COVID-19 Vaccine Research Articles

Temporary Delayed Hypersensitivity Reaction to Botulinum Toxin-A After COVID-19 Vaccination: A Case Series.

The occurrence of a hypersensitivity reaction with the injection of botulinum toxin type A (BTX-A) in cosmetic use is a rare complication. We report the largest case series of temporary delayed hypersensitivity reaction (DHR) with BTX-A following COVID-19 vaccination and the first cases to incobotulinum toxin A (incoBTX-A). A retrospective multicentric case series of patients who developed a DHR to BTX-A after COVID-19 vaccination. Twelve patients were treated with BTX-A injections for the management of facial rhytids. The age range was between 29 and 45years. Ten (83.3%) were female. Ten (83.3%) patients received incoBTX-A, and two received onabotulinum toxin A (onaBTX-A). All patients had COVID-19 vaccination (mRNA vaccine) between 1 and 7months before. Within an average time of 24h after BTX-A injection, all patients developed progressive facial swelling and erythema that were more prominent at the injection points. Intradermal allergic tests to BTX-A were performed in six (50%) patients, and the results were all negative. Adequate clinical control was achieved with systemic corticosteroids and antihistamines. After 1year with no further vaccination, a new BTX-A treatment (provocation test) was performed in all patients with no secondary effects. Previous COVID-19 vaccination and the absence of new adverse events with further BTX-A injections suggest a temporary DHR. Clinicians should be aware of the importance of immunization history and its potential post-vaccine immunogenic effects with BTX-A. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

COVID-19 Breakthrough Infection after Vaccination and Substance Use Disorders: A Longitudinal Cohort of People with and without HIV Receiving Care in the United States Veterans Health Administration.

Research regarding HIV, substance use disorders (SUD), and SARS-CoV-2 infections after COVID-19 vaccination is limited. In the Veterans Aging Cohort Study (VACS)-HIV cohort, we followed vaccinated persons with HIV (PWH) and without HIV (PWoH) from 12/2020 to 3/2022 and linked SARS-CoV-2 test results for laboratory-confirmed breakthrough infection through 9/2022. We examined associations of substance use (alcohol use disorder [AUD], other SUD, smoking status) and HIV status and severity with breakthrough infections, using Cox proportional hazards regression hazard ratios (HR). To test for potential interactions between substance use and HIV, we fit survival models with a multiplicative interaction term. Among 24,253 PWH and 53,661 PWoH, 8.0% of PWH and 7.1% of PWoH experienced COVID-19 breakthrough. AUD (HR 1.42, 95% CI 1.32, 1.52) and other SUD (HR 1.49, 95% CI 1.39, 1.59) were associated with increased risk of breakthrough, and this was similar by HIV status (p-interaction > 0.09). Smoking was not associated with breakthrough. Compared to PWoH, PWH at all HIV severity levels had increased risk of breakthrough ranging from 9% for PWH with CD4 count ≥ 500 cells/µl (HR 1.09, 95% CI 1.02, 1.17) to 59% for PWH with CD4 count < 200 (HR 1.59, 95% CI 1.31, 1.92). Patients with AUD (HR 1.42, 95% CI 1.33, 1.52) and other SUD (HR 1.48, 95% CI 1.38, 1.59) had increased COVID-19 breakthrough risk, regardless of HIV status. HIV was associated with breakthrough; risk was greatest among PWH with lower CD4 count. In addition to inhibiting HIV treatment adherence and increasing HIV progression, AUD and other SUD may increase COVID-19 breakthrough risk.

