Safety of heterologous ChAdOx1-S/BNT162b2 primary schedule versus homologous BNT162b2 vaccination: Insights from an Italian post-marketing study, 2021.

During COVID-19 vaccination campaign, possible ChAdOx1-S-associated risks of thrombosis with thrombocytopenia syndrome led to implement ChAdOx1-S/BNT162b2 heterologous vaccination, despite the limited information on its reactogenicity and safety. We conducted a prospective observational post-marketing surveillance study to assess the safety of this heterologous schedule. A casually selected sample of recipients (n: 85; age: 18-60 years) of ChAdOx1-S/BNT162b2 at the vaccination hub of the Foggia Hospital, Italy, was matched with an equal sample of recipients of homologous BNT162b2. Safety was evaluated 7 days, 1 month and 14 weeks after the primary vaccination series using an adapted version of the "V-safe active surveillance for COVID-19 vaccine safety" CDC standardized questionnaire. After 7 days, local reactions were highly frequent (>80%) in both groups, and systemic reactions were less common (<70%). Moderate or severe pain at the injection site (OR = 3.62; 95%CI, 1.45-9.33), moderate/severe fatigue (OR = 3.40; 95%CI, 1.22-9.49), moderate/severe headache (OR = 4.72; 95%CI, 1.37-16.23), intake of antipyretics (OR = 3.05; 95 CI%, 1.35-6.88), inability to perform daily activities and work (OR = 2.64; 95%CI, 1.24-5.62) were significantly more common with heterologous than homologous vaccination. No significant difference in self-reported health status was recorded 1 month or 14 weeks after the second dose with BNT162b2 or ChAdOx1-S/BNT162b2. Our study confirms the safety of both heterologous and homologous vaccination, with a slight increase in some short-term adverse events for the heterologous regimen. Therefore, administering a second dose of a mRNA vaccine to the recipients of a previous dose of viral vector vaccine may have represented an advantageous strategy to improve flexibility and to accelerate the vaccination campaign.

Impact of Health Workers' Choice of COVID-19 Vaccine Booster on Immunization Levels in Istanbul, Turkey.

BACKGROUND: There are limited data regarding short- and medium-term IgG antibody levels after the CoronaVac and BNT162b2 vaccines. This study aimed to investigate the antibody responses of health workers who initially received two doses of CoronaVac one month apart followed by a booster dose of either CoronaVac or BNT162b2, as well as determine whether either vaccine provided superior results. METHODS: This research represents the second phase of a mixed-methods vaccine cohort study and was conducted between July 2021 and February 2022. The participants (n = 117) were interviewed in person and blood samples were collected before and at 1 and 6 months after the booster vaccination. RESULTS: BNT162b2 was found to have greater immunogenic potential than CoronaVac (p < 0.001). Health workers without chronic disease exhibited statistically significant increases in antibody levels after both vaccines (p < 0.001), whereas only BNT162b2 caused a significant increase in antibody levels in participants with chronic disease (p < 0.001). Samples obtained before and at 1 and 6 months after the booster vaccination revealed no age- or sex-based differences in IgG-inducing potential for either vaccine (p > 0.05). Antibody levels were comparable in both vaccine groups before the booster regardless of COVID-19 history (p > 0.05); however, antibody levels were significantly higher after the BNT162b2 booster at 1 month (<0.001) and at 6 months, except among participants who had a positive history of COVID-19 infection (p < 0.001). CONCLUSIONS: Our results suggest that even a single booster dose of BNT162b2 after initial vaccination with CoronaVac provides a protective advantage against COVID-19, especially for risk groups such as health workers and those with chronic diseases.

Characteristics and outcomes of adverse events after COVID-19 vaccination.

