Human and hamster sera correlate well in identifying antigenic drift among SARS-CoV-2 variants, including JN.1.

Antigenic assessments of SARS-CoV-2 variants inform decisions to update COVID-19 vaccines. Primary infection sera are often used for assessments, but such sera are rare due to population immunity from SARS-CoV-2 infections and COVID-19 vaccinations. Here, we show that neutralization titers and breadth of matched human and hamster pre-Omicron variant primary infection sera correlate well and generate similar antigenic maps. The hamster antigenic map shows modest antigenic drift among XBB sub-lineage variants, with JN.1 and BA.4/BA.5 variants within the XBB cluster, but with fivefold to sixfold antigenic differences between these variants and XBB.1.5. Compared to sera following only ancestral or bivalent COVID-19 vaccinations, or with post-vaccination infections, XBB.1.5 booster sera had the broadest neutralization against XBB sub-lineage variants, although a fivefold titer difference was still observed between JN.1 and XBB.1.5 variants. These findings suggest that antibody coverage of antigenically divergent JN.1 could be improved with a matched vaccine antigen.IMPORTANCEUpdates to COVID-19 vaccine antigens depend on assessing how much vaccine antigens differ antigenically from newer SARS-CoV-2 variants. Human sera from single variant infections are ideal for discriminating antigenic differences among variants, but such primary infection sera are now rare due to high population immunity. It remains unclear whether sera from experimentally infected animals could substitute for human sera for antigenic assessments. This report shows that neutralization titers of variant-matched human and hamster primary infection sera correlate well and recognize variants similarly, indicating that hamster sera can be a proxy for human sera for antigenic assessments. We further show that human sera following an XBB.1.5 booster vaccine broadly neutralized XBB sub-lineage variants but titers were fivefold lower against the more recent JN.1 variant. These findings support updating the current COVID-19 vaccine variant composition and developing a framework for assessing antigenic differences in future variants using hamster primary infection sera.

Assessing vaccinated persons' intention to take the COVID-19 boosters using a combined theoretical framework: an online survey in Egypt.

Vaccines, like the Corona Virus Disease-2019 (COVID-19) vaccines, can control diseases, but vaccine hesitancy reduces their use. It is important to assess the intention to use COVID-19 vaccines boosters and the determinants of this intention to help in developing programs to promote the uptake of boosters. An online survey collected data from adults in Egypt between March and June 2022 using a questionnaire that assessed demographic characteristics, and constructs of the Theory of Planned Behaviour (TPB) and the Health Belief Model (HBM). The survey was uploaded to SurveyMonkey and the links were posted on social media platforms. Binary regression analysis was used and the dependent variable was intention to use boosters of COVID-19 vaccines. The independent variables were indicators of the HBM including perceived susceptibility to COVID-19 infection (medical history) and possibility of disease prevention (awareness of the availability of types of COVID-19 vaccines); and indicators of the TPB including attitude toward COVID-19 vaccines (that they are harmful, that they may lead to death and confidence in locally and foreign manufactured vaccines), perceived norms (the percentage of vaccinated persons in one's circle) and perceived control over booster uptake (presence of government mandates for COVID-19 vaccination). The confounders were sociodemographic factors (age, sex, education, and place of residence). Complete responses were available from 1113 out of 1401 participants (79.4%), with mean (SD) age = 25 (9.5) years, of whom, 66.7% (n = 742) were females and 68.6% (n = 764) were university students. About 39.4% and 31.2% indicated that they would get or would definitely get the booster dose of the COVID-19 vaccines. In multiple regression, intention to use a booster dose was significantly related to not agreeing (AOR = 4.87, P < 0.001) or not agreeing at all (AOR = 8.46, P = 0.001) that vaccines are harmful and to having no confidence (AOR = 0.21, P < 0.001) or no confidence at all (AOR = 0.14, P < 0.001) in foreign-manufactured vaccines. Most university-educated Egyptians in the study intended to take the COVID-19 vaccine booster dose and this intention was associated with attitude toward the harm of the vaccine and confidence in foreign-manufactured vaccines. Awareness campaigns are needed to counteract misinformation and promote booster dose uptake.

A Texting- and Internet-Based Self-Reporting System for Enhanced Vaccine Safety Surveillance With Insights From a Large Integrated Health Care System in the United States: Prospective Cohort Study.

