevention, the U.S. Food and Drug Administration, the Department of Defense, the Department of Veterans Affairs, and the Indian Health Service. Using the adverse event of myocarditis following mRNA COVID-19 vaccination as a model, we demonstrate how the multiple, complementary monitoring systems worked to rapidly detect, assess, and verify a vaccine safety signal. In addition, longer-term follow-up was conducted to evaluate the recovery status of myocarditis cases following vaccination. Finally, the process for timely and transparent communication and dissemination of COVID-19 vaccine safety data is described, highlighting the responsiveness and robustness of the U.S. vaccine safety monitoring infrastructure during the national COVID-19 vaccination program.

This scoping review examines the role of digital solutions in active, participant-centered surveillance of adverse events following initial release of COVID-19 vaccines. The goals of this paper were to examine the existing literature surrounding digital solutions and technology used for active, participant centered, AEFI surveillance of novel COVID-19 vaccines approved by WHO. This paper also aimed to identify gaps in literature surrounding digital, active, participant centered AEFI surveillance systems and to identify and describe the core components of active, participant centered, digital surveillance systems being used for post-market AEFI surveillance of WHO approved COVID-19 vaccines, with a focus on the digital solutions and technology being used, the type of AEFI detected, and the populations under surveillance. The findings highlight the need for customized surveillance systems based on local contexts and the lessons learned to improve future vaccine monitoring and pandemic preparedness.

BACKGROUND: The Global COVID Vaccine Safety (GCoVS) Project, established in 2021 under the multinational Global Vaccine Data Network™ (GVDN®), facilitates comprehensive assessment of vaccine safety. This study aimed to evaluate the risk of adverse events of special interest (AESI) following COVID-19 vaccination from 10 sites across eight countries.
METHODS: Using a common protocol, this observational cohort study compared observed with expected rates of 13 selected AESI across neurological, haematological, and cardiac outcomes. Expected rates were obtained by participating sites using pre-COVID-19 vaccination healthcare data stratified by age and sex. Observed rates were reported from the same healthcare datasets since COVID-19 vaccination program rollout. AESI occurring up to 42 days following vaccination with mRNA (BNT162b2 and mRNA-1273) and adenovirus-vector (ChAdOx1) vaccines were included in the primary analysis. Risks were assessed using observed versus expected (OE) ratios with 95 % confidence intervals. Prioritised potential safety signals were those with lower bound of the 95 % confidence interval (LBCI) greater than 1.5.
RESULTS: Participants included 99,068,901 vaccinated individuals. In total, 183,559,462 doses of BNT162b2, 36,178,442 doses of mRNA-1273, and 23,093,399 doses of ChAdOx1 were administered across participating sites in the study period. Risk periods following homologous vaccination schedules contributed 23,168,335 person-years of follow-up. OE ratios with LBCI > 1.5 were observed for Guillain-Barré syndrome (2.49, 95 % CI: 2.15, 2.87) and cerebral venous sinus thrombosis (3.23, 95 % CI: 2.51, 4.09) following the first dose of ChAdOx1 vaccine. Acute disseminated encephalomyelitis showed an OE ratio of 3.78 (95 % CI: 1.52, 7.78) following the first dose of mRNA-1273 vaccine. The OE ratios for myocarditis and pericarditis following BNT162b2, mRNA-1273, and ChAdOx1 were significantly increased with LBCIs > 1.5.
CONCLUSIONS: This multi-country analysis confirmed pre-established safety signals for myocarditis, pericarditis, Guillain-Barré syndrome, and cerebral venous sinus thrombosis. Other potential safety signals that require further investigation were identified.