OBJECTIVES: BNT-162b2, mRNA-1273, and Ad26.COV2.S vaccines data regarding adverse events (AEs) are scarce. In this report, we aimed to describe fatal and non-fatal possible AEs after COVID-19 vaccine administration. METHODS: An observational multicenter study investigating the causes of emergency department visits and hospital admissions within 10 days of COVID-19 vaccination. Patients who received first or second doses of COVID-19 vaccines and presented to the emergency department (ED), as well as those admitted to the hospitals or intensive care units (ICUs) were included. Causes of ED, hospital, and ICU admissions and discharges were collected based on the International Classification of Diseases, Tenth Revision (ICD-10) coding system. RESULTS: Between December 2020 and March 2021, 1842 patients visited the ED within 10 days of COVID-19 vaccine administration. The mean age was 70.3 years. Overall, 1221 patients presented after the first dose of the vaccine and 653 after the second dose. Trauma (14.9%), hypertensive emergency/urgency (7.8%), generalized pain and arthralgia (5.7%), and chest pain (4.4%) were the most common causes of presentation to the ED. Of all ED presentations, mortality rate was at 2.2% (41 patients) with a median follow-up time of 68.0 days, versus 2.6% in unvaccinated ED patients. Postvaccination acute hypoxemic respiratory failure (46.3%), septic shock (24.4%), and cardiogenic shock (12.2%) were the most common causes of death. CONCLUSION: Although reported AEs are not necessarily caused by the vaccination, this study provides further information about possible AEs after COVID-19 immunization, especially those requiring hospital admission. This study also supports prior data that serious AEs post vaccination are much lower than primary COVID-19 infections. Further studies are needed to investigate causalities between vaccines and reported AEs across all age groups.

Variation in antibody titers determined by Abbott and Roche Elecsys SARS-CoV-2 assays in vaccinated healthcare workers.

SARS-CoV-2-specific antibody measurement is important for evaluating COVID-19 vaccine efficacy. We quantified and compared anti-spike (S) antibodies using different commercial immunoassays. We tested serum samples from 70 SARS-CoV-2-naive health care workers 2 weeks after vaccination with a single dose of BNT162b2, 2 and 4 weeks, and 3 months after the second dose of BNT162b2. The following quantitative assays were used: Roche Elecsys Anti-SARS-CoV-2 S (Roche-S), Abbott SARS-CoV-2 IgG II Quant [Abbott-IgG(S)], and Abbott SARS-CoV-2 IgM (Abbott-IgM). All samples tested positive for Roche-S and Abbott-IgG antibodies after the second dose, with 83.6% Abbott-IgM positive rate. Roche-S and Abbott-IgG(S) correlated significantly in all samples (r = 0.920, p < 0.0001), and the Roche-S and Abbott-IgG(S) assay showed a strong correlation with each other at each time point after vaccination. Roche-S and Abbott-IgG(S) antibody titers were correlated with age; their rate of decline was age-dependent in males but not in females. Abbott-IgG(S) antibody titers decreased from 2 weeks after the second dose. Roche-S antibody titers peaked 2 weeks after the second dose in 76.2% of the participants; the titers recovered 3 months post-vaccination after declining at week 4 in 40.7% of the participants. The concordance between Roche-S and Abbott-IgG(S) antibody titers over time was 47.5%. Most participants presented significantly high Roche-S and Abbott-IgG(S) antibody titers after immunization. Some measurements were inconsistent with titer changes between these assays, possibly because of differences in the immunoglobulin-specificity of the kits.

Evaluation of Side Effects After Heterologous Vaccination with BNT162b2 Vaccine in Healthcare Workers Vaccinated with Two Doses of Inactive COVID-19 Vaccine

