COVID-19 Vaccine Research Articles

Development and validation of an Arabic tool for assessment of post-vaccination confidence in COVID-19 vaccines (ARAB-VAX-CONF)

Abstract Background Vaccine confidence is described as a belief that vaccines are effective, safe, and part of a trustworthy health system. The objective of this study was to develop and validate an Arabic tool to evaluate confidence in the received coronavirus disease 2019 (COVID-19) vaccines (ARAB-VAX-CONF). Methods The research team developed the ARAB-VAX-CONF based on three areas specified by the Centers for Disease Control and Prevention (CDC): confidence in vaccine effectiveness, confidence in vaccine safety, and confidence in the healthcare system. The analysis includes data from 406 eligible vaccinated persons (≥ 18 years). Cronbach’s alpha was used to measure internal consistency, while convergent, discriminant, exploratory, and confirmatory factor analyses were used to verify construct validity. Results A total of 406 adults were recruited, with a mean age of 33.0 ± 12.2 years. A total of 63.1% were males, 56.7% were married, 21.9% had chronic conditions, 93.3% were nonsmokers, and 39.6% were obligated to obtain vaccines. The three domains of the scale met the criterion of internal consistency (Cronbach’s alpha > 0.7). Convergent validity was identified by the significant inter-item and item-mean score of the domain correlation (P < 0.001). Discriminant validity was reported as the inter-factor correlation matrix (< 0.7). The Kaiser–Meyer–Olkin sampling adequacy measure was 0.80, and Bartlett’s sphericity test was significant (P < 0.001). Exploratory factor analysis indicated that the scale could be summarized into three factors. Confirmatory factor analysis confirmed the adequate psychometric properties and fit with observed data (root-mean-square error of approximation = 0.08, comparative fit index = 0.945, Tucker-Lewis index = 0.924, standardized root-mean-square residual = 0.086, normed fit index = 0.918, and goodness-of-fit index = 0.909). Conclusions The ARAB-VAX-CONF developed in this study is valid and reliable for assessing confidence in vaccine effectiveness, safety, and confidence in the healthcare system. The ARAB-VAX-CONF can support decision-makers in addressing the gap in vaccine confidence among various populations.

Re: Comparison of the test-negative design and cohort design with explicit target trial emulation for evaluating COVID-19 vaccine effectiveness

Re: Comparison of the test-negative design and cohort design with explicit target trial emulation for evaluating COVID-19 vaccine effectiveness

Response to Letter to the Editor, “Re: Comparison of the test-negative design and cohort design with explicit target trial emulation for evaluating COVID-19 vaccine effectiveness”

Response to Letter to the Editor, “Re: Comparison of the test-negative design and cohort design with explicit target trial emulation for evaluating COVID-19 vaccine effectiveness”

Profiling serum immunodominance following SARS-CoV-2 primary and breakthrough infection reveals distinct variant-specific epitope usage and immune imprinting

Over the course of the COVID-19 pandemic, variants have emerged with increased mutations and immune evasive capabilities. This has led to breakthrough infections (BTI) in vaccinated individuals, with a large proportion of the neutralizing antibody response targeting the receptor binding domain (RBD) of the SARS-CoV-2 Spike glycoprotein. Immune imprinting, where prior exposure of the immune system to an antigen can influence the response to subsequent exposures, and its role in a population with heterogenous exposure histories has important implications in future vaccine design. Here, we develop an accessible approach to map epitope immunodominance of the neutralizing antibody response in sera. By using a panel of mutant Spike proteins in a pseudotyped virus neutralization assay, we observed distinct epitope usage in convalescent donors infected during wave 1, or infected with the Delta, or BA.1 variants, highlighting the antigenic diversity of the variant Spikes. Analysis of longitudinal serum samples taken spanning 3 doses of COVID-19 vaccine and subsequent breakthrough infection, showed the influence of immune imprinting from the ancestral-based vaccine, where reactivation of existing B cells elicited by the vaccine resulted in the enrichment of the pre-existing epitope immunodominance. However, subtle shifts in epitope usage in sera were observed following BTI by Omicron sub-lineage variants. Antigenic distance of Spike, time after last exposure, and number of vaccine boosters may play a role in the persistence of imprinting from the vaccine. This study provides insight into RBD neutralizing epitope usage in individuals with varying exposure histories and has implications for design of future SARS-CoV-2 vaccines.

