COVID-19 Vaccine Research Articles

Social patterning of health misinformation in two Eastern Mediterranean populations

Abstract Background Health misinformation, the spread of false or misleading information relevant to health, has been proposed as a major global public health thread by the WHO. We aimed to identify the major social determinants of health misinformation in the general Greek and Cypriot populations. Methods Following proportional quota sampling we recruited a nationwide sample of 585 adults from Greece and Cyprus between January 2022 and May 2023. A newly developed, culturally adopted questionnaire comprising 48 items, was used to assess misinformation on COVID-19 vaccines and the pandemic. Sociodemographic determinants of interest included gender, age, marital status, area of residence, educational attainment, and income. Multiple linear regression was used to determine associations between the aforementioned social factors and the two dimensions of health misinformation, applying mutual adjustment. Results Misinformation about both vaccination and the pandemic was higher in younger age groups (p-trend 0.026 and 0.007, respectively), among those separated, divorced, or widowed (mean difference, 95% CI compared to those single: 9.73, 0.45, 19.01), and among those living in semi-urban compared to urban areas (11.14, 1.32; 20.97 and 9.44, 1.96; 16.92, respectively). We also detected strong inverse socioeconomic gradients in health misinformation based on educational attainment and income (p-trend <0.001, for both). Conclusions Younger individuals, those living alone, those residing in semi-urban areas, and those with lower educational attainment and income are particularly prone to health misinformation. Our adjusted models show that this social phenomenon is not simply explained by differences in education, hence more complex, cultural, political, perceptual, and psychosocial dynamics might be in place. Addressing the social patterning of health misinformation would help manage the issue more effectively and also reduce health inequalities. Key messages • Health misinformation is strongly socially patterned in two Eastern Mediterranean European populations. • Targeting efforts to tackle health misinformation to those more vulnerable, would render such programmes more effective, also helping reduce social inequalities in health.

Latent class analysis of hospitalization, ICU admission, and mortality among COVID-19 patients in Iran

Identifying COVID-19 patients’ clinical phenotypes based on characteristics and comorbidities, as well as their differences, helps in terms of clinical care and potential crises. Our goal is to use Latent Class Analysis (LCA) to identify COVID-19 patient profiles based on demographics, symptoms, and comorbidities, and evaluate their correlation with ICU admission, hospitalization duration, and mortality in a cross-sectional study. We included hospitalized patients with positive SARS-CoV-2 tests in two referral hospitals in the south of Iran between January 2020 and July 2021. Data from 7,968 patients were evaluated in two time-specific intervals, known as “stratum,” based on the point at which the COVID-19 fourth peak and vaccinations were nearly initiated. After applying LCA, three classes identified the most at-risk individuals, including elderly women with hypertension, diabetes, and heart disease, and elderly men with heart and lung conditions, compared to two classes of healthier, younger individuals. Hospital stays were longer in the first stratum compared with the second (P-value = 0.043). ICU admission during the first stratum was significantly higher than in the second stratum (P < 0.001) and lower in classes one and two in the first stratum compared to class three (reference class). Mortality rates were not significantly different between strata (P = 0.054). Hospital stays and mortality rates significantly differed between the classes in each first and second stratum (P < 0.001). Using LCA to investigate COVID-19 patients has provided valuable insights into different patterns and outcomes of the disease. Patient variables, including age, gender, and comorbidities, were associated with greater mortality and ICU admission, which can assist in resource allocation and vaccination planning.

Traceability for strengthening supply chain systems and enhancing real-time visibility: Focus of NAFDAC on advancing vaccine traceability in Nigeria

