The potential adverse effects of coronavirus disease 2019 (COVID-19) vaccinations raise public concerns. Data from Taiwan\'s Vaccine Injury Compensation Program (VICP) can provide valuable insights. This study analyzed the preliminary application data for COVID-19 vaccine compensation in Taiwan\'s VICP, focusing on applicants receiving vaccines between March 2021 and June 2022. Among the 2941 adverse events, 113 cases (3.8%) were deemed causally associated with vaccination, 313 (10.6%) were indeterminate, and 2515 (85.5%) had no causal association. Nearly half (47.6%) of the applicants were over 60 years old, and 76.6% had a history of pre-existing chronic diseases. Among the 426 vaccine-associated or indeterminate cases, the most common causes were hematological diseases and thrombosis. There were 920 mortality cases reported, and 97.4% were unassociated with vaccination. Only five deaths were judged to be associated with the COVID-19 vaccination, all involving the adenovirus vector vaccine and thrombosis with thrombocytopenia syndrome. In conclusion, most compensation applications were not causally linked to vaccination. Compared to other countries, the number of applications in Taiwan\'s VICP is relatively high. These findings may indicate a need to adjust the application requirements for compensation in Taiwan\'s program.

There is evidence suggesting that COVID-19 vaccination may be associated with small, transitory effects on uterine bleeding, possibly including menstrual timing, flow, and duration, in some individuals. However, changes in health care seeking, diagnosis, and workup for abnormal uterine bleeding in the COVID-19 vaccine era are less clear.
This study aimed to assess the impact of COVID-19 vaccination on incident abnormal uterine bleeding diagnosis and diagnostic evaluation in a large integrated health system.
Using segmented regression, we assessed whether the availability of COVID-19 vaccines was associated with changes in monthly, population-based rates of incident abnormal uterine bleeding diagnoses relative to the prepandemic period in health system members aged 16 to 44 years who were not menopausal. We also compared clinical and demographic characteristics of patients diagnosed with incident abnormal uterine bleeding between December 2020 and October 13, 2021 by vaccination status (never vaccinated, vaccinated in the 60 days before diagnosis, vaccinated >60 days before diagnosis). Furthermore, we conducted detailed chart review of patients diagnosed with abnormal uterine bleeding within 1 to 60 days of COVID-19 vaccination in the same time period.
In monthly populations ranging from 79,000 to 85,000 female health system members, incidence of abnormal uterine bleeding diagnosis per 100,000 person-days ranged from 8.97 to 19.19. There was no significant change in the level or trend in the incidence of abnormal uterine bleeding diagnoses between the prepandemic (January 2019-January 2020) and post-COVID-19 vaccine (December 2020-December 2021) periods. A comparison of clinical characteristics of 2717 abnormal uterine bleeding cases by vaccination status suggested that abnormal bleeding among recently vaccinated patients was similar or less severe than abnormal bleeding among patients who had never been vaccinated or those vaccinated >60 days before. There were also significant differences in age and race of patients with incident abnormal uterine bleeding diagnoses by vaccination status (Ps<.02). Never-vaccinated patients were the youngest and those vaccinated >60 days before were the oldest. The proportion of patients who were Black/African American was highest among never-vaccinated patients, and the proportion of Asian patients was higher among vaccinated patients. Chart review of 114 confirmed postvaccination abnormal uterine bleeding cases diagnosed from December 2020 through October 13, 2021 found that the most common symptoms reported were changes in timing, duration, and volume of bleeding. Approximately one-third of cases received no diagnostic workup; 57% had no etiology for the bleeding documented in the electronic health record. In 12% of cases, the patient mentioned or asked about a possible link between their bleeding and their recent COVID-19 vaccine.
The availability of COVID-19 vaccination was not associated with a change in incidence of medically attended abnormal uterine bleeding in our population of over 79,000 female patients of reproductive age. In addition, among 2717 patients with abnormal uterine bleeding diagnoses in the period following COVID-19 vaccine availability, receipt of the vaccine was not associated with greater bleeding severity.

