3rd Dose Research Articles

Neuroprotective effects of chlorogenic acid against oxidative stress in rats subjected to lithium-pilocarpine-induced status epilepticus.

Epilepsy is a condition marked by sudden, self-sustained, and recurring brain events, showcasing unique electro-clinical and neuropathological phenomena that can alter the structure and functioning of the brain, resulting in diverse manifestations. Antiepileptic drugs (AEDs) can be very effective in 30% of patients in controlling seizures. Several factors contribute to this: drug resistance, individual variability, side effects, complexity of epilepsy, incomplete understanding, comorbidities, drug interactions, and no adherence to treatment. Therefore, research into new AEDs is important for several reasons such as improved efficacy, reduced side effects, expanded treatment options, treatment for drug-resistant epilepsy, improved safety profiles, targeted therapies, and innovation and progress. Animal models serve as crucial biological tools for comprehending neuronal damage and aiding in the discovery of more effective new AEDs. The utilization of antioxidant agents that act on the central nervous system may serve as a supplementary approach in the secondary prevention of epilepsy, both in laboratory animals and potentially in humans. Chlorogenic acid (CGA) is a significant compound, widely prevalent in numerous medicinal and food plants, exhibiting an extensive spectrum of biological activities such as neuroprotection, antioxidant, anti-inflammatory, and analgesic effects, among others. In this research, we assessed the neuroprotective effects of commercially available CGA in Wistar rats submitted to lithium-pilocarpine-induced status epilepticus (SE) model. After 72-h induction of SE, rats received thiopental and were treated for three consecutive days (1st, 2nd, and 3rd doses). Next, brains were collected and studied histologically for viable cells in the hippocampus with staining for cresyl-violet (Nissl staining) and for degenerating cells with Fluoro-Jade C (FJC) staining. Moreover, to evaluate oxidative stress, the presence of malondialdehyde (MDA) and superoxide dismutase (SOD) was quantified. Rats administered with CGA (30 mg/kg) demonstrated a significant decrease of 59% in the number of hippocampal cell loss in the CA3, and of 48% in the hilus layers after SE. A significant reduction of 75% in the cell loss in the CA3, shown by FJC+ staining, was also observed with the administration of CGA (30 mg/kg). Furthermore, significant decreases of 49% in MDA production and 72% in the activity of SOD were seen, when compared to animals subjected to SE that received vehicle. This study introduces a novel finding: the administration of CGA at a dosage of 30 mg/kg effectively reduced oxidative stress induced by lithium-pilocarpine, with its effects lasting until the peak of neural damage 72 h following the onset of SE. Overall, the research and development of new AEDs are essential for advancing epilepsy treatment, improving patient outcomes, and ultimately enhancing the quality of life for individuals living with epilepsy.

Early B cell transcriptomic markers of measles-specific humoral immunity following a 3rd dose of MMR vaccine.

B cell transcriptomic signatures hold promise for the early prediction of vaccine-induced humoral immunity and vaccine protective efficacy. We performed a longitudinal study in 232 healthy adult participants before/after a 3rd dose of MMR (MMR3) vaccine. We assessed baseline and early transcriptional patterns in purified B cells and their association with measles-specific humoral immunity after MMR vaccination using two analytical methods ("per gene" linear models and joint analysis). Our study identified distinct early transcriptional signatures/genes following MMR3 that were associated with measles-specific neutralizing antibody titer and/or binding antibody titer. The most significant genes included: the interleukin 20 receptor subunit beta/IL20RB gene (a subunit receptor for IL-24, a cytokine involved in the germinal center B cell maturation/response); the phorbol-12-myristate-13-acetate-induced protein 1/PMAIP1, the brain expressed X-linked 2/BEX2 gene and the B cell Fas apoptotic inhibitory molecule/FAIM, involved in the selection of high-affinity B cell clones and apoptosis/regulation of apoptosis; as well as IL16 (encoding the B lymphocyte-derived IL-16 ligand of CD4), involved in the crosstalk between B cells, dendritic cells and helper T cells. Significantly enriched pathways included B cell signaling, apoptosis/regulation of apoptosis, metabolic pathways, cell cycle-related pathways, and pathways associated with viral infections, among others. In conclusion, our study identified genes/pathways linked to antigen-induced B cell proliferation, differentiation, apoptosis, and clonal selection, that are associated with, and impact measles virus-specific humoral immunity after MMR vaccination.

Determinants of health as predictors for differential antibody responses following SARS-CoV-2 primary and booster vaccination in an at-risk, longitudinal cohort.