Objective: Vaccination is the most effective way to control the COVID-19 pandemic all over the world. We aimed to evaluate the relationship between antibody titers and vaccine side effects after the BNT162b2 vaccine was administered as a reminder dose in healthcare workers (HCW) who received two doses of inactivated SARS-CoV-2 vaccine name CoronaVac (Sinovac Life Sciences, Beijing, China).Methods: A total of 428 HCWs participated in the study. Participants who received the mRNA vaccine as a reminder dose were evaluated with a questionnaire regarding antibody values and vaccine side effects. Three weeks after the first BNT162b2 vaccine, the same questionnaire was applied face-to-face to HCW, and the same questionnaire was applied to those who received a second reminder dose via telephone.Results: Out of 428, 373 (87.1%) HCWs preferred one and 55 (12.9%) two doses of the BNT162b2 vaccine as reminder doses after being vaccinated with an inactivated vaccine. It was observed that side effects were more frequent in women aged 18-40 after a single dose of the BNT162b2 vaccine (p<0.001). The most common side effects are redness, swelling, and pain at the injection site, with a rate of 59.6%. Fatigue-weakness was the most common systemic reaction, with a rate of 58.6%. Axillary lymphadenopathy was observed seen in 3 (1.1%) HCWs. The median value of IgG titers in the third week after the reminder dose was found to be higher in HCW with side effects than those without side effects (p<0.001). When the cumulative incidence rate of vaccinated people was evaluated over 389 people, no cases were ob-served on the 14th and 30th days after the first reminder dose of BNT162b2. However, the first case was observed on the 60th day, and after the second reminder dose, cases were seen on the 14th, 30th, and 60th days.Conclusion: Since the side effects detected after the BNT162b2 reminder dose were mild to moderate and progressed with local symptoms, it was concluded that highly protective mRNA vaccines could be safely preferred for protection from COVID-19.

Acute Adverse Events After BNT162b2 mRNA and Inactivated SARS-CoV-2 Vaccines in People who had COVID-19 Vaccines

Objective: Considering the classical vaccine development processes, COVID-19 vaccines were developed in a concise period. However, safety cannot be compromised for the rapid development of vaccines. Therefore, we aimed to in-vestigate and compare the incidence of acute adverse events between vaccine doses and vaccine types in patients who were previously diagnosed with COVID-19 and those who were not.Method: The study was conducted prospectively between July 1, 2021, and October 31, 2021. Participants who were vaccinated with the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine and the Sinovac inactivated SARS-CoV-2 vaccine (CoronaVac) were recruited in the cohort study. The cohort was divided into two vaccine categories and sub-branches: those with COVID-19 in each vaccine category and those without. Eight days after the vaccination, all participants in the cohort were provided with an assessment questionnaire regarding the adverse events they experienced.Results: A total of 1607 vaccine doses were followed in the study, 18.7% (n=301) of which were the inactivated SARS-CoV-2 vaccine and 81.3% (n=1306) were the BNT162b2 vaccine. According to the statistics, the risk of developing adverse events with the BNT162b2 vaccine was shown to be 5.8 times higher than the inactivated SARS-CoV-2 vaccine (OR: 5.83;95% CI: 4.34-7.84). In addition, the risk of suffering such adverse events was 1.6 times higher in patients who were previously diagnosed with COVID-19 (OR: 1.61;95% CI: 1.29-2.00) as opposed to patients who were not.Conclusion: Based on the results, we can conclude that acute adverse events were more prevalent after vaccination with the BNT162b2 vaccine than the inactivated SARS-CoV-2 vaccine. Furthermore, compared to those who did not have COVID-19, it was evident that patients who were previously diagnosed with COVID-19 were prone to experience mild, temporary, and manageable adverse events.

Intramuscular mRNA BNT162b2 vaccine against SARS-CoV-2 induces neutralizing salivary IgA.

Intramuscularly administered vaccines stimulate robust serum neutralizing antibodies, yet they are often less competent in eliciting sustainable "sterilizing immunity" at the mucosal level. Our study uncovers a strong temporary neutralizing mucosal component of immunity, emanating from intramuscular administration of an mRNA vaccine. We show that saliva of BNT162b2 vaccinees contains temporary IgA targeting the receptor-binding domain (RBD) of severe acute respiratory syndrome coronavirus-2 spike protein and demonstrate that these IgAs mediate neutralization. RBD-targeting IgAs were found to associate with the secretory component, indicating their bona fide transcytotic origin and their polymeric multivalent nature. The mechanistic understanding of the high neutralizing activity provided by mucosal IgA, acting at the first line of defense, will advance vaccination design and surveillance principles and may point to novel treatment approaches and new routes of vaccine administration and boosting.