First-in-Human Phase I Trial to Assess the Safety and Immunogenicity of an Orf Virus-Based COVID-19 Vaccine Booster

The emergence of SARS-CoV-2 has necessitated the development of versatile vaccines capable of addressing evolving variants. Prime-2-CoV_Beta, a novel Orf virus-based COVID-19 vaccine, was developed to express the SARS-CoV-2 spike and nucleocapsid antigens. This first-in-human, phase I, dose-finding clinical trial was conducted to assess the safety, reactogenicity, and immunogenicity of Prime-2-CoV_Beta as a booster in healthy adults. From June 2022 to June 2023, 60 participants in Germany received varying doses of Prime-2-CoV_Beta. The study demonstrated a favorable safety profile, with no serious adverse events (AEs) reported. All AEs were mild (107) or moderate (10), with the most common symptoms being pain at the injection site, fatigue, and headache. Immunogenicity assessments revealed robust vaccine-induced antigen-specific immune responses. High doses notably elicited significant increases in antibodies against the spike and nucleocapsid proteins as well as neutralizing antibodies against SARS-CoV-2 and its variants. Additionally, the vaccine did not induce ORFV-neutralizing antibodies, indicating the potential for repeated administration. In conclusion, Prime-2-CoV_Beta was safe, well tolerated, and immunogenic, demonstrating potential as a broadly protective vaccine against SARS-CoV-2 and its variants. These promising results support further evaluation of higher doses and additional studies to confirm efficacy and long-term protection. This trial was registered at ClinicalTrials, NCT05389319.

Placental Histopathological Changes and the Level of Anti-Spike Antibody After Covid-19 Vaccination During Pregnancy: A Case Series

Background: COVID-19 infection during pregnancy could be associated with placental histopathological changes such as vascular diseases and malperfusion. There are studies showing that mRNA vaccines are not associated with significant placental pathological changes. Our objective was to evaluate the placental histopathology in pregnant women who received Sinopharm, an inactivated virus vaccine, during pregnancy. Case Presentation: The study included placental samples collected from mothers who gave birth of living singletons through elective cesarean sections performed between March 2022 and May 2022 at Imam Khomeini Hospital Complex. The study included women who had no history of positive reverse transcription polymerase chain reaction (RT-PCR) testing for COVID-19 during pregnancy, and had received at least one dose of COVID-19 vaccine during their pregnancy. Humoral levels of anti-SARS-CoV-2 spike IgG were measured in both the mothers and neonates. Results: The study included 20 mother-neonate pairs. The mean maternal age was 34±3.6 years, and all mothers received Sinopharm vaccine as their first and second doses. The last vaccine dose was administered during pregnancy, with 3 mothers receiving it in the first trimester, 9 in the second trimester, and 8 in the third trimester. The histopathological findings in the placental samples included decidual vasculopathy, subchorionic thrombosis, and chronic histiocytic intervillositis. All mothers and neonates, except one pair, were positive for anti-spike antibody. Conclusion: Multiple abnormal histopathological findings were reported in placenta of vaccinated mothers. However, similar to previous studies, these placental findings are considered mild lesions and have been observed in both vaccinated and unvaccinated mothers.

Managing Information Overload in a Pandemic: Influence of Social Media on Vaccine Attitudes in the Digital Age

Purpose: This study examined how social media influences public health decisions, focusing on how information overload during a pandemic impacts vaccine hesitancy and acceptance across demographics. It analyzed conflicting vaccine information to understand social media's role in shaping attitudes and identify strategies to mitigate its negative effects. Methodology: This study employed a multi-stage sampling method to gather data from diverse age groups, education levels, and occupations. This approach combines various techniques at different stages, making it suitable for large, geographically dispersed populations. By segmenting the population into manageable units, multi-stage sampling improves the accuracy, reliability, and representativeness of the data collected. Findings: The findings reveal that most respondents consider vaccine information on social media unreliable, underscoring the need for greater trust in online discussions. Many feel overwhelmed by conflicting messages, highlighting the necessity for clearer communication. Social media significantly shapes attitudes toward COVID-19 vaccines, with many shifting views after engaging with online content. Additionally, participants report mental health impacts from the constant stream of vaccine information, illustrating information overload. Unique Contributions to Theory, Policy and Practice: This study advances the information overload model by illustrating how excessive and conflicting vaccine information on social media disrupts comprehension and harms mental health. It emphasizes social media's role in shaping health attitudes and advocates for interdisciplinary approaches that incorporate psychological resilience into public health strategies. Findings highlight the need for regulations against misinformation to improve the credibility of online health information and promote trusted sources, particularly verified health organizations. The study also calls for health literacy initiatives to empower the public in navigating misinformation and suggests strategies for managing information overload through social media disengagement. Targeted initiatives that leverage trusted information sources can effectively combat vaccine hesitancy and boost community engagement in public health campaigns, ultimately improving health outcomes.