Post vaccine immunity following COVID-19 mRNA vaccination may be driven by extrinsic, or controllable and intrinsic, or inherent health factors. Thus, we investigated the effects of extrinsic and intrinsic on the peak antibody response following COVID-19 primary vaccination and on the trajectory of peak antibody magnitude and durability over time. Participants in a longitudinal cohort attended visits every 3 months for up to 2 years following enrollment. At baseline, participants provided information on their demographics, recreational behaviors, and comorbid health conditions which guided our model selection process. Blood samples were collected for serum processing and spike antibody testing at each visit. Cross-sectional and longitudinal models (linear-mixed effects models) were generated to assess the relationship between selected intrinsic and extrinsic health factors on peak antibody following vaccination and to determine the influence of these predictors on antibody over time. Following cross-sectional analysis, we observed higher peak antibody titers after primary vaccination in females, those who reported recreational drug use, younger age, and prior COVID-19 history. Following booster vaccination, females and Hispanics had higher peak titers after the 3rd and 4th doses, respectively. Longitudinal models demonstrated that Moderna mRNA-1273 recipients, females, and those previously vaccinated had increased peak titers over time. Moreover, drug users and half-dose Moderna mRNA-1273 recipients had higher peak antibody titers over time following the first booster, while no predictive factors significantly affected post-second booster antibody responses. Overall, both intrinsic and extrinsic health factors play a significant role in shaping humoral immunogenicity after initial vaccination and the first booster. The absence of predictive factors for second booster immunogenicity suggests a more robust and consistent immune response after the second booster vaccine administration.

Investigating the effect of serum level of uric acid on the immunogenicity of hepatitis B vaccination in dialysis patients

IntroductionHBV infection is a significant concern in dialysis patients, influenced by various factors. This study aims to investigate the impact of serum uric acid levels on the immunogenicity of hepatitis Bvaccination in dialysis patients.MethodA cross-sectional study was conducted, involving 125 hemodialysis patients. Prior to dialysis, assessments were made for uric acid, vitamin D, HBsAg, andHBsAb. Patients were divided into two groups based on uric acid levels: high level (≥ 6.5 mg/dl) and low level (< 6.5 mg/dl). Each group received three doses of a high-dose hepatitis B vaccine (40 mcg) at 0, 1, and 6 months. After 8 weeks of the 3rd dose of the vaccine, the anti-hepatitis B antibody titer (HBsAb) was measured and recorded. Data were analyzed using SPSS version 22.ResultsAmong patients with high uric acid, 30 (26.8%) had low HBsAb and 82 (73.2%) had high HBsAb (> 10). In patients with low uric acid, 1 (7.7%) had low HBsAb and 12 (92.3%) had high HBsAb (> 10). There was no statistically significant difference inHBsAb between the two groups. The immune response of HBsAb and uric acid did not show significance based on demographic variables and laboratory results.ConclusionThis study found no correlation between uric acid levels and the immunogenicity of hepatitis B vaccination in hemodialysis patients. However, it is important to note that the group with low serum uric acid was very small compared to the other group and this may have influenced these results. Further studies with larger patient populations are needed to provide more conclusive evidence in this area.

Uptake of fIPV3 and implementation challenges as perceived by auxiliary nurse midwives at two primary healthcare centers in urban Bengaluru: a mixed-method study

Background: India introduced fractional-dose inactivated poliovirus vaccine (fIPV) into its routine immunization program as part of the polio eradication and endgame strategic plan. The study aimed to assess the uptake of the 3rd dose of fIPV among eligible beneficiaries and explore the implementation challenges perceived by auxiliary nurse midwives (ANMs) at two primary healthcare centers in urban Bengaluru. Methods: A mixed-method study was conducted between April and May 2023. A cross-sectional design was used for quantitative objectives, while in-depth interviews were conducted with ANMs for qualitative insights. Data were collected through vaccination registers, questionnaires, and key informant interviews. The study population included all eligible beneficiaries for the 3rd dose of fIPV from January to March 2023. Results: Out of 296 eligible beneficiaries, 139 (47%) had received the 3rd dose of fIPV. The challenges faced by ANMs in fIPV3 implementation included difficulties in recording and reporting activities, fear of managing adverse events, lack of confidence in administering intradermal injections, obtaining consent from parents, inadequate training, and concerns about vaccine wastage and increased workload. Conclusions: The uptake of fIPV3 was suboptimal, and ANMs encountered several challenges during implementation. To enhance fIPV3 integration into the vaccination schedule, the health system needs to improve awareness among the community, strengthen health worker capacity, and provide better training and support. Strengthening routine immunization programs can contribute to sustained polio eradication efforts.