The status and influencing factors of COVID-19 vaccination in patients with COPD

In this study, we investigated the status and influencing factors of coronavirus disease 2019 (COVID-19) vaccination in patients with chronic obstructive pulmonary disease (COPD). A questionnaire on COVID-19 vaccination in patients with COPD was developed. The clinical characteristics, COVID-19 vaccination status, other relevant vaccinations, and vaccination status of the patients with COPD were collected anonymously. Logistic regression analysis was used to analyze the factors influencing COVID-19 vaccination in patients with COPD. There were 1898 returned questionnaires, of which 1874 were valid. The proportion of patients who completed the COVID-19 vaccination program was 78.60%. Factors influencing the COVID-19 vaccination rate were: the age of individuals who were 75–85 years old and > 85 years old, acute exacerbation 3–4 times in the previous year, comorbid cardiovascular and endocrine system diseases, failure to take regular medication for COPD, application of non-invasive ventilation machines, believing that their current health condition has deteriorated, believing that the current COVID-19 vaccine is not safe, medical staff not specifying whether they would recommend vaccination against COVID-19, medical staff not recommending the COVID-19 vaccine, and fear of adverse reactions and aggravation of COPD. Patients with COPD had a high COVID-19 vaccination rate in China, whereas patients with pneumonia, influenza, and herpes zoster had a low vaccination rate. Improving the patients’ understanding of the safety and effectiveness of the vaccine and promoting effective communication between medical staff and patients would help increase the vaccination rate of patients with COPD.

Caregiver Intent and Willingness to Accept COVID-19 Vaccine in the Pediatric Emergency Department.

While COVID-19 vaccine (CV) acceptance is improving, little is known about parental acceptance of CV in the pediatric emergency department (PED). The aims of the study are to assess rates of CV uptake among eligible children presenting to the PED, describe caregiver willingness to accept CV in the PED, and assess potential ED-based interventions to increase CV acceptance. We surveyed caregivers of 384 children aged ≥6 months presenting to the PED for minor illness/injury. Demographics, COVID-19/other vaccine history, and intent/willingness to receive CV were recorded. Participants were recontacted by phone 6-12 months after vaccine eligibility to assess CV status, barriers to CV, willingness to receive CV in the ED, and preferences for ED-based vaccine-related interventions. Data were analyzed using standard descriptive statistics. In initial surveys, 31.6% of caregivers planned to vaccinate their child; 32.2% would likely accept CV in the PED. Follow-up data was available for 302 (78.6%) previously unvaccinated participants; only 59 (19.5%) had received CV at follow-up. Of those unvaccinated at follow-up, 27 (28.7%) intended to vaccinate, nearly all of whom would accept CV in the PED. Factors associated with increased likelihood of vaccination included initial intent to vaccinate (P = 0.004), definite/probable acceptance of CV in the PED (P = 0.035), and child age 5+ (P = 0.005). Nearly one-fourth of unvaccinated families reported barriers to CV access. Interventions most likely to persuade families to vaccinate included: discussing CV with a provider (25.5%), receiving an information sheet (23.4%), and offering CV without an ED visit (22.3%). CV acceptance was low in this cohort. A gap population of unvaccinated children whose caregivers intend to vaccinate exists, and many of these would accept CV in the ED. This data supports the presence of CV programs in the ED to close this gap.

Uveal Effusion Syndrome Temporally Associated with Primary COVID-19 Infection.

To report a case of uveal effusion syndrome in association with primary COVID-19 infection to share our experience and insight in diagnosing and managing this unique case. A 56-year-old woman presented with angle closure glaucoma of both eyes. Further examination and imaging revealed the etiology to be related to bilateral uveal effusions and choroidal thickening in the setting of recent COVID-19 infection. The patient's glaucoma was managed with bilateral iridotomies and medical therapy, while the precipitating uveal effusions resolved with treatment on oral steroids. While uveal effusion syndrome has been associated with COVID-19 vaccination, it has not yet been reported after primary infection. Recognition of this rare phenomenon will allow for better diagnosis and treatment in future cases.

Aplastic Anemia Following COVID-19 Vaccination: A Systematic Review of Case Reports and Case Series

Aplastic Anemia Following COVID-19 Vaccination: A Systematic Review of Case Reports and Case Series

Death Risk Response of High-Altitude Resident Populations to COVID-19 Vaccine: A Retrospective Cohort Study.

