This study evaluated the feasibility of ChatGPT and Gemini, two off-the-shelf large language models (LLMs), to automate causality assessments, focusing on Adverse Events Following Immunizations (AEFIs) of myocarditis and pericarditis related to COVID-19 vaccines.

We assessed 150 COVID-19-related cases of myocarditis and pericarditis reported to the Vaccine Adverse Event Reporting System (VAERS) in the United States of America (USA). Both LLMs and human experts conducted the World Health Organization (WHO) algorithm for vaccine causality assessments, and inter-rater agreement was measured using percentage agreement. Adherence to the WHO algorithm was evaluated by comparing LLM responses to the expected sequence of the algorithm. Statistical analyses, including descriptive statistics and Random Forest modeling, explored case complexity (e.g., string length measurements) and factors affecting LLM performance and adherence.

ChatGPT showed higher adherence to the WHO algorithm (34%) compared to Gemini (7%) and had moderate agreement (71%) with human experts, whereas Gemini had fair agreement (53%). Both LLMs often failed to recognize listed AEFIs, with ChatGPT and Gemini incorrectly identifying 6.7% and 13.3% of AEFIs, respectively. ChatGPT showed inconsistencies in 8.0% of cases and Gemini in 46.7%. For ChatGPT, adherence to the algorithm was associated with lower string complexity in prompt sections. The random forest analysis achieved an accuracy of 55% (95% confidence interval: 35.7-73.5) for predicting adherence to the WHO algorithm for ChatGPT.

Notable limitations of ChatGPT and Gemini have been identified in their use for aiding causality assessments in vaccine safety. ChatGPT performed better, with higher adherence and agreement with human experts. In the investigated scenario, both models are better suited as complementary tools to human expertise.

This Phase IV prospective observational study aimed to evaluate the frequency of solicited and unsolicited adverse reactions within seven days following the administration of each dose of CoronaVac (14-day interval) by age group (18-59 years and ≥60 years). Participants (n = 538; 487 adults and 51 older adults) were enrolled from three public health centers in São Paulo, Brazil from May 2021 to January 2022. The study involved a two-dose vaccination regimen administered 14 days apart. Solicited and unsolicited adverse reactions (ARs) were assessed within seven days after each dose, and medically attended adverse events following immunization (AEFI) were monitored for 42 days. Safety data were collected through participant diary cards, telephone follow-ups, and on-site visits. Among adults, the most frequently reported local AR after the first and second doses was pain (256 [52.6%] and 129 [29.5%], respectively), while the most common systemic AR was headache (158 [34.5%] and 51 [11.6%], respectively). Most local and systemic solicited ARs were of Grade 1 or 2 severity, with ARs being more prevalent in adults following the first dose. One serious adverse event related to the vaccine was reported in adults, with no fatalities. Nine adult participants experienced adverse events of special interest, including five cases of COVID-19. These findings support the overall safety profile of CoronaVac in adults and older adult individuals, with adverse events being generally mild and self-limited.

Background: Despite adverse events following immunization (AEFI) being well described in vaccine trials, there is a need to produce more real-world data on events supposedly attributed to vaccination against COVID-19. This study aims to estimate the prevalence of AEFI in the first dose of COVID-19 vaccines in the state of Brazil and to verify whether such events differ among the types of vaccines offered in this country. Methods: A population-based study using linked administrative data on vaccine registry and adverse events following immunization in 2021 and 2022. The study included 10,169,378 individuals aged 18 or over who lived in Bahia and received the first dose of COVID-19 vaccines. We calculated AEFI prevalence and verified differences among vaccines by logistic regression to estimate crude and adjusted by sex and age group prevalence ratio (PR). Results: The prevalence of AEFI was 74.3 per 100,000 doses applied, with a higher rate of nonserious events, mainly following the ChAdOx1-S. More than two-thirds of these adverse effects occurred in women, and almost half were between 30 and 49 years old. The individuals who received ChAdOx1-S had a 125% higher prevalence than those who received CoronaVac. Those who received BNT162b2 and Ad26.COV2.S had a 71% and 58%, respectively, lower prevalence of AEFI than those who received CoronaVac. Conclusions: The use of vaccines against COVID-19 has proven to be positive and effective in combating SARS-CoV-2, significantly reducing morbidity and mortality from the disease. We cannot deny the presence of adverse events in the context of vaccination. However, the vaccines have proven to be safe and reliable. The results of this study offer relevant data that can contribute to the qualification of AEFI pharmacovigilance in Brazil and worldwide.

