Overcoming Engineering Challenges to Enable Commercial-Scale mRNA Vaccine Manufacturing

Increasing production capacity may necessitate the facility to cater for higher hazardous area category (e.g., H-Occupancy) design features, such as specialized building construction and potential blast zones. [...]an assessment should cover: * Quantification of flammable material use for production steps, including buffer preparation and LNP storage * Equipment and facility cleaning strategies that contribute to the facility flammable materials inventory * Impact of HVAC design to avoid hazardous atmospheres (e.g., full fresh air), use of local exhaust ventilation (LEV) or fume hoods * Solvent distribution methods (e.g., closed solvent delivery and waste removal systems) * Location of solvent bulk storage outside of the processing area/ facility, and piping in what is necessary plus removing spent solvent in a timely manner (e.g., piped transfer to a waste tank for removal by a specialist contractor). At present, the process cannot be fully single-use, so thought needs to be put into the cleaning and sterilization processes, plus the analytical support infrastructure needed for reusable product-contact surfaces. [...]it is recommended that for each mRNA project, consideration is given to the following aspects to determine the link between the equipment available and the facility design: * Need for custom/proprietary equipment * Independent production rooms with "through-wall" buffer transfer through iris ports in from logistics corridor (Buffer Prep/Hold) * Room electrical classification needs versus process step. * Equipment selection versus electrical and fire code requirements * Benefits and limitations of implementing single-use technologies, given that the process will be hybrid (with stainless steel). [...]the limited capacity for outsourcing of supporting functions, such as facility environmental monitoring or product sterility testing, should be considered during concept design.

Hematological changes as a consequence of COVID-19 and its vaccines / Alteraciones hematológicas como consecuencia de COVID-19 y sus vacunas

El virus SARS-CoV-2 continúa infectando a millones de individuos en el mundo. Aunque los síntomas más frecuentes observados en los pacientes con COVID-19 son fiebre, fatiga y tos, en los casos severos la hipercoagulabilidad y la inflamación son dos condiciones que pueden producir complicaciones y causar daño en órganos, poniendo en riesgo la vida del paciente. Con el fin de clasificar a los pacientes durante el triaje, se han explorado diferentes marcadores hematológicos, incluidos el recuento de plaquetas, linfocitos y eosinófilos, y la relación neutrófilos/ linfocitos, entre otros. Por su parte, para la evaluación de las coagulopatías, se vienen determinando marcadores como el dímero D y el fibrinógeno. En esta revisión se abordan las coagulopatías y los parámetros hematológicos en pacientes con COVID-19, al igual que las anormalidades en la coagulación como la trombocitopenia trombótica inmune inducida por las vacunas contra el SARS-CoV-2

The SARS-CoV-2 virus continues to infect millions of individuals around the world. Although the most frequent symptoms observed in patients with COVID-19 are fever, fatigue and cough, in severe cases hypercoagulability and inflammation are two conditions that can cause complications and organ failure, putting the patient's life at risk. In order to classify patients during triage, different hematological markers have been explored, including platelet, lymphocyte, and eosinophil counts, and the neutrophil/lymphocyte ratio, among others. Furthermore, for the evaluation of coagulopathies, markers such as D-dimer and fibrinogen are being evaluated. This review addresses the coagulopathies and hematological parameters in patients with COVID-19, as well as coagulation abnormalities such as immune thrombotic thrombocytopenia induced by SARS-CoV-2 vaccines

Virus-like Particle Vaccines and Platforms for Vaccine Development.