Incidencia y factores asociados con las reacciones adversas tras la primera dosis de la vacuna Pfizer-BioNTech en trabajadores de la salud.

OBJECTIVE: To determine the incidence of adverse reactions (AR) after the first dose of Pfizer-BioNTech vaccine, and to identify some factors associated with AR. METHOD: A retrospective cohort study was conducted. Data were obtained through an epidemiological survey answered online. Multivariate analyses were performed to identify factors associated with early (< 2 h) and late (≥ 2 h) AR. RESULTS: A total of 2295 health care workers were included; in them, the cumulative incidence of AR was 18.2% (95% confidence interval: 16.6-19.8), where the majority were late (78.2%). The associated factors that increased the risk of early AR were being female (odds ratio [OR]: 2.23, p = 0.002) and belonging to the medical staff (OR: 1.56; p = 0.041). In late AR were being female (OR: 1.94; p < 0.0001); on the other hand, diabetes (OR: 0.46; p = 0.021), asthma (OR: 0.53; p = 0.040) and smoking (OR: 0.44, p = 0.002) were inversely associated factors. Interestingly, history of COVID-19 was not associated with either early or late AR. CONCLUSIONS: The risk of presenting some type of AR due to the Pfizer-BioNTech vaccine in health care workers is < 20%.

OBJETIVO: Determinar la incidencia de reacciones adversas (RA) tras la primera dosis de la vacuna Pfizer-BioNTech e identificar algunos factores asociados con ellas. MÉTODO: Se realizó un estudio de cohorte retrospectiva. Los datos fueron obtenidos mediante una encuesta epidemiológica contestada en línea. Se realizaron análisis multivariados para identificar factores asociados con las RA tempranas (< 2 h) y tardías (≥ 2 h). RESULTADOS: Se incluyeron 2295 trabajadores de la salud; en ellos, la incidencia acumulada de RA fue del 18.2% (intervalo de confianza del 95%: 16.6-19.8%) y la mayoría fueron tardías (78.2%). Las RA tempranas más frecuentes fueron dolor local, cefalea y mareo; en las tardías fueron dolor local, cefalea y fatiga. No se documentaron casos de anafilaxia; sin embargo, en el grupo de RA tempranas y tardías hubo un caso y tres casos, respectivamente, con síntomas sistémicos que afectaron a dos órganos diferentes. Los factores asociados que incrementaron el riesgo de RA tempranas fueron ser mujer (odds ratio [OR]: 2.23; p = 0.002) y pertenecer al personal médico (OR: 1.56; p = 0.041). En las RA tardías fue ser mujer (OR: 1.94; p < 0.0001); por su parte, la diabetes (OR: 0.46; p = 0.021), el asma (OR: 0.53; p = 0.040) y el tabaquismo (OR: 0.44; p = 0.002) fueron factores asociados inversamente. Es interesante que la historia de COVID-19 no se asoció con RA tempranas ni tardías. CONCLUSIONES: El riesgo de presentar algún tipo de RA debido a la vacuna Pfizer-BioNTech en trabajadores de la salud es < 20%.

Temporal association between COVID-19 vaccination and Raynaud's phenomenon: A case series.

COVID-19 vaccine-related adverse events are mostly minor to moderate, and serious events are rare. Single cases of Raynaud's phenomenon (RP) in temporal proximity to COVID-19 vaccination have been reported. Demographic data, medical history, and detailed information regarding vaccination status and RP characteristics were obtained from patients with confirmed RP after COVID-19 vaccination. Fifteen participants reported the initial manifestation of RP, which occurred in 40% after the first, in 33% after the second, and in 27% after the third vaccination. RP development and occurrence of episodes were not linked to any specific vaccine type. New onset of disease was observed in 40% of the vaccinees after BNT162b2, in 33% after mRNA-1273, and in 27% after ChAdOx1 vaccination. Three out of four participants with preexisting RP prior to COVID-19 vaccination reported aggravation in frequency and intensity after immunization. Although COVID-19 vaccination is pivotal in controlling the pandemic, the observed temporal association between vaccine administration and RP occurrence warrants global activities to support pharmacovigilance for the detection of adverse reactions, one of which may include RP.