Factors impacting antibody kinetics, including fever and vaccination intervals, in SARS-CoV-2-naïve adults receiving the first four mRNA COVID-19 vaccine doses

To evaluate the antibody response following the initial four doses of mRNA vaccines (BNT162b2 or mRNA-1273) in SARS-CoV-2-naïve healthy adults and investigate factors influencing antibody titer increases, this prospective cohort study was conducted in Japan from March 2021. The study included participants who received either the 1st and 2nd doses (n = 467), 3rd dose (n = 157), or 4th dose (n = 89). Blood samples were collected before and up to 6 months after each dose, and anti-receptor-binding domain antibody levels were measured. Multivariate analysis (usin multiple linear regression or linear mixed models) revealed several factors significantly associated with higher post-vaccination antibody levels, including mRNA-1273 vaccine (after the 1st and 2nd dose), male gender (after the 3rd and 4th doses), younger age (after the 1st and 2nd dose), non-smoking status (after the 2nd dose), non-use of immunosuppressive agents (after the 1st dose), higher pre-vaccination antibody titers (after the 2nd, 3rd, and 4th doses), and higher post-vaccination fever (after the 2nd and 4th doses). Furthermore, longer intervals since the last dose were significantly associated with higher antibody levels after the 3rd and 4th doses. These findings provide valuable insights for optimizing vaccination strategies.

Safety monitoring of bivalent mRNA COVID-19 vaccine among pregnant persons in the vaccine adverse event reporting System – United States, September 1, 2022 – March 31, 2023

BackgroundPregnant persons are at increased risk of severe COVID-19 illness. Bivalent mRNA COVID-19 vaccination is recommended for everyone, including pregnant persons. However, data are limited on the safety of bivalent mRNA COVID-19 vaccination during pregnancy. ObjectiveTo evaluate and summarize reports to the Vaccine Adverse Event Reporting System (VAERS), a national spontaneous reporting system, among pregnant persons who received bivalent mRNA COVID-19 vaccine. MethodsVAERS U.S. reports of adverse events (AEs) in pregnant persons who received the bivalent mRNA COVID-19 vaccine from 9/1/2022–03/31/2023 were identified. Clinicians reviewed all reports and available medical records. AEs of these reports were compared with AEs reported to VAERS following monovalent mRNA COVID-19 booster vaccination in pregnancy. ResultsVAERS received 136 reports for pregnant persons who received bivalent mRNA COVID-19 vaccine; 87 (64 %) after BNT162b2 (Pfizer-BioNTech), and 48 (35 %) after mRNA-1273 (Moderna); 28 (20.6 %) reports were classified as serious. The most common pregnancy-specific outcomes reported included 12 (8.8 %) spontaneous abortions (<20 weeks gestation), 6 (4.4 %) episodes of preterm delivery, and 5 (3.7 %) reports of preeclampsia. One stillbirth (≥20 weeks gestation) was reported. No maternal or infant deaths were reported. There were 6 reports of AEs in infants, which included 3 reports of admissions to the neonatal intensive care unit: two infants with low birth weight, and one infant with a patent ductus arteriosus and patent foramen ovale. Non-pregnancy-specific adverse events were mostly COVID-19 infection and systemic reactions (e.g., headache, fatigue). Pregnancy-specific conditions were reported less frequently after bivalent mRNA COVID-19 vaccination compared to monovalent mRNA COVID-19 booster vaccination (3rd and 4th dose). ConclusionsBased on this review of reports to VAERS, the safety profile of bivalent mRNA COVID-19 vaccination in pregnant persons was comparable to that observed for monovalent mRNA COVID-19 booster vaccination (3rd and 4th dose) in pregnant persons.

In Vitro Evaluation of Effect of Storage Time on Immunogenicity of the 10-Valent Pneumococcal Conjugate Vaccine Using Baby Rabbit Complement &amp; HL-60 Cells

Background: The efficacy and effectiveness of a vaccine is influenced by several factors including storage duration. Additionally, vaccines may be sufficiently administered but functionality of antibody generated may be hampered with by other factors such as nutritional status of the patient. As such, one of the ways of assessing vaccine efficacy is assessing the functionality of the antibodies generated. The 10v-PCV is a highly effective vaccine used to prevent invasive pneumococcal diseases in children. However, here in Kenya, cases of pneumococcal diseases are high and challenging to treat. This study thus aimed to evaluate the effect of storage of PCV-10 storage time on the functionality of Abs generated. Methodology; An in vitro experimental research design was employed for this study. opsonophagocytic activity assay using HL-60 Cells &amp; Baby rabbit complement was used to assess whether or not the Pneumococci Serotype IgG antibodies elicited following administration with 10v-PCV vaccine are functional. Only 10v-PCV vaccine with same production date were procured. Twenty experimental rabbits of same gender were procured and used injected intraperitoneally with 3 doses of 100µl (0.34g) of 10v-PCV vaccine after every four weeks. Antibody functionality was then assessed using the opsonophagocytic activity assay method. Results: An average of 28.9% of pneumococcus exposed to the vaccine-induced secreted antibodies were killed by the pneumococcal IgG antibody. The highest percentage of number of bacteria killed was achieved after the 3rd dose of vaccination. There was no significant influence of storage duration on opsonophagocytic activity of generated antibodies. Conclusion: Storing of 10v-PCV vaccine up to 12 weeks does not significantly affect the opsonophagocytic activity of pneumococcal IgG antibodies.