Virus-like particles (VLPs) have gained a lot of interest within the past two decades. The use of VLP-based vaccines to protect against three infectious agents-hepatitis B virus, human papillomavirus, and hepatitis E virus-has been approved; they are very efficacious and offer long-lasting immune responses. Besides these, VLPs from other viral infectious agents (that infect humans, animals, plants, and bacteria) are under development. These VLPs, especially those from human and animal viruses, serve as stand-alone vaccines to protect against viruses from which the VLPs were derived. Additionally, VLPs, including those derived from plant and bacterial viruses, serve as platforms upon which to display foreign peptide antigens from other infectious agents or metabolic diseases such as cancer, i.e., they can be used to develop chimeric VLPs. The goal of chimeric VLPs is to enhance the immunogenicity of foreign peptides displayed on VLPs and not necessarily the platforms. This review provides a summary of VLP vaccines for human and veterinary use that have been approved and those that are under development. Furthermore, this review summarizes chimeric VLP vaccines that have been developed and tested in pre-clinical studies. Finally, the review concludes with a snapshot of the advantages of VLP-based vaccines such as hybrid/mosaic VLPs over conventional vaccine approaches such as live-attenuated and inactivated vaccines.

Immunosuppressive therapy and humoral response to third mRNA COVID-19 vaccination with a six-month interval in rheumatic disease patients.

OBJECTIVES: To evaluate the long-term impact of immunosuppressive therapeutic agents on antibody response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) mRNA vaccination in patients with autoimmune rheumatic diseases (AIRD) in order to propose a strategy for annual vaccination. METHODS: This prospective multicentre cohort study evaluated the humoral response to second and third BNT162b2 and/or mRNA-1273 vaccines in 382 Japanese AIRD patients classified into 12 different medication groups and in 326 healthy controls (HCs). The third vaccination was administered six months after the second vaccination. Antibody titres were measured using the Elecsys Anti-SARS-CoV-2 S assay. RESULTS: The seroconversion rate and antibody titres were lower in AIRD patients than in HCs 3-6 weeks after the second vaccination and 3-6 weeks after the third vaccination. Seroconversion rates were <90% after the third vaccination in patients receiving mycophenolate mofetil and rituximab. A multivariate analysis was conducted, adjusting for age, sex, and glucocorticoid dosage. Antibody levels after the third vaccination were significantly lower in the groups prescribed tumour necrosis factor (TNF) inhibitor with or without methotrexate, abatacept and rituximab or cyclophosphamide than those of HCs. The third vaccination induced an adequate humoral response in patients treated with sulfasalazine, bucillamine, methotrexate monotherapy, iguratimod, interleukin-6 inhibitors or calcineurin inhibitors including tacrolimus. CONCLUSIONS: Repeated vaccinations in many immunosuppressed patients produced antibody responses similar to those observed in HCs. In contrast, annual vaccination in patients receiving TNF inhibitors, abatacept, mycophenolate mofetil and rituximab may require caution.

Importance of the SARS-CoV-2 genome and spike protein in the immunopathogenesis of COVID-19 and in the efficacy of vaccines.

Coronavirus (CoV) infections cause respiratory and enteric diseases with clinical manifestations ranging from faint to severe, even lead to death of patients. High connectivity between nations and infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), represent a global health problem as the coronavirus disease 19 (COVID-19). This CoV-2 that cause SARS, which appeared in Wuhan, China, in December 2019 originated COVID-19 and declared as pandemic a few months posterior its appearance. In this review, the genomic and spike protein characteristics of SARS-CoV-2, the role of SARS-CoV-2 in the COVID-19 pathogenesis, cytokine storm, the role of cytotoxic T and B cells against SARS-CoV-2, as well as the vaccines efficacy (taking into account mutations in the spike protein) are described.

Los coronavirus (CoV) causan enfermedades respiratorias y entéricas leves, graves o críticas, pudiendo ocasionar la muerte del paciente. Debido a la alta conectividad entre naciones y a la transmisión, actualmente la COVID-19 representa un verdadero problema de salud pública en todo el mundo. El CoV-2 causante del síndrome respiratorio agudo grave (SARS-CoV-2) apareció a finales de diciembre de 2019 en Wuhan, China, y en marzo de 2020 la COVID-19 fue declarada pandemia. En esta revisión se describen las características del genoma y de la proteína espiga del SARS-CoV-2, su papel en la inmunopatogénesis de la COVID-19, la tormenta de citocinas, la actividad citotóxica inducida por células T y la producción de anticuerpos contra el SARS-CoV-2 mediada por células B, así como la eficacia de algunas vacunas, tomando en cuenta las mutaciones presentes en la proteína espiga.

