Atypical Kawasaki Disease after COVID-19 Vaccination: A New Form of Adverse Event Following Immunization

Kawasaki disease (KD) is a medium-vessel vasculitis that is typically presented during childhood; fewer than 100 cases of KD have been reported worldwide in adult patients who met the criteria according to the American College of Rheumatology. This study presents the case of an 18-year-old patient with no previous history of any disease, who presented atypical KD with liver and kidney dysfunction, with a good response to intravenous immunoglobulin therapy. The symptoms began 22 days after the application of the COVID-19 vaccine (nonreplicating viral vector Vaxzevria), and other conditions were ruled out. The term Adverse Events Following Immunization (AEFI)encompasses all the reactions that follow the application of any vaccine with no necessary causal relationship and can be due to the vaccine product, quality of the vaccine, immunization errors, or anxiety or just happen to be coincident events. These reactions should be reported so that clinicians can identify compatible cases and consider that the presentation of this disease, despite being atypical, can be manifested in adult patients. Likewise, case reports are an important basis for the pharmacovigilance of vaccines.

Post-HPV-Vaccination Mast Cell Activation Syndrome: Possible Vaccine-Triggered Escalation of Undiagnosed Pre-Existing Mast Cell Disease?

For nearly a decade, case reports and series have emerged regarding dysautonomias—particularly postural orthostatic tachycardia syndrome (POTS)—presenting soon after vaccination against human papilloma virus (HPV). We too have observed a number of such cases (all following vaccination with the Gardasil product), and have found several to have detectable mast cell activation syndrome (MCAS) as well as histories suggesting that MCAS was likely present long before vaccination. We detail 11 such cases here, posing a hypothesis that HPV vaccination (at least with the Gardasil product) may have triggered or exacerbated MCAS in teenagers previously not recognized to have it. Only recently recognized, MCAS is being increasingly appreciated as a prevalent and chronic multisystem disorder, often emerging early in life and presenting with inflammatory ± allergic phenomena following from known mast cell (MC) mediator effects. There is rising recognition, too, of associations of MCAS with central and peripheral neuropathic disorders, including autonomic disorders such as POTS. Given the recognized potential for many antigens to trigger a major and permanent escalation of baseline MC misbehavior in a given MCAS patient, we hypothesize that in our patients described herein, vaccination with Gardasil may have caused pre-existing (but not yet clinically recognized) MCAS to worsen to a clinically significantly degree, with the emergence of POTS and other issues. The recognition and management of MCAS prior to vaccinations in general may be a strategy worth investigating for reducing adverse events following HPV vaccinations and perhaps even other types of vaccinations.

IgG and IgA Antibodies Post SARS-CoV-2 Vaccine in the Breast Milk and Sera of Breastfeeding Women

The COVID-19 pandemic has carried massive global health and economic burden that is currently counteracted by a challenging anti-COVID-19 vaccination campaign. Indeed, mass vaccination against COVID-19 is expected to be the most efficacious intervention to mitigate the pandemic successfully. The primary objective of the present study is to test the presence of neutralizing anti-SARS-CoV-2 antibodies (IgA and IgG) in the breast milk and sera samples from vaccinated women at least 20 days after the complete vaccine cycle. A secondary aim is to compare the IgG antibodies level in maternal serum and breast milk. The third target is to evaluate the presence of the IgG antibodies in breast milk after several weeks from the vaccination. Finally, we collected information on the health status of infants in the days following maternal vaccination. Forty-two mothers were enrolled in the study. Thirty-six received the Pfizer/BioNTech vaccine, four the Astra Zeneca vaccine, one the Moderna vaccine and another woman Astra Zeneca in the first dose and Pfizer/BioNTech in the second dose. All 42 milk samples confirmed the presence of anti-SARS-CoV-2 IgG, and none showed IgA presence. Regarding the matched 42 sera samples, 41 samples detected IgG presence, with one sample testing negative and only one positive for seric IgA. None of the 42 infants had fever or changes in sleep or appetite in the seven days following the maternal vaccination. The level of IgG antibodies in milk was, on average, lower than that in maternal serum. According to our analysis, the absence of IgA could suggest a rapid decrease after vaccination even if frequent breastfeeding could favour its persistence. IgG were present in breast milk even 4 months after the second vaccine dose. Information on the immunological characteristics of breast milk could change mothers’ choices regarding breastfeeding.