Humoral and T Cell Immune Responses against SARS-CoV-2 after Primary and Homologous or Heterologous Booster Vaccinations and Breakthrough Infection: A Longitudinal Cohort Study in Malaysia.

Vaccine efficacy against SARS-CoV-2 could be compromised by the emergence of SARS-CoV-2 variants and it is important to study how it impacts the booster vaccination regime. We investigated the humoral and T cell responses longitudinally in vaccinated uninfected (n = 25) and post-COVID-19 individuals (n = 8), and those who had received a BNT162b2 booster following complete two-doses regimes of either BNT162b2 (homologous) (n = 14) or ChAdOx1-S (heterologous) (n = 15) vaccines, by means of a SARS-CoV-2 pseudovirus neutralization test and QuantiFERON SARS-CoV-2 assay. Vaccinated post-COVID-19 individuals showed higher neutralizing antibodies with longer durability against SARS-CoV-2 wild type (WT) and Omicron spikes, but demonstrated similar declining T cell responses compared to the uninfected vaccinated. Two doses of BNT162b2 induced higher neutralizing antibodies against WT and T cell responses than ChAdOx1-S for six months. The BNT162b2 booster confers a greater humoral response against WT, but a similar cross-neutralizing antibody against Omicron and T cell responses in the homologous booster group compared to the heterologous booster group. Breakthrough infection in the homologous booster group (n = 11) significantly increased the neutralizing antibody, but T cell responses remained low. Our data may impact government public health policy regarding the administration of mix-and-match vaccines, where both vaccination regimes can be employed should there be shortages of certain vaccines.

Antibody titer 6 months after the third dose of COVID-19 mRNA vaccination

Objectives: Administration of the third dose of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine was initiated on December 1, 2021, in Japan. However, data on the long-term effects of this third vaccination remain scarce. Here, we examined the levels of SARS-CoV-2 antibodies in those who received the Pfizer BioNTech (BNT162b2) vaccine, 6 months after the third vaccination. Method(s): Samples from 40 healthy volunteers were used to measure SARS-CoV-2 antibodies with chemiluminescent assays against the receptor-binding domain (RBD) of the virus. Result(s): At 445 days after the first dose of BNT162b2, which is 180 days after the third vaccination, the mean anti-RBD IgG level was 159.4 AU/mL (SD 100.1 AU/mL), which was significantly higher than 144 days after the second vaccination, while mean anti-RBD IgM was baseline level (0.4 C.O.I.). The decline in IgG, 180 days after the third vaccination, was 74.1% (SD 16.1%), which was significantly lower than the 88.6% (SD 4.4%) decline observed 144 days after the second vaccination. Furthermore, we revealed that the reduction in IgG from 14 to 180 days after the third vaccination showed a significant inverse correlation with age, and the higher antibody response in younger participants at 14 days after the third vaccination disappeared at longer time points. Conclusion(s): The long-term durability of the IgG titer was significantly higher following the third vaccination compared with the second vaccination, and the reduction in IgG titer after the third vaccination inversely correlated with age.Copyright © 2022 the author(s), published by De Gruyter, Berlin/Boston.

Identification of genes related to immune enhancement caused by heterologous ChAdOx1-BNT162b2 vaccines in lymphocytes at single-cell resolution with machine learning methods.

