Specific immunological characteristics and risk factor of XBB variants re-infection in nasopharyngeal carcinoma patients after BA.5 infection.

OBJECTIVES: The specific humoral immune response resulting from inactivated vaccination following by BA.5 infection, and predictors of XBB variants re-infection in BA.5 infection-recovered nasopharyngeal carcinoma (BA.5-RNPC) patients, were explored. METHODS: Serum SARS-CoV-2 specific antibody levels were assessed using enzyme-linked-immunosorbent-assay. Univariate and multivariate binary logistic regression analyses were conducted to identify factors associated with the magnitude of specific humoral immunity and susceptibility to re-infection by XBB variants. RESULTS: Our data demonstrates that SARS-CoV-2 specific antibody levels were comparable between BA.5-RNPC patients and BA.5 infection-recovered-non-cancerous (BA.5-RNC) individuals. Specifically, serum levels of anti-ancestral-S1-IgG, anti-ancestral-nucleocapsid-protein (NP)-IgG, anti-BA.5-receptor binding domain (RBD)-IgG and anti-XBB.1.1.6-RBD-IgG were higher in BA.5-RNPC patients compared to those without a prior infection. Compared to BA.5-RNPC patients without vaccination, individuals who received inactivated vaccination exhibited significantly higher levels of anti-ancestral-S1-IgG and anti-XBB.1.16-RBD-IgG. Multivariate logistic regression analysis revealed that inactivated vaccination was the most significant predictor of all tested SARS-CoV-2 specific antibodies response. Subsequent analysis indicated that a low globulin level is an independent risk factor for XBB re-infection in BA.5-RNPC patients. CONCLUSIONS: The SARS-CoV-2 specific antibodies have been improved in vaccinated BA.5-RNPC patients. However, the baseline immunity status biomarker IgG is an indicators of XBB variant re-infection risk in BA.5-RNPC patients.

Predicting COVID-19 vaccine uptake: Comparing the health belief model and theory of planned behavior.

The COVID-19 outbreak has had a significant impact on the global health landscape, underscoring the crucial role that vaccinations play in achieving herd immunity and reducing the effects of pandemics. Given the importance of this issue, it is imperative to gain a deeper understanding of the various factors that influence individuals' decisions to seek vaccination. This study aimed to compare the prediction level of the Health Belief Model (HBM), the Theory of Planned Behavior (TPB), and a combined model in explaining the intention of adults to receive COVID-19 immunization. A cross-sectional online survey was conducted among adults (n = 505) in Saudi Arabia. The survey contained variables related to the HBM and TPB. The prediction level of the two models as well as a combined model were evaluated utilizing Structural Equation Modeling (SEM). Among the recruited 505 participants, 88% fell within the 18 to 30 age range, and 54.5% were male. The proposed HBM model accounted for 68% of the variation in intention, whereas the TPB model explained 78.2% of the variation in COVID-19 vaccination intention. The combined model showed greater explanatory power (82%). The variables of susceptibility (ß = 0.20, p < .001), severity (ß = 0.49, p < .001), advantages (ß = 0.63, p < .001), and obstacles (ß = - 0.24, p < .001), perceptions of behavioral control (ß = 1.58, p < .001) and attitudes (ß = 0.44, p < .001) were found to significantly predict increased vaccination intentions in the combined model. However, the subjective norm construct did not significantly predict vaccination intentions (ß = 0.06, p = .34). The TPB has greater explanatory power than the HBM in predicting the intention to obtain COVID-19 vaccination. However, the combined model showed a greater prediction level. Understanding and identifying people's perceived health beliefs and practices is critical for developing successful COVID-19 intervention methods.

Comparing COVID-19 vaccination coverage, adverse reactions and impact of social determinants of health on vaccine hesitancy in ADRD/MCI and non-ADRD/MCI population: protocol for a retrospective cross-sectional study.

