COVID-19 Vaccine Research Articles

Factors Influencing Moroccans’ Intention to Get the COVID-19 Vaccine: Results From a Cross-Sectional Study

Factors Influencing Moroccans’ Intention to Get the COVID-19 Vaccine: Results From a Cross-Sectional Study

Adapting COVID-19 research infrastructure to capture influenza and respiratory syncytial virus alongside SARS-CoV-2 in UK healthcare workers winter 2022/23 and beyond: protocol for a pragmatic sub-study

Introduction During the COVID-19 pandemic, extensive research was conducted on SARS-CoV-2; however, important questions about other respiratory pathogens remain unanswered. A severe influenza season in 2022–2023 with simultaneous circulation of SARS-CoV2 and respiratory syncytial virus is anticipated. This sub-study aims to determine the incidence and impact of these respiratory viruses on healthcare workers, the symptoms they experienced, the effectiveness of both COVID-19 and influenza vaccination and the burden of these infections on the National Health Service (NHS) workforce. Methods and analysis This is a longitudinal prospective cohort sub-study, utilising the population and infrastructure of the SARS-CoV-2 Immunity & Reinfection Evaluation (SIREN) study, which focuses on hospital staff in the UK. Participants undergo fortnightly nucleic acid amplification testing on a multiplex assay including SARS-CoV-2, influenza A and B and RSV, regardless of symptoms. Questionnaires are completed every two weeks, capturing symptoms, sick days, exposures, and vaccination records. Serum samples are collected monthly or quarterly from participants associated with a SIREN site. This sub-study commenced on 28/11/22 to align with the predicted influenza season and participants’ influenza vaccine status. The SIREN Participant Involvement Panel shaped the aims and methods for the study, highlighting its acceptability. UK devolved administrations were supported to develop local protocols. Analysis plans include incidence of asymptomatic and symptomatic infection, comparisons of vaccination coverage, assessment of sick day burden, and effectiveness of seasonal influenza against infection and time off work. Data are also integrated into UKHSA nosocomial modelling. Ethics and dissemination The protocol was approved by the Berkshire Research Ethics Committee (IRAS ID 284460, REC Reference 20SC0230) on 14/11/2022. Participants were informed in advance. As the frequency and method of sampling remained the same, implied consent processes were approved by the committee. Participants returning to the study give informed consent. Regular reports to advisory groups and peer-reviewed publications are planned to disseminate findings and inform decision making. Clinical trial registration number: ISRCTN11041050; registration date: 12 January 2021. Sub study included in protocol version: v8.0, and amended in v9.0

An Immunoinformatic Approach for Identifying and Designing Conserved Multi-Epitope Vaccines for Coronaviruses

Background/Objectives: The COVID-19 pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has exposed the vulnerabilities and unpreparedness of the global healthcare system in dealing with emerging zoonoses. In the past two decades, coronaviruses (CoV) have been responsible for three major viral outbreaks, and the likelihood of future outbreaks caused by these viruses is high and nearly inevitable. Therefore, effective prophylactic universal vaccines targeting multiple circulating and emerging coronavirus strains are warranted. Methods: This study utilized an immunoinformatic approach to identify evolutionarily conserved CD4+ (HTL) and CD8+ (CTL) T cells, and B-cell epitopes in the coronaviral spike (S) glycoprotein. Results: A total of 132 epitopes were identified, with the majority of them found to be conserved across the bat CoVs, pangolin CoVs, endemic coronaviruses, SARS-CoV-2, and Middle East respiratory syndrome coronavirus (MERS-CoV). Their peptide sequences were then aligned and assembled to identify the overlapping regions. Eventually, two major peptide assemblies were derived based on their promising immune-stimulating properties. Conclusions: In this light, they can serve as lead candidates for universal coronavirus vaccine development, particularly in the search for pan-coronavirus multi-epitope universal vaccines that can confer protection against current and novel coronaviruses.