Despite technological advancements, healthcare professionals must actively prioritize patient safety. Reporting adverse drug reactions is a critical aspect of this responsibility, and the most accessible healthcare providers, community pharmacists, and pharmacy technicians play a key role. Therefore, this study assessed their knowledge and practices regarding adverse drug reaction reporting in Croatia. A total of 180 participants were included. Pharmacists demonstrated significantly better knowledge than technicians (94.78 vs. 73.97, p = 0.024). Chronic medication users also showed greater understanding compared to non-users (104.96 vs. 85.39, p = 0.021). Knowledge improved with the number of adverse drug reactions reported, and most participants (72.78%) had reported adverse drug reactions. Pharmacists were 83.60% more likely to report adverse drug reactions than technicians (p < 0.001). These findings reveal a gap in pharmacy technicians' integration into pharmacovigilance, underscoring a need to strengthen their role in adverse drug reaction reporting and patient safety.

COVID-19 is a viral disease caused by the SARS-CoV-2, leading to several variants. This study aimed to examine the effectiveness of booster doses against the Delta and Omicron variants over different follow-up times. Study Design: This was a longitudinal meta-analysis.

Searches were performed in PubMed, Cochrane Library, Scopus, and Web of Science databases, and eighty studies were selected for investigation. The analyses were separately performed on the unvaccinated control group (UNVCG) and the complete two doses of the vaccine control group (C2DCG) against Delta and Omicron variants. Three outcomes were examined, including symptomatic infection, hospitalization, and death.

Vaccine effectiveness (VE) in UNVCG studies for symptomatic infection revealed a non-linear trend against Omicron with a peak of 67.3%, declining to 27.1% after 25 weeks after a booster dose. The mean of VE for hospitalization over time started to decrease after four weeks against Omicron and after eight weeks against Delta. The VE reached a peak at week eight (96.0%) and started to decline with a VE of 93.3% after 20 weeks after the booster dose against Delta. It was 90.8% at week four and decreased to 73.4% after 25 weeks after the booster dose against Omicron. VE in the C2DCG studies demonstrated more decreases in outcomes over time.

Our findings showed a tendency to decrease effectiveness over time based on outcomes and variants. The early protection levels were lower in Omicron. Moreover, the VE decrease over time was stronger in Omicron compared to the Delta variant.

Clinical trials feature centrally in the development of drugs and vaccines to determine safety and efficacy. Clinical development can be slow and may have a duration of more than ten years. Global public health threats such as Ebola virus disease (EVD) and COVID-19 have demonstrated that it is possible to accelerate clinical trials while maintaining safety and efficacy. We investigated acceleration in clinical trials over the past decade and identified factors associated with acceleration for drugs targeting infectious diseases.

A cross-sectional study was performed of all medicinal compounds targeting infectious diseases that received marketing authorisation by the European Medicines Agency (EMA) between 2012 and 2022. We calculated median clinical development time in years between the first phase 1 trial enrolment date and the authorisation date. Multivariable linear regression analysis was performed to identify factors associated with shorter development times.

Eighty-one trajectories were included. The median clinical development time was 7.3 years (IQR 4.4-12.3). The fastest times belonged to drugs and vaccines targeting COVID-19 (1.3 years, IQR 0.8-1.6), EVD (5.5 years, IQR 5.1-5.8), and Hepatitis A-E (5.5 years, IQR 3.9-8.2). Factors associated with shorter development times were outbreak setting (-5.4 years [95% CI, -8.2 to -2.6]), accelerated assessment status (-4.0 years [95% CI, -7.6 to -0.5]), and drugs with combined compounds (-2.7 years [95% CI, -4.9 to -0.4]).

Clinical development time for infectious disease-related drugs and vaccines was relatively short, and outbreak setting and accelerated EMA assessment were associated with shorter development times.

Amsterdam Public Health research institute.

Pharmacovigilance plays a central role in safeguarding public health by continuously monitoring the safety of vaccines, being critical in a climate of vaccine hesitancy, where public trust is paramount. Pharmacovigilance strategies employed to gather information on adverse events following immunization (AEFIs) include pre-registration data, media reports, clinical trials, and societal reporting. Early detection of AEFIs during clinical trials is crucial for thorough safety analysis and preventing serious reactions once vaccines are deployed. This review highlights the importance of societal reporting, encompassing contributions from community members, healthcare workers, and pharmaceutical companies. Technological advancements such as quick response (QR) codes can facilitate prompt AEFI reporting. While vaccines are demonstrably safe, the possibility of adverse events necessitates continuous post-marketing surveillance. However, underreporting remains a challenge, underscoring the critical role of public engagement in pharmacovigilance. This narrative review comprehensively examines and synthesizes key aspects of virus vaccine pharmacovigilance, with special considerations for specific population groups. We explore applicable legislation, the spectrum of AEFIs associated with major vaccines, and the unique challenges and perspectives surrounding pharmacovigilance in this domain.