BACKGROUND: SMS text messaging- and internet-based self-reporting systems can supplement existing vaccine safety surveillance systems, but real-world participation patterns have not been assessed at scale. OBJECTIVE: This study aimed to describe the participation rates of a new SMS text messaging- and internet-based self-reporting system called the Kaiser Permanente Side Effect Monitor (KPSEM) within a large integrated health care system. METHODS: We conducted a prospective cohort study of Kaiser Permanente Southern California (KPSC) patients receiving a COVID-19 vaccination from April 23, 2021, to July 31, 2023. Patients received invitations through flyers, SMS text messages, emails, or patient health care portals. After consenting, patients received regular surveys to assess adverse events up to 5 weeks after each dose. Linkage with medical records provided demographic and clinical data. In this study, we describe KPSEM participation rates, defined as providing consent and completing at least 1 survey within 35 days of COVID-19 vaccination. RESULTS: Approximately, 8% (164,636/2,091,975) of all vaccinated patients provided consent and completed at least 1 survey within 35 days. The lowest participation rates were observed for parents of children aged 12-17 years (1349/152,928, 0.9% participation rate), and the highest participation was observed among older adults aged 61-70 years (39,844/329,487, 12.1%). Persons of non-Hispanic White race were more likely to participate compared with other races and ethnicities (13.1% vs 3.9%-7.5%, respectively; P<.001). In addition, patients residing in areas with a higher neighborhood deprivation index were less likely to participate (5.1%, 16,503/323,122 vs 10.8%, 38,084/352,939 in the highest vs lowest deprivation quintiles, respectively; P<.001). Invitations through the individual's Kaiser Permanente health care portal account and by SMS text message were associated with the highest participation rate (19.2%, 70,248/366,377 and 10.5%, 96,169/914,793, respectively), followed by email (19,464/396,912, 4.9%) and then QR codes on flyers (25,882/2,091,975, 1.2%). SMS text messaging-based surveys demonstrated the highest sustained daily response rates compared with internet-based surveys. CONCLUSIONS: This real-world prospective study demonstrated that a novel digital vaccine safety self-reporting system implemented through an integrated health care system can achieve high participation rates. Linkage with participants' electronic health records is another unique benefit of this surveillance system. We also identified lower participation among selected vulnerable populations, which may have implications when interpreting data collected from similar digital systems.

Using regression tree analysis to examine demographic and geographic characteristics of COVID-19 vaccination trends over time, United States, May 2021-April 2022, National Immunization Survey Adult COVID Module.

Using data from the nationally representative National Immunization Survey (NIS), we applied conditional linear regression tree methodology to examine relationships between demographic and geographic factors and propensity of receiving various doses of COVID-19 vaccine over time; these analyses identified temporal changes in these relationships that heretofore had not been identified using conventional logistical regression methodologies. Three regression tree models were built using an R package, Recursive Partitioning for Modeling Survey (rpms), to examine propensities over time of receiving a (1) first dose of a two-dose COVID-19 mRNA primary vaccination series or single dose of the Janssen vaccine (vaccine initiation), (2) primary series completion, and (3) monovalent booster dose, using a conditional linear effect model. Persons ≥50 years were more likely to complete a primary series and receive a first booster dose; persons reporting having received non-COVID-19 vaccines recently were more likely to initiate vaccination, complete the primary series, and get a first booster dose; persons reporting having work or school requirements were more likely to complete the primary series. Persons not reporting having received non-COVID-19 vaccines in 2 years but reporting having work or school vaccination requirements were more likely to initiate vaccination than those without work/school requirements. Among persons not reporting having received non-COVID-19 vaccines in 2 years and not reporting having work or school vaccination requirements, those aged ≥50 years were more likely to initiate vaccination than were younger adults. Propensity of receiving various doses was correlated with age, having recently received non-COVID 19 vaccines, and having vaccination requirements at work or school. Regression tree methodology enabled modeling of different COVID-19 vaccination dose propensities as a linear effect of time, revealed changes in relationships over time between demographic factors and propensity of receipt of different doses, and identified populations that may benefit from vaccination outreach efforts.

Neonatal and maternal outcomes of mRNA versus Non-mRNA COVID-19 vaccines in pregnant patients: a systematic review and meta-analysis.

Objective: To compare the effectiveness and safety of non-mRNA versus mRNA COVID-19 vaccines on pregnant women and their newborns in a systematic review with meta-analysis. Data sources: We searched PubMed, Embase, and Cochrane Central in May 2023. Study selection: The search strategy yielded 4451 results, 16 studies were fully reviewed. We selected case-control studies analysing non-mRNA versus mRNA vaccines. Data collection and analysis: we assessed the risk of bias using the Cochrane Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool. Standardised mean differences were pooled using random-effect models. Data synthesis: We identified 8 prospective and retrospective studies with a total of 32,153 patients. Non-mRNA vaccines were associated with a higher incidence of fever (OR 2.67; 95% CI 2.08-3.43; p<0.001), and a lower incidence of fetal or neonatal death (OR 0.16; 95% CI 0.08-0.33; p<0.001). In subgroup analyses, the Jansen vaccine (Ad26.COV2.S) was found to have a higher rate of premature labor/delivery (OR 4.48; 95% CI 1.45-13.83; p=0.009) and missed/spontaneous abortion (OR 1.90; 95% CI 1.09-3.30; p=0.02), as compared with the Pfizer (BNT162b2) vaccine. Conclusion: non-mRNA vaccines are associated with a lower incidence of fetal or neonatal death among pregnant women who receive a Covid19 vaccine, although at an increased rate of pyrexia compared with mRNA vaccines. Other studies are required for better assessment. PROSPERO: CRD42023421814.