INTRODUCTION: COVID-19 vaccination is crucial for vulnerable people with underlying chronic conditions such as Alzheimer's disease and related dementias (ADRD) and mild cognitive impairment (MCI). These individuals face unique challenges, including higher risk of COVID-19, difficulties in adopting preventive behaviours and vaccine hesitancy due to concerns about adverse reactions. Therefore, efforts to promote vaccination, including boosters tailored to the currently circulating virus, are essential for people with ADRD/MCI. OBJECTIVE: The primary purpose of this study protocol is to conduct a comprehensive analysis of COVID-19 vaccination coverage and adverse reactions among individuals with ADRD/MCI in comparison to those without ADRD/MCI. Additionally, the proposed study aims to investigate the impact of social determinants of health on COVID-19 vaccination and vaccine hesitancy in individuals with ADRD/MCI. METHODS AND ANALYSIS: A retrospective cross-sectional study will be conducted utilising data from the All of Us (AoU) Researcher Workbench. Relevant data fields are extracted from sources including demographic information, COVID-19 Vaccine Survey, Basic Survey, Health Access & Utilization, Social Determinants of Health, and Electronic Health Record (EHR) data. Data on vaccination, adverse reactions and vaccine hesitancy will be collected through COVID-19 vaccine survey questionnaires. Propensity score matching and binary logistic regression will be applied to assess the vaccination rates and vaccine hesitancy, while controlling for demographic characteristics and social determinants of health factors. ETHICS AND DISSEMINATION: This study protocol received approval from the Institutional Review Board at Florida State University (STUDY00004571). Results will be disseminated through publication in peer-reviewed journals and presented at scientific conferences.

Covid-19 infection and vaccination during first trimester and risk of congenital anomalies: Nordic registry based study.

OBJECTIVES: To evaluate the risk of major congenital anomalies according to infection with or vaccination against covid-19 during the first trimester of pregnancy. DESIGN: Prospective Nordic registry based study. SETTING: Sweden, Denmark, and Norway. PARTICIPANTS: 343 066 liveborn singleton infants in Sweden, Denmark, and Norway, with an estimated start of pregnancy between 1 March 2020 and 14 February 2022, identified using national health registries. MAIN OUTCOME MEASURE: Major congenital anomalies were categorised using EUROCAT (European Surveillance of Congenital Anomalies) definitions. The risk after covid-19 infection or vaccination during the first trimester was assessed by logistic regression, adjusting for maternal age, parity, education, income, country of origin, smoking, body mass index, chronic conditions, and estimated date of start of pregnancy. RESULTS: 17 704 (5.2%) infants had a major congenital anomaly. When evaluating risk associated with covid-19 infection during the first trimester, the adjusted odds ratio ranged from 0.84 (95% confidence interval 0.51 to 1.40) for eye anomalies to 1.12 (0.68 to 1.84) for oro-facial clefts. Similarly, the risk associated with covid-19 vaccination during the first trimester ranged from 0.84 (0.31 to 2.31) for nervous system anomalies to 1.69 (0.76 to 3.78) for abdominal wall defects. Estimates for 10 of 11 subgroups of anomalies were less than 1.04, indicating no notable increased risk. CONCLUSIONS: Covid-19 infection and vaccination during the first trimester of pregnancy were not associated with risk of congenital anomalies.

Specific long-term changes in anti-SARS-CoV-2 IgG modifications and antibody functions in mRNA, adenovector, and protein subunit vaccines.

Various vaccine platforms were developed and deployed against the COVID-19 disease. The Fc-mediated functions of IgG antibodies are essential in the adaptive immune response elicited by vaccines. However, the long-term changes of protein subunit vaccines and their combinations with messenger RNA (mRNA) vaccines are unknown. A total of 272 serum and plasma samples were collected from individuals who received first to third doses of the protein subunit Medigen, the mRNA (BNT, Moderna), or the adenovector AstraZeneca vaccines. The IgG subclass level was measured using enzyme-linked immunosorbent assay, and Fc-N glycosylation was measured using liquid chromatography coupled to tandem mass spectrometry. Antibody-dependent-cellular-phagocytosis (ADCP) and complement deposition (ADCD) of anti-spike (S) IgG antibodies were measured by flow cytometry. IgG1 and 3 reached the highest anti-S IgG subclass level. IgG1, 2, and 4 subclass levels significantly increased in mRNA- and Medigen-vaccinated individuals. Fc-glycosylation was stable, except in female BNT vaccinees, who showed increased bisection and decreased galactosylation. Female BNT vaccinees had a higher anti-S IgG titer than that of males. ADCP declined in all groups. ADCD was significantly lower in AstraZeneca-vaccinated individuals. Each vaccine produced specific long-term changes in Fc structure and function. This finding is critical when selecting a vaccine platform or combination to achieve the desired immune response.

Analysis of the impact of COVID-19 variants and vaccination on the time-varying reproduction number: statistical methods.