This study explores the successful implementation of activities aimed at scaling traceability for COVID-19 and routine immunization (RI) vaccines to the local government area and selected healthcare facilities in Nigeria, funded by the Bill and Melinda Gates Foundation. The study was executed by the National Agency for Food and Drug Administration and Control (NAFDAC) and sought to enhance supply chain systems by deploying advanced traceability mechanisms and ensuring real-time stock visibility. The article discusses the accomplishments, challenges, and regulatory framework of NAFDAC, emphasizing GS1 technology-driven traceability, and presents the results of the field scanning activities conducted in July 2023. The approach involved a phased public sector pilot, showcasing the feasibility and challenges of tracking vaccine movement through the supply chain. The result shows the detection of 43 unique products across 1022 facilities from a total of 110,113 scans, offering valuable insights into vaccine distributions. The strategic goals of the project aligned with developing safety surveillance systems in low- and middle-income countries (LMICs) to facilitate patient access to global health products. Similarly, significant improvement in traceability through automated data capture (barcode scanning) and expanded coverage for COVID-19 and selected RI vaccines in Nigeria was found. Against this background, the information derived from this report will build confidence in patients regarding vaccine authenticity, establish a transparent and robust supply chain, and foster pharmacovigilance capability through integration with the track-and-trace systems. Thus, the study provides invaluable insights and opportunities for global health practitioners, policymakers, and researchers to incorporate track-and-trace into regulatory systems by other national regulatory authorities.

Quantifiable Cross-cultural Research on Medical Mistrust is Necessary for Effective and Equitable Vaccination in Low- and Middle-income Countries.

Perceptions of healthcare personnel and institutions substantially impact healthcare behaviors. In the US, minority experiences with racist events like the Tuskegee study, alongside everyday experiences of marginalization and discrimination, drive medical mistrust in populations that are already burdened with health inequalities. However, the concept of medical mistrust is rarely applied outside of industrialized contexts. Histories of colonialism, underfunded healthcare institutions, and the enormous cultural and ethnolinguistic diversity present in low- and middle-income countries (LMICs) make medical mistrust a likely contributor to health behavior in these contexts. In the era of COVID-19 and emergent malaria vaccines, there is an urgent need to mitigate factors leading to medical mistrust, which impedes interest in novel vaccines. Doing so requires substantial investment in research that examines the causes of medical mistrust across diverse communities, develops methodological tools that can effectively measure medical mistrust across diverse cultural and ethno-linguistic contexts, and applies this data to policy and public health messaging. This commentary highlights the role of medical mistrust in vaccination and argues for its utility in addressing vaccine decision-making in LMICs.

A New Natural Language Processing-Inspired Methodology (Detection, Initial Characterization, and Semantic Characterization) to Investigate Temporal Shifts (Drifts) in Health Care Data: Quantitative Study.

Proper analysis and interpretation of health care data can significantly improve patient outcomes by enhancing services and revealing the impacts of new technologies and treatments. Understanding the substantial impact of temporal shifts in these data is crucial. For example, COVID-19 vaccination initially lowered the mean age of at-risk patients and later changed the characteristics of those who died. This highlights the importance of understanding these shifts for assessing factors that affect patient outcomes. This study aims to propose detection, initial characterization, and semantic characterization (DIS), a new methodology for analyzingchanges in health outcomes and variables over time while discovering contextual changes for outcomes in large volumes of data. The DIS methodology involves 3 steps: detection, initial characterization, and semantic characterization. Detection uses metrics such as Jensen-Shannon divergence to identify significant data drifts. Initial characterization offers a global analysis of changes in data distribution and predictive feature significance over time. Semantic characterization uses natural language processing-inspired techniques to understand the local context of these changes, helping identify factors driving changes in patient outcomes. By integrating the outcomes from these 3 steps, our results can identify specific factors (eg, interventions and modifications in health care practices) that drive changes in patient outcomes. DIS was applied to the Brazilian COVID-19 Registry and the Medical Information Mart for Intensive Care, version IV (MIMIC-IV) data sets. Our approach allowed us to (1) identify drifts effectively, especially using metrics such as the Jensen-Shannon divergence, and (2) uncover reasons for the decline in overall mortality in both the COVID-19 and MIMIC-IV data sets, as well as changes in the cooccurrence between different diseases and this particular outcome. Factors such as vaccination during the COVID-19 pandemic and reduced iatrogenic events and cancer-related deaths in MIMIC-IV were highlighted. The methodology also pinpointed shifts in patient demographics and disease patterns, providing insights into the evolving health care landscape during the study period. We developed a novel methodology combining machine learningand natural language processing techniques to detect, characterize, and understand temporal shifts in health care data. This understanding can enhance predictive algorithms, improve patient outcomes, and optimize health care resource allocation, ultimatelyimproving the effectiveness of machine learning predictive algorithms applied to health care data. Our methodology can be applied to a variety of scenarios beyond those discussed in this paper.