Immunogenicity and safety of BNT162b2 vaccination in adolescents with systemic lupus erythematosus.

We evaluated the immunogenicity and safety of BNT162b2 vaccination in adolescents with systemic lupus erythematosus (adoSLE) receiving either high- or low-dose immunosuppressant (High-IS and Low-IS). Patients aged 12-18years diagnosed with SLE were enrolled. High-IS was defined as >7.5mg/day prednisolone or with other immunosuppressant, while Low-IS was defined as only ≤7.5mg/day of prednisolone and no immunosuppressant. Two doses of BNT162b2 vaccination were given 4weeks apart, followed by a booster (third) dose at 4-6months later. Anti-spike receptor binding domain (anti-RBD) IgG against Wuhan, neutralising antibody (NT) against Wuhan and Omicron variants, and cellular immune response by IFN-γ-ELISpot assay were evaluated following vaccination. Adverse events (AEs) and SLE flare were monitored. A total of 73 participants were enrolled, 40 and 33 in the High-IS and Low-IS group, respectively. At 4weeks following the 2nd dose, overall anti-RBD IgG seropositivity was 97.3%, with no difference between the groups (p = .498). AdoSLE on High-IS had lower anti-RBD IgG (p < .001), Wuhan NT (p < .001), and IFN-γ-ELISpot (p = .022) than those on Low-IS. A 3rd dose induced significantly higher antibody responses than after the 2nd dose (p < .001) in both groups and established seroconversion against Omicron variants, with persistent lower antibody levels in High-IS group. SELENA-SLEDAI scores within 12weeks after 2-dose vaccination was higher than before vaccination (3.1 vs 2.5; p < .036); however, the occurrence of disease flare by SELENA-SLEDAI flare index was not different after vaccination compared to before vaccination, consistent across groups. Non-severe AEs occurred similarly in both groups. AdoSLE on High-IS induced lower SARS-CoV-2 vaccine immune responses than Low-IS. Vaccination can increase disease activity and requires close monitoring for disease flare.

Unveiling the impact of COVID-19 on diabetics: vaccination status and infection rates in a North Indian state-insights from a primary healthcare centre-based non-communicable disease registry

Background: Patients with diabetes are at an increased risk of severe infection and mortality due to COVID-19. Absence of effective pharmacological treatments, vaccination remains one of the most effective means of controlling the pandemic. Our study aims to investigate the prevalence of COVID-19 infection among patients with diabetes mellitus and assess the coverage of COVID-19 vaccination among these patients. Methods: The patients were identified from a primary healthcare centre (PHC) based non-communicable disease (NCD) registry at PHC Najafgarh, New Delhi. A total of 480 patients were included in this study. The data was retrieved from NCD registry and vaccination status was confirmed from their vaccination certificates. Results: In our study 91.3% (438) of diabetic patients had received the first dose of COVID-19 vaccine and the coverage for second dose and third dose among these same patients are 84.6% and 27.3% respectively. Conclusions: Only a quarter of all the patients have received precautionary dose (3rd dose), and almost a tenth of all the patients have not even received a single dose of COVID-19 vaccine, the patients should be counselled and encouraged for vaccination. Also, it is recommended to take COVID-19 vaccination into consideration while taking the medical history of diabetics.

CLDN18.2 chimeric antigen receptor T cell therapy for patients with advanced gastric and pancreatic adenocarcinoma: Results of ELIMYN18.2 phase 1b clinical trial.