The widely used ChAdOx1 nCoV-19 (ChAd) vector and BNT162b2 (BNT) mRNA vaccines have been shown to induce robust immune responses. Recent studies demonstrated that the immune responses of people who received one dose of ChAdOx1 and one dose of BNT were better than those of people who received vaccines with two homologous ChAdOx1 or two BNT doses. However, how heterologous vaccines function has not been extensively investigated. In this study, single-cell RNA sequencing data from three classes of samples: volunteers vaccinated with heterologous ChAdOx1-BNT and volunteers vaccinated with homologous ChAd-ChAd and BNT-BNT vaccinations after 7 days were divided into three types of immune cells (3654 B, 8212 CD4+ T, and 5608 CD8+ T cells). To identify differences in gene expression in various cell types induced by vaccines administered through different vaccination strategies, multiple advanced feature selection methods (max-relevance and min-redundancy, Monte Carlo feature selection, least absolute shrinkage and selection operator, light gradient boosting machine, and permutation feature importance) and classification algorithms (decision tree and random forest) were integrated into a computational framework. Feature selection methods were in charge of analyzing the importance of gene features, yielding multiple gene lists. These lists were fed into incremental feature selection, incorporating decision tree and random forest, to extract essential genes, classification rules and build efficient classifiers. Highly ranked genes include PLCG2, whose differential expression is important to the B cell immune pathway and is positively correlated with immune cells, such as CD8+ T cells, and B2M, which is associated with thymic T cell differentiation. This study gave an important contribution to the mechanistic explanation of results showing the stronger immune response of a heterologous ChAdOx1-BNT vaccination schedule than two doses of either BNT or ChAdOx1, offering a theoretical foundation for vaccine modification.

Higher plasma levels of thymosin-α1 are associated with a lower waning of humoral response after COVID-19 vaccination: an eight months follow-up study in a nursing home.

BACKGROUND: Older people achieve lower levels of antibody titers than younger populations after Covid-19 vaccination and show a marked waning humoral immunity over time, likely due to the senescence of the immune system. Nevertheless, age-related predictive factors of the waning humoral immune response to the vaccine have been scarcely explored. In a cohort of residents and healthcare workers from a nursing home that had received two doses of the BNT162b2 vaccine, we measured specific anti-S antibodies one (T1), four (T4), and eight (T8) months after receiving the second dose. Thymic-related functional markers, including thymic output, relative telomere length, and plasma thymosin-α1 levels, as well as immune cellular subsets, and biochemical and inflammatory biomarkers, were determined at T1, and tested for their associations with the magnitude of the vaccine response (T1) and the durability of such response both, at the short- (T1-T4) and the long-term (T1-T8). We aimed to identify age-related factors potentially associated with the magnitude and persistence of specific anti-S immunoglobulin G (IgG)-antibodies after COVID-19 vaccination in older people. RESULTS: Participants (100% men, n = 98), were subdivided into three groups: young (< 50 years-old), middle-age (50-65 years-old), and older (≥65 years-old). Older participants achieved lower antibody titers at T1 and experienced higher decreases in both the short- and long-term. In the entire cohort, while the magnitude of the initial response was mainly associated with the levels of homocysteine [ß (95% CI); - 0.155 (- 0.241 to - 0.068); p = 0.001], the durability of such response at both, the short-term and the long-term were predicted by the levels of thymosin-α1 [- 0.168 (- 0.305 to - 0.031); p = 0.017, and - 0.123 (- 0.212 to - 0.034); p = 0.008, respectively]. CONCLUSIONS: Higher plasma levels of thymosin-α1 were associated with a lower waning of anti-S IgG antibodies along the time. Our results suggest that plasma levels of thymosin-α1 could be used as a biomarker for predicting the durability of the responses after COVID-19 vaccination, possibly allowing to personalize the administration of vaccine boosters.

The Humoral Response of Patients With Cancer to Breakthrough COVID-19 Infection or the Fourth BNT162b2 Vaccine Dose.