Vaccine Adverse Events ReportingSystem (VAERS) is a promising resource of tracking adverse events following immunization. Medical Dictionary for Regulatory Activities (MedDRA) terminology used for coding adverse events in VAERS reports has several limitations. We focus on developing an automated system for semantic extraction of adverse events following vaccination and their temporal relationships for a better understanding of VAERS data and its integration into other applications. The aim of the present studyis to summarize the lessons learned during the initial phase of this project in annotating adverse events following influenza vaccination and related to Guillain-Barré syndrome (GBS). We emphasize on identifying the limitations of VAERS and MedDRA.
We collected 282 VAERS reports documented between 1990 and 2016 and shortlisted those with at least 1,100 characters in the report. We used a subset of 50 reports for the preliminary investigation and annotated all adverse events following influenza vaccination by mapping to representative MedDRA terms. Associated time expressions were annotated when available. We used 16 System Organ Class (SOC) level MedDRA terms to map GBS related adverse events and expanded some SOC terms to Lowest Level Terms (LLT) for granular representation. We annotated three broad categories of events such as problems, clinical investigations, and treatments/procedures. The inter-annotator agreement of events achieved was 86%. Incomplete reports, typographical errors, lack of clarity and coherence, repeated texts, unavailability of associated temporal information, difficulty to interpret due to incorrect grammar, use of generalized terms to describe adverse events / symptoms, uncommon abbreviations, difficulty annotating multiple events with a conjunction / common phrase, irrelevant historical events and coexisting events were some of the challenges encountered. Some of the limitations we noted are in agreement with previous reports.
We reported the challenges encountered and lessons learned during annotation of adverse events in VAERS reports following influenza vaccination and related to GBS. Though the challenges may be due to the inevitable limitations of public reporting systems and widely reported limitations of MedDRA, we emphasize the need to understand these limitations and extraction of other supportive information for a better understanding of adverse events following vaccination.

There is a growing literature base regarding menstrual changes following COVID-19 vaccination among premenopausal people. However, relatively little is known about uterine bleeding in postmenopausal people following COVID-19 vaccination.
This study aimed to examine trends in incident postmenopausal bleeding diagnoses over time before and after COVID-19 vaccine introduction, and to describe cases of new-onset postmenopausal bleeding after COVID-19 vaccination.
For postmenopausal bleeding incidence calculations, monthly population-level cohorts consisted of female Kaiser Permanente Northwest members aged ≥45 years. Those diagnosed with incident postmenopausal bleeding in the electronic medical record were included in monthly numerators. Members with preexisting postmenopausal bleeding or abnormal uterine bleeding, or who were at increased risk of bleeding due to other health conditions, were excluded from monthly calculations. We used segmented regression analysis to estimate changes in the incidence of postmenopausal bleeding diagnoses from 2018 through 2021 in Kaiser Permanente Northwest members meeting the inclusion criteria, stratified by COVID-19 vaccination status in 2021. In addition, we identified all members with ≥1 COVID-19 vaccination between December 14, 2020 and August 14, 2021, who had an incident postmenopausal bleeding diagnosis within 60 days of vaccination. COVID-19 vaccination, diagnostic procedures, and presumed bleeding etiology were assessed through chart review and described. A temporal scan statistic was run on all cases without clear bleeding etiology.
In a population of 75,530 to 82,693 individuals per month, there was no statistically significant difference in the rate of incident postmenopausal bleeding diagnoses before and after COVID-19 vaccine introduction (P=.59). A total of 104 individuals had incident postmenopausal bleeding diagnosed within 60 days following COVID-19 vaccination; 76% of cases (79/104) were confirmed as postvaccination postmenopausal bleeding after chart review. Median time from vaccination to bleeding onset was 21 days (range: 2-54 days). Among the 56 postmenopausal bleeding cases with a provider-attributed etiology, the common causes of bleeding were uterine or cervical lesions (50% [28/56]), hormone replacement therapy (13% [7/56]), and proliferative endometrium (13% [7/56]). Among the 23 cases without a clear etiology, there was no statistically significant clustering of postmenopausal bleeding onset following vaccination.
Within this integrated health system, introduction of COVID-19 vaccines was not associated with an increase in incident postmenopausal bleeding diagnoses. Diagnosis of postmenopausal bleeding in the 60 days following receipt of a COVID-19 vaccination was rare.