356 Background: Autologous anti-claudin 18.2 (CLDN18.2) CAR T cell, satricabtagene autoleucel (satri-cel), was developed to treat solid tumors. We report the completed results of the Phase 1b ELIMYN18.2 study (Cohort A) in gastric/gastroesophageal junction (GC/GEJ) and pancreatic cancer (PC). Methods: This single-arm, open-label, Phase 1b/2 study (NCT04404595) evaluated the safety and efficacy of satri-cel in patients with CLDN18.2-positive advanced GC/GEJ or PC. Cohort A consisted of a modified 3+3 design. After a conditioning regimen of fludarabine, cyclophosphamide, and nab-paclitaxel, patients were administered 1-3 cycles of satri-cel. The primary objectives were safety and determination of the recommended Phase 2 dose (RP2D). Adverse Events (AEs) were graded per CTCAE 5.0, objective response rate (ORR), and clinical benefit rate (CBR) including CR, PR, and ≥6-month SD were assessed by the investigator per RECIST 1.1. Results: As of May 14, 2023, twenty-four patients underwent leukapheresis in Cohort A. Nineteen patients (7 GC/GEJ and 12 PC) with a median of 3 (range: 1-8) prior therapeutic lines had satri-cel at three dose levels (DLs) between 250×106 and 600×106 cells. Seven patients received a 2nd dose and two patients received a 3rd dose of satri-cel at a median of 113 and 259 days, respectively, post-first infusion. All 19 patients experienced at least one AE. No DLTs occurred and 17 patients experienced cytokine release syndrome (CRS). Two cases of Grade 3 CRS were reported, and all other CRS were Grade 1 or 2. Two Grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS) occurred. All CRS and ICANS were resolved. No severe gastrointestinal-related AEs were found. No increased toxicities were reported after any reinfusion. No satri-cel treatment-related death occurred. For all patients, the best ORR was 26.3%, the median DOR was 3.7 months and the CBR was 42.1%. The median PFS was 5.2 months, and overall survival was 12.8 months (95% CI 5.7-NE) after leukapheresis, and the median PFS was 3.3 months, and overall survival was 8.9 months (95% CI 3.3-NE) after the first infusion. In the GC/GEJ group, the ORR was 42.9% (3/7), the median DOR was 6.9 months and the CBR was 57.1%. In the PC group, the ORR was 16.7% (2/12), the median DOR was 3.4 months and the CBR was 33.3%. An ORR of 42.9% (3/7) and a CBR of 71.4% were reported at the DL3 of 600×106 cells which was selected as RP2D. At DL3, one GC patient achieved a CR and two PC patients had PR, suggesting the PC group achieved an ORR of 40% (2/5) and the GC group achieved an ORR of 50% (1/2). In addition, tumor shrinkage was detected in 73.7 % (14/19) of patients. Conclusions: The safety profile and therapeutic efficacy of satri-cel were shown to be promising in heavily pretreated patients with CLDN18.2-positive advanced GC/GEJ and PC . In the Phase 2 study, the first patient with GC received satri-cel in May 2023. Clinical trial information: NCT04404595 .

A 12-month follow-up study of patients with systemic lupus erythematosus after immunization against SARS-CoV-2.

To identify all post-BNT162b2 vaccination (BioNTech and Pfizer) events during the ensuing 12months in patients with systemic lupus erythematosus (SLE) from the Immuno-Rheumatology Department at Cayetano Heredia Hospital's cohort, Lima, Perú. A 12-month follow-up study was conducted from the first dose of immunization with the BNT162b2 vaccine, which was given between May and June 2021, to SLE patients from this cohort. The initial population was constituted by 100 patients (100 patients received the 1st dose, 90 the 2nd dose, and 85 the 3rd dose of this vaccine); 33 patients presented a SLE reactivation (flare), 9% (9/100) post 1st dose, 26.6% (24/90) post 2nd dose, and 16.4% (14/85) post 3rd dose. The most common types of flare were articular (26) and renal (14) with 5/33 (15.1%) requiring hospitalization for flare management. A negative association with flare occurrence was found between the use of hydroxychloroquine RR 0.43 (0.21-0.85) and the opposite was the case for azathioprine RR 2.70 (1.39-5.25). During follow-up, 26 patients developed SARS-CoV-2 infection of whom three required hospitalization, one of whom died. 33 of 100 SLE patients immunized with BNT162b2 vaccine against SARS-CoV-2, presented SLE flares (47 episodes in total); 5 of these patients required in-hospital management and all fully recovered; 26 patients had SARS-CoV-2 infection; three required hospitalization, one died.

Equity in vaccine coverage in Uganda from 2000 to 2016: revealing the multifaceted nature of inequity