Comparative assessment of a COVID-19 vaccine after technology transfer to Iran from critical quality attributes to clinical and immunogenicity aspects

During COVID-19 pandemic, international pharmaceutical companies put effort to build global manufacturing networks for vaccines. Soberana Plus vaccine, a recombinant protein based vaccine (RBD dimer), with the trade name of PastoCovac Plus in Iran, is based on a protein subunit platform in Cuba and completed preclinical and toxicological assessments. This study aimed at presenting the steps of vaccine technology transfer from Cuba to Iran. This study provides the first practical comparability results in Iran to ensure the quality, safety and efficacy of a protein subunit vaccine against COVID-19 after a successful technology transfer from Cuba. PastoCovac Plus was transferred to Iran at the formulation stage. The assessment of the active ingredient pharmaceutical (API) was achieved through physicochemical and clinical data collection and tests to assure if there was any adverse impact on the vaccination results. In order to assess the quality of the vaccine product after technology transfer, we sought different properties including regulatory features, physicochemical quality, vaccine potency and stability as well as its immunogenicity and safety. Following the evaluation of the clinical quality attributes (CQAs) based on the standard protocols, the results showed that the two vaccines are highly similar and comparable, with no considerable effect on safety or efficacy profiles. The CQAs were all in the acceptance limits in terms of safety and efficacy as well as clinical evaluation results. The immunogenicity evaluation also confirmed no significant differences between the vaccines regarding reinfection (P = 0.199) or vaccine breakthrough (P = 0.176). Furthermore, the level of anti-spike and neutralizing antibodies in the both vaccine groups was not significantly different indicating the equality of performance between the two vaccines. According to the results of the quality and clinical assessment of this study, we achieved an acceptable quality attributes and acceptant limits in terms of safety and efficacy of the vaccines pre and post technology transfer.

Leaky Vaccines: A Wicked Problem in Accelerated Vaccine Development

While no vaccine can provide 100 percent protection, a high standard of regulatory safety, efficacy and quality is essential for public trust and the uptake of vaccines as essential global public health tools. This article addresses a growing concern that suboptimal “leaky” vaccines threaten emergency response to pandemics as well as routine public health programs. Agile regulatory standards now advance earlier approval of vaccines and therapeutics that may have suboptimal effectiveness. The benefit-harm trade- offs that play an enormous role in regulatory assessment and all stages of vaccine development and delivery deserve better public scrutiny, transparency, and accountability. Drawing on the case of the first licensed malaria vaccine, RTS,S Mosquirix™, in light of the rapid approval of COVID-19 vaccines, we consider the socio-technical implications of leaky vaccines in global vaccine logics and suggest possibilities for building legitimacy to inform the next generation of regulatory technology policy.

2023 Nobel Prize in Physics and Medicine

The 2023 Nobel Prize in Physiology and Medicine was awarded jointly to Katalin Karikó and Drew Weissman for their contributions to the development of mRNA vaccines against COVID-19. Dr. Karikó obtained her doctoral degree from the University of Szeged before moving to the United States and obtaining the position of an adjunct professor at the University of Pennsylvania.1 Dr. Weissman obtained an M.D. and a Ph.D. degree at Boston University and subsequently obtained a faculty position at the Perelman School of Medicine at the University of Pennsylvania. The two researchers met during their shared time at the University of Pennsylvania and collaborated in exploring mechanisms in which mRNA can be used to stimulate immunity development in the body.2 By modifying nucleotides in mRNAs, the pair discovered that the subsequent introduction of mRNAs into cells led to reduced inflammatory responses and increased immune protein production. Before the COVID-19 pandemic, most vaccines stimulated immune responses via attenuated viruses, proteins, or viral genetic code-carrying vectors. These vaccines, while effective, required substantial resources to produce the number of cell cultures needed to synthesize adequate supplies of vaccine to combat pandemics, such as COVID-19.3 Contrastingly, mRNA vaccines can be prepared without cell cultures through in vitro transcription and nucleotides can be modified to adapt to mutating pathogens - flexibilities that allowed more than 12 billion COVID-19 vaccines to be produced and administered in less than three years of the start of the pandemic.4,5

COVID-19 vaccine uptake and associated factors among individuals living in a peri-urban area in Uganda: A cross-sectional study.