Healthcare providers’ hospital breastfeeding practices during the COVID-19 endemic and associated factors in Thailand: a cross-sectional study

Abstract Background During COVID-19, healthcare providers were limited in their ability to provide breastfeeding support while women encountered breastfeeding difficulties. Enhancing appropriate breastfeeding care practices among healthcare providers in hospitals may improve the safety of breastfeeding during an endemic. However, little is known about the breastfeeding care practices by healthcare providers and associated factors during the endemic impact. Objective To investigate the effect of the endemic on breastfeeding care practices by healthcare providers in hospitals and examine their associated factors in Thailand. Methods A descriptive comparative design was conducted through an online survey with 350 healthcare providers across five regions of Thailand between January and March 2022. The convenience sampling was used to recruit healthcare providers who had at least two years of experience supporting breastfeeding practices and were full-time working in the obstetric and pediatric departments of public tertiary hospitals. Analysis of variance and the independent t-test with relevant statistical corrections were utilized for comparisons of associated factors on breastfeeding care practices in healthcare providers. Results The mean breastfeeding care practices in hospitals during the COVID-19 endemic by healthcare providers was 39.17 (SD = 4.64, range 23 to 50). Four factors were statistically significant differences in breastfeeding care practices score, including work position (F = 7.03, df = 2.0, p = 0.001), types of COVID-19 vaccination (F = 6.95, df = 2, p = 0.001), education (F = 4.78, df = 2, p = 0.009), and monthly family income (F = 4.25, df = 3, p = 0.006), respectively. In addition, dose of COVID-19 vaccination and types of COVID-19 vaccination were significantly associated with individual breastfeeding support in hospitals (p < 0.05). Conclusions Healthcare providers’ breastfeeding care practices in hospitals during the COVID-19 endemic were mostly at a moderate level in the Thai context. Hospital policy for maternal and child health support should strongly recommend the effective and safe practice of breastfeeding to encourage mothers to continue their breastfeeding duration.

Factors related to acceptance of COVID-19 vaccine booster doses among patients with autoimmune and rheumatic diseases in Japan: A single-center cross-sectional survey.

We studied the current state and factors associated with the acceptance or hesitancy of booster doses of the coronavirus disease 2019 (COVID-19) vaccine among patients with autoimmune and rheumatic diseases (ARDs) in Japan. A single-center cross-sectional survey was conducted among outpatients with ARDs who visited the Immuno-Rheumatology Center at St. Luke's International Hospital from 1 October to 30 November in 2023. We investigated patient characteristics, COVID-19 vaccination-related status, decision-making preferences, health-related status and independent factors associated with the acceptance or hesitancy of booster doses of the COVID-19 vaccine. A total of 241 patients were included in the analyses, and 198 patients (82.2%) received booster doses while 43 (17.8%) did not. Older age (adjusted odds ratio [aOR] = 0.43, 95% CI: 0.19, 0.95, P = 0.037), having rheumatoid arthritis (RA) (aOR = 0.41, 95% CI: 0.19, 0.92, P = 0.030) and having a physician recommend receiving the vaccine (aOR = 0.47, 95% CI: 0.23, 0.95, P = 0.035) were independently associated with receiving booster doses. The main reasons for hesitancy regarding booster doses were concerns about adverse reactions and long-term safety. Our findings could help physicians counsel patients with ARDs regarding their acceptance of COVID-19 vaccine booster doses to promote appropriate decision-making.

Media Exposure to Highly Skilled Immigrants and Attitudes Toward Immigration

AbstractCan exposure to successful immigrants in the mass media affect perceptions of immigrants and alter attitudes toward immigration? To address this question, I study the case of Ozlem Tureci and Ugur Sahin, the co-developers of the Pfizer-BioNTech COVID-19 vaccine, and children of Turkish immigrants in Germany. I first demonstrate that German media favorably highlighted the Turkish roots and migration history of vaccine developers. Leveraging the quasi-experimental setting with the announcement of the success of the vaccine, I then posit that the wide broadcasting of the vaccine’s success and its developers’ identity should have positive spillover effects on public attitudes towards immigration. Amongst those who were exposed to this announcement, compared to those who were not, there is a 4 percentage-point increase in support of easing immigration opportunities. I suggest that this effect is driven by a change in perceptions and knowledge on issues relating to immigration and integration. These findings imply that promoting successful immigrants in the media has the potential to diminish prejudice; however, it is crucial to address varying biases toward different immigrant groups.