BackgroundThis study analyses vaccine coverage and equity among children under five years of age in Uganda based on the 2016 Uganda Demographic and Health Survey (UDHS) dataset. Understanding equity in vaccine access and the determinants is crucial for the redress of emerging as well as persistent inequities.MethodsApplied to the UDHS for 2000, 2006, 2011, and 2016, the Vaccine Economics Research for Sustainability and Equity (VERSE) Equity Toolkit provides a multivariate assessment of immunization coverage and equity by (1) ranking the sample population with a composite direct unfairness index, (2) generating quantitative measure of efficiency (coverage) and equity, and (3) decomposing inequity into its contributing factors. The direct unfairness ranking variable is the predicted vaccination coverage from a logistic model based upon fair and unfair sources of variation in vaccination coverage. Our fair source of variation is defined as the child’s age – children too young to receive routine immunization are not expected to be vaccinated. Unfair sources of variation are the child’s region of residence, and whether they live in an urban or rural area, the mother’s education level, the household’s socioeconomic status, the child’s sex, and their insurance coverage status. For each unfair source of variation, we identify a “more privileged” situation.ResultsThe coverage and equity of the Diphtheria-Pertussis-Tetanus vaccine, 3rd dose (DPT3) and the Measles-Containing Vaccine, 1st dose (MCV1) – two vaccines indicative of the health system’s performance – improved significantly since 2000, from 49.7% to 76.8% and 67.8% to 82.7%, respectively, and there are fewer zero-dose children: from 8.4% to 2.2%. Improvements in retaining children in the program so that they complete the immunization schedule are more modest (from 38.1% to 40.8%). Progress in coverage was pro-poor, with concentration indices (wealth only) moving from 0.127 (DPT3) and 0.123 (MCV1) in 2000 to -0.042 and -0.029 in 2016. Gains in overall equity (composite) were more modest, albeit significant for most vaccines except for MCV1: concentration indices of 0.150 (DPT3) and 0.087 (MCV1) in 2000 and 0.054 and 0.055 in 2016. The influence of the region and settings (urban/rural) of residence significantly decreased since 2000.ConclusionThe past two decades have seen significant improvements in vaccine coverage and equity, thanks to the efforts to strengthen routine immunization and ongoing supplemental immunization activities such as the Family Health Days. While maintaining the regular provision of vaccines to all regions, efforts should be made to alleviate the impact of low maternal education and literacy on vaccination uptake.

Effect of Covid pandemic on immunization status of children in tertiary care Hospital of North India: reason for partial and non-immunization a cross-sectional study

BackgroundLow immunization coverage in India attributes to many factors including sociodemographic factors and people’s behavior. COVID-19 pandemic resulted in disruptions in achieving optimum availability and utilization of immunization services. This study was carried out to find out the immunization status of children in the post COVID era and various factors responsible for non-immunization during the pandemic.MethodsThis cross-sectional study included parents of 225 admitted children aged 1–6 years were interviewed using a semi-structured open-ended questionnaire. Children were classified as completely immunized, partially immunized and unimmunized on the basis of vaccines missed given under first year of life. Reasons for non-immunization and delay/missed vaccination during COVID-19 pandemic were recorded.ResultsOf the 225 children, 162 (72%; 95% CI 66–78%) were completely immunized, 55 (24.4%; 95% CI 19–30%) were partially immunized and 8 (3.6%; 95% CI 1–6%) were unimmunized. Parents with hospital deliveries, higher education level and lesser birth order were more likely to have children with better immunization status (p < 0.05). First dose of measles scheduled at 9 months and 3rd dose of pentavalent vaccine/OPV/Rotavirus vaccine scheduled at 14 weeks were most commonly missed vaccines among partially immunized. Lack of awareness (n = 36, 57.1%; 95% CI 45–70%) was the common reason for partial and non-immunization followed by illness of child (n = 21, 33.3%; 95% CI 21–45%) and COVID-19 pandemic (n = 11, 17.4%; 95% CI 8–27%). Pandemic was reason for delay in 50 (22.2%; 95% CI 17–28%) children. Restrictions of movement (64%; 95% CI 50–78%), fear of being exposed to COVID-19 (52%; 95% CI 38–66%) were the most common reasons for delay during the pandemic. Of the 50 children who had delay due to pandemic, 39 children (17.3%; 95% CI 12–22%) received their catch-up immunization after the pandemic. No child remained completely unimmunized due to COVID-19 pandemic.ConclusionsAlthough COVID-19 pandemic resulted in disruptions in routine immunization services, sociodemographic factors such as awareness for immunization, parental education and various beliefs for immunization were responsible for the children remaining unimmunized or partially immunized after the pandemic.

B and T cell responses to the 3rd and 4th dose of the BNT162b2 vaccine in dialysis patients

ABSTRACT Patients on dialysis (PoD) are at high risk of severe morbidity and mortality from COVID-19. Characterizing long-term vaccine immune responses in these patients will help optimize vaccine schedule for PoD. This study aimed to determine whether long-term humoral and B and T cell-responses post 3rd and 4th dose of the BNT162b2 vaccine differed between PoD and controls. Non-infected PoD and controls vaccinated with BNT162b2 were recruited in Ziv Medical Center, Israel, between 2021 and 2022. Specimens were collected 1–2 months pre 3rd dose; 1–3 months post 3rd dose; 4–5 months post 3rd dose and 3–5 months post the 4th dose. Anti-SARS-CoV-2 spike (spike) specific antibodies, spike specific memory B cells, and spike specific CD154+ T cells as well as cytokines producing CD4+/CD8+ T cells were measured using standardized assays and compared between PoD and controls at each time point using Mann Whitney and Fisher’s exact tests. We recruited 22 PoD and 20 controls. Antibody levels in PoD were lower compared to controls pre 3rd dose but not post 3rd and 4th doses. Frequencies of spike specific memory B cell populations were similar between PoD and controls overall. Frequencies of spike specific T cells, including those producing IFNγ and TNFα, were not lower in PoD. B and T cell mediated immune response in PoD following a 3rd and a 4th dose of the BNT162b2 vaccine was not inferior to controls up to 5 months post vaccination. Our results suggest that standard BNT162b2 vaccination is suitable for this group.