The Corona virus disease (COVID-19) is a respiratory illness that is caused by SARS-CoV-2 virus. This virus was first reported in China in December 2019. It then spread to all countries and from March 11, 2020, the World Health Organization declared the COVID-19 outbreak a pandemic. In Uganda, the disease was first reported in March 2020 and COVID-19 vaccines became available by January 2021. Although COVID-19 vaccines were available in Uganda, uptake remained low. The aim of this study was to establish COVID-19 vaccine uptake awareness in a peri-urban setting in Entebbe City, Uganda. This was a cross-sectional study conducted among 127 men and 263 women who reside in Entebbe City, Uganda. Data was collected on socio-behavioral characteristics, knowledge, attitude, and practice (KAP) about COVID-19 vaccine using interviewer administered questionnaires. Uptake of COVID-19 vaccine was defined as the proportion of participants who had received at least one dose of the COVID-19 vaccine. We used descriptive statistics to estimate awareness of COVID-19 vaccines. The 'chi-square test' and 'modified Poisson regression' were used to assess variations in uptake of COVID-19 vaccines among respondents and their socio-demographics as well as other characteristics. Ninety-nine percent (388 out of 390) of the study population were aware of at least one brand of COVID-19 vaccines in the country. Thirty-five percent (138 out of 390) knew that the vaccine immunity was achieved 14 days after the 2nd dose and 98.7% (385 out of 390) admitted that observing the standard operating procedure for COVID-19 infection prevention was necessary after vaccination. There was a gap in knowledge on vaccine safety reported by 74.6% (291 out of 390) participants. Some participants 37.2% (145 out of 390) had concerns about the vaccine. Of these, 57.9% (84 out of 145) believed that the vaccines were not helpful; and 30.3% (44 out of 145) feared serious side effects. Sixty-six percent (257 out of 390) believed that vaccines were not working and 79.0% (308 out of 390) admitted that vaccines were promoted for financial gain. At the time of performing the study, 36.2% and 22.3% had received the 1st and 2nd dose respectively. The main sources of information on COVID-19 vaccine were television (TV) and social media (p-value 0.001). In a multivariate model, COVID-19 vaccine acceptability was associated with salaried and self-employment (p-value 0.046). The other predicative factors were awareness of the COVID-19 vaccine (p-value <0.001) and having vaccine concerns (p-value 0.013). Uptake of COVID-19 vaccination in Entebbe community was low, partly attributed to knowledge gaps and concerns about vaccine safety and effectiveness. This highlights the need to enhance dissemination of information about COVID-19 vaccine. The lessons learnt in this study would be relevant for other emerging infections by informing vaccination implementation programs in similar settings.

Behaviorally Informed Text Message Nudges to Schedule COVID-19 Vaccinations: A Randomized Controlled Trial.

Vaccine hesitancy, especially related to COVID-19 vaccinations among Veterans, may limit uptake. Behaviorally informed text-based messages have the potential to improve uptake of COVID-19 vaccinations. To evaluate the impact of two different behaviorally informed text message nudges on COVID-19 vaccine scheduling and completion, compared to standard control message. Prospective, three-arm patient-level randomized quality improvement trial. Between March and May 2021, 20,523 Veterans were eligible for the initial series of COVID-19 vaccination, enrolled at two large Veterans Health Administration sites. Arm 1 (Control): standard scheduling message; Arm 2 (Social Good): standard message plus behaviorally informed text message "When you get a vaccine now, you help protect yourself, your family, and your community"; and Arm 3 (Scarcity): standard plus behaviorally informed text message "Only a limited number of vaccine appointments are available." Outcomes were vaccine scheduling and/or completion rate within 7 days of receipt of text message (primary), and within 14 days and 30 days after receipt of text message (secondary). Veterans had an overall rate of 19% of scheduling or receiving a vaccination in 7 days. In our adjusted intention-to-treat analysis, we found no difference between intervention social good or scarcity (aOR 0.98, 95% CI, 0.88-1.09, for both arms) compared to standard scheduling message. We found no statistical differences in our secondary outcomes. During the initial phases of vaccine roll-out, two behaviorally informed text messages did not increase COVID-19 vaccination rates among Veterans compared to a standard scheduling message.

How well do different COVID-19 vaccines protect against different viral variants? A systematic review and meta-analysis.