Since January 2022 in Israel, high-risk populations with underlying health conditions were advised to receive a fourth dose of the BNT162b2 vaccine (Pfizer-BioNTech) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We monitored vaccine-induced immunity among oncology patients undergoing systemic anti-cancer therapy before and after the 4th-BNT162b2-dose. Three groups of patients were included in the study: those who received 3rd-BNT162b2-dose and had no breakthrough infection (control), those who received 3rd-BNT162b2-dose and had the breakthrough infection, and those who received the 4th-BNT162b2-dose and had no breakthrough infection. Anti-SARS-CoV-2 immunoglobulin-G (IgG) levels of the control group exhibited a rapid decrease over time, whereas IgG titers of patients with breakthrough-infections or patients vaccinated with the 4th-BNT162b2-dose were considerably elevated, consistent with the capacity of the second booster to induce anti-SARS-CoV-2 IgG levels. Additionally, oncology patients' humoral immune response was significantly greater after breakthrough-infection than in response to the 4th dose of BNT162b2.

Clinical Effects of BNT162b2 Vaccine on the Short-Term Course of Chronic Spontaneous Urticaria Patients.

Background: The clinical effects of Pfizer-BioNTech coronavirus disease 2019 (COVID-19; BNT162b2) vaccine on the clinical course of chronic spontaneous urticaria (CSU) is unclear. Aims and Objectives: To evaluate the clinical effects of BNT162b2 vaccine on the clinical course of CSU. Methods: In this study, 90 CSU patients vaccinated with one or two repeated doses of BNT162b2 vaccine were included. Urticaria Activity Score over 28 days (UAS28), Urticaria Control Test (UCT), Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL), and Medication Scores (MSs) were obtained before the vaccination, 28 days after the first and, if available, after the second dose of BNT162b2 vaccine. The demographic, clinical, and laboratory features were compared between the subjects with exacerbated (group A) and non-exacerbated (group B) disease activity. Results: Among the 90 study participants, 14 (15.5%) experienced exacerbations in their urticarial activity after the first or repeated doses of BNT162b2 vaccinations. The demographic, clinical, and laboratory features were similar between the exacerbated and non-exacerbated CSU patients. However, the rate of adverse reactions within 48 hours, such as hives, injection site reactions and wheals lasting <1 hour, were significantly higher in group A than in group B (P = 0.004, P < 0.001, P = 0.001, P = 0.018). Conclusions: BNT162b2 vaccination caused an exacerbation in 15.5% of CSU patients during the short-term follow-up. The long-term evaluation can be informative about the lasting effects of BNT162b2 vaccine on the clinical course of CSU patients.

The third dose of BNT162b2 COVID-19 vaccine is efficacious and safe for systemic lupus erythematosus patients receiving belimumab.

INTRODUCTION: Over 95% of healthy subjects develop anti-COVID IgG antibodies after receiving two doses of BNT162b2 COVID-19 vaccine. In comparison, 20%-30% of SLE patients do not seroconvert following 1-2 doses of COVID vaccines, potentially due to immunosuppression. The aim of this study was to assess immunogenicity and safety of BNT vaccine in SLE patients treated with Belimumab and especially the yield of a booster third dose in this population. METHODS: SLE patients treated with Belimumab in the Sheba Medical Center, Israel, were included in this study. All were recommended to receive the BNT vaccine according to national guidelines; and were advised to perform serologic tests after receiving second and third doses. Clinical data included demographics, SLE treatments, adverse effects to vaccines and SLEDAI scores performed 2 weeks before vaccinations and 6-12 weeks after receiving the second or third dose of the vaccine. RESULTS: Our cohort included 17 patients, 14 (82.35%) females, median age 50 ± 14.2 years, and disease duration 12 ± 10.57 years. Belimumab therapy was given for a mean of 6 ± 2.5 years. Of them, 15/17 patients received 3-doses of BNT vaccine. Serologic assessment was performed for 10 patients, 7/10(70%) became seropositive following the second dose, while 2/3 patients seroconverted only after the third dose. Vaccinations were well tolerated with minimal adverse events and no disease flares. SLEDAI scores before and after vaccinations were 4 ± 3.8 and 4 ± 2.7 (p = 0.69), respectively. CONCLUSIONS: Immunization with the BNT vaccine is efficacious and safe for SLE patients treated with Belimumab. Following the third dose of vaccine, immunogenicity among SLE patients mounted to 90%, thereby approximating the general healthy population. No SLE disease flares and/or significant adverse events were noted in our cohort. Assessment of seroconversion and consideration of subsequent boosters of COVID-vaccine should be considered in this group of patients.

