3rd Dose Research Articles

Association of mRNA COVID-19 vaccination and reductions in Post-COVID Conditions following SARS-CoV-2 infection in a US prospective cohort of essential workers.

While there is evidence that COVID-19 vaccination protects against development of post-COVID conditions (PCC) after severe infection data are limited on whether vaccination reduces the risk after cases of less-severe non-hospitalized COVID-19 disease with more recent SARS-CoV-2 variant viruses. This study assessed whether COVID-19 vaccination was protective against subsequent development of PCC in persons with predominantly mild initial infections during both Delta and Omicron variant predominance. This study utilized a case-control design, nested within the HEROES-RECOVER cohort. Participants aged ≥18 years with PCR-confirmed SARS-CoV-2 infection between 6/28/2021 and 9/14/2022 were surveyed for PCC, defined by symptoms lasting >1 month after initial infection Cases were participants self-reporting PCC and controls were participants that did not self-report PCC. The exposure was mRNA COVID-19 vaccination (2 or 3 monovalent doses) versus no COVID-19 vaccination. Logistic regression was used to compare the odds of PCC among vaccinated and unvaccinated persons; additional analyses evaluating PCC subtypes were also performed. A total of 936 participants with documented SARS-CoV-2 infection were included; of these 23.6% (221) reported PCC and 83.3% (779) were vaccinated. Participants who received a 3rd COVID-19 monovalent mRNA dose prior to infection had lower odds of PCC-related gastrointestinal, neurological, and other symptoms compared to unvaccinated participants (aOR: 0.37; 95% CI: 0.16-0.85; aOR: 0.56; 95% CI: 0.32-0.97; aOR:0.48; 95% CI: 0.25-0.91). COVID-19 vaccination protected against development of PCC among persons with mild infection during both Delta and Omicron variant predominance, supporting vaccination as an important tool for PCC prevention.

Effect of Intravitreal Bevacizumab (Anti VEGF) Injection on Renal Function

Background: Vascular endothelial growth factor (VEGF) plays an important role in the development of both Proliferative Diabetic Retinopathy (PDR) & Diabetic Macular Odema (DMO). An intravitreal anti-VEGF agent is an effective new modality of treatment. Some studies have dealt with systemic effects of intravitreal injection of anti-VEGF. However, decreasing renal function has been reported recently. Aims: To investigate the effect of intravitreal bevacizumab (anti VEGF) injection on renal function. Methods: This quasi-experimental study was carried out in the Department of ophthalmology, Bangabandhu Sheikh Mujib Medical University, Dhaka, during March 2019 to August 2021. A total of 40 patients with retinopathy treated with intravitreal injection bevacizumab were included in this study, out of which 20 patients having diabetic kidney disease (DKD) and rest 20 patients without diabetic kidney disease (No DKD). The patients having Diabetic Kidney Disease (DKD) whose Urinary Albumin Creatinine Ratio (UACR) > 30 mg/g or Effective Glomerular Filtration Rate (eGFR) < 60mL/min/1.73m2, No Diabetic Kidney Disease (No DKD) whose UACR < 30 mg/g or eGFR > 60mL/min/1.73m2. Patients of both sexes and age above 18 years were enrolled in this study. Pre- injection and 1 month after 3rd dose of intravitreal injection of bevacizumab, UACR, Serum Creatinine and eGFR were measured and compared. Results: It was observed that half (50.0%) of the patients in DKD and more than half (65.0%) in No DKD belonged to age group 50-59 years. Male was predominant in both the groups. The mean pre-injection of serum creatinine was 1.23±0.53 mg/dl in DKD and 0.87±0.22 mg/dl in No DKD. The mean post-injection of serum creatinine was 1.19±0.45 mg/dl in DKD and 0.87±0.16 mg/dl in No DKD. The mean pre-injection of UACR was 1294.9±968.26 mg/g in DKD and 13.8±5.99 mg/g in No DKD. The mean post-injection of UACR was 1142.11±1024.06 mg/g in DKD and 13.01±6.87 mg/g in No DKD. The mean difference of serum creatinine, eGFR and UACR were not significant (p>0.05) between pre-injection and post-injection in both groups. Conclusion: Serum creatinine, eGFR and UACR were almost similar between pre-injection and post-injection in patients with diabetic kidney disease (DKD) and patients without diabetic kidney disease (No DKD).

Knowing the Antibody Status may influence compliance of health care workers to COVID-19 booster dose