Introduction: The COVID-19 pandemic has profoundly impacted global health systems, requiring the monitoring of infection waves and strategies to control transmission. Estimating the time-varying reproduction number is crucial for understanding the epidemic and guiding interventions. Methods: Probability distributions of serial interval are estimated for Pre-Delta and Delta periods. We conducted a comparative analysis of time-varying reproduction numbers, taking into account population immunity and variant differences. We incorporated the regional heterogeneity and age distribution of the population, as well as the evolving variants and vaccination rates over time. COVID-19 transmission dynamics were analyzed with variants and vaccination. Results: The reproduction number is computed with and without considering variant-based immunity. In addition, values of reproduction number significantly differed by variants, emphasizing immunity's importance. Enhanced vaccination efforts and stringent control measures were effective in reducing the transmission of the Delta variant. Conversely, Pre-Delta variant appeared less influenced by immunity levels, due to lower vaccination rates. Furthermore, during the Pre-Delta period, there was a significant difference between the region-specific and the non-region-specific reproduction numbers, with particularly distinct pattern differences observed in Gangwon, Gyeongbuk, and Jeju in Korea. Discussion: This research elucidates the dynamics of COVID-19 transmission concerning the dominance of the Delta variant, the efficacy of vaccinations, and the influence of immunity levels. It highlights the necessity for targeted interventions and extensive vaccination coverage. This study makes a significant contribution to the understanding of disease transmission mechanisms and informs public health strategies.

Adverse Events of COVID-19 Vaccines in the United States: Temporal and Spatial Analysis.

BACKGROUND: The COVID-19 pandemic, caused by SARS-CoV-2, has had a profound impact worldwide, leading to widespread morbidity and mortality. Vaccination against COVID-19 is a critical tool in controlling the spread of the virus and reducing the severity of the disease. However, the rapid development and deployment of COVID-19 vaccines have raised concerns about potential adverse events following immunization (AEFIs). Understanding the temporal and spatial patterns of these AEFIs is crucial for an effective public health response and vaccine safety monitoring. OBJECTIVE: This study aimed to analyze the temporal and spatial characteristics of AEFIs associated with COVID-19 vaccines in the United States reported to the Vaccine Adverse Event Reporting System (VAERS), thereby providing insights into the patterns and distributions of the AEFIs, the safety profile of COVID-19 vaccines, and potential risk factors associated with the AEFIs. METHODS: We conducted a retrospective analysis of administration data from the Centers for Disease Control and Prevention (n=663,822,575) and reports from the surveillance system VAERS (n=900,522) between 2020 and 2022. To gain a broader understanding of postvaccination AEFIs reported, we categorized them into system organ classes (SOCs) according to the Medical Dictionary for Regulatory Activities. Additionally, we performed temporal analysis to examine the trends of AEFIs in all VAERS reports, those related to Pfizer-BioNTech and Moderna, and the top 10 AEFI trends in serious reports. We also compared the similarity of symptoms across various regions within the United States. RESULTS: Our findings revealed that the most frequently reported symptoms following COVID-19 vaccination were headache (n=141,186, 15.68%), pyrexia (n=122,120, 13.56%), and fatigue (n=121,910, 13.54%). The most common symptom combination was chills and pyrexia (n=56,954, 6.32%). Initially, general disorders and administration site conditions (SOC 22) were the most prevalent class reported. Moderna exhibited a higher reporting rate of AEFIs compared to Pfizer-BioNTech. Over time, we observed a decreasing reporting rate of AEFIs associated with COVID-19 vaccines. In addition, the overall rates of AEFIs between the Pfizer-BioNTech and Moderna vaccines were comparable. In terms of spatial analysis, the middle and north regions of the United States displayed a higher reporting rate of AEFIs associated with COVID-19 vaccines, while the southeast and south-central regions showed notable similarity in symptoms reported. CONCLUSIONS: This study provides valuable insights into the temporal and spatial patterns of AEFIs associated with COVID-19 vaccines in the United States. The findings underscore the critical need for increasing vaccination coverage, as well as ongoing surveillance and monitoring of AEFIs. Implementing targeted monitoring programs can facilitate the effective and efficient management of AEFIs, enhancing public confidence in future COVID-19 vaccine campaigns.

Challenging Pandemic Law: From Vaccine Mandates to Judicial Review of Vaccine Approvals.

Over recent years, dozens of legal challenges have been instituted in response to government action during the COVID-19 pandemic. While public health orders have been challenged on several grounds, few cases have succeeded. Fewer cases still have called into question decisions made by the Therapeutic Goods Administration (TGA) to approve the COVID-19 vaccines. This section provides a brief update on one recent, partially successful COVID-19 health directions case before examining two applications in the Federal Court of Australia seeking judicial review of the TGA's approval of the COVID-19 vaccines. The section argues that, while both TGA applications were dismissed for lack of standing, they illustrate how and why third parties will ordinarily not be entitled to challenge administrative decisions about therapeutic goods.