Vásquez-Velásquez, Cinthya, Diego Fano-Sizgorich, and Gustavo F Gonzales. Death risk response of high-altitude resident populations to COVID-19 vaccine: Retrospective cohort study. High Alt Med Biol. 00:00-00, 2024. Background: Peru had one of the highest mortality rates caused by the coronavirus disease 2019 (COVID-19) pandemic worldwide. Vaccination significantly reduces mortality. However, the effectiveness of vaccination might differ at different altitudinal levels. The study aimed to evaluate the effect modification of altitude on the association between vaccination and COVID-19 mortality in Peru. Methodology: A retrospective cohort, using open access databases of deaths, COVID-19 cases, hospitalizations, and vaccination was obtained from the Peruvian Ministry of Health. Deaths due to COVID-19 were evaluated in vaccinated and nonvaccinated patients. Crude (RR) and adjusted relative risks (aRR) were calculated using generalized linear models of Poisson family with robust variances. Models were adjusted for age, sex, pandemic wave, and Human Development Index. To evaluate the interaction by altitude, a stratified analysis by this variable was performed. The variable altitude was categorized as, 0-499 m (828,298 cases), 500-1,499 m (64,735 cases), 1,500-2,499 m (106,572 cases), and ≥2,500 m (179,004 cases). The final sample studied included 1,362,350 cases. Results: The vaccine showed a considerable reduction of death risk with the second (aRR: 0.41, 95% confidence interval [CI]: 0.38-0.44) and third doses (aRR: 0.21, 95% CI: 0.20-0.23). In the adjusted and interaction model, it can be observed that medium and high altitude present a higher risk of death compared to sea level (aRR: 2.58 and 2.03, respectively). Likewise, the two doses' group presents an aRR:1.22 for medium altitude (1,500-2,499 m) and 1.6 for high altitude (≥2,500 m), compared with low-altitude population, suggesting that the action of vaccination at high altitude is altered by the effect of the altitude itself. Conclusions: Altitude might modify the protective effect of SARS-CoV-2 vaccine against COVID-19 death.

Long-term risk of autoimmune diseases after mRNA-based SARS-CoV2 vaccination in a Korean, nationwide, population-based cohort study

The long-term association between mRNA-based coronavirus disease 2019 (COVID-19) vaccination and the development of autoimmune connective tissue diseases (AI-CTDs) remains unclear. In this nationwide, population-based cohort study involving 9,258,803 individuals, we aim to determine whether the incidence of AI-CTDs is associated with mRNA vaccination. The study spans over 1 year of observation and further analyses the risk of AI-CTDs by stratifying demographics and vaccination profiles and treating booster vaccination as time-varying covariate. We report that the risk of developing most AI-CTDs did not increase following mRNA vaccination, except for systemic lupus erythematosus with a 1.16-fold risk in vaccinated individuals relative to controls. Comparable results were reported in the stratified analyses for age, sex, mRNA vaccine type, and prior history of non-mRNA vaccination. However, a booster vaccination was associated with an increased risk of some AI-CTDs including alopecia areata, psoriasis, and rheumatoid arthritis. Overall, we conclude that mRNA-based vaccinations are not associated with an increased risk of most AI-CTDs, although further research is needed regarding its potential association with certain conditions.

Pityriasis Rubra Pilaris Following Administration of the Pfizer-BioNTech COVID-19 Vaccine Successfully Treated with Acitretin and Dupilumab

Pityriasis Rubra Pilaris Following Administration of the Pfizer-BioNTech COVID-19 Vaccine Successfully Treated with Acitretin and Dupilumab

Incidence of diabetes after SARS-CoV-2 infection in England and the implications of COVID-19 vaccination: a retrospective cohort study of 16 million people

Incidence of diabetes after SARS-CoV-2 infection in England and the implications of COVID-19 vaccination: a retrospective cohort study of 16 million people

Association between COVID-19 vaccination and atrial arrhythmias in individuals with cardiac implantable electronic devices.