A Comparison of the Outcomes of COVID-19 Vaccinated and Nonvaccinated Patients Admitted to an Intensive Care Unit in a Low-Middle-Income Country.

Patients critically afflicted with coronavirus disease 2019 (COVID-19) often need intensive care unit (ICU) admission, despite comprehensive vaccination campaigns. The challenges faced by healthcare systems in low-middle-income countries, including limited infrastructure and resources, play a pivotal role in shaping the outcomes for these patients. This study aimed to meticulously compare outcomes between COVID-19 vaccinated and nonvaccinated patients admitted to the ICU. In addition, demographic factors and the ICU course influencing mortality were also assessed. A retrospective review of records from the COVID-ICU of Aga Khan University Hospital spanning July 2021-March 2022 included 133 patients. Statistical analyses, encompassing the Mann-Whitney U-test and chi-square/Fisher exact test, discerned quantitative and qualitative differences. Stepwise multivariable logistic regression models with forward selection identified factors associated with hospital mortality. Results revealed comparable cohorts: vaccinated (48.13%) and nonvaccinated (51.87%). Vaccinated individuals, characterized by advanced age and higher Charlson Comorbidity Index, exhibited more critical disease (89.1%; p value: 0.06), acute respiratory distress syndrome (96.9%; p value: 0.013) and elevated inflammatory markers. Despite these differences, both cohorts exhibited similar overall outcomes. Factors such as decreased PaO2/FiO2 ratio on admission and complications during ICU stay were significantly associated with in-hospital mortality. In conclusion, despite advanced age and increased frailty among vaccinated patients, their mortality rate remained comparable to nonvaccinated counterparts. These findings underscore the pivotal role of vaccination in mitigating severe outcomes within this vulnerable population.

Side effects associated with homogenous and heterogenous doses of Oxford-AstraZeneca vaccine among adults in Bangladesh: an observational study.

Assessment of side effects associated with COVID-19 vaccination is required to monitor safety issues and acceptance of vaccines in the long term. We found a significant knowledge gap in the safety profile of COVID-19 vaccines in Bangladesh. We enrolled 1805 vaccine recipients from May 5, 2021, to April 4, 2023. Kruskal-Wallis test and χ2 test were performed. Multivariable logistic regression was also performed. First, second and third doses were administered among 1805, 1341, and 923 participants, respectively. Oxford-AstraZeneca (2946 doses) was the highest administered followed by Sinopharm BIBP (551 doses), Sinovac (214 doses), Pfizer-BioNTech (198 doses), and Moderna (160 doses), respectively. Pain at the injection site (80-90%, 3200-3600), swelling (85%, 3458), redness (78%, 3168), and heaviness in hand (65%, 2645) were the most common local effects, and fever (85%, 3458), headache (82%, 3336), myalgia (70%, 2848), chills (67%, 2726), muscle pain (60%, 2441) were the most prevalent systemic side effects reported within 48 h of vaccination. Thrombosis was only reported among the Oxford-AstraZeneca recipients (3.5-5.7%). Both local and systemic effects were significantly associated with the Oxford-AstraZeneca (p-value < 0.05), Pfizer-BioNTech (p-value < 0.05), and Moderna (p-value < 0.05) vaccination. Chronic urticaria and psoriasis were reported by 55-60% of the recipients after six months or later. The highest percentage of local and systemic effects after 2nd and 3rd dose were found among recipients of Moderna followed by Pfizer-BioNTech and Oxford-AstraZeneca. Homogenous doses of Oxford-AstraZeneca and heterogenous doses of Moderna and Pfizer-BioNTech were significantly associated with elevated adverse effects. Females, aged above 60 years with preexisting health conditions had higher risks. Vaccination with Pfizer-BioNTech (OR 4.34, 95% CI 3.95-4.58) had the highest odds of severe and long-term effects followed by Moderna (OR 4.15, 95% CI 3.92-4.69) and Oxford-AstraZeneca (OR 3.89, 95% CI 3.45-4.06), respectively. This study will provide an integrated insight into the safety profile of COVID-19 vaccines.