BACKGROUND: Myocarditis and myopericarditis are well described adverse events of special interest (AESI) following COVID-19 vaccinations. Although reports are reassuring regarding initial clinical outcomes, information about longer term outcomes remains limited. We aimed to further this knowledge and report outcomes to 6 months post diagnosis from a single population cohort.
METHODS: Reports of myocarditis following COVID-19 vaccination were followed up by SAEFVIC (Surveillance of Adverse Events Following Vaccination in the Community), the state-wide vaccine safety service for Victoria, Australia. Confirmed myocarditis cases (Brighton Collaboration Criteria levels 1-3) were followed up via surveys at 1, 3 and 6 months post symptom onset. Responses received between 22 February 2021 and 30 September 2022 were analysed.
RESULTS: 87.5 % (N = 182) of eligible participants completed at least 1 survey report. 377 reports were analysed. 76.9 % of completed reports were from male patients. The median age of patients was 21 years [IQR: 16 to 32]. 54.8 % (n = 74) of survey reports at 6 months, reported ongoing symptoms. At all follow-up time points, females were significantly more likely to have ongoing symptoms. At 6 months, 51.9 % of male respondents reported symptom resolution compared to 22.6 % of female patients (p = 0.002). Females were also more likely to continue medication and have ongoing exercise restrictions. However, males were significantly more likely to have higher initial peak troponin results and abnormal initial cardiac imaging investigations.
CONCLUSIONS: There appears to be a significant proportion of patients who experience ongoing symptoms to 6 months post onset amongst patients that experience these AESI. Male patients were more likely to report earlier and more complete symptom recovery, despite significantly higher average initial peak troponin. This difference in phenotypic presentation in females compared to males warrants further investigation and there is a need for longer term follow up data.

BACKGROUND: Identifying and monitoring adverse events following vaccination contributed to the safety and effectiveness of COVID-19 mass vaccination campaigns. In March 2021, international reports emerged of an adverse event following vaccination with adenovirus vector COVID-19 vaccines (ChAdOx1-S [recombinant] and Ad26.COV2.S) of thrombosis with low platelet counts, referred to as thrombosis with thrombocytopenia syndrome (TTS). We described TTS reports in Canada following adenovirus vector COVID-19 vaccines and investigated whether the observed number of events were higher than expected.
METHODS: Reports of TTS following receipt of ChAdOx1-S [recombinant] or Ad26.COV2.S meeting the Canadian case definition for TTS and diagnostic certainty levels 1-3 of the Brighton Collaboration case definition, submitted to the Canadian Adverse Events Following Immunization Surveillance System and Canada Vigilance Database between February 26, 2021 and October 31, 2022 were included. Demographics and characteristics of the TTS reports are described along with an analysis comparing the observed number of reports to the expected number.
RESULTS: As of October 31, 2022, 56 reports of TTS following administration of ChAdOx1-S [recombinant] and no reports following Ad26.COV2.S vaccines were reported in Canada, of which 37 had functionally positive anti-PF4 antibodies. The median age was 56 years; males accounted for 54 % of reports. Five deaths were reported. The observed number of reports exceeded the expected for all ages and sexes combined, as well as for males aged 30-49 and 60-69 years, and females aged 40-59 years.
CONCLUSIONS: Based on international surveillance data, Canada evaluated a statistical signal of TTS following adenovirus vector vaccines. The investigation of this signal demonstrated how post-market vaccine safety surveillance systems were successful in investigating rare adverse events during the rollout of COVID-19 vaccines in Canada. As adenovirus vector vaccines continue to be administered, characterization of the association between the vaccine and TTS informs immunization programs and policies.