Translatability scoring in prospective and retrospective COVID drug development cases.

BACKGROUND: The ongoing pandemic of severe acute respiratory syndrome coronavirus 2 has led to an enormous surge of clinical research. So far, the speed and success rate of related drug development projects, especially of vaccines, is unprecedented. For the first time, this situation allowed for the opportunistic evaluation of a translatability score, originally proposed in 2009, in a prospective manner. METHODS: Several vaccines and treatments under development in clinical phase III trials were selected for translational scoring with the translatability score. Six prospective and six retrospective case studies were performed. The scores had to be determined for a fictive date before any results of the phase III trial were reported in any media. Spearman correlation analysis and a Kruskal Wallis test were performed for statistical evaluation. RESULTS: A significant correlation between the translatability scores and the clinical outcomes in translation was found, as judged on the basis of positive/intermediate/negative endpoint studies or market approval. The Spearman correlation analysis of all cases (r = 0.91, p < 0.001), the prospective cases alone (r = 0.93, p = 0.008), and the retrospective cases alone (r = 0.93, p = 0.008) showed a strong correlation between the score and outcome; R2 demonstrated a score-derived determination of outcomes by 86%. CONCLUSIONS: The score detects strengths and weaknesses of a given project, resulting in the opportunity of selective amelioration of a project, as well as prospective portfolio risk balancing. Its substantial predictive value that has been demonstrated here for the first time could be of particular interest for biomedical industry (pharmaceutical and device manufacturers), funding agencies, venture capitalists, and researchers in the area. Future evaluations will have to address the generalizability of results obtained in an exceptional pandemic situation, and the potential adaptations of weighing factors/items to particular therapeutic areas.

Long-acting vaccine delivery systems.

Bolus vaccines are often administered multiple times due to rapid clearance and reduced transportation to draining lymph nodes resulting in inadequate activation of T and B lymphocytes. In order to achieve adaptive immunity, prolonged exposure of antigens to these immune cells is crucial. Recent research has been focusing on developing long-acting biomaterial-based vaccine delivery systems, which can modulate the release of encapsulated antigens or epitopes to facilitate enhanced antigen presentation in lymph nodes and subsequently achieve robust T and B cell responses. Over the past few years, various polymers and lipids have been extensively explored to develop effective biomaterial-based vaccine strategies. The article reviews relevant polymer and lipid-based strategies used to prepare long-acting vaccine carriers and discusses their results concerning immune responses.

The effect of COVID-19 vaccination on anticoagulation stability in adolescents and young adults using vitamin K antagonists.

INTRODUCTION: The European Medicine Agency has authorized COVID-19 vaccination in adolescents and young adults (AYAs) from 12 years onwards. In elderly vitamin K antagonist (VKA) users, COVID-19 vaccination has been associated with an increased risk of supra- and subtherapeutic INRs. Whether this association is also observed in AYAs using VKA is unknown. Our aim was to describe the stability of anticoagulation after COVID-19 vaccination in AYA VKA users. MATERIALS AND METHODS: A case-crossover study was performed in a cohort of AYAs (12-30 years) using VKAs. The most recent INR results before vaccination, the reference period, were compared with the most recent INR after the first and, if applicable, second vaccination. Several sensitivity analyses were performed in which we restricted our analysis to stable patients and patients without interacting events. RESULTS: 101 AYAs were included, with a median age [IQR] of 25 [7] years, of whom 51.5 % were male and 68.3 % used acenocoumarol. We observed a decrease of 20.8 % in INRs within range after the first vaccination, due to an increase of 16.8 % in supratherapeutic INRs. These results were verified in our sensitivity analyses. No differences were observed after the second vaccination compared to before and after the first vaccination. Complications after vaccination occurred less often than before vaccination (9.0 vs 3.0 bleedings) and were non-severe. CONCLUSIONS: the stability of anticoagulation after COVID-19 vaccination was decreased in AYA VKA users. However, the decrease might not be clinically relevant as no increase of complications nor significant dose adjustments were observed.