Despite the multiple benefits of vaccination, cardiac adverse Events Following COVID-19 Immunization (c-AEFI) have been reported. These events as well as the severe cardiac involvement reported in Multisystem inflammatory syndrome in children (MIS-C) appear more frequent in young adult males. Herein, we firstly report on the inflammatory profiles of patients experiencing c-AEFI in comparison with age, pubertal age and gender matched MIS-C with cardiac involvement. Proteins related to systemic inflammation were found higher in MIS-C compared to c-AEFI, whereas a higher level in proteins related to myocardial injury was found in c-AEFI. In addition, higher levels of DHEAS, DHEA, and cortisone were found in c-AEFI which persisted at follow-up. No anti-heart muscle and anti-endothelial cell antibodies have been detected. Overall current comparative data showed a distinct inflammatory and androgens profile in c-AEFI patients which results to be well restricted on heart and to persist months after the acute event.

BCG vaccination and revaccination are increasingly being considered for the protection of adolescents and adults against tuberculosis and, more broadly, for the off-target protective immunological effects against other infectious and noninfectious diseases. Within an international randomized controlled trial of BCG vaccination in healthcare workers (the BRACE trial), we evaluated the incidence of local and serious adverse events, as well as the impact of previous BCG vaccination on local injection site reactions (BCG revaccination). Prospectively collected data from 99% (5351/5393) of participants in Australia, Brazil, Spain, The Netherlands and the UK was available for analysis. Most BCG recipients experienced the expected self-limiting local injection site reactions (pain, tenderness, erythema, swelling). BCG injection site itch was an additional common initial local symptom reported in 49% of BCG recipients. Compared to BCG vaccination in BCG-naïve individuals, BCG revaccination was associated with increased frequency of mild injection site reactions, as well as earlier onset and shorter duration of erythema and swelling, which were generally self-limiting. Injection site abscess and regional lymphadenopathy were the most common adverse events and had a benign course. Self-resolution occurred within a month in 80% of abscess cases and 100% of lymphadenopathy cases. At a time when BCG is being increasingly considered for its off-target effects, our findings indicate that BCG vaccination and revaccination have an acceptable safety profile in adults.

There has been much interest in the possible adverse events associated with available anti-coronavirus disease of 2019 (COVID-19) vaccines, given the rapid pace at which they had to be developed during the pandemic. One such adverse event is myocarditis post-COVID-19 vaccination. Several pathophysiological mechanisms have been proposed that might help us understand the relationship between the messenger ribonucleic acid (mRNA) vaccine and the occurrence of myocarditis, though we are yet to ascertain the causal link between them. Although the actual absolute incidence of myocarditis post-COVID-19 vaccination remains low among the large, general population that has been vaccinated, there has been a high relative incidence of this adverse event. We aim to review the existing literature and bring to light what we have so far understood with respect to the association between COVID-19 vaccination and myocarditis. This will help in better understanding the burden of the pathology along with alleviating apprehensions associated with it.
CONCLUSIONS:

BACKGROUND: This study documents imprecision in Japanese reports of adverse events following immunization (AEFI). In doing so, it presents methods to analyze this imprecision.
METHODS: These methods include use of unique Japanese data on the validity of certain AEFIs. They also include ways to estimate AEFI rates, which allow comparison of AEFI data between countries. Using US AEFI data for comparison, we show how differences in AEFI reporting systems likely influence AEFI statistics.
RESULTS: Although our comparisons of AEFI rates are not precise, many of the difference we detected between Japanese and US statistics make sense and reflect differences in the societal and medical perspectives on various vaccines or can be explained by differences in the reporting systems including reporting sources. For example, differences in societal and medical perspective probably underly the extraordinarily high Japanese rates of anaphylaxis and other AEs following HPV immunizations from 2010 to 2016 compared to US rates and to Japanese rates for other vaccines. High US rates of reported Guillain-Barré syndrome following influenza vaccination relative to Japanese rates and to rates for other US vaccines are consistent with data suggesting that the index of suspicion for such reactions could affect AEFI rates. The findings that over half of Japanese anaphylaxis reports for every vaccine are erroneous, and that close to half of \"serious\" Japanese AEFI cases probably are not serious may be due in part not only to explanations unique to Japan, but also to factors that apply to the USA and other countries. Differences in reporting systems account for a much higher rate of non-serious AEFI reports in the USA compared to Japan. Japanese marketing authorization holders are probably at least as assiduous and timely in their reporting of AEFIs as health care providers, though granular level differences are apparent in reporting by various sources.
CONCLUSIONS: The methods we used to analyze the validity of Japanese statistics can be used to analyze the validity of AEFI reports from other countries and aid the harmonization of adverse event reporting systems. Eventually, similar reporting systems might be adapted for drugs and medical devices.