Myocarditis and Pericarditis are Temporally Associated with BNT162b2 COVID-19 Vaccine in Adolescents: A Systematic Review and Meta-analysis.

The incidence of myocarditis and pericarditis has been documented in adolescents after COVID-19 vaccinations. This study aims to assess the risk of myopericarditis in adolescents following COVID-19 vaccination, using a meta-analysis of the published cases. We performed a comprehensive literature search of the following databases on July 5, 2023: MEDLINE, EMBASE, PubMed, and the Cochrane Library. We performed a meta-analysis using a random-effects model to estimate the incidence of myopericarditis per million of administered COVID-19 vaccine doses or COVID-19 infections. A total of 33 studies were included in the meta-analysis. The incidence of myopericarditis per million COVID-19 infections (1583.9 cases, 95% CI 751.8-2713.8) was approximately 42 times higher than that for COVID-19 vaccine administrations (37.6 cases, 95% CI 24.2-53.8). The risk of myopericarditis after COVID-19 vaccination was particularly high among the 16-19 age group (39.5 cases per million, 95% CI 25.8-56.0), males (43.1 cases per million, 95% CI 21.6-71.9), and those who received the second dose (47.7 cases per million, 95% CI 22.2-82.2). There were no significant differences in the incidence of myopericarditis per million COVID-19 vaccine administrations between Europe, the Western Pacific, and the Americas (p = 0.51). Adolescents faced a potential risk of myopericarditis after COVID-19 vaccination, but this risk is less harmful than that of myopericarditis following COVID-19 infection.

Waning immune response to CoronaVac in health care workers from different age groups.

Introduction: The waning of serum antibodies against severe acute respiratory syndrome coronavirus 2 observed in several studies raises questions about long-term immunity. Lower antibody levels are associated with new cases of COVID-19 even postvaccination, leading to the administration of booster doses. Objectives: To evaluate the postvaccination immune humoral response and the relationship between postvaccination seropositivity rates and demographic data among health care workers 6 months after CoronaVac vaccination. Methods: This was a cross-sectional study including health care workers vaccinated with two doses of CoronaVac after 6 months or more. The present study was conducted with the analysis of postvaccination serology test to assess the level of humoral response (anti-receptor binding domain IgG) after vaccination. Results: A total of 325 participants were enrolled, of whom 76% were female, with a median age of 42 years (20-85; interquartile range 31-53). Overall, 18.8% (61) of the participants results were seropositive for anti-receptor binding domain IgG; 81.2% did not have sufficient quantitative titers. The IgG titers obtained from female health care workers did not differ from those obtained from seropositive male health care workers, regardless of age. Conclusions: A group of positive quantitative titers was identified in the serology test for IgG antibodies against severe acute respiratory syndrome coronavirus 2. Further studies are needed to determine the durability of postvaccination antibodies and how serology testing can be used to determine the ideal timing for booster doses of the vaccine.

Introdução: O declínio dos anticorpos séricos contra a síndrome respiratória aguda grave do coronavirus 2 observado em vários estudos levanta questões sobre a imunidade a longo prazo. Níveis mais baixos de anticorpos estão associados a novos casos de covid-19 mesmo após a vacinação, levando à administração de doses de reforço. Objetivos: Avaliar a resposta imunitária humoral após a vacinação e a relação entre as taxas de soropositividade após a vacinação e dados demográficos em trabalhadores da saúde por mais de 6 meses após a imunização com CoronaVac. Métodos: Estudo transversal incluindo profissionais de saúde vacinados com duas doses de CoronaVac após 6 meses ou mais. O estudo foi realizado com a análise do teste sorológico após a vacinação para avaliar os níveis de resposta humoral (anti-domínio de ligação ao receptor IgG) após a vacinação. Resultados: Neste estudo foram incluídos 325 participantes, 76% do sexo feminino e a idade mediana foi de 42 anos (20-85; intervalo interquartil 31-53). No geral, 18,8% (61) dos resultados dos participantes foram soropositivos para IgG anti-domínio de ligação ao receptor; 81,2% não apresentaram títulos quantitativos suficientes. Os títulos de IgG obtidos para os profissionais de saúde do sexo feminino não foram diferentes daqueles obtidos para os participantes do sexo masculino com soropositividade, independentemente da idade. Conclusões: Foi possível identificar um grupo com títulos quantitativos positivos no teste sorológico para anticorpo IgG contra a síndrome respiratória aguda grave do coronavírus 2. Mais investigações são necessárias para determinar a durabilidade dos anticorpos após a vacinação e como os testes sorológicos podem determinar o momento ideal das doses de reforço da vacina.