Conspiracy Thinking, Conspiracy Beliefs, Denialism, Motivation, and COVID-19 Vaccination Intentions in Costa Rica

ABSTRACT An observational cross-sectional study was conducted among inhabitants of Costa Rica to examine motivational determinants of COVID-19 vaccination intentions (CVI), as well as to better understand the role of a set of conspiracy-related variables within the framework of the Theory of Planned Behavior (TPB). Data were collected online, and a subsample of those not yet vaccinated (N = 406, age = 44.35, S. D. = 13.23, 74.9% women) was selected. They reported TPB-variables, risk perception, conspiracy-related variables, and sociodemographic information. Structural equation was used to model the assumption that conspiracy beliefs presented direct and indirect effects on intentions. Conspiracy thinking, denialism, and sociodemographic information were also specified as determinants of conspiracy beliefs and vaccination intentions. Most determinants presented direct effects on intentions. Only perceived behavioral control, denialism, and conspiracy thinking presented no direct effects on intentions. Conspiracy beliefs had indirect effects on intentions via most TPB-variables and risk perception. Conspiracy beliefs were predicted only by conspiracy thinking, gender (male), and education. Sociodemographic variables had no effects on intentions. Evidence suggested that a mechanism integrating conspiracy-related variables, risk perception, and TPB-variables predicted CVI. Education and gender played a role in the onset of conspiracy beliefs and thereafter vaccination intentions.

Does Experience of Vaccination Improve Vaccine Confidence and Trust? Policy Feedback Effects of Mass COVID-19 Vaccination in the United States.

Policy feedback research has demonstrated that a highly tangible policy that shapes public attitudes through direct and day-to-day experiences often reshapes public opinion, with the effect of generating supportive or skeptical constituencies that determine the sustainability of future programs. This paper examines the impact of mass vaccination efforts on attitudes towards vaccines in a context of high vaccine hesitancy in the U.S. We analyzed 73,092 survey responses from 9,229 participants in the longitudinal data from the Understanding America Study project, covering December 2020 to July 2023. Using two-way fixed-effects ordinary least squares regression and ordinal logistic regression, we estimated the changes in attitudes towards vaccines, including trust in vaccine manufacturing and approval processes, following COVID-19 vaccinations. COVID-19 vaccination was associated with improved perceptions of vaccine effectiveness and social benefits and reduced mistrust in vaccine-related processes. However, it did not significantly alleviate concerns regarding vaccine side effects and illness. The strongest effects were observed among respondents initially hesitant but who eventually vaccinated. The experience of COVID-19 vaccination generally improved attitudes and confidence in COVID-19 vaccines among the U.S. public, particularly among vaccine-hesitant people. These effects could have positive impacts on future immunization programs by mitigating vaccine hesitancy.

Late onset pancytopenia post chimeric antigen receptor T cell therapy triggered by a COVID-19 vaccination: a case report

Cytopenia is a common side effect after chimeric antigen receptor T cell (CAR-T) therapy but is unusual at late timepoints when it is most commonly due to bone marrow (BM) failure, myelodysplasia (MDS) or other secondary malignancies. In this case report, we describe a patient who developed severe aplastic anaemia 18 months after CD19 CAR-T therapy, and shortly after COVID-19 vaccination. This is the first description of severe aplastic anaemia triggered by COVID-19 vaccination as a cause of post-CAR-T cytopenia. The patient described was treated with a combination of eltrombopag and ciclosporin due to frailty and had a rapid and complete clinical response to this therapy, providing an effective option for the treatment of immune-related cytopenia post-CAR-T in an increasingly elderly and frail population.