While the efficacy of coronavirus disease 2019 (COVID-19) vaccines has been evaluated in numerous trials, comprehensive evidence on how protection by different vaccines has varied over time remains limited. We aimed to compare protective effects of different vaccines against different viral variants. To achieve this, we searched Medline, Cochrane Library and Embase for randomized controlled trials assessing the efficacy of COVID-19 vaccines. Forest plots using Mantel-Haenszel and random-effects models were generated showing risk ratios (RRs) and 95% CIs by vaccines and variants. We included 36 studies with 90 variant-specific primary outcomes. We found a RR of 0.26 (95% CI 0.21 to 0.31) against all variants overall, with the highest protective effects against the wild-type (RR 0.13; 95% CI 0.10 to 0.18), followed by Alpha (RR 0.26; 95% CI 0.18 to 0.36), Gamma (RR 0.34; 95% CI 0.21 to 0.55), Delta (RR 0.39; 95% CI 0.28 to 0.56) and Beta (RR 0.49; 95% CI 0.40 to 0.62) variants. Nucleic acid vaccines showed the highest protection levels against all variants (RR 0.11; 95% CI 0.08 to 0.15), followed by protein subunit, inactivated virus and viral vector. In conclusion, we found high but heterogenous levels of protection for most COVID-19 vaccines, with decreasing protective effects for vaccines based on traditional technologies as SARS-CoV-2 variants emerged over time. Novel nucleic acid-based vaccines offered substantially higher and more consistent protection.

COVID-19 vaccination modified the effect of nirmatrelvir-ritonavir on post-acute mortality and rehospitalization: a retrospective cohort study.

While previous research examined coronavirus disease 2019 (COVID-19) antiviral-vaccine interactions through exploratory subgroup analysis, none specifically designed for examining this interaction or its impact on post-acute outcomes. This study examined the interaction between nirmatrelvir-ritonavir and complete COVID-19 vaccination on reducing the risk of post-acute outcomes among COVID-19 patients. We followed COVID-19 patients hospitalized between 11 March 2022 and 10 October 2023, until 31 October 2023 in Hong Kong. Exposure groups were based on nirmatrelvir-ritonavir usage and vaccination status (fully or not fully vaccinated). Post-acute death and all-cause rehospitalization were the study outcomes. Propensity score weighting was applied to balance covariates among exposure groups, including age, sex, Charlson Comorbidity Index, and concomitant treatments. Multiplicative and additive interactions between nirmatrelvir-ritonavir and vaccination status were assessed. A total of 50,438 COVID-19 patients were included in this study and arranged into four exposure groups. Significant additive interaction on post-acute rehospitalization was observed (relative excess risk, 0.10; 95% CI, 0.02-0.19; p-value, 0.018; attributable proportion, 0.07; 95% CI, 0.01-0.12; p-value, 0.017; synergy index, 1.26; 95% CI, 1.02-1.55; p-value, 0.032). The interaction on post-acute mortality was marginally significant. In the subgroup analysis, the interaction effect is more pronounced in older adults, female, and CoronaVac recipients. In conclusion, our study demonstrated an additive interaction between nirmatrelvir-ritonavir and complete vaccination on post-acute outcomes, suggesting greater long-term benefits of the antiviral for fully vaccinated individuals compared to not fully vaccinated patients.

A study of some psychological variables as predictors of COVID-19 vaccination anxiety among Faculty Members of Ain Shams University

The study aimed to investigate the relative contribution of each of psychasthenia, psychological flexibility, suggestibility, and conspiracy beliefs in predicting the anxiety of vaccination with the anti COVID-19 vaccine among faculty members at Ain Shams University (ASU). Examining the difference in the sample’s scores on the vaccination anxiety scale and its sub-factors according to the variables (age—chronic diseases—academic specialization—previous infection with COVID-19—gender), the sample of the study included 139 faculty members at Ain Shams University aged ranged from 23 to 78 years, with a mean of 49.52 years, and a standard deviation of 13.29 years. The vaccination anxiety scale, psychasthenia scale, psychological flexibility scale, suggestibility scale, and conspiracy beliefs scale were used to collect data. The results revealed that the variables of suggestibility and conspiracy beliefs significantly contribute to predicting the vaccination anxiety among faculty members at Ain Shams University. There is a significant difference in the average scores on the vaccination anxiety scale according to age, with the difference in favor of the age group less than fifty years, as well as according to the presence/absence of a previous infection with COVID-19, with the vaccination anxiety being higher for those who were previously infected. There has been no observed significant difference according to the presence/absence of chronic diseases or academic specialization.