Empowering Unvaccinated Youth: Feasibility, Acceptability, and Efficacy of a COVID-19 Serious Game-Based Intervention.

Objective: To evaluate a serious game-based intervention's feasibility, acceptability, and efficacy in encouraging coronavirus disease (COVID-19) vaccination among 11-14-year-olds in the United States and assess participant experiences. Materials and Methods: The study, grounded in social cognitive theory and health belief model, recruited and engaged 32 English-speaking parent-child dyads with unvaccinated youths via snowball sampling and social media outreach. These dyads were randomly assigned to either the COVID-19 serious game-based intervention group (n = 16) or a usual care group (n = 16). The study measured beliefs, self-efficacy, and intentions regarding vaccination using surveys before and after the intervention, with follow-up at 2 months to evaluate vaccine uptake. Semistructured interviews provided insights into the gaming experience and study process. Results: All 32 eligible parent-youth dyads (16 in each group) completed the study with full participation. Most participants were Black or African American fathers, making up 75% and 81.3% of the intervention and control groups, respectively. The intervention impacted vaccine uptake, with 75% of the intervention group vaccinating their children compared with 37.5% of the control group [χ2(1, n = 32) = 4.57, P = 0.033]. Key factors for vaccine uptake included parents' motivation and youths' perceived susceptibility, with correlations of r(30) = 0.66, P = 0.006, and r(30) = 0.55, P = 0.029, respectively. The intervention reshaped youth perceptions about self and community protection. Participants expressed overall satisfaction with both the intervention and the study process. Conclusions: The intervention was found to be feasible and acceptable, with potential for integration into youth vaccination strategies to support COVID-19 vaccine decision-making.

Assessing vaccine hesitancy among healthcare providers in Brazil: the influence of vaccine status and professional experience.

OBJECTIVE: Assess the occurrence of vaccine hesitancy among pediatricians and their patients and identify potential predictors to mitigate hesitancy among them. METHODS: The study is a cross-sectional survey using an online questionnaire sent to pediatricians affiliated with the Brazilian Society of Pediatrics. The data was analyzed using statistical methods such as exploratory factor analysis, principal component analysis, correspondence analysis, and generalized linear mixed models. RESULTS: A total of 982 respondents, with a majority being females (77.4%), participated in the research. Among them, the proportion of pediatricians with complete vaccine status was 41.14%, while 90.6% had undergone medical residency. Furthermore, 9.3% worked in public healthcare settings, 30.4% in private settings, and 60.3% in mixed healthcare settings. The analysis revealed a significant association between vaccine status and pediatricians' misconceptions about COVID-19 vaccines, with those having complete vaccine status showing lower misconceptions (mean difference of -0.15, p = 0.010). Moreover, pediatricians with medical residency experience exhibited fewer misconceptions about COVID-19 vaccines (mean difference of -0.33, p = 0.002). Additionally, correspondence analysis unveiled the presence of two distinct profiles among pediatricians, showcasing variations in vaccine education, professional experience, and vaccine confidence perceptions. CONCLUSION: The study highlights the influence of vaccine status and medical residency experience on pediatricians' attitudes and misconceptions about vaccines, emphasizing the need for targeted educational interventions to promote vaccine confidence and combat hesitancy within the healthcare provider community.

Estudio cualitativo sobre información, confianza y acceso a la vacunación contra COVID-19 en adolescentes en un centro de salud de Buenos Aires / Qualitative study on information, trust in and access to COVID-19 vaccines among adolescents at a healthcare center in Buenos Aires

Introducción. En la adolescencia, se comienzan a tomar decisiones autónomas sobre la salud. En la vacunación intervienen dimensiones contextuales, grupales y relativas a cada vacuna. Se busca conocer el proceso de información, confianza y decisión de vacunarse contra COVID-19 en adolescentes usuarios de un centro de salud en Buenos Aires. Objetivos. Identificar ámbitos y canales a través de los cuales los adolescentes accedieron a información sobre la vacuna contra COVID-19 en un centro de salud de Buenos Aires. Describir sus opiniones respecto a los distintos discursos sobre vacunación. Describir su participación en la vacunación contra COVID-19. Identificar barreras y facilitadores respecto del acceso a la vacunación contra COVID-19 en esta población. Población y métodos. Investigación cualitativa. Se hicieron entrevistas semiestructuradas a adolescentes usuarios del efector. La muestra fue heterogénea; su tamaño se definió por saturación teórica. Se realizó un análisis temático de los datos. Resultados. Se realizaron 14 entrevistas. Los entrevistados recibieron información sobre la vacuna contra COVID-19 de sus familias, la televisión y las redes sociales. Todos recibieron tanto publicidad oficial como discursos reticentes a la vacunación. Analizaron la información recibida y formaron opinión autónoma. Su decisión sobre vacunarse no siempre fue respetada. La desconfianza, la baja percepción del riesgo, el temor a las inyecciones, las barreras administrativas y geográficas fueron motivos de no vacunación. Conclusiones. Se requieren estrategias de comunicación destinadas a adolescentes que promuevan su participación en el acceso a la vacunación.