Molecular mimicry of SARS-COV-2 antigens as a possible natural anti-cancer preventive immunization.

Background: In the present study we investigated whether peptides derived from the entire SARS-CoV-2 proteome share homology to TAAs (tumor-associated antigens) and cross-reactive CD8+ T cell can be elicited by the BNT162b2 preventive vaccine or the SARS-CoV-2 natural infection. Methods and results: Viral epitopes with high affinity (<100nM) to the HLA-A*02:01 allele were predicted. Shared and variant-specific epitopes were identified. Significant homologies in amino acidic sequence have been found between SARS-CoV-2 peptides and multiple TAAs, mainly associated with breast, liver, melanoma and colon cancers. The molecular mimicry of the viral epitopes and the TAAs was found in all viral proteins, mostly the Orf 1ab and the Spike, which is included in the BNT162b2 vaccine. Predicted structural similarities confirmed the sequence homology and comparable patterns of contact with both HLA and TCR α and ß chains were observed. CD8+ T cell clones cross-reactive with the paired peptides have been found by MHC class l-dextramer staining. Conclusions: Our results show for the first time that several SARS-COV-2 antigens are highly homologous to TAAs and cross-reactive T cells are identified in infected and BNT162b2 preventive vaccinated individuals. The implication would be that the SARS-Cov-2 pandemic could represent a natural preventive immunization for breast, liver, melanoma and colon cancers. In the coming years, real-world evidences will provide the final proof for such immunological experimental evidence. Moreover, such SARS-CoV-2 epitopes can be used to develop "multi-cancer" off-the-shelf preventive/therapeutic vaccine formulations, with higher antigenicity and immunogenicity than over-expressed tumor self-antigens, for the potential valuable benefit of thousands of cancer patients around the World.

The type of COVID-19 vaccination does not affect reproductive function and pregnancy outcomes in infertile couples.

Introduction: Studies on the effect of vaccine type and two other vaccines other than inactivated vaccines approved in China on in vitro fertilization (IVF) pregnancy outcomes are rare. To complement and confirm the existing findings, this research aimed to investigate whether there are adverse effects of different vaccine types in females and males on reproductive function and clinical pregnancy. Methods: This retrospective study enrolled 6,455 fresh embryo transfer cycles at the First Affiliated Hospital of Zhengzhou University between May 1, 2021, and October 31, 2022. The primary outcome is the clinical pregnancy rate (CPR). At the same time, the secondary results are the number of oocytes retrieved, two pronuclei (2PN) rate, blastocyst formation rate, high-quality blastocyst rate, and semen parameters (volume, density, sperm count, forward motility rate, total motility rate, immobility rate, and DNA fragment index (DFI) rate). Results: In the comparison of ovarian stimulation indicators, no statistically significant differences (P > 0.05) were found in Gn days, endometrial thickness, 2PN rate, metaphase 2 (MII) rate, high-quality embryo rate, and blastocyst formation rate. No significant differences (P>0.05) were found in age, body mass index (BMI), education level, and semen parameters (volume, density, sperm count, forward motility rate, total motility rate, immobility rate, and DFI rate) in these four groups. The multivariate regression model showed that neither the types of vaccines nor the vaccination status of both infertile couples significantly affected clinical pregnancy. Discussion: The type of vaccine does not appear to have an unfavorable effect on ovarian stimulation, embryo development, semen parameters, and clinical pregnancy.

Vaccine Politics.

A vaccine law and policy expert reflects on the dangers of the influence of politics on public health decision making.

The COVID-19 Uninsured Program: Nearly 39 Million Vaccine Doses Were Funded, 2020-22.

The COVID-19 Uninsured Program, administered by the Health Resources and Services Administration (HRSA), reimbursed providers for administering COVID-19 vaccines to uninsured US adults from December 11, 2020, through April 5, 2022. Using HRSA claims data covering forty-two states, we estimated that the program funded about 38.9 million COVID-19 vaccine doses, accounting for 5.7 percent of total doses distributed and 10.9 percent of doses administered to adults ages 19-64.

Production of Recombinant Viral Antigens Using the Baculovirus-Insect Cell Expression System.