Long-term cardiovascular events in individuals hospitalised with COVID-19: a retrospective cohort

Abstract Background The post-COVID condition involves a range of persistent or new symptoms affecting various organs, including an increased risk of cardiovascular issues. As there are limited data on cardiovascular events in post-acute COVID-19 patients, we aimed to estimate their incidence and assess its association with patient and infection characteristics in Portugal. Methods We conducted a registry-based retrospective cohort study from seven hospitals across Portugal, including individuals hospitalised due to COVID-19 between March 2020 and March 2021. Our outcome of interest was cardiovascular events in the post-acute phase of COVID-19, occurring at least 30 days after the positive SARS-CoV-2 test. The variables of interest considered were the severity of the episode, existing cardiovascular risk and vaccination status before the SARS-CoV-2 test. Person-years and incidence rates were estimated. A Cox proportional hazard regression model was employed to assess risk factors. Results We included 1,803 patients in the analysis, of which 143 (7.9%) experienced at least one cardiovascular event following COVID-19 hospitalisation. The overall incidence rate of having at least one cardiovascular event was 34.65 per 1,000 person-years (95% confidence interval (CI): 29.20; 40.82). We found a higher risk of cardiovascular events for individuals with pre-existing cardiovascular risk (adjusted hazard ratio (aHR): 3.76, 95% CI: 1.53; 9.24) and lower risk for individuals with at least one vaccine dose before the SARS-CoV-2 test (partial - aHR: 0.44, 95%CI: 0.30; 0.64, complete - aHR: 0.46, 95%CI: 0.2; 0.80). We did not find a significant difference between the severity of the COVID-19 episode and the risk of having cardiovascular events post-COVID-19. Conclusions Our results indicate the presence of cardiovascular complications post-COVID-19, emphasising the need for healthcare systems to initiate screening and preventive strategies for individuals deemed at elevated risk. Key messages • COVID-19 vaccination decreases the risk of cardiovascular events post-COVID-19. • Healthcare systems should start screening and preventive strategies for individuals with pre-existing risk of cardiovascular events.

5.I. Scientific session: Epidemiological insights into vaccine hesitancy in Europe: building bridges and overcoming barriers

Abstract Vaccine hesitancy remains a pivotal challenge in public health, undermining immunization efforts and the containment of infectious diseases across Europe. This scientific session aims to dissect the complex nature of vaccine hesitancy, uncovering epidemiological trends and barriers to vaccine acceptance, particularly in diverse demographic contexts. The objective is to facilitate a comprehensive understanding among public health stakeholders and to foster actionable strategies through enriched dialogue and interaction. This session will delve into recent studies and projects that highlight the variability of vaccine hesitancy within Europe. First, an exploration of COVID-19 vaccine acceptance will reveal how sociodemographic factors influence vaccine-related behaviors across 20 European nations. This will be complemented by an analysis of targeted interventions designed to enhance vaccine uptake among migrant populations, drawing lessons from the RIVER-EU project. Additionally, a focus on national efforts to combat measles vaccine hesitancy will provide a case study on the challenges and successes in altering public health narratives. Based on the feedback received on last year’s session, the format is intended not only to provide a platform to present empirical evidence and insights but also to encourage a participatory environment where attendees can exchange ideas and propose innovative solutions. For this reason, the session will engage the audience through an interactive discussion period at the end of each of the three presentations, stimulating thought-provoking dialogues that could lead to effective and innovative public health practices. Fostering international and interdisciplinary collaboration in the field of vaccine hesitancy is key for continued monitoring and reporting on the vaccine hesitancy phenomenon and inspiring actionable solutions. Key messages • Sociodemographic factors are associated with vaccine hesitancy across Europe indicating the potential for targeted strategies. • A platform to share insights and inspire actionable public health solutions to combat vaccine hesitancy amomg European public health professionals is needed.