IgG4 Antibodies Induced by Repeated Vaccination May Generate Immune Tolerance to the SARS-CoV-2 Spike Protein.

Less than a year after the global emergence of the coronavirus SARS-CoV-2, a novel vaccine platform based on mRNA technology was introduced to the market. Globally, around 13.38 billion COVID-19 vaccine doses of diverse platforms have been administered. To date, 72.3% of the total population has been injected at least once with a COVID-19 vaccine. As the immunity provided by these vaccines rapidly wanes, their ability to prevent hospitalization and severe disease in individuals with comorbidities has recently been questioned, and increasing evidence has shown that, as with many other vaccines, they do not produce sterilizing immunity, allowing people to suffer frequent re-infections. Additionally, recent investigations have found abnormally high levels of IgG4 in people who were administered two or more injections of the mRNA vaccines. HIV, Malaria, and Pertussis vaccines have also been reported to induce higher-than-normal IgG4 synthesis. Overall, there are three critical factors determining the class switch to IgG4 antibodies: excessive antigen concentration, repeated vaccination, and the type of vaccine used. It has been suggested that an increase in IgG4 levels could have a protecting role by preventing immune over-activation, similar to that occurring during successful allergen-specific immunotherapy by inhibiting IgE-induced effects. However, emerging evidence suggests that the reported increase in IgG4 levels detected after repeated vaccination with the mRNA vaccines may not be a protective mechanism; rather, it constitutes an immune tolerance mechanism to the spike protein that could promote unopposed SARS-CoV2 infection and replication by suppressing natural antiviral responses. Increased IgG4 synthesis due to repeated mRNA vaccination with high antigen concentrations may also cause autoimmune diseases, and promote cancer growth and autoimmune myocarditis in susceptible individuals.

Relapse of minimal change disease following the third mRNA COVID-19 vaccination: a case report and literature review.

Mass vaccination is the most important strategy to terminate the coronavirus disease 2019 (COVID-19) pandemic. Reports suggest the potential risk of the development of new-onset or relapse of minimal change disease (MCD) following COVID-19 vaccination; however, details on vaccine-associated MCD remain unclear. A 43-year-old man with MCD, who had been in remission for 29 years, developed nephrotic syndrome 4 days after receiving the third dose of the Pfizer-BioNTech vaccine. His kidney biopsy revealed relapsing MCD. Intravenous methylprednisolone pulse therapy followed by oral prednisolone therapy was administered, and his proteinuria resolved within 3 weeks. This report highlights the importance of careful monitoring of proteinuria after COVID-19 vaccination in patients with MCD, even if the disease is stable and no adverse events occurred during previous vaccinations. Our case report and literature review of COVID-19 vaccine-associated MCD indicated that MCD relapse tends to occur later after vaccination and slightly more often following the second and subsequent vaccine doses than new-onset MCD.

Reprogramming viral immune evasion for a rational design of next-generation vaccines for RNA viruses.

Type I interferons (IFNs-α/ß) are antiviral cytokines that constitute the innate immunity of hosts to fight against viral infections. Recent studies, however, have revealed the pleiotropic functions of IFNs, in addition to their antiviral activities, for the priming of activation and maturation of adaptive immunity. In turn, many viruses have developed various strategies to counteract the IFN response and to evade the host immune system for their benefits. The inefficient innate immunity and delayed adaptive response fail to clear of invading viruses and negatively affect the efficacy of vaccines. A better understanding of evasion strategies will provide opportunities to revert the viral IFN antagonism. Furthermore, IFN antagonism-deficient viruses can be generated by reverse genetics technology. Such viruses can potentially serve as next-generation vaccines that can induce effective and broad-spectrum responses for both innate and adaptive immunities for various pathogens. This review describes the recent advances in developing IFN antagonism-deficient viruses, their immune evasion and attenuated phenotypes in natural host animal species, and future potential as veterinary vaccines.