The Sars-CoV-2 pandemic caused great concern for this novel virus among patients with primary immunodeficiency (PID) or inborn errors of immunity (IEI) and their families. When COVID-19 vaccination program started, no data existed on adverse events (AEs) in this particular patient population, nor if patients felt hesitancy being vaccinated.
To explore i) reasons for COVID-19 vaccination hesitancy, ii) the number and symptoms of AEs and their severity, durability and management.
The organisations International Patient Organisation for Primary Immunodeficiencies (IPOPI), European Society for Immunodeficiencies (ESID) and International Nursing Group for Immunodeficiencies (INGID) distributed a global self-administered online survey.
The survey was completed by 1317 patients (mean 47, range 12-100, years) from 40 countries. 41.7% of the patients denoted some hesitancy to COVID-19 vaccination, mainly having doubts about postvaccination protection related to their underlying PID and concerns about negative long-term effects. More women (22.6%) reported \"very\" or \"pretty much\" hesitancy compared to men (16.4%) (P<0.05). The most common systemic AEs were fatigue, muscle/body pain and headache, usually the same day or the day after the vaccination and lasting for 1-2 days. 27.8% of the respondents reported severe systemic AEs after any dose of COVID-19 vaccine. Only a minority (7.8%) of these patients visited a health-care professional and 20 patients (1.5%) were hospitalized or seen at emergency room without specifying subsequent admission at the hospital. Significantly more local and systemic AEs were reported after the second dose. No differences regarding AEs were observed across different PID subgroups or vaccine types.
At the time of the survey, almost half of the patients reported having felt hesitancy to COVID-19 vaccination highlighting the importance and need of developing joint international guidelines and education programs about COVID-19 vaccination. The types of AEs were comparable to healthy controls, but more frequent AEs were reported. Clinical studies and prospective, detailed registration of AEs related to COVID-19 vaccines in this patient population is of great importance. It is crucial to elucidate whether there is a coincidental or causal association between COVID-19 vaccine and some severe systemic AEs. Our data do not contradict that patients with PID can be advised to be vaccinated against COVID-19, in accordance with applicable national guidelines.

BACKGROUND: Despite continuing efforts to improve the inclusion of underserved groups in clinical research, gaps in diversity remain. Participation of special populations is especially important when facing problems of unprecedented complexity such as the COVID-19 pandemic. A better understanding of factors associated with the immune response in diverse populations would advance future preventive and curative approaches.
OBJECTIVE: The objective of this study was to investigate the factors potentially responsible for adverse events following COVID-19 immunization. The study population included adults from rural areas, transitional countries, and those with medically understudied conditions, across a broad age range.
METHODS: The study evolved from peer support networks developed during the COVID-19 pandemic. Participants were recruited digitally through online neighborhood and health communities. Some of the participants volunteered as study investigators assisting with offline recruitment and safety monitoring. Individuals who consented to participate were asked to share their vaccination experiences either using constantly evolving web-based surveys or via one-on-one communication. Inferential statistical analysis to estimate differences between study groups was performed using parametric and nonparametric tests.
RESULTS: Of 1430 participants who shared their vaccination experiences, 648 had outcome measures at their 1.5-year follow-up. Significant differences were found between age groups, types of vaccine adverse events (VAEs), incidences of breakthrough infections, and health conditions linked to the microbiome. Pairwise comparisons showed that VAEs interfering with daily activities were significantly higher in both younger (18-59 years) and older age groups (80-100 years, P<.001) than in the 60-79-year age group. Short-term VAEs were associated with lower incidence of breakthrough COVID-19 infections relative to those who reported either minimal or long-term adverse events (P<.001). A genetic origin was suggested for some adverse reactions.
CONCLUSIONS: The findings of this study demonstrate that vaccine adverse reactions in older individuals are being overlooked, and the incidence of VAEs impairing immunity may be higher than previously perceived. Better preventive measures are needed for all those at risk for life-threatening and long-term adverse events due to vaccination. Supportive community-based studies focusing on these populations could add important data to the current body of knowledge. Further and more comprehensive studies should follow.
BACKGROUND: ClinicalTrials.gov NCT04832932; https://clinicaltrials.gov/ct2/show/NCT04832932.
UNASSIGNED: RR2-10.1101/2021.06.28.21256779.