Capillary leak syndrome following COVID-19 vaccination: Data from the European pharmacovigilance database Eudravigilance.

Capillary leak syndrome (CLS) emerged as new adverse event after immunization (AEFI) associated to COVID-19 vaccination. CLS is a rare condition characterized by increased capillary permeability, resulting in hypoalbuminemia, hypotension, and edema mainly in the upper and lower limbs. Our pharmacovigilance study aims to evaluate the CLS onset following receipt of COVID-19 mRNA vaccines (mRNA-1273 and BNT162b2) compared to viral vector vaccines (Ad26.COV2-S and ChAdOx1-SARS-COV-2). We carried a cross-sectional study using all Individual Case Safety Reports (ICSRs) reporting a COVID-19 vaccine as suspected drug and CLS as AEFI, which were collected in the pharmacovigilance database EudraVigilance from January 1st, 2021, to January 14th, 2022. We applied the Reporting Odds Ratio (ROR) 95% CI for the disproportionality analysis. During our study period, CLS was described as AEFI in 84 out of 1,357,962 ICRs reporting a vaccine COVID-19 as suspected drug and collected in the EV database. Overall, the ICSR reported by CLS were mainly related to the viral vector COVID-19(ChAdOx1-SARS-COV-2 = 36; Ad26.COV2-S = 9). The mRNA COVID-19 vaccines were reported in 39 ICSRs (BNT162b2 =33; mRNA-1273 =6). Majority of ICSRs were reported by healthcare professionals (71.4%). Majority of the patients were adult (58.3%) and the female gender accounted in more than 65% of ICSRs referred both to classes vaccines. In particular, women were more represented in ICSRs referred to mRNA-1273 (83.3%) and to ChAdOx1-SARS-COV-2 (72.2%). The CLS outcome was more frequently favorable in mRNA ICSRs (33,3%) than the viral vector ones (13.3%). Among the ICSRs reporting CLS with unfavorable outcome, we found also 9 fatal cases (BNT162b2 = 1; ChAdOx1-SARS-COV-2 = 4; Ad26.COV2-S = 4). From disproportionality analysis emerged a lower CLS reporting probability after vaccination with mRNA vaccines compared to viral vector-based ones (ROR 0.5, 95% CI 0.3-0.7; p <0.001).Our findings, even if subject to the limitations of spontaneous reporting systems, suggest a small but statistically significant safety concern for CLS following receipt of COVID-19 viral vector vaccines, in particular with Ad26.COV2-S. Cytokine-release following T-cell activation could be involved in CLS occurrence, but a precise mechanism has been not yet identified. COVID-19 vaccines remain attentive as possible triggers of CLS.

Anaphylaxis rates following mRNA COVID-19 vaccination in children and adolescents: Analysis of data reported to EudraVigilance.

AIM: The present study aimed to estimate the anaphylaxis rates following mRNA COVID-19 vaccination in children and adolescents in Europe. METHODS: We retrieved data on 371 anaphylaxis cases following mRNA COVID-19 vaccination in children ≤ 17 years old notified to EudraVigilance as of October 8, 2022. Overall, 27,120,512 doses of BNT162b2 vaccine and 1,400,300 doses of mRNA-1273 vaccine have been delivered to children during the study period. RESULTS: The overall mean anaphylaxis rate was 12.81 [95% confidence interval (CI): 11.49-14.12] per 106 mRNA vaccine doses [12.14 (95% CI: 6.37-17.91) per 106 doses for mRNA-1273 and 12.84 (95% CI: 11.49-14.19) per 106 doses for BNT162b2]. Children 12-17 years old accounted for 317 anaphylaxis cases, followed by 48 cases in children 3-11 years old, and 6 cases in children 0-2 years old. Children 10-17 years old had a mean anaphylaxis rate of 13.52 (95% CI: 12.03-15.00) cases per 106 mRNA vaccine doses and children 5-9 years old had a mean anaphylaxis rate of 9.51 (95% CI: 6.82-12.20) cases per 106 mRNA vaccine doses. There were two fatalities, both in the 12-17 years age group. The fatal anaphylaxis rate was 0.07 cases per 106 mRNA vaccine doses. CONCLUSIONS: Anaphylaxis is a rare adverse event after receiving an mRNA COVID-19 vaccine in children. Continuous surveillance of serious adverse events is needed to guide vaccination policies as we move towards SARS-CoV-2 endemicity. Larger real-world studies on COVID-19 vaccination in children, using clinical case confirmation, are imperative.