Introduction. During adolescence, individuals start to make autonomous decisions about their health. Vaccination involves contextual, group, and vaccine-specific dimensions. We sought to know the information, trust, and decision to receive the COVID-19 vaccine among adolescents who attended a healthcare center in Buenos Aires. Objectives. To identify settings and channels through which adolescents accessed information about the COVID-19 vaccine at a healthcare center in Buenos Aires. To describe their opinions about the different statements on vaccination. To describe their participation in COVID-19 vaccination. To identify barriers and facilitators to COVID-19 vaccination in this population. Population and methods. Qualitative study. Semi-structured interviews with adolescents who attended this healthcare facility. The sample was heterogeneous; the sample size was estimated by theoretical saturation. A thematic analysis of data was done. Results. A total of 14 interviews were conducted. Interviewees obtained information about the COVID-19 vaccine from their families, TV, and social media. All received information from both official campaigns and anti-vaccine communications. They analyzed the information they received and formed their own opinion. Their decision about the vaccine was not always respected. Hesitancy, a low perception of risk, fear of needles, administrative and geographic barriers were reasons for not receiving the vaccine. Conclusions. Communication strategies targeted at adolescents are required that encourage their involvement in access to vaccination.

Pediatric Coronavirus Disease 2019 Vaccine Experiences, Practices, and Attitudes in Rural Primary Care Clinicians.

OBJECTIVE: Pediatric coronavirus disease 2019 (COVID-19) vaccination rates remain low in rural areas. A strong clinician recommendation improves vaccine uptake, but the pediatric COVID-19 vaccine recommendation practices of rural primary care clinicians have not been reported. Our objectives were to describe, among rural Colorado pediatric clinicians: 1) recommendation practices for COVID-19 vaccine compared to influenza and school-entry required vaccines, and 2) personal attitudes. METHODS: From July to October 2023, surveys were distributed to clinicians in rural Colorado identified as pediatric vaccine providers in counties designated as rural through the Colorado Immunization Information System using mail and email. RESULTS: Of 89 survey respondents, 37% of clinicians strongly recommended COVID-19 vaccines for children 6 months-5 years old, compared to 79% for influenza (P = 0.05) and 92% for school-entry required vaccines (P = 0.04). For children 6-11 and 12-17 years old, 43% and 44% of clinicians strongly recommended COVID-19 vaccines, respectively, compared to 71% and 70% for influenza (P < 0.01), and 91% for school-entry required vaccines (P < 0.01). Forty four percent of clinicians agreed that COVID-19 vaccines are important for pediatric patients. The most common clinician-perceived challenges to discussing pediatric COVID-19 vaccines included a lack of parent interest in more information (76% "somewhat" or "strongly" agree), lack of ability to change parents' minds (71%), and concerns that the vaccines are too political (40%). CONCLUSIONS: Most rural Colorado clinicians do not strongly recommend pediatric COVID-19 vaccines compared to influenza and school-entry required vaccines. Efforts to improve pediatric COVID-19 vaccine uptake should aim to strengthen clinicians' recommendations of these vaccines.

Subsequent Vaccination against SARS-CoV-2 after Vaccine-Induced Immune Thrombotic Thrombocytopenia.

Background: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but severe complication following vaccination with adenovirus vector-based COVID-19 vaccines. Antibodies directed against platelet factor 4 (PF4) are thought to be responsible for platelet activation and subsequent thromboembolic events in these patients. Since a single vaccination does not lead to sufficient immunization, subsequent vaccinations against COVID-19 have been recommended. However, concerns exist regarding the possible development of a new thromboembolic episode after subsequent vaccinations in VITT patients. Methods: We prospectively analyzed follow-up data from four VITT patients (three women and one man; median age, 44 years [range, 22 to 62 years]) who subsequently received additional COVID-19 vaccines. Platelet counts, anti-PF4/heparin antibody level measurements, and a functional platelet activation assay were performed at each follow-up visit. Additionally, we conducted a literature review and summarized similar reports on the outcome of subsequent vaccinations in patients with VITT. Results: The patients had developed thrombocytopenia and thrombosis 4 to 17 days after the first vaccination with ChAdOx1 nCoV-19. The optical densities (ODs) of anti-PF4/heparin antibodies decreased with time, and three out of four patients tested negative within 4 months. One patient remained positive even after 10 months post first vaccination. All four patients received an mRNA-based vaccine as a second vaccination against SARS-CoV-2. No significant drop in platelet count or new thromboembolic complications were observed during follow-up. We identified seven publications reporting subsequent COVID-19 vaccination in VITT patients. None of the patients developed thrombocytopenia or thrombosis after the subsequent vaccination. Conclusion: Subsequent vaccination with an mRNA vaccine appears to be safe in VITT patients.