Substantial morbidity and mortality due to cardiovascular diseases in hospitalized vaccinated and un-vaccinated patients with COVID-19 from 16 countries: the WHF COVID-19 Long-term study

Abstract Background Long-term adverse consequences of the COVID-19 affect many organ systems, and this requires the identification and appropriate care of diverse symptoms. Purpose The World Heart Federation (WHF) international study describes the burden of clinical sequelae of COVID-19 up to 1 year after hospitalization, including patients from low- middle-and high-income countries. Methods We prospectively recruited patients hospitalized due to COVID-19 from 16 countries between January 2022 and June 2023. Patients were followed up at 1, 3, 6, and 9-12 months after hospital discharge. A standardized questionnaire administered by telephone collected data on long COVID symptoms, quality of life using the EuroQol 5 Dimension scale (EQ-5D), and disease outcomes including new onset diabetes and hypertension, major adverse cardiovascular events (MACE), and mortality. We report a descriptive analysis including demographic characteristics and outcomes up to one year after initial hospitalization. Results Of 2504 patients, the majority were Asian (78%), and male (56%). Mean age was 59.2 years (SD 19.9). Low- and lower-middle-income country participants constituted 65% of the cohort, with upper middle-income and high-income representing 20% and 15%, respectively. Follow-up rate was complete for 86%. 55% had received at least two doses of COVID-19 vaccination. At 1 month, 63% reported at least one persistent symptom, which decreased to 28% at 9-12 months. Fatigue was reported by 45% at 1-month and 17% at final follow-up. Anxiety occurred in 20% and 9% at these respective timepoints, and breathlessness in 12% and 6%. At 9-12 months, moderate to severe impairment of usual activities as measured by EQ-5D occurred in 19%, anxiety/depression in 10%, and mobility problems in 10%. The most frequent post-discharge new-onset illnesses were pulmonary embolism (7%), kidney problems (4%), and hypertension (3%). In-hospital mortality was 4% (n=102), and a further 12% (265 patients) died by one-year. The most common cause was sudden cardiac death (59%), respiratory disease including pulmonary embolism (13%), and stroke (6%). Conclusions We observed a significant burden of post-COVID-19 complications with one fifth of patients with persistent difficulties in usual activities at one year. This underscores the urgent need to understand the underlying mechanisms for organ damage and death, and for targeted preventive strategies and proactive management approaches to reduce them.

The NHS London Legacy and Health Equity Partnership: Evaluation of an equity lens framework

Abstract Background Disparities in COVID-19 vaccination uptake emphasised stark inequalities linked to ethnicity and deprivation, highlighting lack of trust and access barriers. London health leaders committed to create a community-centred legacy through the development of the NHS Legacy and Health Equity Partnership (LHEP); A novel 2-year programme aiming to close the equity gap in vaccinations, screening and access to health, focused on underserved communities, delivered in collaboration with London partners and communities. LHEP focused on 12 unique programmes with a key role of system leadership. Outputs included 15 reports, 6 conference presentations, 7 academic publications, 6 community workshops and 5 toolkits including development of an overarching LHEP framework aiming for long-term legacy. Methods An evaluation was designed to assess the benefits and limitations of the programme and framework through 16 semi-structured interviews and 5 focus groups delivered with key stakeholders. Ethical approval was obtained from the UKHSA Research Ethics Group. Data was coded inductively and drawn into themes. Results LHEP was said to add value through a) a dedicated team championing health equity and visible focus of leadership within the equity space b) fostering community engagement enabling dialogue between health systems and communities c) advocating co-production, building trust, focusing on communities in vulnerable circumstances d) programme innovation and agility d) drawing from COVID-19 lessons and disseminating learning. Interviewees stressed a legacy beyond vaccinations, establishing London as a blueprint for others. Conclusions Lessons were drawn into the ‘LHEP Approach for Health Equity’, a concise framework to guide partners to embed health equity, gathering 4 key tenets to ensure ‘no community is left behind’; data, evidence and learning; commitment from leaders and strong partnerships, allow for innovation and consider sustainability and communities at the centre. Key messages • Legacy and Health Equity Partnership is a 2-year multistakeholder programme aiming to tackle inequalities for the diverse communities of London that built evidence and led system change. • Evaluation stressed the impact of establishing London as a blueprint to follow and a framework to guide and support partners striving for health equity.