Effectiveness of the Coronavirus Disease 2019 Bivalent Vaccine.

Background: The purpose of this study was to evaluate whether a bivalent coronavirus disease 2019 (COVID-19) vaccine protects against COVID-19. Methods: The study included employees of Cleveland Clinic in employment when the bivalent COVID-19 vaccine first became available. Cumulative incidence of COVID-19 over the following 26 weeks was examined. Protection provided by vaccination (analyzed as a time-dependent covariate) was evaluated using Cox proportional hazards regression, with change in dominant circulating lineages over time accounted for by time-dependent coefficients. The analysis was adjusted for the pandemic phase when the last prior COVID-19 episode occurred and the number of prior vaccine doses. Results: Among 51 017 employees, COVID-19 occurred in 4424 (8.7%) during the study. In multivariable analysis, the bivalent-vaccinated state was associated with lower risk of COVID-19 during the BA.4/5-dominant (hazard ratio, 0.71 [95% confidence interval, .63-79]) and the BQ-dominant (0.80 [.69-.94]) phases, but decreased risk was not found during the XBB-dominant phase (0.96 [.82-.1.12]). The estimated vaccine effectiveness was 29% (95% confidence interval, 21%-37%), 20% (6%-31%), and 4% (-12% to 18%), during the BA.4/5-, BQ-, and XBB-dominant phases, respectively. The risk of COVID-19 also increased with time since the most recent prior COVID-19 episode and with the number of vaccine doses previously received. Conclusions: The bivalent COVID-19 vaccine given to working-aged adults afforded modest protection overall against COVID-19 while the BA.4/5 lineages were the dominant circulating strains, afforded less protection when the BQ lineages were dominant, and effectiveness was not demonstrated when the XBB lineages were dominant.

BBIBP-CorV Vaccination against the SARS-CoV-2 Virus Affects the Gut Microbiome.

Several observational studies have confirmed that the severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) might substantially affect the gastrointestinal (GI) system by replicating in human small intestine enterocytes. Yet, so far, no study has reported the effects of inactivated SARS-CoV-2 virus vaccines on gut microbiota alterations. In this study, we examined the effects of the BBIBP-CorV vaccine (ChiCTR2000032459, sponsored by the Beijing Institute of Biological Products/Sinopharm), on gut microbiota. Fecal samples were collected from individuals whoreceived two doses of intramuscular injection of BBIBP-CorV and matched unvaccinated controls. DNA extracted from fecal samples was subjected to 16S ribosomal RNA sequencing analysis. The composition and biological functions of the microbiota between vaccinated and unvaccinated individuals were compared. Compared with unvaccinated controls, vaccinated subjects exhibited significantly reduced bacterial diversity, elevated firmicutes/bacteroidetes (F/B) ratios, a tendency towards Faecalibacterium-predominant enterotypes, and altered gut microbial compositions and functional potentials. Specifically, the intestinal microbiota in vaccine recipients was enriched with Faecalibacterium and Mollicutes and with a lower abundance of Prevotella, Enterococcus, Leuconostocaceae, and Weissella. Microbial function prediction by phylogenetic investigation of communities using reconstruction of unobserved states (PICRUSt) analysis further indicated that Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in carbohydrate metabolism and transcription were positively associated with vaccine inoculation, whereas capacities in neurodegenerative diseases, cardiovascular diseases, and cancers were negatively affected by vaccines. Vaccine inoculation was particularly associated with gut microbiota alterations, as was demonstrated by the improved composition and functional capacities of gut microbiota.

Myocarditis Following COVID-19 Vaccination: A Systematic Review.