The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the waning of immunity over time has necessitated the use of booster doses of original coronavirus disease 2019 (COVID-19) vaccines. This has also led to the development and implementation of variant-adapted messenger RNA (mRNA) vaccines that include an Omicron sub-lineage component in addition to the antigen based on the wild-type virus spike protein. Subsequent emergence of the recombinant XBB sub-lineages triggered the development of monovalent XBB-based variant-adapted mRNA vaccines, which are available for vaccination campaigns in late 2023. Misconceptions about new variant-adapted vaccines may exacerbate vaccine fatigue and drive the lack of vaccine acceptance. This article aims to address common concerns about the development and use of COVID-19 variant-adapted mRNA vaccines that have emerged as SARS-CoV-2 has continued to evolve.

The concept of pharmacovigilance (PV) is currently highlighted after emergency authorization and worldwide distribution of the urgently launched COVID-19 novel vaccinations. As they typically serve as the initial point of patient contact for medication-related issues, understanding the knowledge, perspectives, and attitudes of community pharmacists in PV and reporting adverse drug reactions (ADRs) is crucial to improving the healthcare system and public health policies. However, previous studies in Jordan have not focused entirely on community pharmacists. This study aimed to assess community pharmacists' knowledge, perspectives, and attitudes on PV and ADRs reporting in Jordan. The applied methodology in this study was based on a cross-sectional study design using a validated questionnaire distributed to a convenient sample of Jordanian community pharmacists. Seventeen questions were designed from different pieces of literature relating to knowledge, perspectives, and attitudes of PV among community pharmacists. Descriptive statistics (frequencies and percentages) were used to report the results data. The study questionnaire was completed by 180 of 325 community pharmacists willing to participate (a response rate of 55.4%). Of them (n = 132, 73%) were aware of the concept of PV. Additionally (n = 84, 47%) of the community pharmacists would use the concept and policy of PV in their everyday work. Nevertheless, only (n = 36, 20.0%) of the community pharmacists thought an ADR should be reported if seen, and approximately 120 pharmacists (67.0%) believed it was essential to report ADRs as patient health matters. Although community pharmacists in Jordan showed a considerable awareness level of PV, they demonstrated a low level of its application. Thus, ADR reporting is not considered a mainstay among them, and the implementation of PV is not yet addressed. The results from this study shed light on community pharmacists' perceptions and attitudes regarding ADR reporting and PV.

Important physiological changes are observed in patients with obesity, such as intestinal permeability, gastric emptying, cardiac output, and hepatic and renal function. These differences can determine variations in the pharmacokinetics of different drugs and can generate different concentrations at the site of action, which can lead to sub therapeutic or toxic concentrations. Understanding the physiological and immunological processes that lead to the clinical manifestations of COVID-19 is essential to correlate obesity as a risk factor for increasing the prevalence, severity, and lethality of the disease. Several drugs have been suggested to control COVID- 19 like Lopinavir, Ritonavir, Ribavirin, Sofosbuvir, Remdesivir, Oseltamivir, Oseltamivir phosphate, Oseltamivir carboxylate, Hydroxychloroquine, Chloroquine, Azithromycin, Teicoplanin, Tocilizumab, Anakinra, Methylprednisolone, Prednisolone, Ciclesonide and Ivermectin. Similarly, these differences between healthy people and obese people can be correlated to mechanical factors, such as insufficient doses of the vaccine for high body mass, impairing the absorption and distribution of the vaccine that will be lower than desired or can be linked to the inflammatory state in obese patients, which can influence the humoral immune response. Additionally, different aspects make the obese population more prone to persistent symptoms of the disease (long COVID), which makes understanding these mechanisms fundamental to addressing the implications of the disease. Thus, this review provides an overview of the relationship between COVID-19 and obesity, considering aspects related to pharmacokinetics, immunosuppression, immunization, and possible implications of long COVID in these individuals.

Influenza causes significant morbidity and mortality, but influenza vaccine uptake remains below most countries' targets. Vaccine policy recommendations vary, as do procedures for reviewing and appraising the evidence.

During a series of roundtable discussions, we reviewed procedures and methodologies used by health ministries in four European countries to inform vaccine recommendations. We review the type of evidence currently recommended by each health ministry and the range of approaches toward considering randomized controlled trials (RCTs) and real-world evidence (RWE) studies when setting influenza vaccine recommendations.