EMSIG: Uncovering Factors Influencing COVID-19 Vaccination Across Different Subgroups Characterized by Embedding-Based Spatial Information Gain

Background/Objectives: COVID-19 and its variants continue to pose significant threats to public health, with considerable uncertainty surrounding their impact. As of September 2024, the total number of deaths reached 8.8 million worldwide. Vaccination remains the most effective strategy for preventing COVID-19. However, vaccination rates in the Deep South, U.S., are notably lower than the national average due to various factors. Methods: To address this challenge, we developed the Embedding-based Spatial Information Gain (EMSIG) method, an innovative tool using machine learning techniques for subgroup modeling. EMSIG helps identify subgroups where participants share similar perceptions but exhibit high variance in COVID-19 vaccine doses. It introduces spatial information gain (SIG) to screen regions of interest (ROI) subgroups and reveals their specific concerns. Results: We analyzed survey data from 1020 participants in Alabama. EMSIG identified 16 factors encompassing COVID-19 hesitancy and trust in medical doctors, pharmacists, and public health authorities and revealed four distinct ROI subgroups. The five factors, including COVID-19 perceived detriment, fear, skepticism, side effects related to COVID-19, and communication with pharmacists, were commonly shared across at least three subgroups. A subgroup primarily composed of Democrats with a high flu-shot rate expressed concerns about pharmacist communication, government fairness, and responsibility. Another subgroup, characterized by older, white Republicans with a relatively low flu-shot rate, expressed concerns about doctor trust and the intelligence of public health authorities. Conclusions: EMSIG enhances our understanding of specific concerns across different demographics, characterizes these demographics, and informs targeted interventions to increase vaccination uptake and ensure equitable prevention strategies.

Exploring the Interplay: COVID-19 Vaccination’s Influence on Long-term Symptoms and Quality of Life in Post-COVID Recovery

Exploring the Interplay: COVID-19 Vaccination’s Influence on Long-term Symptoms and Quality of Life in Post-COVID Recovery

Investigating the Effect of COVID-19 Vaccination on the Course of Disease and Recurrence of Attacks in Patients with Multiple Sclerosis

Background: The COVID-19 pandemic, with its high mortality rate, has underscored the urgent need for the rapid production of vaccines. This has prompted research into the effects of vaccines on specific populations, including patients with immune diseases such as multiple sclerosis (MS). Objectives: This study aimed to examine the impacts of COVID vaccination on individuals with MS. Methods: A retrospective cohort study was conducted involving 302 patients with relapsing-remitting MS who had received the coronavirus vaccine. These patients were referred to the MS clinic of two referral hospitals affiliated with Tehran University of Medical Sciences. The data collection instrument used was a checklist that included demographic information and disease-related details, such as the duration of the disease, underlying conditions, type and timing of vaccine administration, and the occurrence of attacks before and after the vaccination rounds. Results: During the first and second rounds of vaccination, the majority of patients (90.7% and 87.1%, respectively) received the Sinopharm vaccine. In the third round, approximately one-third (32.8%) did not receive the vaccine, and in the fourth round, the majority of individuals (85.8%) also did not receive it. However, most vaccinated individuals had received the Sinopharm vaccine. Among the sample, 34 individuals (11.3%) were newly diagnosed with MS after receiving the vaccine. Additionally, 41.7% of individuals experienced an attack within three months after receiving one of the vaccine doses. Conclusions: Vaccinations during the COVID era have significantly contributed to saving lives and preventing death. However, they have also had consequences that need careful examination and consideration in future vaccine production and epidemic management. The results obtained from this study can be associated with the vaccine, but given the retrospective nature of the study, further research on the long-term effects of the vaccine is needed to generalize the findings.

