Risk and characteristics of attacks occurring after vaccination in patients with neuromyelitis optica spectrum disorders: A systematic review and meta-analysis.

BACKGROUND: Vaccination in patients with neuromyelitis optica spectrum disorders (NMOSD) is challenging because there is a concern that vaccines can lead to clinical attacks. However, little is known about the risk and the characteristics of attacks occurring after vaccination. METHODS: We performed a systematic review and meta-analysis using PubMed and Embase databases to estimate a summary frequency of attacks occurring after vaccination and describe the clinical features of theses attacks. We defined attacks occurring after vaccination as typical NMOSD attacks that occurred up to 30 days after vaccine administration.  For the frequency of attacks occurring after vaccination, we selected observational studies that reported the number of attacks and total number of patients that received vaccines; for the clinical description of the attacks, case reports and case series were also included. RESULTS: We included 377 participants from 5 studies to estimate the frequency of NMOSD attacks occurring after vaccination. We found a summary frequency of of 2% (95% CI 1-4%, I2 = 0%). We evaluated 17 studies to identify that 13 different vaccines were associated with NMOSD attacks. A higher-than-expected proportion of males, simultaneous optic neuritis and transverse myelitis attacks, and anti-aquaporin 4 antibody negative cases were identified in vaccine-associated attacks from 24 participants from 17 studies. Nearly two-thirds of attacks occurring after vaccination were an initial event of NMOSD. CONCLUSION: The frequency of NMOSD attacks occurring after vaccination is low and non-specific to different vaccine technologies. Our work reinforces the safety of vaccine recommendations in patients with NMOSD.

Safety Monitoring of mRNA COVID-19 Vaccine Third Doses Among Children Aged 6 Months-5 Years - United States, June 17, 2022-May 7, 2023.

As of May 7, 2023, CDC's Advisory Committee on Immunization Practices (ACIP) recommends that all children aged 6 months-5 years receive at least 1 age-appropriate bivalent mRNA COVID-19 vaccine dose. Depending on their COVID-19 vaccination history and history of immunocompromise, these children might also need additional doses* (1-3). Initial vaccine safety findings after primary series vaccination among children aged 6 months-5 years showed that transient local and systemic reactions were common whereas serious adverse events were rare (4). To characterize the safety of a third mRNA COVID-19 vaccine dose among children aged 6 months-5 years, CDC reviewed adverse events and health surveys reported to v-safe, a voluntary smartphone-based U.S. safety surveillance system established by CDC to monitor health after COVID-19 vaccination (https://vsafe.cdc.gov/en/) and the Vaccine Adverse Event Reporting System (VAERS), a U.S. passive vaccine safety surveillance system co-managed by CDC and the Food and Drug Administration (FDA) (https://vaers.hhs.gov/) (5). During June 17, 2022-May 7, 2023, approximately 495,576 children aged 6 months-4 years received a third dose (monovalent or bivalent) of Pfizer-BioNTech vaccine and 63,919 children aged 6 months-5 years received a third dose of Moderna vaccine.† A third mRNA COVID-19 vaccination was recorded for 2,969 children in v-safe; approximately 37.7% had no reported reactions, and among those for whom reactions were reported, most reactions were mild and transient. VAERS received 536 reports after a third dose of mRNA COVID-19 vaccine for children in these age groups; 98.5% of reports were nonserious and most (78.4%) were classified as a vaccination error.§ No new safety concerns were identified. Preliminary safety findings after a third dose of COVID-19 vaccine for children aged 6 months-5 years are similar to those after other doses. Health care providers can counsel parents and guardians of young children that most reactions reported after vaccination with Pfizer-BioNTech or Moderna vaccine were mild and transient and that serious adverse events are rare.

Best practice implementation on reporting of coronavirus disease 2019 vaccine adverse events following immunization in Uasin Gishu County, Kenya.