Influenza vaccine recommendations should be based on data from both RCTs and RWE studies of efficacy, effectiveness, and safety. Such data should be considered alongside health-economic, cost-effectiveness, and budgetary factors. Although RCT data are more robust and less prone to bias, well-designed RWE studies permit timely evaluation of vaccine benefits, effectiveness comparisons over multiple seasons in large populations, and detection of rare adverse events, under real-world conditions. Given the variability of vaccine effectiveness due to influenza virus mutations and increasing diversification of influenza vaccines, we argue that consideration of both RWE and RCT evidence is the best approach to more nuanced and timely updates of influenza vaccine recommendations.

Concerns remain regarding the rare cardiovascular adverse events, myocarditis and pericarditis (myo/pericarditis), particularly in younger individuals following mRNA COVID-19 vaccination. Our study aimed to comprehensively assess potential safety signals related to these cardiac events following the primary and booster doses, with a specific focus on younger populations, including children as young as 6 months of age. Using the Vaccine Adverse Events Reporting System (VAERS), the United States national passive surveillance system, we conducted a retrospective pharmacovigilance study analyzing spontaneous reports of myo/pericarditis. We employed both frequentist and Bayesian methods and conducted subgroup analyses by age, sex, and vaccine dose. We observed a higher reporting rate of myo/pericarditis following the primary vaccine series, particularly in males and mainly after the second dose. However, booster doses demonstrated a lower number of reported cases, with no significant signals detected after the fourth or fifth doses. In children and young adults, we observed notable age and sex differences in the reporting of myo/pericarditis cases. Males in the 12-17 and 18-24-year-old age groups had the highest number of cases, with significant signals for both males and females after the second dose. We also identified an increased reporting for a spectrum of cardiovascular symptoms such as chest pain and dyspnea, which increased with age, and were reported more frequently than myo/pericarditis. The present study identified signals of myo/pericarditis and related cardiovascular symptoms after mRNA COVID-19 vaccination, especially among children and adolescents. These findings underline the importance for continued vaccine surveillance and the need for further studies to confirm these results and to determine their clinical implications in public health decision-making, especially for younger populations.

The large-scale COVID-19 vaccination campaigns in 2021 and 2022 led to a rapid increase in numbers of received adverse event reports in spontaneous reporting systems. As background incidences of naturally occurring medical events became increasingly relevant for causality assessment of potential associations with the vaccines, a novel approach for signal detection was warranted.

This article illustrates the Observed-over-Expected (O/E) analysis as an additional method for signal detection and risk assessment in large-scaled spontaneous reporting systems.

All individual case safety reports (ICSRs) concerning idiopathic peripheral facial paralysis or Bell's palsy following administration of the COVID-19 vaccines (n = 291) manufactured by Pfizer/BioNTech (Comirnaty), Moderna (Spikevax), AstraZeneca (Vaxzevria) and Janssen (JCOVDEN) received by the National Pharmacovigilance Centre Lareb until 24th March 2022 were included in the O/E analysis, within a risk window of 7 and 14 days following immunisation. Dutch background incidence rates from 2019 and exposure of the Dutch population to the vaccines were obtained from the PHARMO institute and RIVM. The data was stratified in age groups, gender and administered dose in order to differentiate between population subgroups.

Bell's palsy was reported more frequently than expected in several population subgroups following administration of all four COVID-19 vaccines, including children and adolescents. Among children, a high O/E ratio was found for boys aged 5-14 years after receiving the Pfizer/BioNTech vaccine. Regarding adolescents and young adults, women aged 15-24 years receiving Pfizer/BioNTech and Moderna, and men aged 15-24 years receiving Janssen developed Bell's palsy more often than expected. Furthermore, O/E ratios were high for individuals aged 25-64, regarding females receiving Pfizer, Moderna and AstraZeneca and males receiving Janssen. As facial paralysis was not labelled as an adverse event for the Janssen vaccine, this analysis contributed to signalling the association and warranting further regulatory action.

The O/E method is a useful approach for signal detection of potential adverse reactions when handling large numbers of ICSRs. Further research is needed to attest to the causality on a clinical basis.

Post-marketing vaccine safety surveillance aims to monitor and quantify adverse events following immunization in a population, but little is known about their implementation in low- and middle-income countries (LMICs). We aimed to synthesize methodological approaches used to assess adverse events following COVID-19 vaccination in LMICs.