The impact of mRNA-based coronavirus disease-2019 (COVID-19) vaccines on atrial arrhythmias (AA) and ventricular arrhythmias incidence is unknown. BIOTRONIK Home Monitoring data and Medicare Claims data were utilized to identify individuals implanted with a cardiac implantable electronic device (CIED) between 2010 and 2020 who received one or more doses of COVID-19 vaccine in 2021. The burden of AA (%) in the 3 months postvaccination was compared to those noted in the preceding 3 months using the Wilcoxon signed rank test. Sub-analyses comparing the effects of the influenza vaccine against the COVID-19 vaccine were also evaluated for individuals who received the influenza vaccine in 2020. A 1:1 propensity score match comparison between COVID-19 vaccine and non-vaccinated patients was also performed. First and second doses of the COVID-19 vaccine were administered to 7757 and 6579 individuals with a CIED (age 76.2 ± 9.0 years, 49% males), respectively. While a small but statistically significant increase in the burden of AA was noted in the 3 months postvaccination compared to the preceding 3 months after the first dose of the COVID-19 vaccine (0.43 ± 9.04%, p = .028) a similar rise in AA was found following the influenza vaccine and for matched patients who did not receive the COVID-19 vaccine. No significant difference in device therapies was seen pre- and postvaccination. Though we report a small but significant increase in the number of CIED-detected AAs following vaccination for COVID-19 over a 3-month window, we believe these results correlate more with time and the progressive nature of AF rather than the vaccine itself. While these data should not dissuade from the use of these vaccines, increased vigilance and prompt treatment of AF is required for high-risk groups, specifically males over 70 years of age, following vaccination.

Effect of Cash Benefits on Health Care Utilization and Health: A Randomized Study.

Poverty is associated with greater barriers to health care and worse health outcomes, but it remains unclear whether income support can improve health. To examine the effect of cash benefits on health care utilization and health. The City of Chelsea, Massachusetts, a low-income community near Boston, randomly assigned individuals by lottery to receive cash benefits. Participants' medical records were linked across multiple health systems. Outcomes were assessed during the intervention period from November 24, 2020, to August 31, 2021. Cash benefits via debit card of up to $400 per month for 9 months. The primary outcome was emergency department visits. Secondary outcomes included specific types of emergency department visits, outpatient use overall and by specialty, COVID-19 vaccination, and biomarkers such as cholesterol levels. Among 2880 individuals who applied for the lottery, mean age was 45.1 years and 77% were female. The 1746 participants randomized to receive the cash benefits had significantly fewer emergency department visits compared with the control group (217.1 vs 317.5 emergency department visits per 1000 persons; adjusted difference, -87.0 per 1000 persons [95% CI, -160.2 to -13.8]). This included reductions in emergency department visits related to behavioral health (-21.6 visits per 1000 persons [95% CI, -40.2 to -3.1]) and substance use (-12.8 visits per 1000 persons [95% CI, -25.0 to -0.6]) as well as those that resulted in a hospitalization (-27.3 visits per 1000 persons [95% CI, -53.6 to -1.1]). The cash benefit had no statistically significant effect on total outpatient visits (424.3 visits per 1000 persons [95% CI, -118.6 to 967.2]), visits to primary care (-90.4 visits per 1000 persons [95% CI, -308.1 to 127.2]), or outpatient behavioral health (83.5 visits per 1000 persons [95% CI, -182.9 to 349.9]). Outpatient visits to other subspecialties were higher in the cash benefit group compared with the control group (303.1 visits per 1000 persons [95% CI, 32.9 to 573.2]), particularly for individuals without a car. The cash benefit had no statistically significant effect on COVID-19 vaccination, blood pressure, body weight, glycated hemoglobin, or cholesterol level. In this randomized study, individuals who received a cash benefit had significantly fewer emergency department visits, including those related to behavioral health and substance use, fewer admissions to the hospital from the emergency department, and increased use of outpatient subspecialty care. Study results suggest that policies that seek to alleviate poverty by providing income support may have important benefits for health and access to care.

COVID-19 Vaccine Effectiveness on the Severity of Disease: A Case-control Study in Southeastern Iran

COVID-19 Vaccine Effectiveness on the Severity of Disease: A Case-control Study in Southeastern Iran

SARS-CoV-2 monoclonal antibody treatment followed by vaccination shifts human memory B cell epitope recognition suggesting antibody feedback.