OBJECTIVES: This project's aim was to implement vaccine safety surveillance best practices to improve reporting of adverse events following immunization (AEFI) during coronavirus disease 2019 (COVID-19) vaccination roll out in Uasin Gishu County. INTRODUCTION: Weak vaccine safety surveillance systems in developing countries has contributed to underreporting of AEFIs undermining public confidence in immunization efforts, contributing to low uptake of vaccines critical in the fight against communicable diseases. METHODS: The JBI Practical Application of Clinical Evidence System (JBI PACES) and Getting Research into Practice (GRiP) audit tool for promoting change in healthcare practice was utilized. Preimplementation and postimplementation audit cycles carried out utilized six best practice recommendations. Context-specific strategies and resources were used to address the gaps identified. RESULTS: Less than half of the AEFIs reported were in accordance with the local policy recommendation, and most of the AEFIs reported were submitted in a timely manner in the baseline and follow-up cycle. Slight improvement was recorded in the number of health facilities with AEFIs reporting forms. An improvement of 33.7% was recorded in the number of health workers providing COVID-19 vaccination services who had received education and practical training on vaccine pharmacovigilance. CONCLUSION: Underreporting and delayed submission of COVID-19 vaccine AEFI was evident among the healthcare providers offering COVID-19 vaccination services, the majority of healthcare providers had received training on vaccine pharmacovigilance, and AEFI hard copy reporting forms were not adequate in the health facilities. Public education on vaccine safety before administration of vaccine needs emphasis in order to improve reporting of AEFI.

COVID-19 vaccine safety inquiries to the centers for disease control and prevention immunization safety office.

BACKGROUND: Following the authorization and recommendations for use of the U.S. COVID-19 vaccines, the Centers for Disease Control and Prevention (CDC)'s Immunization Safety Office (ISO) responded to inquiries and questions from public health officials, healthcare providers, and the general public on COVID-19 vaccine safety. METHODS: We describe COVID-19 vaccine safety inquiries, by topic, received and addressed by ISO from December 1, 2020-August 31, 2022. RESULTS: Of the 1978 COVID-19 vaccine-related inquiries received, 1655 specifically involved vaccine safety topics. The most frequently asked-about topics included deaths following vaccination, myocarditis, pregnancy, and reproductive health outcomes, understanding or interpreting data from the Vaccine Adverse Event Reporting System (VAERS), and thrombosis with thrombocytopenia syndrome. CONCLUSIONS: Inquiries about vaccine safety generally reflect issues that receive media attention. ISO will continue to monitor vaccine safety inquiries and provide accurate and timely information to healthcare providers, public health officials, and the general public.

Heparin-Induced Thrombotic Thrombocytopenia (HITT) and Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT): Similar but Different.

Heparin-induced thrombocytopenia (HIT) represents an autoimmune process whereby antibodies are formed against heparin in complex with platelet factor 4 (PF4) after heparin administration. These antibodies can be detected by a variety of immunological assays, including ELISA (enzyme-linked immunosorbent assay) and by chemiluminescence on the AcuStar instrument. However, pathological HIT antibodies are those that activate platelets in a platelet activation assay and cause thrombosis in vivo. We would tend to call this condition heparin-induced thrombotic thrombocytopenia (HITT), although some workers instead use the truncated abbreviation HIT. Vaccine-induced (immune) thrombotic thrombocytopenia (VITT) instead reflects an autoimmune process whereby antibodies are formed against PF4 after administration of a vaccine, most notably adenovirus-based vaccines directed against COVID-19 (coronavirus disease 2019). Although both VITT and HITT reflect similar pathological processes, they have different origins and are detected in different ways. Most notable is that anti-PF4 antibodies in VITT can only be detected immunologically by ELISA assays, tending to be negative in rapid assays such as that using the AcuStar. Moreover, functional platelet activation assays otherwise used for HITT may need to be modified to detect platelet activation in VITT.

Assessing vaccine safety during a pandemic: Recent experience and lessons learned for the future.

During the roll out of vaccines during a pandemic, questions regarding vaccine safety often arise. This was surely true during the SARS-CoV-2 pandemic. Different tools and capabilities exist during the pre-authorization phase and post introduction each with its strengths and limitations. Here we review the various tools and their strengths and limitations and discuss what functioned well in high income settings and the limitations that unequal vaccine safety pharmacovigilance capacity imposed upon middle and low income countries.

Acute encephalomyelitis in a 52-year-old male post messenger ribonucleic acid severe acute respiratory syndrome coronavirus 2 vaccination: a case report.