Insect cell expression has been successfully used for the production of viral antigens as part of commercial vaccine development. As expression host, insect cells offer advantage over bacterial system by presenting the ability of performing post-translational modifications (PTMs) such as glycosylation and phosphorylation thus preserving the native functionality of the proteins especially for viral antigens. Insect cells have limitation in exactly mimicking some proteins which require complex glycosylation pattern. The recent advancement in insect cell engineering strategies could overcome this limitation to some extent. Moreover, cost efficiency, timelines, safety, and process adoptability make insect cells a preferred platform for production of subunit antigens for human and animal vaccines. In this chapter, we describe the method for producing the SARS-CoV2 spike ectodomain subunit antigen for human vaccine development and the virus like particle (VLP), based on capsid protein of porcine circovirus virus 2 (PCV2d) antigen for animal vaccine development using two different insect cell lines, SF9 & Hi5, respectively. This methodology demonstrates the flexibility and broad applicability of insect cell as expression host.

COVID-19 Vaccine Effectiveness in Autumn and Winter 2022 to 2023 Among Older Europeans.

Importance: In the context of emerging SARS-CoV-2 variants or lineages and new vaccines, it is key to accurately monitor COVID-19 vaccine effectiveness (CVE) to inform vaccination campaigns. Objective: To estimate the effectiveness of COVID-19 vaccines administered in autumn and winter 2022 to 2023 against symptomatic SARS-CoV-2 infection (with all circulating viruses and XBB lineage in particular) among people aged 60 years or older in Europe, and to compare different CVE approaches across the exposed and reference groups used. Design, Setting, and Participants: This case-control study obtained data from VEBIS (Vaccine Effectiveness, Burden and Impact Studies), a multicenter study that collects COVID-19 and influenza data from 11 European sites: Croatia; France; Germany; Hungary; Ireland; Portugal; the Netherlands; Romania; Spain, national; Spain, Navarre region; and Sweden. Participants were primary care patients aged 60 years or older with acute respiratory infection symptoms who were recruited at the 11 sites after the start of the COVID-19 vaccination campaign from September 2022 to August 2023. Cases and controls were defined as patients with positive and negative, respectively, reverse transcription-polymerase chain reaction (RT-PCR) test results. Exposures: The exposure was COVID-19 vaccination. The exposure group consisted of patients who received a COVID-19 vaccine during the autumn and winter 2022 to 2023 vaccination campaign and 14 days or more before symptom onset. Reference group included patients who were not vaccinated during or in the 6 months before the 2022 to 2023 campaign (seasonal CVE), those who were never vaccinated (absolute CVE), and those who were vaccinated with at least the primary series 6 months or more before the campaign (relative CVE). For relative CVE of second boosters, patients receiving their second booster during the campaign were compared with those receiving 1 booster 6 months or more before the campaign. Main Outcomes and Measures: The outcome was RT-PCR-confirmed, medically attended, symptomatic SARS-CoV-2 infection. Four CVE estimates were generated: seasonal, absolute, relative, and relative of second boosters. CVE was estimated using logistic regression, adjusting for study site, symptom onset date, age, chronic condition, and sex. Results: A total of 9308 primary care patients were included, with 1687 cases (1035 females; median [IQR] age, 71 [65-79] years) and 7621 controls (4619 females [61%]; median [IQR] age, 71 [65-78] years). Within 14 to 89 days after vaccination, seasonal CVE was 29% (95% CI, 14%-42%), absolute CVE was 39% (95% CI, 6%-60%), relative CVE was 31% (95% CI, 15% to 44%), and relative CVE of second boosters was 34% (95% CI, 18%-47%) against all SARS-CoV-2 variants. In the same interval, seasonal CVE was 44% (95% CI, -10% to 75%), absolute CVE was 52% (95% CI, -23% to 82%), relative CVE was 47% (95% CI, -8% to 77%), and relative CVE of second boosters was 46% (95% CI, -13% to 77%) during a period of high XBB circulation. Estimates decreased with time since vaccination, with no protection from 180 days after vaccination. Conclusions and Relevance: In this case-control study among older Europeans, all CVE approaches suggested that COVID-19 vaccines administered in autumn and winter 2022 to 2023 offered at least 3 months of protection against symptomatic, medically attended, laboratory-confirmed SARS-CoV-2 infection. The effectiveness of new COVID-19 vaccines against emerging SARS-CoV-2 variants should be continually monitored using CVE seasonal approaches.

Unmasking vaccine hesitancy and refusal: a deep dive into Anti-vaxxer perspectives on COVID-19 in Spain.