COVID-19 vaccination has significantly reduced both the morbidity and mortality rates associated with SARS-CoV-2 infection. Vaccines, especially mRNA vaccines, have been proposed in several studies to complicate viral myocarditis. Thus, our systematic and meta-analysis review aims to further investigate the possibility of an association between COVID-19 vaccines and myocarditis. We systematically searched PubMed, Web of Science, Scopus, Ovid, and Google Scholar and did a gray search of other databases using the following keywords and terms: "Myocarditis ("Myocarditis" Mesh) OR "Chagas Cardiomyopathy" Mesh) AND "COVID-19 Vaccines" Mesh. The studies were limited to only English articles that reported myocardial inflammation or myocarditis associated with COVID-19 vaccines. Pooled risk ratio with its 95% confidence interval was analyzed by RevMan software (5.4) to perform the meta-analysis. Our study included 671 patients from 44 studies with a mean age of 14-40 years. Nevertheless, myocarditis was noted in a mean of (3.227) days, and 4.19 per million vaccination recipients experienced myocarditis. Most cases were clinically presented with manifestations of cough, chest pain, and fever. Laboratory tests revealed increased C-reactive protein, and troponin with all other cardiac markers in most patients. Cardiac magnetic resonance imaging (MRI) revealed late gadolinium enhancement with myocardial edema and cardiomegaly. Also, electrocardiograms revealed ST-segment elevation in most patients. Furthermore, the incidence of myocarditis was statistically significantly lower in the COVID-19 vaccine group as compared with the control group (RR = 0.15, 95% CI = 0.10-0.23, p-value < 0.00001). No significant association was found between COVID-19 vaccines and the incidence of myocarditis. The study's findings highlight the importance of implementing evidence-based COVID-19 prevention strategies, such as vaccination, to reduce the public health impact of COVID-19 and its associated complications.

Guillain-Barré syndrome following COVID-19 vaccination: An updated systematic review of cases.

Key Clinical Message: Guillain-Barré syndrome (GBS) is a rare but possible complication that may occur after COVID-19 vaccination. In this systematic review, we found that GBS presented in patients with an average age of 58. The average time for symptoms to appear was 14.4 days. Health care providers should be aware of this potential complication. Abstract: Most instances of Guillain-Barré syndrome (GBS) are caused by immunological stimulation and are discovered after vaccinations for tetanus toxoid, oral polio, and swine influenza. In this systematic study, we investigated at GBS cases that were reported after receiving the COVID-19 vaccination. Based on PRISMA guidelines, we searched five databases (PubMed, Google Scholar, Ovid, Web of Science, and Scopus databases) for studies on COVID-19 vaccination and GBS on August 7, 2021. To conduct our analysis, we divided the GBS variants into two groups, acute inflammatory demyelinating polyneuropathy and non-acute inflammatory demyelinating polyneuropathy (AIDP and non-AIDP), and compared the two groups with mEGOS and other clinical presentation In this systematic review, 29 cases were included in 14 studies. Ten cases belonged to the AIDP variant, 17 were non-AIDP (one case had the MFS variant, one AMAN variant, and 15 cases had the BFP variant), and the two remaining cases were not mentioned. Following COVID-19 vaccination, GBS cases were, on average, 58 years of age. The average time it took for GBS symptoms to appear was 14.4 days. About 56 percent of the cases (56%) were classified as Brighton Level 1 or 2, which defines the highest level of diagnostic certainty for patients with GBS. This systematic review reports 29 cases of GBS following COVID-19 vaccination, particularly those following the AstraZeneca/Oxford vaccine. Further research is needed to assess all COVID-19 vaccines' side effects, including GBS.

Understanding preclinical and clinical immunogenicity risks in novel biotherapeutics development.