For this systematic review, we searched articles published from 1 December 2019 to 18 February 2022 in main databases, including MEDLINE and Embase. We included all peer-reviewed observational COVID-19 vaccine safety monitoring studies. We excluded randomized controlled trials and case reports. We extracted data using a standardized extraction form. Two authors assessed study quality using the modified Newcastle-Ottawa Quality Assessment Scale. All findings were summarized narratively using frequency tables and figures.

Our search found 4254 studies, of which 58 were eligible for analysis. Many of the studies included in this review were conducted in middle-income countries, with 26 studies (45%) in lower-middle-income and 28 (48%) in upper-middle-income countries. More specifically, 14 studies were conducted in the Middle East region, 16 in South Asia, 8 in Latin America, 8 in Europe and Central Asia, and 4 in Africa. Only 3% scored 7-8 points (good quality) on the Newcastle-Ottawa Scale methodological quality assessment, while 10% got 5-6 points (medium). About 15 studies (25.9%) used a cohort study design and the rest were cross-sectional. In half of them (50%), vaccination data were gathered from the participants' self-reporting methods. Seventeen studies (29.3%) used multivariable binary logistic regression and three (5.2%) used survival analyses. Only 12 studies (20.7%) performed model diagnostics and validity checks (e.g., the goodness of fit, identification of outliers, and co-linearity).

Published studies on COVID-19 vaccine safety surveillance in LMICs are limited in number and the methods used do not often address potential confounders. Active surveillance of vaccines in LMICs are needed to advocate vaccination programs. Implementing training programs in pharmacoepidemiology in LMICs is essential.

Vaccination is considered the best measure to overcome the Sars-Cov2 pandemic. However, changing national recommendations on sequence and time frame necessitate the collection of real-word data on adverse events of Sars-CoV2 vaccination protocols outside of pivotal trials. We report results from a survey on the adverse events and the operational consequences of a Sars-CoV2 vaccination campaign with partly mixed vaccination protocol as well as booster vaccination. While the spectrum of adverse effects in our cohort appeared to be similar to pivotal studies, there were substantial differences in both frequency and distribution with only 3 out of 10 participants staying symptom-free. In over 26% of vaccinees symptoms were so severe, that they stayed at home with mean days on sick leave being 1.5 per person using mixed vaccination protocol. Being aware, that these results might partially be attributable to nocebo effects they are of importance for future vaccination campaigns.

More than 2 years has passed since the pandemic was declared in 2019 due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was later declared to be the pathogen causing coronavirus disease 2019 (COVID-19). During this time, many healthcare systems faced numerous challenges to control the high morbidity and mortality of the disease. Unlike previous pandemics, the actions against this pandemic started quickly on both the global and country levels. These actions were, scientifically, to study the virus as well as transmission process and to develop medications and vaccines against it. Also, we had to protect people from transmission by knowing how best to apply precautionary methods. However, there were some unexpected negative consequences of the pandemic and one of those the World Health Organization (WHO) called 'infodemic'. This term infodemic refers to the manipulation of a population's behavior in the assessment of information (or, more accurately, lack of assessment) related to the use of medications, particularly vaccines. Unfortunately, even with positive development in science, there was limited and often contradictory amount of information on the safety and efficacy profile of drugs and vaccines. Therefore, this made it harder for public health agencies to determine the impact of the incidence of adverse reactions and events associated with interventions such as vaccines. Hence, risk communication needs to be emphasized during any pandemic, as ignoring risk communications to different stakeholders could undermine all well-intended therapeutic interventions. Given this, it is important that the different stakeholders involved (health authorities, societies, healthcare professionals, etc.) assess the different behavioral patterns within their respective populations and propose appropriate strategies to act. Such an approach complement having risk management and communication plans for this and future pandemics. The aim of this article is to explore how information management, risk management, and risk communication during the pandemic can provide valuable lessons for the future.

Impact of risk communication on patient's safety during the pandemic More than 2 years have gone by since the pandemic was declared in 2019 due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Many challenges have been confronted by the healthcare system during this time to control the high impact of this disease. This pandemic, unlike others that humanity has faced, is characterized by a special feature: today, we have an enormous amount of information only a click away. This situation has been of great benefit to humanity and has allowed the development of science; nevertheless, misinformation (infodemics) has been a major problem, which has revealed the behavior of the population regarding the evaluation of information (or better, lack of assessment) related to the use of medications and particularly of vaccines. Given this, it is important that the different people involved (health authorities, societies, healthcare professionals, etc.) assess the behavior and propose appropriate strategies to act and have plans for this and future pandemics. This article intends to explore from the authors' perspective how information management, risk management, and risk communication during the pandemic can provide valuable lessons for the future.