Immunogenicity and Safety of a Third COVID-19 BNT162b2 mRNA Vaccine Dose in 5- to 11-Year Olds.

In this ongoing study, substantially increased ancestral SARS-CoV-2 neutralizing responses were observed 1 month after a third 10-µg BNT162b2 dose given to 5 to 11-year olds versus neutralizing responses post-dose 2. After dose 3, increased neutralizing responses against Omicron BA.1 and BA.4/BA.5 strains were also observed. The safety/tolerability profile was acceptable. (NCT04816643).

Humoral response after BNT162b2 vaccine in Japanese hemodialysis patients.

Background: Hemodialysis patients are more likely to be severely affected if infected by COVID-19. Contributing factors include chronic kidney disease, old age, hypertension, type 2 diabetes, heart disease, and cerebrovascular disease. Therefore, action against COVID-19 for hemodialysis patients is an urgent issue. Vaccines are effective in preventing COVID 19 infection. In hemodialysis patients, however, responses to hepatitis B and influenza vaccines are reportedly weak. The BNT162b2 vaccine has shown an efficacy rate of about 95% in the general population, but as far as we know there are only several reports of efficacy data in hemodialysis patients in Japan. Methods: We assessed serum anti-SARS-CoV-2 IgG antibody (Abbott SARS-CoV-2 IgG II Quan) in 185 hemodialysis patients and 109 health care workers. The exclusion criterion was positivity for SARS-CoV-2 IgG antibody before vaccination. Adverse reactions to BNT162b2 vaccine were evaluated through interviews. Results: Following vaccination, 97.6% of the hemodialysis group and 100% of the control group were positive for the anti-spike antibody. The median level of anti-spike antibody was 2,728.7 AU/mL (IQR, 1,024.2-7,688.2 AU/mL) in the hemodialysis group and 10,500 AU/ml (IQR, 9,346.1-2,4500 AU/mL) in the health care workers group. The factors involved in the low response to the BNT152b2 vaccine included old age, low BMI, low Cr index, low nPCR, low GNRI, low lymphocyte count, steroid administration, and complications related to blood disorders. Conclusions: Humoral responses to BNT162b2 vaccine in hemodialysis patients are weaker than in a healthy control sample. Booster vaccination is necessary for hemodialysis patients, especially those showing a weak or non-response to the two-dose BNT162b2 vaccine.Trial registration UMIN, UMIN000047032. Registered 28 February 2022, https://center6.umin.ac.jp/cgi-bin/ctr/ctr_reg_rec.cgi.

Acquired hemophilia A (AHA) due to anti-SARS-CoV-2 vaccination: A systematic review.

Vaccination against SARS-CoV2 has been the largest vaccination campaign over the past two decades. The aim of this study is to qualitatively assess the reported cases of acquired hemophilia A (AHA) that developed after COVID-19 vaccination to further elaborate on incidence, presentation, treatment, and outcomes.We queried Medline (PubMed), Google Scholar, and Embase databases to find reported cases of AHA after COVID-19 vaccines. We found 14 studies (19 cases) for this descriptive analysis. Most patients were elderly (mean age 73 years) and males (n = 12) with multiple comorbidities. All cases developed after mRNA vaccines - BNT162b2 Pfizer-BioNTech (n = 13) and mRNA-1273 Moderna (n = 6). All except one patient were treated, with the most common therapy being a combination of steroids, immunosuppression, and rFVIII (n = 13). Two patients died due to acute respiratory distress, and gall bladder rupture with persistent bleeding, respectively. While evaluating a patient with bleeding diathesis after COVID-19 vaccination, AHA should be kept in the differential diagnosis. Given the low incidence, we believe that the benefit of vaccination still outweighs the risk of disease acquisition.