Risk of COVID-19 in Children throughout the Pandemic and the Role of Vaccination: A Narrative Review.

At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, persons ≥65 years of age and healthcare personnel represented the most vulnerable groups with respect to risk of infection, severe illness, and death. However, as the pandemic progressed, there was an increasingly detrimental effect on young children and adolescents. Severe disease and hospitalization increased over time in pediatric populations, and containment measures created substantial psychosocial, educational, and economic challenges for young people. Vaccination of children against COVID-19 has been shown to reduce severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and severe outcomes in pediatric populations and may also help to prevent the spread of variants of concern and improve community immunity. This review discusses the burden of COVID-19 on children throughout the pandemic, the role of children in disease transmission, and the impact of COVID-19 vaccination.

Safety and Immunogenicity of the Intranasal Vaccine Candidate Mambisa and the Intramuscular Vaccine Abdala Used as Booster Doses for COVID-19 Convalescents: A Randomized Phase 1-2 Clinical Trial.

A phase 1-2, prospective, multicenter, randomized, open-label clinical trial (Code RPCEC00000382), with parallel groups, involving 1161 participants, was designed to assess the safety and immunogenicity of two Cuban COVID-19 vaccines (Mambisa and Abdala) in boosting COVID-19 immunity of convalescent adults after receiving one dose of either vaccine. The main safety outcome was severe vaccination adverse events occurring in <5% of vaccinees. Main immunogenicity success endpoints were a ≥4-fold anti-RBD IgG seroconversion or a ≥20% increase in ACE2-RBD inhibitory antibodies in >55% of vaccinees in Phase 1 and >70% in Phase 2. Neutralizing antibody titers against SARS-CoV-2 variants were evaluated. Both vaccines were safe-no deaths or severe adverse events occurred. Mild intensity adverse events were the most frequent (>73%); headaches predominated for both vaccines. Phase 1 responders were 83.3% (p = 0.0018) for Abdala. Mambisa showed similar results. Phase 2 responders were 88.6% for Abdala (p < 0.0001) and 74.2% for Mambisa (p = 0.0412). In both phases, anti-RBD IgG titers, inhibition percentages and neutralizing antibody titers increased significantly after the booster dose. Both vaccines were safe and their immunogenicity surpassed the study endpoints.

Impact of Anti-SARS-CoV-2 Vaccination on Disease Severity and Clinical Outcomes of Individuals Hospitalized for COVID-19 Throughout Successive Pandemic Waves: Data from an Italian Reference Hospital.

This is a retrospective observational study including all COVID-19 patients admitted at our Institute throughout three successive pandemic waves, from January 2021 to June 2023. The main in-hospital outcomes (clinical progression [CP], defined as admission to Intensive Care Unit [ICU]/death, and death within 28 days) were compared among participants unvaccinated (NV), fully vaccinated (FV), with one (FV&B1) and two (FV&B2) booster doses. Vaccinated participants were stratified into recently and waned FV/FV&B1/FV&B2, depending on the time elapsed from last dose (≤ and >120 days, respectively). There were 4488 participants: 2224 NV, 674 FV, 1207 FV&B1, and 383 FV&B2. Within 28 days, there were 604 ICU admissions, 396 deaths, and 737 CP. After adjusting for the main confounders, the risk of both in-hospital outcomes was reduced in vaccinated individuals, especially in those who received the booster dose (approximately by 36% for FV and >50% for FV&B1 and FV&B2 compared to NV). Similarly, after restricting the analysis to vaccinated participants only, we observed a risk reduction of approximately 40% for FV&B1 and 50% for FV&B2, compared to FV, regardless of the distance since the last dose. Our data confirm the vaccine's effectiveness in preventing severe COVID-19 and support the efforts to increase the uptake of booster doses, mainly among older and frailer individuals, still at a greater risk of clinical progression.

Predictors of Hospitalization in Breakthrough COVID-19 among Fully Vaccinated Individuals with Immune-Mediated Rheumatic Diseases: Data from SAFER-Study.