The Global COVID Vaccine Safety (GCoVS) project was established in 2021 under the multinational Global Vaccine Data Network (GVDN) consortium to facilitate the rapid assessment of the safety of newly introduced vaccines. This study analyzed data from GVDN member sites on the background incidence rates of conditions designated as adverse events of special interest (AESI) for COVID-19 vaccine safety monitoring.
Eleven GVDN global sites obtained data from national or regional healthcare databases using standardized methods. Incident events of 13 pre-defined AESI were included for a pre-pandemic period (2015-19) and the first pandemic year (2020). Background incidence rates (IR) and 95% confidence intervals (CI) were calculated for inpatient and emergency department encounters, stratified by age and sex, and compared between pre-pandemic and pandemic periods using incidence rate ratios.
An estimated 197 million people contributed 1,189,652,926 person-years of follow-up time. Among inpatients in the pre-pandemic period (2015-19), generalized seizures were the most common neurological AESI (IR ranged from 22.15 [95% CI 19.01-25.65] to 278.82 [278.20-279.44] per 100,000 person-years); acute disseminated encephalomyelitis was the least common (<0.5 per 100,000 person-years at most sites). Pulmonary embolism was the most common thrombotic event (IR 45.34 [95% CI 44.85-45.84] to 93.77 [95% CI 93.46-94.08] per 100,000 person-years). The IR of myocarditis ranged from 1.60 [(95% CI 1.45-1.76) to 7.76 (95% CI 7.46-8.08) per 100,000 person-years. The IR of several AESI varied by site, healthcare setting, age and sex. The IR of some AESI were notably different in 2020 compared to 2015-19.
Background incidence of AESIs exhibited some variability across study sites and between pre-pandemic and pandemic periods. These findings will contribute to global vaccine safety surveillance and research.

UNASSIGNED: Vaccination is a safe and effective way to prevent disease and save lives, but it may also produce some undesirable adverse events (AEs)which may affect healthy individuals. Therefore, the monitoring of AE following immunization (AEFIs) is necessary. The objective of this study was to assess the AEs following COVID-19 vaccinations in a tertiary care hospital.
UNASSIGNED: The study was conducted as active vaccine safety surveillance for a period of 6 months among the COVID-19 vaccine beneficiaries of the study site. Active surveillance was conducted via initiating two telephone contacts. The first surveillance was conducted in 8 days and the second surveillance after 28 days of post-vaccination. All identified AEs following immunizations (AEFIs) were reported and analysed by the AEFI investigation team at the study site. The causality assessment of each identified AEFI was performed using the World Health Organization\'s causality assessment algorithm.
UNASSIGNED: A total of 2927 enrolled study population completed the study with a response rate of 80.85%. The study identified 902 AEFIs from 614 study populations with an incidence rate of 20.97%. Of which 794 and 79 AEFIs were associated with COVISHIELD™ and COVAXIN®, respectively. The majority of the events were reported among the age group of 18-29 years. Overall, only three events were serious and no deaths were reported among the study population. A total of 75.59% of events had a consistent causal association with vaccination and were categorized as vaccine product-related reactions. The study identified various factors such as gender (p = 0.019), age (p < 0.05), co-morbid status (p = 0.032) and dose number (p = 0.001) as potential predictors for development of AEFI.
UNASSIGNED: The study identified only 0.33% of events as serious, and 99.67% of the study population recovered from the AEFIs, which reveals that COVISHIELD™ and COVAXIN® have a generally favourable safety profile. However, close monitoring is required to identify the potential signals, as the safety data from the clinical trials are limited.

BACKGROUND: Regarding the paucity of evidence on the side effects of the booster dose of Oxford AstraZeneca vaccine in vaccinated people with Sinopharm or Sputnik V, we aimed to set up a cohort event monitoring (CEM) study to capture adverse events occurring in individuals who will receive the booster doses of AstraZeneca (either the first or second booster dose) following being vaccinated with Sinopharm or sputnik V vaccines in Iran.
METHODS: The present study is an active COVID-19 vaccine safety surveillance through an observational prospective cohort study that will be conducted in vaccination centers in Iran. The study will be conducted in twelve provinces of Iran. Study sites are vaccination centers where the AstraZeneca vaccine is administered to the cohort population. The study population includes all individuals who have received two doses of Sinopharm or Sputnik V vaccines and either the first or second booster dose of AstraZeneca according to the national guidelines for immunization in Iran in 2023. We are planning to include 30,000 eligible people in this study. Each individual will be followed up for 13 weeks after either the first or second booster dose of the AstraZeneca vaccine. Furthermore, convenience sampling is used to include participants in the present study. Participation in the study will be strictly voluntary.
CONCLUSIONS: With the planned study we will provide a valid epidemiological evidence to improve the understanding of the safety of the booster dose of the AstraZeneca and to better evaluate the effectiveness of public health interventions. This could help policy makers in managing the COVID-19 pandemic according to scientific evidence.