BACKGROUND: Acute disseminated encephalomyelitis is a well-known, but rare, side effect of some vaccines, or symptom following a febrile illness. CASE: A 69-year-old, otherwise healthy Hispanic male presented with acute fever, confusion, and later progressive weakness after receiving the first dose of the mRNA-1273 (Moderna) severe acute respiratory syndrome coronavirus 2 vaccine. Considering the progressive deterioration of the patient, despite being on multiple immunosuppressive agents, a brain biopsy was obtained, which revealed nonspecific meningoencephalitis. CONCLUSION: In this case, we highlight the need for a regulatory framework to assist clinicians and patients with coverage of treatment for acute disseminated encephalomyelitis. The use of intravenous immunoglobulin in conjunction with glucocorticoids seems to be an effective treatment option.

Pregnancy exposure registries for drugs and vaccines in low-income and middle-income countries: scoping review protocol.

INTRODUCTION: Data regarding the safety of drugs and vaccines in pregnant women are typically unavailable before licensure. Pregnancy exposure registries (PERs) are an important source of postmarketing safety information. PERs in low-income and middle-income countries (LMICs) are uncommon but can provide valuable safety data regarding their distinct contexts and will become more relevant as the introduction and use of new drugs and vaccines in pregnancy increase worldwide. Strategies to support PERs in LMICs must be based on a better understanding of their current status. We developed a scoping review protocol to assess the landscape of PERs that operate in LMICs and characterise their strengths and challenges. METHODS AND ANALYSIS: This scoping review protocol follows the Joanna Briggs Institute manual for scoping reviews. The search strategy will be reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews Checklist. We will search PubMed, Embase, CINAHL and WHO's Global Index Medicus, as well as the reference lists of retrieved full-text records, for articles published between 2000 and 2022 that describe PERs or other resources that systematically record exposures to medical products during pregnancy and maternal and infant outcomes in LMICs. Title and abstracts will be screened by two authors and data extracted using a standardised form. We will undertake a grey literature search using Google Scholar and targeted websites. We will distribute an online survey to selected experts and conduct semistructured interviews with key informants. Identified PERs will be summarised in tables and analysed. ETHICS AND DISSEMINATION: Ethical approval is not required for this activity, as it was determined not to involve human subjects research. Findings will be submitted to an open access peer-reviewed journal and may be presented at conferences, with underlying data and other materials made publicly available.

An Introduction to the Japanese Immunization Program: Past, Present, and Future Perspectives.

In Japan, immunization is regulated by the Immunization Law, enacted shortly after World War II ended. It has been subsequently revised in response to social changes; however, after public health conditions improved, adverse events following immunization have received more public attention than the effectiveness of vaccination. This kind of public opinion had a major impact on the immunization program, leading to a so-called "vaccine gap" around a decade ago, that is, the less availability of vaccines for routine vaccination as compared with other countries. However, in recent years, several vaccines have been approved and are being routinely administered with the same schedule as in other countries. National immunization programs are influenced by various factors, such as cultures, customs, habits and ideas. This paper summarizes the status of immunization schedule and practices in Japan, process of policymaking, and possible future issues.

Considerations for unblinding individual study participants during vaccine trials.

Premature unblinding of individual participants is rarely reported in publications, but such unblinding can disrupt vaccine trials by causing worry and drop-out of other participants or "pseudo unblinding," in which participants or investigators over-interpret certain symptoms as being related to receiving an investigational product. This review summarizes appropriate reasons for unblinding in vaccine trials. Regulatory guidance could be improved by distinguishing guidance for vaccine trials from drug trials, with the recognition that unblinding individual participants in vaccine studies is rarely needed for management of adverse events following immunization.

Neurological sequelae of vaccines.