Breakthrough COVID-19 (occurring in fully vaccinated people) has been described. Data on its characteristics among immune-mediated rheumatic disease (IMRD) patients are scarce. This study describes breakthrough COVID-19 occurring in IMRD patients participating in the SAFER-study, a Brazilian multicentric cohort evaluating the safety, effectiveness, and immunogenicity of SARS-CoV-2 vaccines in patients with autoimmune diseases. A descriptive analysis of the population and a binary logistic regression model were performed to evaluate the predictors of COVID-19-related hospitalization. A p-value < 0.05 was significant. The included 160 patients were predominantly females (83.1%), with a mean (SD) age of 40.23 (13.19) years. The patients received two (19%), three (70%), or four (11%) vaccine doses. The initial two-dose series was mainly with ChAdOx1 (Oxford/AstraZeneca) (58%) or BBIBP-CorV (Sinopharm-Beijing) (34%). The first booster (n = 150) was with BNT162b2 (BioNtech/Fosun Pharma/Pfizer) (63%) or ChAdOx1 (29%). The second booster (n = 112) was with BNT162b2 (40%) or ChAdOx1 (26%). The COVID-19 hospitalization rate was 17.5%. IMRD moderate/high activity (OR: 5.84; CI: 1.9-18.5; p = 0.002) and treatment with corticosteroids (OR: 2.94; CI: 1.02-8.49; p = 0.0043) were associated with higher odds of hospitalization, while increasing the number of vaccine doses was protective (OR: 0.37; CI: 0.15-0.9; p = 0.032). These findings, along with previous reassuring results about the safety of the COVID-19 vaccines, argue in favor of booster vaccination in IMRD patients.

Safety of COVID-19 Vaccines among People with History of Allergy: A European Active Surveillance Study.

Background: Conventional vaccines rarely cause severe allergic reactions. However, the rapid development and approval of COVID-19 vaccines left limited initial data on their adverse reactions, particularly in individuals with a history of allergy. The aim of this study was to assess and compare the safety profile of different doses and brands of COVID-19 vaccines in subjects with a history of allergy vs. those without a history of allergy. Methods: From February 2021 to February 2023, a web-based prospective study gathered vaccinee-reported outcomes using electronic questionnaires across eleven European countries. Baseline and up to six follow-up questionnaires captured data on vaccinee demographics, as well as both solicited and unsolicited adverse reactions. Results: Overall, 3476 vaccinees with a history of allergy were matched with 13,872 vaccinees from the general population at the first vaccination cycle and were included in the analysis. A total of 825 vaccinees with a history of allergy who had received a booster dose, matched to 3297 vaccinees from the general population, were included in the analysis. Higher rates of ADRs occurred after the first vaccination cycle compared to after the booster dose (64-91% vs. 56-79%). However, most reported ADRs were solicited and not serious, and no case of anaphylaxis was reported. Women and vaccinees with a history of allergy reported ADRs more frequently than men and the matched controls, respectively. Compared to other COVID-19 vaccines, a higher proportion of vaccinees experiencing at least one ADR following their first vaccination cycle was observed with Comirnaty and Vaxzevria. Statistically significant differences were observed among the study cohorts for median TTO after the second dose, and for median TTR following the first vaccination cycle and booster dose (p < 0.001). Conclusions: Typically, any drug or vaccine use carries a risk of severe allergic reactions, yet the benefits of vaccination generally outweigh these potential risks, as shown with the COVID-19 vaccines.

Effectiveness of COVID-19 Vaccines in People with Severe Mental Illness: A Systematic Review and Meta-Analysis.

Prior to the introduction of COVID-19 vaccines, patients with severe mental illness (SMI) were at greater risk of COVID-19-related outcomes than the general population. It is not yet clear whether COVID-19 vaccines have reduced the risk gap. We systematically searched nine international databases and three Chinese databases to identify relevant studies from December 2020 to December 2023 to compare the risk of COVID-19-related outcomes for SMI patients to those without SMI after vaccination. Random effects meta-analysis was performed to estimate the pooled odds ratio (OR) with 95% confidence intervals (CI). Subgroup analysis, sensitivity analysis, and publication bias analysis were conducted with R software 4.3.0. A total of 11 observational studies were included. Compared with controls, SMI patients were associated with a slightly increased risk of infection (pooled OR = 1.10, 95% CI, 1.03-1.17, I2 = 43.4%), while showing a 2-fold higher risk of hospitalization (pooled OR = 2.66, 95% CI, 1.13-6.22, I2 = 99.6%), even after both groups have received COVID-19 vaccines. Limited evidence suggests a higher mortality risk among SMI patients compared to controls post vaccination, but the findings did not reach statistical significance. SMI patients remain at increased risk compared to their peers in COVID-19-related outcomes even after vaccination. Vaccination appears an effective approach to prevent severe COVID-19 illness in SMI patients, and actions should be taken by healthcare providers to improve vaccination coverage in these vulnerable groups.