The U.S. Food and Drug Administration (FDA) Biologics Effectiveness and Safety (BEST) Initiative conducts active surveillance of adverse events of special interest (AESI) after COVID-19 vaccination. Historical incidence rates (IRs) of AESI are comparators to evaluate safety.
We estimated IRs of 17 AESI in six administrative claims databases from January 1, 2019, to December 11, 2020: Medicare claims for adults ≥ 65 years and commercial claims (Blue Health Intelligence®, CVS Health, HealthCore Integrated Research Database, IBM® MarketScan® Commercial Database, Optum pre-adjudicated claims) for adults < 65 years. IRs were estimated by sex, age, race/ethnicity (Medicare), and nursing home residency (Medicare) in 2019 and for specific periods in 2020.
The study included >100 million enrollees annually. In 2019, rates of most AESI increased with age. However, compared with commercially insured adults, Medicare enrollees had lower IRs of anaphylaxis (11 vs 12-19 per 100,000 person-years), appendicitis (80 vs 117-155), and narcolepsy (38 vs 41-53). Rates were higher in males than females for most AESI across databases and varied by race/ethnicity and nursing home status (Medicare). Acute myocardial infarction (Medicare) and anaphylaxis (all databases) IRs varied by season. IRs of most AESI were lower during March-May 2020 compared with March-May 2019 but returned to pre-pandemic levels after May 2020. However, rates of Bell\'s palsy, Guillain-Barré syndrome, narcolepsy, and hemorrhagic/non-hemorrhagic stroke remained lower in multiple databases after May 2020, whereas some AESI (e.g., disseminated intravascular coagulation) exhibited higher rates after May 2020 compared with 2019.
AESI background rates varied by database and demographics and fluctuated in March-December 2020, but most returned to pre-pandemic levels after May 2020. It is critical to standardize demographics and consider seasonal and other trends when comparing historical rates with post-vaccination AESI rates in the same database to evaluate COVID-19 vaccine safety.

Post-licensure adverse events following immunization (AEFI) surveillance is conducted to monitor vaccine safety, such as identifying batch/brand issues and rare reactions, which consequently improves community confidence. The integration of technology has been proposed to improve AEFI surveillance, however, there is an absence of description regarding which digital solutions are successfully being used and their unique characteristics.
The objectives of this scoping review were to 1) map the research landscape on digital systems used for active, participant-centred, AEFI surveillance and 2) describe their core components.
We conducted a scoping review informed by the PRISMA Extension for Scoping Reviews (PRSIMA-ScR) guideline. OVID-Medline, Embase Classic + Embase, and Medrxiv were searched by a medical librarian from January 1, 2000 to January 28th, 2021. Two independent reviewers determined which studies met inclusion based on pre-specified eligibility criteria. Data extraction was conducted using pre-made tables with specific variables by one investigator and verified by a second.
Twenty-seven publications met inclusion, the majority of which came from Australia (n = 15) and Canada (n = 6). The most studied active, participant-centred, digital AEFI surveillance systems were SmartVax (n = 8) (Australia), Vaxtracker (n = 7) (Australia), and Canadian National Vaccine Safety (CANVAS) Network (Canada) (n = 6). The two most common methods of communicating with vaccinees reported were short-message-service (SMS) (n = 15) and e-mail (n = 14), with online questionnaires being the primary method of data collection (n = 20).
Active, participant-centred, digital AEFI surveillance is an area actively being researched as depicted by the literature landscape mapped by this scoping reviewWe hypothesize that the AEFI surveillance approach herein described could become a primary method of collecting self-reported subjective symptoms and reactogenicity from vaccinees, complementing existing systems. Future evaluation of identified digital solutions is necessary to bring about improvements to current vaccine surveillance systems to meet contemporary and future public health needs.