Therapeutic monoclonal antibodies (mAbs) have been studied in humans, but the impact on immune memory of mAb treatment during an ongoing infection has remained unclear. We evaluated the effect of infusion of the anti-SARS-CoV-2 spike receptor binding domain (RBD) mAb bamlanivimab on memory B cells (MBCs) in SARS-CoV-2-infected individuals. Bamlanivimab treatment skewed the repertoire of memory B cells targeting Spike towards non-RBD epitopes. Furthermore, the relative affinity of RBD memory B cells was weaker in mAb-treated individuals compared to placebo-treated individuals over time. Subsequently, after mRNA COVID-19 vaccination, memory B cell differences persisted and mapped to a specific reduction in recognition of the class II RBD site, the same RBD epitope recognized by bamlanivimab. These findings indicate a substantial role of antibody feedback in regulating memory B cell responses to infection, and single mAb administration can continue to impact memory B cell responses to additional antigen exposures months later.

A trivalent protein-based pan-Betacoronavirus vaccine elicits cross-neutralizing antibodies against a panel of coronavirus pseudoviruses

The development of broad-spectrum coronavirus vaccines is essential to prepare for future respiratory virus pandemics. We demonstrated broad neutralization by a trivalent subunit vaccine, formulating the receptor-binding domains of SARS-CoV, MERS-CoV, and SARS-CoV-2 XBB.1.5 with Alum and CpG55.2. Vaccinated mice produced cross-neutralizing antibodies against all three human Betacoronaviruses and others currently exclusive to bats, indicating the epitope preservation of the individual antigens during co-formulation and the potential for epitope broadening.

A scoping review of global COVID-19 vaccine hesitancy among pregnant persons

Uptake of the COVID-19 vaccine among pregnant persons is lower than the general population. This scoping review explored pregnant people’s attitudes towards the COVID-19 vaccine, reasons for vaccine hesitancy, and whether attitudes about COVID-19 vaccines differ by country of origin. A scoping review was conducted across PubMed, Embase, CINHAL, and Scopus. Inclusion criteria were articles published in English from 2019–2022 focused on attitudes towards COVID-19 vaccination among pregnant persons. Data analysis was done via the 5Cs framework for vaccine hesitancy: Constraints, Complacency, Calculation, Confidence, and Collective Responsibility. 44 articles were extracted. A lack of confidence in vaccine safety was the most prevalent theme of hesitancy among pregnant persons. This was largely driven by a lack of access to information about the vaccine as well as mistrust of the vaccine and medical professionals. Meanwhile, vaccine acceptance was mostly driven by a desire to protect themselves and their loved ones. Overall, COVID-19 vaccine hesitancy among pregnant persons continues to be high. Vaccine hesitancy is primarily driven by fear of the unknown side effects of the vaccine on pregnant persons and their fetuses along with a lack of information and medical mistrust. Some differences can be seen between high income and low- and middle-income countries regarding vaccine hesitancy, showing that a single solution cannot be applied to all who are vaccine hesitant. General strategies, however, can be utilized to reduce vaccine hesitancy, including advocating for inclusion of pregnant persons in clinical trials and incorporating consistent COVID-19 vaccine counseling during prenatal appointments.

Vaccine Uptake and Perspectives Among Latina Immigrant Mothers in Rural Communities in a Midwestern State.

Examine the prevalence of and characteristics related to COVID-19 vaccine uptake. Quantitative and qualitative data collected at two-time points via phone interviews. Rural Midwestern communities. 109 Latina mothers with incomes < 185% FPL, at least one child < age 12 recruited from a Midwestern state based on two previous studies. Mothers responded to the following variables through a survey: Vaccine uptake measured by responses to, Have you received a vaccination shot for COVID-19. Tested predictors of vaccine uptake included: income, gender, education, immigration status, confidence in vaccine, belief the pandemic is over). Mothers' perspectives regarding the vaccine explored via responses to Why haven't you received COVID-19 vaccine?. Binary logistic regression analysis was conducted. Demographic variables and attitudes toward the vaccine served as predictors of mothers' vaccine uptake. Qualitative data were analyzed to shed light on mothers' perspectives on receiving the vaccine. Mother's confidence in the vaccine predicted vaccine uptake in 2021 (aOR=1.332, 95% CI: 1.07-1.65) and 2022 (aOR=1.48, 95%CI: 1.11-1.97). In 2021, income also predicted vaccine uptake (aOR=1; 95% CI: 1-1.002). Overarching themes: "vaccination is not necessary","mistrust of the vaccine", and "vaccine as protector". Vaccinated mothers viewed the vaccine as a protection from being infected or gravely ill. For unvaccinated mothers, messages are needed that communicate the vaccine can protect them from virus transmission from household members who unknowingly are infected, as well as from different virus strains.