Safety Monitoring of mRNA COVID-19 Vaccines in Children Aged 5 to 11 Years by Using EudraVigilance Pharmacovigilance Database: The CoVaxChild Study.

Although the safety profiles of mRNA COVID-19 vaccines (mRNA-1273 and BNT162b2) were evaluated in pre-authorization clinical trials, real-world data allow us to better define their benefit/risk ratio in the paediatric population. The current study aimed to evaluate the safety profiles of mRNA COVID-19 vaccines in children by analysing the pharmacovigilance data of the European spontaneous reporting system database EudraVigilance (EV) in the period from 1 January 2021, to 1 October 2022. During our study period, overall 4838 ICSRs related to mRNA COVID-19 vaccines referring to 5-11-year-old subjects were retrieved from EV, of which 96.9% were related to BNT162b2 and 49.3% were related to males. A total of 12,751 Adverse Events Following Immunization (AEFIs) were identified, of which 38.7% were serious. The most frequently reported AEFIs were pyrexia, headache, and vomiting. Only 20 Individual Case Safety Reports (ICSRs) reported Multisystem Inflammatory Syndrome (MIS) as an AEFI, all related to BNT162b2. The majority of MIS cases were females, and six cases were completely resolved at the time of reporting. Our results show a favourable risk-benefit profile for all mRNA COVID-19 vaccines in this paediatric sub-population, supporting their use in children. Considering the peculiarity and fragility of children, continuous safety monitoring of COVID-19 vaccines is required.

Vaccine Vigilance System: Considerations on the Effectiveness of Vigilance Data Use in COVID-19 Vaccination.

(1) Background: The safety of medicines has been receiving increased attention to ensure that the risks of taking medicines do not outweigh the benefits. This is the reason why, over several decades, the pharmacovigilance system has been developed. The post-authorization pharmacovigilance system is based on reports from healthcare professionals and patients on observed adverse reactions. The reports are collected in databases and progressively evaluated. However, there are emerging concerns about the effectiveness of the established passive pharmacovigilance system in accelerating circumstances, such as the COVID-19 pandemic, when billions of doses of new vaccines were administered without a long history of use. Currently, health professionals receive fragmented new information on the safety of medicines from competent authorities after a lengthy evaluation process. Simultaneously, in the context of accelerated mass vaccination, health professionals need to have access to operational information-at least on organ systems at higher risk. Therefore, the aim of this study was to perform a primary data analysis of publicly available data on suspected COVID-19 vaccine-related adverse reactions in Europe, in order to identify the predominant groups of reported medical conditions after vaccination and their association with vaccine groups, as well as to evaluate the data accessibility on specific syndromes. (2) Methods: To achieve the objectives, the data publicly available in the EudraVigilance European Database for Suspected Adverse Drug Reaction Reports were analyzed. The following tasks were defined to: (1) Identify the predominant groups of medical conditions mentioned in adverse reaction reports; (2) determine the relative frequency of reports within vaccine groups; (3) assess the feasibility of obtaining information on a possibly associated syndrome-myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). (3) Results: The data obtained demonstrate that the predominant medical conditions induced after vaccination are relevant to the following categories: (1) "General disorders and administration site conditions", (2) "nervous system disorders", and (3) "musculoskeletal and connective tissue disorders". There are more reports for mRNA vaccines, but the relative frequency of reports per dose administered, is lower for this group of vaccines. Information on ME/CFS was not available, but reports of "chronic fatigue syndrome" are included in the database and accessible for primary analysis. (4) Conclusions: The information obtained on the predominantly reported medical conditions and the relevant vaccine groups may be useful for health professionals, patients, researchers, and medicine manufacturers. Policymakers could benefit from reflecting on the design of an active pharmacovigilance model, making full use of modern information technologies, including big data analysis of social media and networks for the detection of primary signals and building an early warning system.