Childhood Immunisation Coverage during the COVID-19 Epidemic in Italy

The COVID-19 pandemic has affected national healthcare systems worldwide, with around 282 million cumulative confirmed cases reported in over 220 countries and territories as of the end of 2021. The Italian National Health System was heavily affected, with detrimental impacts on preventive service delivery. Routine vaccination services were disrupted across the country during the first months of the pandemic, and both access to and demand for vaccines have decreased during the pandemic. In many cases, parents preferred to postpone scheduled appointments for routine paediatric vaccinations because of stay-at-home orders or fear of COVID-19 infection when accessing care. The objective of the current study was to assess the routine childhood vaccine coverage (VC) rates during the COVID-19 epidemic in Italy. We compared 2020 and 2019 VC by age group and vaccine type. The Italian Ministry of Health collected anonymised and aggregated immunisation national data through the local health authorities (LHAs). Results were considered statistically significant at a two-tailed p-value ≤ 0.05. VC rates for mandatory vaccinations decreased in 2020 compared to 2019 (range of VC rate decrease: −1% to −2.7%), while chicken pox increased (+2.2%) in 7-year-old children. Recommended vaccinations were moderately affected (range of VC rate decrease in 2020 vs. 2019: −1.4% to −8.5%), with the exception of anti-HPV in males, Men ACWY, and anti-rotavirus vaccination (VC increase 2020 vs. 2019: +1.8%, +4.7% and +9.4%, respectively). In the COVID-19 era, the implementation of coherent, transparent, and effective communication campaigns and educational programs on safe childhood vaccinations, together with the increase in the number of healthcare staff employed, is essential to support strategies to reinforce vaccination confidence and behaviour, thus avoiding health threats due to VPD during and beyond COVID-19 times.

Cyberchondria, Fear of COVID-19, and Risk Perception Mediate the Association between Problematic Social Media Use and Intention to Get a COVID-19 Vaccine

Vaccination is the most effective way to control the COVID-19 pandemic, but vaccination hesitancy threatens this effort worldwide. Consequently, there is a need to understand what influences individuals’ intention to get a COVID-19 vaccine. Restriction of information gathering on societal developments to social media may influence attitudes towards COVID-19 vaccination through exposure to disinformation and imbalanced arguments. The present study examined the association between problematic social media use and intention to get the COVID-19 vaccine, taking into account the mediating roles of cyberchondria, fear of COVID-19, and COVID-19 risk perception. In a cross-sectional survey study, a total of 10,843 residents of Qazvin City, Iran completed measures on problematic social media use, fear of COVID-19, cyberchondria, COVID-19 risk perception, and intention to get a COVID-19 vaccine. The data were analyzed using structural equation modeling (SEM). The results showed that there was no direct association between problematic social media use and intention to get a COVID-19 vaccine. Nonetheless, cyberchondria, fear of COVID-19, and COVID-19 risk perception (each or serially) mediated associations between problematic social media use and intention to get a COVID-19 vaccine. These results add to the understanding of the role of problematic social media use in COVID-19 vaccine hesitancy, i.e., it is not the quantity of social media use per se that matters. This knowledge of the mediating roles of cyberchondria, fear of COVID-19, and COVID-19 risk perception can be used by public health experts and policymakers when planning educational interventions and other initiatives in COVID-19 vaccination programs.

Emerging Socioeconomic Disparities in COVID-19 Vaccine Second-Dose Completion Rates in the United States

Although COVID-19 vaccination plans acknowledge a need for equity, disparities in two-dose vaccine initiation have been observed in the United States. We aim to assess if disparity patterns are emerging in COVID-19 vaccination completion. We gathered (n = 843,985) responses between February and November 2021 from a web survey. Individuals self-reported demographics and COVID-19 vaccination status. Dose initiation and completion rates were calculated incorporating survey weights. A multi-variate logistic regression assessed the association between income and completing vaccination, accounting for other demographics. Overall, 57.4% initiated COVID-19 vaccination, with 84.5% completing vaccination. Initiation varied by income, and we observed disparities in completion by occupation, race, age, and insurance. Accounting for demographics, higher incomes are more likely to complete vaccination than lower incomes. We observe disparities in completion across annual income. Differences in COVID-19 vaccination completion may lead to two tiers of protection in the population, with certain sub-groups being better protected from future infection.

Using Google Trends to Predict COVID-19 Vaccinations and Monitor Search Behaviours about Vaccines: A Retrospective Analysis of Italian Data

Google Trends data are an efficient source for analysing internet search behaviour and providing valuable insights into community dynamics and health-related problems. In this article, we aimed to evaluate if Google Trends data could help monitor the COVID-19 vaccination trend over time and if the introduction of COVID-19 vaccines modified the interest of pregnant women in vaccination. Data related to Google internet searches and the number of vaccine doses administered in Italy were used. We found moderate to strong correlations between search volumes of vaccine-related terms and the number of vaccines administered. In particular, a model based on Google Trends with a 3-week lag showed the best performance in fitting the number of COVID-19 vaccinations over time. We also observed that the introduction of COVID-19 vaccines affected the search interest for the argument “vaccination in pregnancy” both quantitatively and qualitatively. There was a significant increase in the search interest after the launch of the COVID-19 vaccination campaign in Italy. Qualitative analysis suggested that this increase was probably due to concerns about COVID-19 vaccines. Thus, our study suggests the benefits of using Google Trends data to predict the number of COVID-19 vaccine doses administered, and to monitor feelings about vaccination.