Effect of the COVID-19 vaccination on feto-maternal outcomes: A prospective cohort study among Indian pregnant women

Background & objectives Studies on the effects of COVID-19 vaccination among pregnant women in Asian settings, more specifically in India, are scarce. The present study evaluated the feto-maternal outcomes among Indian pregnant women who received the COVID-19 vaccine. Methods A prospective cohort study was undertaken among 430 pregnant women from two primary health centres (PHC) in Chandigarh, India during 2021-2022. The feto-maternal outcomes evaluated in the study included abortions, live birth/stillbirth, term/pre-term/post-term delivery, mode of delivery (normal vaginal/caesarean section/forceps), birth weight and intrauterine growth retardation. Results Of the 430 study participants, 295 pregnant women received COVID-19 vaccines, with an uptake rate of 68.6 per cent. Majority of vaccinated women (280- who completed the study) were in their second trimester (133, 47.5%), while 92 (32.9%) were in their third, and 55 (19.6%) were in their first trimester when they were enrolled in the study. Neonatal intensive care unit (NICU) admission was significantly lower among the vaccinated pregnant women, while other feto-maternal and neonatal outcomes were similar between vaccinated and unvaccinated pregnant women. Interpretation & conclusions The findings of this study suggest COVID-19 vaccination in pregnant women in India might be safe, in terms of feto-maternal outcomes

Does Policy Uncertainty Boost Vaccine Hesitancy? Political Controversy, the FDA and COVID-19 Vaccine Hesitancy in Fall 2020.

Vaccine hesitancy is associated with political and institutional distrust, but there is little research on how people's trust responds to political events. We revisit the fall of 2020 when evaluation of new COVID-19 vaccines collided with an impending national election. Drawing on a political Bayesian perspective, we assess abrupt changes in attention to political events and test hypotheses on subpopulation response: (1) partisan, (2) educational, and (3) ethnic and racial. Analysis of daily changes in news reporting and social media use in 2020, combined with detailed analysis of two-large scale surveys fielded at the time, focusing on questions of COVID-19 vaccine hesitancy and safety concerns about COVID-19 vaccines. Vaccine hesitancy in the US spiked from late August to early October 2020. We identify several plausible triggers for this spike, all pertaining to the FDA and electoral politics. Heightened vaccine hesitancy occurred among Democrats, Asian and Black citizens, as well as college-educated respondents. Turbulence mainly affected those who were initially most trusting in government and vaccines. Asian-American vaccine confidence recovered; that of Black Americans did not. Electoral politics may destabilize citizen assumptions about vaccine authorization and boost uncertainty, thereby undermining public willingness to take approved vaccines.

Factors Predicting COVID-19 Vaccine Effectiveness and Longevity of Humoral Immune Responses

The COVID-19 pandemic, caused by SARS-CoV-2, prompted global efforts to develop vaccines to control the disease. Various vaccines, including mRNA (BNT162b2, mRNA-1273), adenoviral vector (ChAdOx1, Ad26.COV2.S), and inactivated virus platforms (BBIBP-CorV, CoronaVac), elicit high-titer, protective antibodies against the virus, but long-term antibody durability and effectiveness vary. The objective of this study is to elucidate the factors that influence vaccine effectiveness (VE) and the longevity of humoral immune responses to COVID-19 vaccines through a review of the relevant literature, including clinical and real-world studies. Here, we discuss the humoral immune response to different COVID-19 vaccines and identify factors influencing VE and antibody longevity. Despite initial robust immune responses, vaccine-induced immunity wanes over time, particularly with the emergence of variants, such as Delta and Omicron, that exhibit immune escape mechanisms. Additionally, the durability of the humoral immune responses elicited by different vaccine platforms, along with the identification of essential determinants of long-term protection—like pre-existing immunity, booster doses, hybrid immunity, and demographic factors—are critical for protecting against severe COVID-19. Booster vaccinations substantially restore neutralizing antibody levels, especially against immune-evasive variants, while individuals with hybrid immunity have a more durable and potent immune response. Importantly, comorbidities such as diabetes, cardiovascular disease, chronic kidney disease, and cancer significantly reduce the magnitude and longevity of vaccine-induced protection. Immunocompromised individuals, particularly those undergoing chemotherapy and those with hematologic malignancies, have diminished humoral responses and benefit disproportionately from booster vaccinations. Age and sex also influence immune responses, with older adults experiencing accelerated antibody decline and females generally exhibiting stronger humoral responses compared to males. Understanding the variables affecting immune protection is crucial to improving vaccine strategies and predicting VE and protection against COVID-19.