IMPORTANCE: Vaccines are a safe and efficacious way to prevent a variety of infectious diseases. Over the course of their existence, vaccines have prevented immeasurable morbidity and mortality in humans. Typical symptoms of systemic immune activation are common after vaccines and may include local soreness, myalgias, nausea, and malaise. In the vast majority of cases, the severity of the infectious disease outweighs the risk of mild adverse reactions to vaccines. Rarely, vaccines may be associated with neurological sequela that ranges in severity from headache to transverse myelitis, acute disseminated encephalomyelitis, and Guillain-Barre syndrome (GBS). Often, a causal link cannot be confirmed, and it remains unclear if disease onset is directly related to a recent vaccination. OBSERVATIONS: This review serves to summarize reported neurologic sequelae of commonly used vaccines. It will also serve to discuss potential pathogenesis. It is important to note that many adverse events or reactions to vaccines are self-reported into databases, and causal proof cannot be obtained. CONCLUSIONS AND RELEVANCE: Recognition of reported adverse effects of vaccines plays an important role in public health and education. Early identification of these symptoms can allow for rapid diagnosis and potential treatment. Vaccines are a safe option for prevention of infectious diseases.

Potential mechanisms of vaccine-induced thrombosis.

Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare syndrome characterized by high-titer anti-platelet factor 4 (PF4) antibodies, thrombocytopenia and arterial and venous thrombosis in unusual sites, as cerebral venous sinuses and splanchnic veins. VITT has been described to occur almost exclusively after administration of ChAdOx1 nCoV-19 and Ad26.COV2.S adenovirus vector- based COVID-19 vaccines. Clinical and laboratory features of VITT resemble those of heparin-induced thrombocytopenia (HIT). It has been hypothesized that negatively charged polyadenylated hexone proteins of the AdV vectors could act as heparin to induce the conformational changes of PF4 molecule that lead to the formation of anti-PF4/polyanion antibodies. The anti-PF4 immune response in VITT is fostered by the presence of a proinflammatory milieu, elicited by some impurities found in ChAdOx1 nCoV-19 vaccine, as well as by soluble spike protein resulting from alternative splice events. Anti-PF4 antibodies bind PF4, forming immune complexes which activate platelets, monocytes and granulocytes, resulting in the VITT's immunothrombosis. The reason why only a tiny minority of patents receiving AdV-based COVID-19 vaccines develop VITT is still unknown. It has been hypothesized that individual intrinsic factors, either acquired (i.e., pre-priming of B cells to produce anti-PF4 antibodies by previous contacts with bacteria or viruses) or inherited (i.e., differences in platelet T-cell ubiquitin ligand-2 [TULA-2] expression) can predispose a few subjects to develop VITT. A better knowledge of the mechanistic basis of VITT is essential to improve the safety and the effectiveness of future vaccines and gene therapies using adenovirus vectors.

COVID-19 Vaccine Safety First Year Findings in Adolescents.

BACKGROUND AND OBJECTIVES: The Food and Drug Administration expanded Emergency Use Authorization for use of Pfizer-BioNTech (BNT-162b2) coronavirus disease 2019 vaccine to include people ages 12 years and older on May 10, 2021. We describe adverse events observed during the first full year of the US coronavirus disease 2019 vaccination program for adolescents ages 12 to 17 years. METHODS: We conducted descriptive analyses using data from 2 complementary US vaccine safety monitoring systems: v-safe, a voluntary smartphone-based system that monitors reactions and health impacts, and the Vaccine Adverse Event Reporting System (VAERS), the national spontaneous reporting system. We reviewed reports and calculated adverse event reporting rates using vaccine administration data. RESULTS: Among 172 032 adolescents ages 12 to 17 years enrolled in v-safe, most reported reactions following BNT-162b2 were mild to moderate, most frequently reported on the day after vaccination, and more common after dose 2. VAERS received 20 240 adverse event reports; 91.5% were nonserious. Among adverse events of interest, we verified 40 cases of multisystem inflammation syndrome in children (1.2 cases per million vaccinations), 34 (85%) of which had evidence of prior severe acute respiratory syndrome coronavirus 2 infection; and 570 cases of myocarditis (17.7 cases per million vaccinations), most of whom (77%) reported symptom resolution at the time of report. CONCLUSIONS: During the first year BNT-162b2 was administered to adolescents ages 12 to 17 years, most reported adverse events were mild and appeared self-limited. Rates of myocarditis were lower than earlier reports. No new serious safety concerns were identified.

Real-World Monitoring of COVID-19 Vaccines: An Industry Expert View on the Successes, Challenges, and Future Opportunities.