Differential Immunogenicity of mRNA-based and Inactivated Virus COVID-19 Vaccines in Patients with Inflammatory Rheumatic Disease - A Prospective Study up to 12 Months Post-3rd Dose

Background During the COVID-19 pandemic, 2 types of COVID-19 vaccines were made available in Hong Kong - the mRNA-based vaccine and the inactivated virus vaccine. All residents were required to complete 3 vaccinations. There is concern that immunogenicity acquired from COVID-19 vaccinations could be unsustainable in patients with inflammatory rheumatic disease (IRD) due to the underlying condition and immunosuppressive medication used. Therefore, this study aims to investigate the immunogenicity of COVID-19 vaccines and its sustainability in IRD patients. Methods This single-centre cohort was assembled prospectively from 8/2021 - 2/2022 in Hong Kong. Peripheral blood samples were collected from the patients before, 28 (± 3) days and 12 months after the third dose of COVID-19 vaccination. The neutralising antibody titre against the SARS-CoV-2 virus was quantified by ELISA. Results A total of 83 patients (age: 51.4± 11.7 years; 72.3% female; 17 rheumatoid arthritis, 17 psoriatic arthritis, 12 axial spondylarthritis, 37 systematic lupus erythematosus) attended all 3 visits. The vaccine distribution is summarized in Fig. 1A. Majority (96.4%) of patients had positive neutralising antibodies before the 3rd vaccine dose despite a low mean titre of 38.2± 29.7%. The antibody titre improved significantly after the 3rd dose (85.9± 23.8%) and was maintained at the 12-month visit (87.5± 22.6%). The mean antibody levels pre- and post-3rd dose were higher in patients who took mRNA-based vaccine (Fig. 1B). The presence of COVID-19 infection during the follow-up period led to significantly higher antibody titre at the 12-month visit (Table 1). There were no significant associations between immunogenicity and age, type of IRD, biologic/targeted Disease Modifying Anti-Rheumatic Drugs usage as well as additional booster doses. Conclusion 3 doses of COVID-19 vaccine produced sustained humoral response in IRD patients. The immunogenicity appeared to be dependent on the type of vaccines received in the short term and breakthrough infection in longer term.

Immunogenicity of COVID-19 adsorbed inactivated vaccine (CoronaVac) and additional doses of mRNA BNT162b2 vaccine in immunocompromised adults compared with immunocompetent persons.

Inactivated COVID-19 vaccines data in immunocompromised individuals are scarce. This trial assessed the immunogenicity of two CoronaVac doses and additional BNT162b2 mRNA vaccine doses in immunocompromised (IC) and immunocompetent (H) individuals. Adults with solid organ transplant (SOT), hematopoietic stem cell transplant, cancer, inborn immunity errors or rheumatic diseases were included in the IC group. Immunocompetent adults were used as control group for comparison. Participants received two CoronaVac doses within a 28-day interval. IC received two additional BNT162b2 doses and H received a third BNT162b2 dose (booster). Blood samples were collected at baseline, 28 days after each dose, pre-booster and at the trial end. We used three serological tests to detect antibodies to SARS-CoV-2 nucleocapsid (N), trimeric spike (S), and receptor binding domain (RBD). Outcomes included seroconversion rates (SCR), geometric mean titers (GMT) and GMT ratio (GMTR). A total of 241 IC and 100 H adults participated in the study. After two CoronaVac doses, IC had lower SCR than H: anti-N, 33.3% vs 79%; anti-S, 33.8% vs 86%, and anti-RBD, 48.5% vs 85%, respectively. IC also showed lower GMT than H: anti-N, 2.3 vs 15.1; anti-S, 58.8 vs 213.2 BAU/mL; and anti-RBD, 22.4 vs 168.0 U/mL, respectively. After the 3rd and 4th BNT162b2 doses, IC had significant anti-S and anti-RBD seroconversion, but still lower than H after the 3rd dose. After boosting, GMT increased in IC, but remained lower than in the H group. CoronaVac two-dose schedule immunogenicity was lower in IC than in H. BNT162b2 heterologous booster enhanced immune response in both groups.

Do immunosuppressive treatments influence immune responses against adenovirus-based COVID-19 vaccines in patients with multiple sclerosis? An Argentine multicenter study.