Immunoprofiling Identifies Functional B and T Cell Subsets Induced by an Attenuated Whole Parasite Malaria Vaccine as Correlates of Sterile Immunity

Immune correlates of protection remain elusive for most vaccines. An identified immune correlate would accelerate the down-selection of vaccine formulations by reducing the need for human pathogen challenge studies that are currently required to determine vaccine efficacy. Immunization via mosquito-delivered, radiation-attenuated P. falciparum sporozoites (IMRAS) is a well-established model for efficacious malaria vaccines, inducing greater than 90% sterile immunity. The current immunoprofiling study utilized samples from a clinical trial in which vaccine dosing was adjusted to achieve only 50% protection, thus enabling a comparison between protective and non-protective immune signatures. In-depth immunoprofiling was conducted by assessing a wide range of antigen-specific serological and cellular parameters and applying our newly developed computational tools, including machine learning. The computational component of the study pinpointed previously un-identified cellular T cell subsets (namely, TNFα-secreting CD8+CXCR3−CCR6− T cells, IFNγ-secreting CD8+CCR6+ T cells and TNFα/FNγ-secreting CD4+CXCR3−CCR6− T cells) and B cell subsets (i.e., CD19+CD24hiCD38hiCD69+ transitional B cells) as important factors predictive of protection (92% accuracy). Our study emphasizes the need for in-depth immunoprofiling and subsequent data integration with computational tools to identify immune correlates of protection. The described process of computational data analysis is applicable to other disease and vaccine models.

Harnessing Mycobacterium bovis BCG Trained Immunity to Control Human and Bovine Babesiosis

Babesiosis is a disease caused by tickborne hemoprotozoan apicomplexan parasites of the genus Babesia that negatively impacts public health and food security worldwide. Development of effective and sustainable vaccines against babesiosis is currently hindered in part by the absence of definitive host correlates of protection. Despite that, studies in Babesia microti and Babesia bovis, major causative agents of human and bovine babesiosis, respectively, suggest that early activation of innate immune responses is crucial for vertebrates to survive acute infection. Trained immunity (TI) is defined as the development of memory in vertebrate innate immune cells, allowing more efficient responses to subsequent specific and non-specific challenges. Considering that Mycobacterium bovis bacillus Calmette-Guerin (BCG), a widely used anti-tuberculosis attenuated vaccine, induces strong TI pro-inflammatory responses, we hypothesize that BCG TI may protect vertebrates against acute babesiosis. This premise is supported by early investigations demonstrating that BCG inoculation protects mice against experimental B. microti infection and recent observations that BCG vaccination decreases the severity of malaria in children infected with Plasmodium falciparum, a Babesia-related parasite. We also discuss the potential use of TI in conjunction with recombinant BCG vaccines expressing Babesia immunogens. In conclusion, by concentrating on human and bovine babesiosis, herein we intend to raise awareness of BCG TI as a strategy to efficiently control Babesia infection.

Immunogenicity of a Two-Dose Human Papillomavirus Vaccine Schedule in HIV-Infected Adolescents with Immune Reconstitution

HIV-infected patients are at increased risk of human papillomavirus (HPV) acquisition and HPV-associated diseases. This study set out to determine whether a two-dose (2D) HPV vaccination schedule was sufficient in HIV-infected adolescents with immune reconstitution (IR) following antiretroviral treatment. Participants aged 9–15 years who had CD4 cell counts > 500 cells/mm3 and HIV-1 RNA < 40 copies/mL for at least one year were assigned to the 2D schedule, while older participants or those without IR received a three-dose (3D) schedule. Antibodies to HPV-16 and -18 were measured using a pseudovirion-based neutralization assay. A total of 96 subjects were enrolled; 31.3% and 68.7% received the 2D and 3D schedule, respectively. Of these, 66.7% and 57.6% of the 2D and 3D participants, respectively, were male. The seroconversion rates for HPV-16 and HPV-18 were 100% in all cases, except for HPV-18 in males who received the 3D schedule (97.4%). In males, the anti-HPV-16 geometric mean titers (GMTs) were 6859.3 (95% confidence interval, 4394.3–10,707.1) and 7011.1 (4648.8–10,573.9) in the 2D and 3D groups (p = 0.946), respectively, and the anti-HPV-18 GMTs were 2039.3 (1432.2–2903.8) and 2859.8 (1810.0–4518.4) in the 2D and 3D (p = 0.313) groups, respectively. In females, the anti-HPV-16 GMTs were 15,758.7 (8868.0–28,003.4) and 26,241.6 (16,972.7–40,572.3) in the 2D and 3D groups (p = 0.197), respectively, and the anti-HPV-18 GMTs were 5971.4 (3026.8–11,780.6) and 9993.1 (5950.8–16,781.1) in the 2D and 3D groups (p = 0.271), respectively. In summary, a 2D schedule is as immunogenic in young adolescents with IR as a 3D schedule in older subjects and those without IR.