Dissemination in Social Media and Blogs of Public Health Information and Misinformation on Covid-19 Containment in Switzerland

Future epidemics are perceived as inevitable. Dissemination of information can enhance awareness, serving as an initial stride towards fostering desired epidemic-controlling actions among the public. In this study, a qualitative content analysis of Covid-19- and Switzerland-related social media and blog contributions points at a limited adoption of public health key messages and a negative reputation of the informing authorities. The authorities are to a marginal extent the source of information and a controversial sentiment towards vaccination emerges. In addition, we find a large share of disseminated information that is not conducive to pandemic containment. Within this, a substantial volume of misinformation emerges in statements on Covid-19-related issues. The misinformation consists primarily of unsubstantiated health consequences of the Covid-19 vaccination (both efficacy and side effects), and, less often, of trivialisation or denial of the pandemic. Furthermore, in a phase of political campaigning on a Covid-law referendum in Switzerland, social media contributors often portray pandemic containment as an undue, unlawful, or autocratic imposition on individual and collective freedom, and as a tool deployed for political repression. In addition, the pandemic or its containment are embedded in various conspiracies by users and containment measures are contested with religious, naturopathic or esoteric arguments.

Post COVID-Vaccine Cerebritis: A Case Report

We are reporting here a case of a 33-year-old male who presented to the Emergency Departmentat Lahore General Hospital with a short history of fever and generalised tonic-clonic seizures. The symptoms started one day after getting the first dose of Sinopharm vaccine. He was managed initially on the line of refractory status epilepticus in the ICU and was given empirical cover for meningoencephalitis. CSF analysis report came out normal. MRI of the brain showed left frontal lobe cerebritis. Fits and fever settled and the patient fully recovered on the third day of admission. There are very few reported neurological complications of Covid-19 vaccination. One of the rare complications which we have seen with the sinopharm vaccine is cerebritis. This case raises awareness among physicians and contributes to the existing literature so that more vigilance is done while administrating COVID-19 vaccines.

Exposure to Pollutants and Vaccines’ Effectiveness: A Systematic Review

Background: Many human activities release harmful substances, contaminating the air, water, and soil. Since exposure to environmental pollutants is currently unavoidable, it is important to verify how these compounds may influence individual immune responses to vaccines. Methods: This review was conducted in accordance with the PRISMA statement. The protocol was registered on the PROSPERO platform with the following ID: CRD42024582592. We evaluated all observational, semi-experimental, and experimental studies written in both Italian and English that reported possible effects of exposure to environmental pollutants on the production of vaccine-induced antibodies. Results: Forty-two studies were included. The effects of pollutants were examined mainly in terms of antibody production in relation to mumps, measles and rubella, diphtheria and tetanus, hepatitis A and B, Haemophilus influenzae type B, influenza, tuberculosis, pertussis, Japanese encephalitis, poliomyelitis, and COVID-19 vaccines. Perfluorinated compounds were the most studied pollutants. Conclusions: Correlations between exposure to pollutants and reductions in antibody production were found in quite all the selected studies, suggesting that pollution control policies could contribute to increase the efficacy of vaccination campaigns. However, the heterogeneity of the examined studies did not allow us to perform a meta-analysis, and the literature on each type of vaccine or pollutant is still too limited to generate robust evidence. In order to confirm the findings of the present systematic review, and in the perspective of establishing possible exposure limit values for each type of pollutant, further research in this field is required.

Effectiveness of BNT162b2 XBB vaccine in the US Veterans Affairs Healthcare System

Data evaluating effectiveness of XBB.1.5-adapted vaccines against JN.1-related endpoints are scarce. This nationwide test-negative case-control study within the US Veterans Affairs Healthcare System aims to estimate vaccine effectiveness (VE) of BNT162b2 XBB.1.5-adapted vaccine compared to not receiving an XBB vaccine of any kind against COVID-19 hospitalization, emergency department or urgent care visits (ED/UC), and outpatient visits. Between September 25, 2023 and January 31, 2024, effectiveness was 24–35% during a period of JN.1 predominance and 50–61% during XBB predominance across all outcomes. VE within 60 days of vaccination during the likely JN.1 period was 32% (95% confidence interval 3–52%) against hospitalization, 41% (23–54%) against ED/UC visits, and 31% (1–52%) against outpatient visits. Corresponding VE during the likely XBB period was 62% (44–74%), 52% (37–63%), and 50% (25–66%) by setting, respectively. Here, we show the importance of strain match to maximize the public health impact of COVID-19 vaccination.