Harnessing AI for advancing pathogenic microbiology: a bibliometric and topic modeling approach

IntroductionThe integration of artificial intelligence (AI) in pathogenic microbiology has accelerated research and innovation. This study aims to explore the evolution and trends of AI applications in this domain, providing insights into how AI is transforming research and practice in pathogenic microbiology.MethodsWe employed bibliometric analysis and topic modeling to examine 27,420 publications from the Web of Science Core Collection, covering the period from 2010 to 2024. These methods enabled us to identify key trends, research areas, and the geographical distribution of research efforts.ResultsSince 2016, there has been an exponential increase in AI-related publications, with significant contributions from China and the USA. Our analysis identified eight major AI application areas: pathogen detection, antibiotic resistance prediction, transmission modeling, genomic analysis, therapeutic optimization, ecological profiling, vaccine development, and data management systems. Notably, we found significant lexical overlaps between these areas, especially between drug resistance and vaccine development, suggesting an interconnected research landscape.DiscussionAI is increasingly moving from laboratory research to clinical applications, enhancing hospital operations and public health strategies. It plays a vital role in optimizing pathogen detection, improving diagnostic speed, treatment efficacy, and disease control, particularly through advancements in rapid antibiotic susceptibility testing and COVID-19 vaccine development. This study highlights the current status, progress, and challenges of AI in pathogenic microbiology, guiding future research directions, resource allocation, and policy-making.

COVID-19, COVID-19 vaccination, risk of cardiac myxoma in view of clinical surgery

COVID-19, COVID-19 vaccination, risk of cardiac myxoma in view of clinical surgery

Insights into cancer characteristics among SARS-CoV-2 infected hospitalized patients: a comprehensive analysis from the National Clinical Registry for COVID-19.

Cancer outcome is dependent on multiple predetermining factors including cancer, type of cancer and its related factors. This study aims to investigate the association between COVID-19 & cancer/cancer types, focusing on risk of in-hospital mortality within 30days of hospitalization of COVID-19 patients with cancer. We did a registry (National Clinical Registry for COVID-19) based retrospective observational study including 51,544 patients, of whom 976 were patients with cancer, admitted with COVID-19 between August 2020 and August 2023 across 42 hospitals of India. Out of 51,544 patients, 976 (1.8%) had cancer. Hematological malignancies made up 15.06% (147 cases), while solid cancers accounted for 29.5% (288 cases), with genitourinary (18.4%, 80 cases), gastrointestinal (15.2%, 49 cases), and lung cancers (10.1%, 34 cases) being the most common. Solid cancers had the highest in-hospital mortality rate at 25%. Survival analysis showed that cancer-related hazards were highest at admission but decreased to levels comparable with other morbidities within nine to ten days. For each cancer type, the hazard was significantly elevated compared to that of the cancer-free (Other Comorbidities and No Comorbiditiy) groups during the initial period of hospitalization. The use of Remdesivir, steroids, and anticoagulants reduced mortality risk, and prior COVID-19 vaccination was protective against mortality across all cancer types. This study shows that both cancer in general and specific cancer types significantly increase the risk of severe outcomes among SARS-CoV-2-infected patients, especially immediately after hospitalization. The findings highlight the need for close monitoring and personalized interventions for COVID-19 patients with cancer for at least 10days post-hospitalization, with a more specific high-risk period ranging from 7 to 18days depending on the type of cancer.

The Immunologic Downsides Associated with the Powerful Translation of Current COVID-19 Vaccine mRNA Can Be Overcome by Mucosal Vaccines

The action of mRNA-based vaccines requires the expression of the antigen in cells targeted by lipid nanoparticle–mRNA complexes. When the vaccine antigen is not fully retained by the producer cells, its local and systemic diffusion can have consequences depending on both the levels of antigen expression and its biological activity. A peculiarity of mRNA-based COVID-19 vaccines is the extraordinarily high amounts of the Spike antigen expressed by the target cells. In addition, vaccine Spike can be shed and bind to ACE-2 cell receptors, thereby inducing responses of pathogenetic significance including the release of soluble factors which, in turn, can dysregulate key immunologic processes. Moreover, the circulatory immune responses triggered by the vaccine Spike is quite powerful, and can lead to effective anti-Spike antibody cross-binding, as well as to the emergence of both auto- and anti-idiotype antibodies. In this paper, the immunologic downsides of the strong efficiency of the translation of the mRNA associated with COVID-19 vaccines are discussed together with the arguments supporting the idea that most of them can be avoided with the advent of next-generation, mucosal COVID-19 vaccines.