Managing a 4000-participant cohort with a novel mobile app: data from the RisCoin study in Germany

Abstract Issue RisCoin, a prospective monocentric longitudinal observational study, aimed to identify risk factors for COVID-19 vaccine failure. Secondary aim is to monitor symptoms, SARS-CoV-2 infection, vaccination status of 3816 enrolled healthcare workers (HCW) and 180 patients with inflammatory bowel disease (IBD). Since the LMU University Hospital Munich served both as study sponsor and employer of the HCW, a secured approach was required. Description of the solution Participants accessed the study app (CentraXX, KAIROS GmbH, Germany) via pseudonymized Contact-ID with irreversible anonymization after 6 months. Key app features were the serological results report, bidirectional messaging, and weekly survey for self-reported data on vaccinations, infections, and symptoms. Active app use was defined as submitting &amp;gt;1 weekly survey during the study period 10.2021-12.2022. Results Over 15 months, our study team maintained 1964 two-way communications with 958 participants via the app. Of 3979 participants with app access, 3622 (91%) were active users, 2606 (65%) submitted 1 to 11 surveys, 1016 (26%) made ≥12 submissions (P75, “frequent users”). Frequent users were more likely to be IBD patients (p = 0.001), female (p &amp;lt; 0.001), aged 60 or older (p &amp;lt; 0.001). Staff in administration and nurses were more likely to be frequent users compared to physicians (p &amp;lt; 0.001). Main problems included the initial operational system disparities resulting in app crashes and continuous need for app reactivation. Both led to loss of active participants and required substantial staff resources to onboard and support participants during the study. Lessons The study app enabled secure, flexible, bidirectional communication with all participants. Despite technical issues, the majority actively used the app and provided valuable longitudinal data through weekly survey submissions. Key messages • A study-specific app provides a flexible and secure bidirectional anonymous communication for the study team and participants. • Adherence to app-based communication and data collection for pandemic monitoring was particularly high among patients, nurses and administrative staff.

The Impact of COVID-19 Vaccination and Infection on the Exacerbation of Myasthenia Gravis

Objectives: Myasthenia Gravis (MG) is an autoimmune disorder that can exacerbate for various reasons, including vaccination and infection. This study aimed to investigate the safety of COVID-19 vaccines for MG patients, factors influencing MG exacerbation after COVID-19 infection (MECI), the course and prognosis of MECI, and the impact of COVID-19 vaccine on infected MG patients. Methods: Patients were enrolled from the MG database in the Department of Neurology, Xuanwu Hospital, Capital Medical University. Two questionnaires were administered to collect data concerning COVID-19 vaccination (questionnaire 1, Q1) and infection (questionnaire 2, Q2) during two distinct periods. MG exacerbation was defined as an increase of at least two points in the MG activity of daily living (MG-ADL) score. COVID-19 severity was categorized as “hospitalization” or “home management”; Results: During the first data-collecting period, our database registered 1013 adult patients: 273 (26.9%) had received COVID-19 vaccinations and completed Q1, and 8 (2.9%) experienced MG exacerbation after vaccination. During the second data-collecting period, among the newly registered patients, 366 patients completed Q2. Of these, 244 were infected, with 39 (16.0%) experiencing MECI and 21 (8.6%) requiring hospitalization. Multivariate analysis showed that generalized myasthenia gravis was associated with MECI (OR 3.354, 95% CI: 1.423–7.908, p = 0.006). Among the 244 infected patients, 143 had received COVID-19 vaccinations, including 14 who received their booster dose within 6 months before COVID-19 and 129 who were vaccinated more than 6 months before COVID-19. The remaining 101 were unvaccinated. No significant associations were found between COVID-19 vaccination and COVID-19 severity (p = 0.292) or MECI incidence (p = 0.478); Conclusions: COVID-19 vaccines were found to be safe for MG patients in stable condition. Patients with gMG were more susceptible to experiencing MECI. No significant impact of the vaccine on COVID-19 severity or MECI incidence was observed.