The effect of COVID-19 vaccine on the international financial markets

Existing studies on the COVID-19 pandemic and vaccine development have primarily documented their effects on stock markets, with limited attention to international financial markets. This paper constructs a news-based sentiment index on COVID-19 vaccine development and examines its effects on international financial markets during the first year of the pandemic. We find positive vaccine sentiment decreases the CBOE Volatility Index (VIX) while boosting capital inflows and currency appreciation in emerging markets. It also reduces the unit price of risk in the context of carry trade risk premiums, as positive developments lower future risk and economic uncertainty.

The role of leukocyte activation in suspected Non-IgE excipient-related COVID-19 vaccine reactions: An exploratory hypothesis-driven study of pathogenesis.

Background: Adverse allergic reactions due to the administration of vaccines developed for the protection of coronavirus disease 2019 (COVID-19) have been reported since the initiation of the vaccination campaigns in December 15, 2020. Current analyses provided by the Centers for Disease Control and Prevention and the U.S. Food and Drug Administration in the United States have estimated the rates of anaphylactic reactions in 2.5 and 11.1 per million of messenger RNA (mRNA) 1273 and BNT162b2 vaccines administered, respectively. The mechanisms by which these mRNA vaccines induce adverse vaccine reactions have been the subject of conflicting reports. Although skin testing with excipient components found in mRNA-1273 and BNT162b2 vaccines, such as polyethylene glycol (PEG) and related vaccine lipid products, were originally recommended to identify potential predictive biomarkers of adverse allergic reactions, more recent evidence has suggested that routine skin testing with these vaccine excipients have poor predictability and do not correlate with susceptibility to vaccine injury. Objective: The goal of this proof-of-concept (POC) exploratory study was to investigate the role of leukocyte activation (LA) induced by lipid excipients found in mRNA COVID-19 vaccines in the pathogenesis of COVID-19 mRNA vaccine-associated adverse reactions by using an LA assay developed in our laboratory. Results: An LA assay was performed on blood samples obtained from 30 study subjects who were assigned to three study groups: group 1 consisted of 10 subjects who had received an mRNA COVID-19 vaccine and developed a serious vaccine adverse reaction; group 2 consisted of 10 subjects who had received a COVID-19 vaccine and developed a mild adverse reaction; and group 3 consisted of 10 subjects who had not received a COVID-19 vaccine and were asymptomatic. Five excipients were tested in each of the 10 subjects; hence, a potential of 50 reactions could be expressed in each of the three groups. In the subjects in group 1 who had shown clinically severe vaccine effects, 8 of 50 (16%) had severe LA index (LAI) responses (>144.83), 12 of 50 (24%) had moderate LAI responses (87.62 -144.82), and 30 of 50 (60%) had no reaction (0 - 87.61). In the subjects in group 2 who had shown clinically mild vaccine effects, 4 of 50 (8%) had severe LAI responses (>144.83), 9 of 50 (18%) had moderate LAI responses (87.62 -144.82), and 37 of 50 (74%) had no reaction. In the subjects in group 3 who had not received the vaccine and, therefore, had no clinical vaccine effects, 2 of 50 (4%) had severe LAI responses (>144.83), 10 of 50 (20%) had moderate LAI responses (87.62 -144.82), and 38 of 50 (76%) had no reaction LA index (LAI) responses. Conclusion: The results of this exploratory POC study suggest that the measurement of LA induced by PEG and other vaccine-related lipid excipients found in mRNA COVID-19 vaccines may provide a novel and useful predictive biomarker associated with adverse non-immunoglobulin E (IgE) related allergic reactions to these vaccines. The study results also underscore growing concerns related to these non-IgE hypersensitivity reactions and their potential for pathogenesis of adverse vaccine reactions. This is particularly noteworthy because, with the continuing emergence of novel and evolving variants of severe acute respiratory syndrome corona-virus 2 mutants, yearly immunization with mRNA vaccines will most likely be recommended. Although the study was not sufficiently powered to draw definitive conclusions with regard to associations between vaccine-associated COVID-19 reactions and LA, the trends of a more severe set of clinical reactions seen associated with LAI reactivity scores, particularly with ALC-0159 (2-[{polyethylene glycol} 2000]-N,N-ditetradecylacetamide), suggest a potential benefit worthy of exploration in future randomized controlled trials.