Immunogenicity continues to pose a challenge in the development of biotherapeutics like conventional therapeutic-proteins and monoclonal antibodies as well as emerging modalities such as gene-therapy components, gene editing, and CAR T cells. The approval of any therapeutic is based on a benefit-risk evaluation. Most biotherapeutics address serious medical conditions where the standard of care has a poor outcome. Consequently, even if immunogenicity limits the utility of the therapeutic in a sub-set of patients, the benefit-risk assessment skews in favor of approval. Some cases resulted in the discontinuation of biotherapeutics due to immunogenicity during drug development processes, This special issue presents a platform for review articles offering a critical assessment of accumulated knowledge as well as novel findings related to nonclinical risks that extend our understanding of the immunogenicity of biotherapeutics. Some of the studies in this collection leveraged assays and methodologies refined over decades to support more clinically relevant biological samples. Others have applied rapidly advancing methodologies in pathway-specific analyses to immunogenicity. Similarly, the reviews address urgent issues such as the rapidly emerging cell and gene therapies which hold immense promise but could have limited reach as a significant number of the patient population could potentially not benefit due to immunogenicity. In addition to summarizing the work presented in this special issue we have endeavored to identify areas where additional studies are required to understand the risks of immunogenicity and develop appropriate mitigation strategies.

COVID-19 vaccine acceptance and related behavioral and psychological characteristics in individuals with mental disorders in Korea.

Objective: This study aimed to investigate COVID-19 vaccine acceptance and related factors in individuals with mental disorders in Korea. Methods: We surveyed 572 individuals with mental disorders about their attitudes toward COVID-19 vaccination using a 7-item self-rating questionnaire on vaccine acceptance and hesitancy. We categorized the respondents into groups based on their level of vaccine acceptance using hierarchical clustering. In addition, we evaluated the respondents' vaccination status and trust in sources of information regarding COVID-19 vaccines, and assessed their psychological characteristics using the Patient Health Questionnaire-9, Gratitude Questionnaire-6, and Big Five Inventory-10. Results: Clustering revealed three groups according to vaccine acceptance: 'totally accepting' (n= 246, 43.0%), 'somewhat accepting' (n= 184, 32.2%), and 'hesitant' (n= 142, 24.8%) groups. Three quarters of all participants, who belonged to the 'totally accepting' or 'somewhat accepting' groups, were willing to receive a COVID-19 vaccine despite concerns about its side effects. Individuals in the high vaccine acceptance group were older (F= 12.52, p< 0.001), more likely to receive the influenza vaccine regularly, and more likely to trust formal information sources. Additionally, they had higher levels of gratitude (F= 21.00, p< 0.001) and agreeableness (F= 4.50, p= 0.011), and lower levels of depression (χ2= 11.81, p= 0.003) and neuroticism (F= 3.71, p= 0.025). Conclusion: The present study demonstrated that individuals with mental disorders were generally willing to receive COVID-19 vaccination. However, they weighed its need and effectiveness against potential side effects before coming to a decision. It is important to understand the behavioral and psychological characteristics associated with vaccine acceptance, to effectively communicate its importance to individuals with mental disorders.

Immune-Mediated Organ-Specific Reactions to COVID-19 Vaccines: A Retrospective Descriptive Study.

Severe acute respiratory syndrome coronavirus 2 caused the global COVID-19 pandemic and public health crisis, and it led to the rapid development of COVID-19 vaccines, which can cause rare and typically mild hypersensitivity reactions (HRs). Delayed HRs to COVID-19 vaccines have been reported, and the excipients polyethylene glycol (PEG)2000 and polysorbate 80 (P80) are the suspected culprits. Skin patch tests do not help in diagnosing delayed reactions. We aimed to perform lymphocyte transformation tests (LTT) with PEG2000 and P80 in 23 patients with suspected delayed HRs. Neurological reactions (n = 10) and myopericarditis reactions (n = 6) were the most frequent complications. Seventy-eight percent (18/23) of the study patients were admitted to a hospital ward, and the median time to discharge was 5.5 (IQR, 3-8) days. Some 73.9% of the patients returned to baseline condition after 25 (IQR, 3-80) days. LTT was positive in 8/23 patients (5/10 neurological reactions, 2/4 hepatitis reactions and 1/2 rheumatologic reactions). All myopericarditis cases had a negative LTT. These preliminary results indicate that LTT with PEGs and polysorbates is a useful tool for identifying excipients as causal agents in HRs to COVID-19 vaccines and can play an important role in risk stratification in patients with HRs.