The Performance of Kaizen Tasks Across Three Online Discrete Choice Experiment Surveys: An Evidence Synthesis.

Kaizen is a Japanese term for continuous improvement (kai ~ change, zen ~ good). In a kaizen task, a respondent makes sequential choices to improve an object's profile, revealing a preference path. Including kaizen tasks in a discrete choice experiment has the advantage of collecting greater preference evidence than pick-one tasks, such as paired comparisons. OBJECTIVE ANDMETHODS: So far, three online discrete choice experiments have included kaizen tasks: the 2020 US COVID-19 vaccination (CVP) study, the 2021 UK Children's Surgery Outcome Reporting (CSOR) study, and the 2023 US EQ-5D-Y-3L valuation (Y-3L) study. In this evidence synthesis, we describe the performance of the kaizen tasks in terms of response behaviors, conditional logit and Zermelo-Bradley-Terry (ZBT) estimates, and their standard errors in each of the surveys. Comparing the CVP and Y-3L, including hold-outs (i.e., attributes shared by all alternatives) seems to reduce positional behavior by half. The CVP tasks excluded multi-level improvements; therefore, we could not estimate logit main effects directly. In the CSOR, only 12 of the 21 logit estimates are significantly positive (p < 0.05), possibly due to the fixed attribute order. All Y-3L estimates are significantly positive, and their predictions are highly correlated (Pearson: logit 0.802, ZBT 0.882) and strongly agree (Lin: logit 0.744, ZBT 0.852) with the paired-comparison probabilities. These discrete choice experiments offer important lessons for future studies: (1) include warm-up tasks, hold-outs, and multi-level improvements; (2) randomize the attribute order (i.e., up-down) at the respondent level; and (3) recruit smaller samples of respondents than traditional discrete choice experiments with only pick-one tasks.

Aluminum hydroxide and immunostimulatory glycolipid adjuvant combination for enhanced COVID-19 subunit vaccine immunogenicity

Protein-based subunit vaccines like RBD-Fc are promising tools to fight COVID-19. RBD-Fc fuses the receptor-binding domain (RBD) of the SARS-CoV-2 virus spike protein with the Fc region of human IgG1, making it more immunogenic than RBD alone. Earlier work showed that combining RBD-Fc with iNKT cell agonists as adjuvants improved neutralizing antibodies but did not sufficiently enhance T cell responses, a limitation RBD-Fc vaccines share with common adjuvants. Here we demonstrate that aluminum hydroxide combined with α-C-GC, a C-glycoside iNKT cell agonist, significantly improved the RBD-Fc vaccine’s induction of RBD-specific T-cell responses. Additionally, aluminum hydroxide with α-GC-CPOEt, a phosphonate diester derivative, synergistically elicited more robust neutralizing antibodies. Remarkably, modifying αGC with phosphate (OPO3H2) or phosphonate (CPO3H2) to potentially enhance aluminum hydroxide interaction did not improve efficacy over unmodified αGC with aluminum hydroxide. These findings underscore the straightforward yet potent potential of this approach in advancing COVID-19 vaccine development and provide insights for iNKT cell-based immunotherapy.

Development of a Data Manager for Analyzing the Global Distribution of COVID-19 Vaccines Using Data from 'Our World in Data'

Development of a Data Manager for Analyzing the Global Distribution of COVID-19 Vaccines Using Data from 'Our World in Data'