Pharmacovigilance leaders from major vaccine developers describe the learnings from the coronavirus disease 2019 (COVID-19) pandemic in the area of pharmacovigilance and pharmacoepidemiology. The authors aim to raise awareness of the co-operation among vaccine developers, highlight common challenges, advocate for solutions, and propose recommendations for the future in the areas of real-world safety and effectiveness, safety reporting and evaluation, and regulatory submissions. To enable timely evaluation of real-world safety and effectiveness, multi-sponsor study platforms were implemented, resulting in quicker recruitment over wide geographical areas. Future gains could be derived by developing geographically flexible, common protocols and/or joint company-sponsored studies for multiple vaccines and a collective strategy to build low/middle-income country (LMIC) sentinel sites. Safety reporting, signal detection and evaluation was particularly challenging given the unprecedented number of adverse events reported. New methods were required to manage increased report volume while maintaining the ability to quickly identify and respond to new data that could impact the benefit-risk profile of each vaccine. Worldwide health authority submissions, requests for information and differing regulatory requirements imposed significant burden on regulators and industry. Industry consensus on the safety reporting requirements and joint meetings with regulatory authorities markedly reduced this burden for all stakeholders. The most impactful innovations should be undertaken rapidly and expanded to other vaccines and therapeutics, with a multi-stakeholder approach. The authors of this paper make future recommendations and have launched an initiative named BeCOME (Beyond COVID Monitoring Excellence) with a focus on actions in each of the highlighted areas.

[Anaphylaxis caused by vaccines]. / Anafilaxia causada por vacunas.

Even though the SARS-CoV-2 pandemic represents a historical challenge, science has had an exponential development, and the current vaccination campaigns are proof of this. Unfortunately, along came misinformation and myths regarding their production and their adverse effects. For this reason, we have considered of utter importance to review anaphylaxis, one of the most feared vaccine adverse events.Anaphylaxis can be defined as a life-threatening acute and systemic allergic reaction, with a wide clinical spectrum, which can be explained by many immunological mechanisms, and whose diagnostic complexity demands the fulfillment of strict criteria. Though infrequent, any vaccine has the potential to trigger anaphylaxis. In the United States, for the new SARS-CoV-2 vaccines, rates from 1:200 000 (Pfizer-BioNTech) to 1:360 000 doses (Moderna) have been estimated. Vaccine adverse events can be mediated by hypersensitivity reactions, either allergic or not. Unlike a typical drug allergy, rarely is the active ingredient responsible for the reaction. Therefore, excipients must be considered during the approach to this problem. Vaccine associated anaphylaxis has to be referred to an allergist so as to guarantee the maximum benefit for the patient and improve the vaccines' security profile.

A pesar de la difícil situación que se enfrenta con la actual pandemia de COVID-19, la ciencia ha tenido un desarrollo exponencial. Si bien la inmunización contra esa enfermedad ha sido posible gracias a ello, desafortunadamente se ha acompañado de desinformación y mitos en torno a su fabricación y reacciones adversas. Por tal razón, es importante revisar una de las reacciones adversas a vacunas más temidas para el personal de salud y la población general, la anafilaxia. La anafilaxia se define como una reacción alérgica aguda y sistémica que puede poner en riesgo la vida; se asocia con distintos mecanismos inmunológicos, factores desencadenantes y manifestaciones clínicas. Su diagnóstico puede ser confuso, por lo que se han establecido diferentes criterios. Todas las inmunizaciones tienen el potencial de desencadenar anafilaxia, aunque este evento es poco frecuente. Respecto de las vacunas contra el coronavirus SARS-CoV-2, en Estados Unidos se ha reportado una tasa de anafilaxia de 1:200 000 para la vacuna Pfizer-BioNTech, y de 1:360 000 para la vacuna de Moderna. Al igual que un fármaco, las vacunas pueden presentar efectos adversos mediados por mecanismos de hipersensibilidad, pero a diferencia de lo que sucede con los medicamentos, el principio activo rara vez es el responsable; es más frecuente que las reacciones indeseadas se deban a los excipientes. La sospecha de una anafilaxia secundaria a su aplicación obliga a una oportuna referencia y a un correcto diagnóstico, tanto para el beneficio del paciente como para mejorar el perfil de seguridad de la vacuna.