Thyroid Function in the Time of COVID-19: A Systematic Review of Disease Progression and Vaccination Effect

Objectives: This systematic review sought to address three key questions: (1) what differences in abnormal thyroid function test results are observed between COVID-19 patients and healthy individuals? (2) How does the severity of COVID-19 infection influence the development of thyroid dysfunction? (3) What impact do COVID-19 vaccines have on thyroid function and autoimmune processes? Methods: A literature search was conducted in PubMed, Web of Science, and Scopus from December 2019 to April 2023 to identify studies on thyroid dysfunction in COVID-19 patients without pre-existing thyroid conditions. The search focused on observational and case-control studies. Results: The literature search yielded 329 reports, from which duplicates and unrelated publications were excluded. Ultimately, 21 studies met the inclusion criteria and were selected for review. A second literature search yielded 605 reports, from which 5 studies were selected for inclusion in the systematic review. Conclusions: The findings suggest that SARS-CoV-2 infection can induce transient and reversible thyroid dysfunction, possibly through direct viral effects on the thyroid gland or via indirect immune-mediated mechanisms. Clinicians should be mindful of the potential, albeit rare, thyroid-related adverse effects of COVID-19 vaccines and monitor thyroid function, particularly in high-risk individuals.

How did slovak students perceive the COVID-19 pandemic: Insights from one of the least vaccinated EU countries.

The COVID-19 pandemic brought different challenges to different populations. A less explored group was university students who generally suffered low mortality rates compared to other populations. Yet, they were affected by the psychological impact of lockdowns and limited access to education and socialization. This paper focuses on Slovakia, one of the least vaccinated EU countries. In November 2021 we conducted eight focus groups with 51 university students (45 women; 6 men; M = 23.67; SD = 3.43) and analyzed the data using reflexive thematic analysis. Our results identified the development of prevailing themes associated with COVID-19. Initially, COVID-19 was perceived as unreal but brought certain secondary benefits. We also identified themes of exaggerated disease, conspiracy, resignation, frustration, or adaptation to the disease. We divided the students into three groups based on their COVID-19 vaccine stance: accepting, hesitant, and rejecting. Insights from these groups could guide better communication strategies in the future.

Cross-Reactive Immune Response of Bovine Coronavirus Spike Glycoprotein to SARS-CoV-2 Variants of Concern

The high variability observed in the clinical symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections has been attributed to the presence, in a proportion of infection-naive subjects, of pre-existing cross-reactive immune responses. Here, we demonstrate that the bovine coronavirus spike protein (BoS) may represent a source of protective immunity to SARS-CoV-2. Indeed, vaccination of BALB/c mice with a Bovine herpesvirus 4 (BoHV-4)-based vector expressing BoS induced both cell-mediated and humoral immune responses that cross-react with SARS-CoV-2 spike protein. Although the spike-specific antibodies induced by BoS did not neutralize SARS-CoV-2, the T lymphocytes activated by BoS were able to induce cytotoxicity of cells expressing spike proteins derived from several SARS-CoV-2 variants. These results demonstrate that immunization with BoS may represent a source of cross-reactive immunity to SARS-CoV-2, and that these cross-reactive immune responses may exert protective functions. These results contribute to deciphering the mechanisms responsible for lack or mildness of symptoms observed in many individuals upon SARS-CoV-2 infection and may open new ways for the development of new vaccines for coronaviruses.

Is it Time for Multi-Drug Therapy with Combination of Therapeutic Nucleic Acids?

Therapeutic nucleic acids (TNAs) are a new class of drugs that exhibit different properties and mechanisms of action from those of small molecules or biological drugs. Over twenty oligonucleotide drugs and several COVID-19 vaccines have received regulatory approval for clinical use. A characteristic feature of these TNAs is that they are directed against one specific biological target and one specific RNA or DNA sequence. Consequently, TNAs currently used are administered as monotherapy. Due to the known advantages of multidrug therapy with low molecular weight drugs, it may be time to intensify work on such a treatment protocol, also in the case of TNAs.

MDA5 Is a Major Determinant of Developing Symptoms in Critically Ill COVID-19 Patients.