There are no reports in LATAM related to longitudinal humoral and cellular response to adenovirus based COVID-19 vaccines in people with Multiple Sclerosis (pwMS) under different disease modifying therapies (DMTs) and neutralization of the Omicron and Wuhan variants of SARS-COV-2. IgG anti- SARS-COV-2 spike titer were measured in a cohort of 101 pwMS under fingolimod, dimethyl fumarate, cladribine and antiCD20, as well as 28 healthy controls (HC) were measured 6 weeks after vaccination with 2nd dose (Sputnik V or AZD1222) and 3nd dose (homologous or heterologous schedule). Neutralizing capacity was against Omicron (BA.1) and Wuhan (D614G) variants and pseudotyped particles and Cellular response were analyzed. Multivariate regression analysis showed anti-cd20 (β= -,349, 95% CI: -3655.6 - -369.01, p=0.017) and fingolimod (β=-,399, 95% CI: -3363.8 - -250.9, p=0.023) treatments as an independent factor associated with low antibody response (r2 adjusted=0.157). After the 2nd dose we found a correlation between total and neutralizing titers against D614G (rho=0.6; p<0.001; slope 0.8, 95%CI:0.4-1.3), with no differences between DMTs. Neutralization capacity was lower for BA.1 (slope 0.3, 95%CI:0.1-0.4). After the 3rd dose, neutralization of BA.1 improved (slope: 0.9 95%CI:0.6-1.2), without differences between DMTs. A fraction of pwMS generated anti-Spike CD4+ and CD8+ T cell response. In contrast, pwMS under antiCD20 generated CD8+TNF+IL2+ response without differences with HC, even in the absence of humoral response. The 3rd dose significantly increased the neutralization against the Omicron, as observed in the immunocompetent population. Findings regarding humoral and cellular response are consistent with previous reports.

COVID-19-related Obsessions and Compulsions after the Full Control of the Pandemic: A Sample of the Nonpsychiatric Saudi Young Adults

Abstract Background: Symptoms of obsessive-compulsive disorder (OCD), contamination type has increased due to the COVID-19 pandemic. However, whether these symptoms would decrease after introducing the vaccines is unknown. Thus, this study examined the prevalence of COVID-19-related OCD among young adults who had never been diagnosed with a psychiatric disorder after fully controlling the pandemic. Methods: A sample of 351 young adults from all Saudi regions, whose ages ranged from 18-year-old to 25-year-old, were collected virtually in March and April 2022, via using an Arabic online survey that was distributed through social networks which included socio-demographic characteristics, COVID-19-related items, and COVID-19-related obsessions and compulsions assessment items. Results: Most of the participants were females (83.2%), had received the 3rd dose of the vaccine (69.80%), and reported having no obsessive thoughts or compulsive behaviors related to COVID-19 (91.5%, 96.6%). Despite this, males still had lower scores of OCD symptoms related to COVID-19 compared to females (9.98 vs. 14.29). The results also show that the mean scores of OCD symptoms decreased with each vaccine shot, 16.80 ± 18.91, 14.12 ± 10.85, and 13.27 ± 11.27 for the 1st, 2nd, and 3rd doses, respectively. Conclusion: Introducing the COVID-19 vaccine may reduce the onsets of obsessions and compulsive behaviors related to contamination. Some compulsive behaviors might be considered the new normal as they do not cause functional impairment.

Clinical presentation, associated factors, and course of cutaneous reaction after the booster dose of COVID-19 vaccination.

A booster coronavirus disease 2019 (COVID-19) vaccination was proposed to preserve immunity and prevent new variants of the severe acute respiratory syndrome coronavirus 2 virus. The objectives of this study are to investigate clinical manifestations, associated factors and course of cutaneous reactions after the booster dose of COVID-19 vaccination, compared to the recommended 1st and 2nd doses. This retrospective cohort study was conducted at Siriraj Hospital, Bangkok. Adult patients who reported cutaneous reactions after COVID-19 vaccination from April 2021 to February 2022 were included. Data were collected from electronic medical records and analyzed. A total of 521 subjects with a median age of 38 years were included. Females predominated (80.2%). Most reactions were reported after receiving CoronaVac (49.1%) and ChAdOx1 nCoV-19 (46.3%). The injection site reaction was the most reported. Twenty-one patients reported rash after the 3rd booster dose, with messenger RNA vaccines in most cases. Patients in this group had significantly fewer injection site reactions compared to those with the 1st and 2nd vaccination (70.6% vs. 91.5%) with an increasing proportion of new-onset urticaria (17.6% vs. 5.4%, p=0.023). The rash after the 3rd booster vaccination tended to have a longer duration of reactions (p=0.001). Boosting with a vaccine different from the 1st dose may not affect the reaction. Age and sex did not affect booster rash. In this study, no serious cutaneous reactions were found. Most adverse cutaneous reactions after COVID-19 vaccination are mild in severity, especially after booster vaccination, and should not discourage the benefits of getting vaccinated.