Subacute thyroiditis and COVID-19 vaccines: a case/non-case study.

PURPOSE: Some case reports have suggested a possible association between COVID-19 vaccines and subacute thyroiditis (SAT), however, to our knowledge, no study has analyzed this possible relationship. This study aimed to analyze whether a disproportionate number of cases of SAT were reported in the EudraVigilance database for four COVID-19 vaccines (BNT162b2, mRNA-1273 ChAdOx1-S or Ad26.COV2.S). METHODS: A case/non-case study was conducted to assess the association between SAT and COVID-19 vaccines, calculating the reporting odds ratios (RORs) up to December 2, 2021. Cases were selected using the preferred term 'subacute thyroiditis'. First, cases involving COVID-19 vaccines were compared with those involving all other drugs. Secondly, the RORs for COVID-19 vaccines compared with other viral vaccines (overall and influenza vaccines only) were obtained. RESULTS: Until December 2, 2021, of 1,221,582 spontaneous cases of adverse reactions with the four vaccines, we found 162 SAT cases: BNT162b2 (n = 103), mRNA-1273 (n = 27), ChAdOx1-S (n = 31) and Ad26.COV2.S (n = 1). SAT cases were found to be reported more frequently in association with BNT162b2, mRNA-1273, and ChAdOx1-S vaccines than with other drugs. Moreover, we found a signal of disproportionate reporting for SAT with BNT162b2 and mRNA-1273 vaccines comparing with other viral vaccines (BNT162b2 ROR 3.58, 95% CI 1.92-6.66; mRNA-1273 ROR 3.44, 95% CI 1.71-6.94). However, this association was absent when these COVID-19 vaccines were compared with influenza vaccines. CONCLUSIONS: In EudraVigilance, SAT is relatively more frequently reported in association with mRNA COVID-19 vaccines than with other viral vaccines. Well designed observational studies are needed to confirm these results.

Anaphylaxis rates associated with COVID-19 vaccines are comparable to those of other vaccines.

We retrieved data on 8940 anaphylaxis cases post-COVID-19 vaccination from the US Vaccine Adverse Event Reporting System and the European EudraVigilance from week 52/2020 through week 31/2021 and compared them with those of other vaccines. Overall, 837,830,000 COVID-19 vaccine doses were delivered in the US and Europe during the study period, for which the vaccine name was known. The mean anaphylaxis rate was estimated at 10.67 cases per 106 doses of COVID-19 vaccines (range: 7.99-19.39 cases per 106 doses depending on the vaccine). COVID-19 vaccines ranked fifth in reported anaphylaxis rates, behind rabies, tick-borne encephalitis, measles-mumps-rubella-varicella, and human papillomavirus vaccines (70.77, 20, 19.8, and 13.65 cases per 106 vaccine doses, respectively). COVID-19 vaccines are within the range of anaphylaxis rates reported across several common vaccines in these two passive reporting systems. These data should be communicated to reassure the general population about the safety profile of COVID-19 vaccines.

Preliminary evidence on the safety profile of BNT162b2 (Comirnaty): new insights from data analysis in EudraVigilance and adverse reaction reports from an Italian health facility.

The first vaccine against SARS-CoV-2 made available in Italy has been BNT162b2, the two-dose mRNA-based vaccine developed by Pfizer-BioNTech. The ASST Fatebenefratelli-Sacco hospital is located in one of the areas most affected by the pandemic, and to date over 2000 healthcare professionals have been injected with both vaccine doses. We have collected all spontaneous safety reports in which BNT162b2 was designated as the possible cause. We also have carried out a descriptive analysis of reports submitted in EudraVigilance in the same time-frame and compared our findings with those observed in clinical trials. We have identified several new and unexpected adverse reactions that will be helpful for reviewing the safety profile defined in the Summary of Product Characteristics for this vaccine.