Apart from the skin and mucosal immune barrier, the first line of defense of the human immune system includes MDA5 (ifih1 gene) which acts as a cellular sensor protein for certain viruses including SARS-CoV-2. Upon binding with viral RNA, MDA5 activates cell-intrinsic innate immunity, humoral responses, and MAVS (mitochondrial antiviral signaling). MAVS signaling induces type I and III interferon (IFN) expressions that further induce ISGs (interferon stimulatory genes) expressions to initiate human cell-mediated immune responses and attenuate viral replication. SARS-CoV-2 counteracts by producing NSP1, NSP2, NSP3, NSP5, NSP7, NSP12, ORF3A, ORF9, N, and M protein and directs anti-MDA5 antibody production presumably to antagonize IFN signaling. Furthermore, COVID-19 resembles several diseases that carry anti-MDA5 antibodies and the current COVID-19 vaccines induced anti-MDA5 phenotypes in healthy individuals. GWAS (genome-wide association studies) identified several polymorphisms (SNPs) in the ifih1-ifn pathway genes including rs1990760 in ifih1 that are strongly associated with COVID-19, and the associated risk allele is correlated with reduced IFN production. The genetic association of SNPs in ifih1 and ifih1-ifn pathway genes reinforces the molecular findings of the critical roles of MDA5 in sensing SARS-CoV-2 and subsequently the IFN responses to inhibit viral replication and host immune evasion. Thus, MDA5 or its pathway genes could be targeted for therapeutic development of COVID-19.

Engineered protein subunit COVID19 vaccine is as immunogenic as nanoparticles in mouse and hamster models

Initial studies on the immunogenicity of SARS-CoV-2 (CoV-2) S glycoprotein (“spike”) as a protein subunit vaccine suggested sub-optimal efficacy in mammals. Although protein engineering efforts have produced CoV-2 spike protein sequences with greatly improved immunogenicity, additional strategies for improving the immunogenicity of CoV-2 protein subunit vaccines are scaffolding and the use of adjuvants. Comparisons of the effectiveness of engineered protein-only and engineered protein-nanoparticles vaccines have been rare. To explore this knowledge gap, we inoculated mice with two doses of either sequence-optimized trimeric spike protein or one of several sequence-optimized spike nanoparticles. We measured their immune response up to two months after the first dose. We also measured the immune response and protection against live virus in hamsters inoculated with either sequence-optimized trimeric spike protein or a liposome-based sequence-optimized spike nanoparticle. We found that in the presence of adjuvant, the antibody and neutralization titers elicited by spike-nanoparticles were not significantly greater than those elicited by spike-only in mice, even at doses as low as 0.1 µg/animal. Hamsters vaccinated with spike-only or spike-nanoparticles were equally protected from live virus one month after their first inoculation. These results suggest that sequence-optimized protein subunit vaccines in the form of individual prefusion-stabilized trimers can be as effective in improving immunogenicity as scaffolded forms.

New insights into the increased risk of migraines from COVID-19 infection and vaccination: a Mendelian randomization study

IntroductionMigraine is a prevalent neurological disorder characterized by recurrent attacks, leading to a substantial global disease burden. Recent observational studies have reported the onset and worsening of migraine following COVID-19 infection and vaccination. However, traditional observational study designs have limitations in controlling for confounding factors, potentially resulting in biased and inconsistent conclusions. To address this, we applied Mendelian randomization (MR) to investigate the causal relationship between COVID-19 infection and vaccination with migraine.MethodsThis study utilized summary-level genome-wide association study (GWAS) data from the GWAS catalog and FinnGen database to evaluate the effects of varying degrees of COVID-19 infection and vaccination on migraine. We employed inverse variance weighted (IVW) fixed-effect and random-effect models as the primary methods for MR analysis, with MR-Egger and other approaches as complementary methods. Sensitivity analyses, including Cochran's Q test, MR-Egger intercept regression, and MR-PRESSO, were conducted to ensure robustness of the results.ResultsOur MR analysis revealed no significant causal association between COVID-19 infection and migraine. However, a significant causal association was found between COVID-19 vaccination and migraine (beta = 0.071, P = 0.034). The results were confirmed through a series of sensitivity tests, demonstrating the robustness of the findings.DiscussionThis study provides novel evidence of a significant causal link between COVID-19 vaccination and migraine, while no such association was observed with COVID-19 infection. These findings may have important implications for clinical practice, particularly in planning treatment adjustments and optimizing patient care for individuals with migraines in the context of COVID-19 vaccination.