BACKGROUND: At the time of the emergence of COVID-19, denialist and anti-vaccine groups have also emerged and are shaking public confidence in vaccination. METHODS: A qualitative study was conducted using online focus groups. Participants had not received any doses of vaccination against the disease. A total of five focus group sessions were conducted with 28 participants. They were recruited by snowball sampling and by convenience sampling. RESULTS: The two major topics mentioned by the participants were adverse effects and information. The adverse effects described were severe and included sudden death. In the case of information, participants reported: (1) consultation of websites on which scientists posted anti-vaccination content; and (2) distrust. CONCLUSIONS: At a time when anti-vaccine groups pose a major challenge to public health in general, and to COVID-19 vaccination campaigns in particular, this study is a first step towards gaining deeper insight into the factors that lead to COVID-19 vaccine refusal.

Differences in virus and immune dynamics for SARS-CoV-2 Delta and Omicron infections by age and vaccination histories.

Vaccination against COVID-19 was integral to controlling the pandemic that persisted with the continuous emergence of SARS-CoV-2 variants. Using a mathematical model describing SARS-CoV-2 within-host infection dynamics, we estimate differences in virus and immunity due to factors of infecting variant, age, and vaccination history (vaccination brand, number of doses and time since vaccination). We fit our model in a Bayesian framework to upper respiratory tract viral load measurements obtained from cases of Delta and Omicron infections in Singapore, of whom the majority only had one nasopharyngeal swab measurement. With this dataset, we are able to recreate similar trends in URT virus dynamics observed in past within-host modelling studies fitted to longitudinal patient data.We found that Omicron had higher R0,within values than Delta, indicating greater initial cell-to-cell spread of infection within the host. Moreover, heterogeneities in infection dynamics across patient subgroups could be recreated by fitting immunity-related parameters as vaccination history-specific, with or without age modification. Our model results are consistent with the notion of immunosenescence in SARS-CoV-2 infection in elderly individuals, and the issue of waning immunity with increased time since last vaccination. Lastly, vaccination was not found to subdue virus dynamics in Omicron infections as well as it had for Delta infections.This study provides insight into the influence of vaccine-elicited immunity on SARS-CoV-2 within-host dynamics, and the interplay between age and vaccination history. Furthermore, it demonstrates the need to disentangle host factors and changes in pathogen to discern factors influencing virus dynamics. Finally, this work demonstrates a way forward in the study of within-host virus dynamics, by use of viral load datasets including a large number of patients without repeated measurements.

The Ethiopian National Immunization Technical Advisory Group (E-NITAG): Establishment, Achievements and the Future.

The National Immunization Program (NIP) was introduced in Ethiopia in 1980. The NIP has expanded the number of vaccines from six to more than 14 in 2023. However, decisions on new vaccine introduction and other vaccine-related matters were not systematically deliberated nationally. Thus, the need to establish a national body to deliberate on vaccine and vaccination matters, in addition to the global immunization advisory groups, has been emphasized in the last decade. This article presents the establishment and achievements of the Ethiopian NITAG. The E-NITAG was established in 2016 and maintained its active role in providing recommendations for new vaccine introduction and improving the delivery of routine vaccines. The external assessment indicated the E-NITAG was highly functional and played a critical role in enhancing the vaccination practice in Ethiopia, especially during the COVID-19 pandemic. The absence of a dedicated secretariat staff was the major bottleneck to expanding the role of the E-NITAG beyond responding to MOH requests. The E-NITAG must be strengthened by establishing a secretariat that can eventually grow as an independent institution to address complex vaccine-related issues the NIP needs to address.

Cryptic late-onset myocarditis after coronavirus vaccination.

As we enter a new era of mRNA-based therapeutics, evidence on genetic or environmental factors that might predispose to unknown off-target side effects, gains in importance. Among these factors, exercise appears likely to have influenced otherwise cryptic cases of early-onset postvaccination myocarditis. And the existence of a distinct late-onset myocarditis is now being recognized. Here, three case-history reports suggest crypticity (the author's own case), unless provoked by a preexisting cardiac morbidity (one case), or by immune checkpoint blockade to enhance anticancer autoimmunity (several cases). These reports are supported by noninvasive fluorodeoxyglucose-based cardiac scan comparisons of multiple vaccinated and unvaccinated subjects. In pre-pandemic decades, applications for funds by the leading innovator in mRNA-based therapeutics seldom gained peer-review approval. Thus, at the start of the pandemic, the meager data on such side effects could justify only emergency approval. We must do better.