Developing National Information Systems to Monitor COVID-19 Vaccination: A Global Observational Study.

Strong information systems are essential for safe and effective immunization programs. The COVID-19 vaccine rollout presented all immunization information systems (IIS) with challenging demands-requiring in-depth vaccine implementation data at all health system levels in real time. The system development approaches taken by countries were heterogeneous, with some countries opting to adapt existing systems and others implementing new ones. Using data reported by Member States to the World Health Organization (WHO), we aim to develop a global understanding of (1) the types of IIS used to monitor COVID-19 vaccination implemented in 2021 and (2) the approaches taken by countries to develop these systems. We conducted a descriptive analysis of data reported through a supplemental questionnaire of the WHO/United Nations Children's Emergency Fund (UNICEF) Joint Reporting Form on Immunization, collecting data for 2021 on (1) the use of and developmental approaches taken for 7 IIS functions (appointments, aggregate reporting, individual-level reporting, reminders, home-based records, safety surveillance, and stock management), and (2) modifications needed for digital health frameworks to permit COVID-19 vaccination monitoring. In total, 188 of 194 WHO Member States responded to the supplemental questionnaire, with 155 reporting on the IIS-related questions. Among those reporting, for each of the 7 IIS functions explored, greater than 85% of responding countries reported that the system was in place for COVID-19 vaccines. Among responding countries, "aggregate reporting system" was the system most frequently reported as being in place (n=116, 98.3%), while "reminder system" was the least (n=77, 89%). Among the countries reporting using a system, whether an existing system was adapted for COVID-19 vaccines or a new one was developed varied by system. Additionally, two-thirds (n=127, 67.6%) of countries reported establishing at least one new system, ranging from 72% (n=42) in high-income countries (HICs) to 62% (n=16) in low-income countries. Concurrently, 55.3% (n=104) of countries reported adapting at least one system already in place for COVID-19 vaccines, with 62% (n=36) of HICs reporting this compared to about 53% for other income groups. Of those reporting developing new systems, for each of the systems explored, more than 85% of countries reported that they intended to keep new systems specific to COVID-19 vaccines. Further, 147 of the 188 (78.2%) Member States responding to the supplemental questionnaire responded to the digital health frameworks question. Lastly, 31% (n=46) of responding countries reported needing to adapt them for COVID-19 vaccination systems. HICs had a higher percentage. Nearly all countries have adapted existing or developed new IIS to monitor COVID-19 vaccination. The approaches varied, notably by income group. Reflection is needed on how to sustain the investments made in IIS during the pandemic. Continued support for IIS is critical, given their essential role in program monitoring and performance.

Polymyalgia rheumatica following COVID-19 vaccination: Case series of 3 patients and literature review on polymyalgia rheumatica induced by various vaccines.

Since the onset of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic in 2019, considerable resources have been devoted to developing vaccines to reduce related deaths and the burden of disease. Various vaccine formulations eventually became available and were approved for clinical use. In this article, we have conducted a review of polymyalgia rheumatica (PMR) cases induced by different COVID-19 vaccines [Pfizer: BNT162b2, AstraZeneca: ChAdOx1-S, Moderna: mRNA-1273, and Janssen: Ad26.COV2.S)], as well as non-COVID-19 vaccines, such as influenza, zoster, hepatitis B, and tetanus vaccines. Additionally, this article investigates 3 cases with clinical presentations suggestive of PMR following COVID-19 mRNA vaccination. This study aims to offer valuable insights through sharing diagnostic and therapeutic experiences. Three patients presented with severe pain and stiffness in both shoulder and pelvic girdle muscles, following COVID-19 mRNA vaccination. Clinical presentations, laboratory parameters, and echographic findings confirmed the diagnosis of PMR following COVID-19 mRNA vaccination. Patients received Prednisone and/or Methotrexate adjusted to body weight. Polymyalgia rheumatica resolved successfully without any adverse events. Although direct causality was not definitively established in this article, the BNT162b2 COVID-19 mRNA vaccine, similar to other vaccines, might be considered a potential trigger for PMR. This raises the need for further research into this issue and potentially other immunological outcomes.