Abstract Background Previous studies showed that the fourth SARS-CoV-2 vaccine dose has a protective effect against infection, as well as against severe disease and death. This study aimed to examine whether knowledge of a high level antibody after the 3rd dose may reduce compliance to the 4th booster dose among health care workers. Methods We conducted a prospective cohort study among health care workers vaccinated with the first three doses at Rambam Healthcare Campus, a tertiary hospital in northern Israel. Participants underwent a serological test before the 4th booster vaccine was offered to all of them, with results provided to participants. The population was divided into two groups: those with antibody below 955 AU/ml, and those with 955 AU/ml and higher, a cutoff found protective in a previous study. Multiple logistic regression was carried out to compare the compliance to the 4th booster between the two groups, adjusted for demographic and clinical variables. Results After adjusting for the confounding variables, the compliance was higher in those with antibody levels below 955 AU/ml (OR = 1.41, P = 0.05, 95% CI 1.10-1.96). In addition, male sex, and age of 60 years and above were also associated with higher vaccination rate (OR = 2.28, P < 0.001, 95% CI 1.64 - 3.17), (OR = 1.14, P = 0.043, 95% CI 1.06 - 1.75), respectively. Conclusions Knowledge of the antibody status may affect compliance with the booster dose. Considering waning immunity over time, reduced compliance may affect the protection of health care workers who declined the 4th dose. Key messages • Knowing the antibody status may affect compliance of health care workers with the booster dose. • Reduced compliance of health care workers may affect their protection.

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.

Effects of age and gender on immunogenicity and reactogenicity of SpikoGen recombinant spike protein vaccine: a post-hoc analysis

SpikoGen® COVID-19 vaccine is based on the spike protein extracellular domain of the ancestral Wuhan-Hu-1 strain modified by removal of the furin cleavage site and addition of stabilising mutations expressed as a recombinant protein in insect cells. It is formulated with Advax-CpG55.2™ adjuvant to ensure optimal immunogenicity. In this study, data from several SpikoGen® clinical trials was retrospectively analysed to assess for any effect of gender or age on seroconversion, neutralizing antibody levels or the incidence of adverse events. Following the 1st dose, older age was associated with a reduced rate of fatigue (RR 0.97, p < 0.001), headache (RR 0.98, p = 0.034) and myalgia (RR 0.97, p=0.016), following the 2nd dose, the rate of fatigue (RR 0.98, p = 0.017) but following the 3rd dose no effect of age on adverse events was evident. Similarly, following the 1st dose, men reported a 19% lower incidence of fatigue, 36% lower incidence of headache and 28% lower incidence of myalgia when compared to women. Interestingly, there was no relationship between age or gender and serum neutralizing antibody levels, although after each vaccine dose there was a consistent trend to women having a higher seroconversion rate. There was no correlation between neutralizing antibody levels and adverse events. Unlike what is seen with mRNA vaccines, reactogenicity trended lower after each subsequent SpikoGen® dose. Overall, SpikoGen® exhibited positive immunogenicity and low reactogenicity, indicating that a low incidence of adverse events does not equate to poor immunogenicity. SpikoGen® remains a promising protein-based vaccine platform for COVID-19 protection.

Abstract B030: Assessing COVID-19 vaccination status and symptoms in persons with a history of cancer

Abstract Background: Persons with a history of cancer are at a higher risk of adverse COVID-19 outcomes due to their immunosuppressed status. Vaccination to COVID-19 has proven effective in decreasing complications from COVID-19 infection. This study explored the vaccination status of persons receiving cancer care (received 1st dose/2nd dose/booster) and their symptoms. Methods: Persons with a cancer diagnosis receiving care at a cancer center clinical site were randomly invited to complete a voluntary survey via email, the EMR, or during an in-person appointment. Paper surveys were completed in the clinic, placed in a sealed collection bin, and collected by research staff weekly. Responses were anonymous. Participants were asked if they had received their 1st/2nd COVID-19 vaccine, their symptoms, and if they had/intended to receive the booster. The study was conducted between September 2021 to September 2022. An EMR review of vaccination uptake was conducted to assess representativeness of our sample. Results: 6,302 persons were invited to complete the survey; 1,733 (28%) responded. 1694 (98%) had received at least one vaccine dose. 67.46% of the participants were white, non-Latinx; 25.39% were Black; 3.17% were Asian. 13.25% were 18-50 years; 30.61% were 50-64;36.81% were 65-74; 19.33% were 75+. 33.13% had a breast cancer diagnosis; 5.47% had lung cancer, 5.41% had prostate cancer, 4.29% had colorectal carcinoma, and 47.42% had other cancers. 1016 (58.63%) received their 1st COVID-19 vaccine, 1437 (82.92%) the 1st/2nd dose, and 1052 (60.70%) had received the booster (3rd dose). Frequently reported symptoms were muscle soreness, pain, fatigue, fever and headache. Those over 65 years were significantly more likely to report fatigue (p&amp;lt;0.001), fever (p&amp;lt;0.0001), headache (p&amp;lt;0.0001), nausea (p=0.0005). Black persons were less likely to report fever (OR: 0.54, 95% CI: 0.34 – 0.86, p=0.0097) and more likely to report pain (OR: 1.58, 95% CI: 1.02 – 2.46, p=0.0427). For persons with breast cancer--29.46% reported muscle soreness, 12.95% reported fatigue, 10.13% reported headache, 9.19% reported fever, 7.13% reported pain. We were unable to stratify by other demographics or cancer type due insufficient sample size. EMR review of vaccination uptake revealed 24.17% had not initiated vaccination. Conclusion: Survey respondents were more likely to have initiated the COVID-19 vaccination process. Older adults were more likely to report fatigue, fever, headache and nausea. Black persons were less likely to report fever and more likely to report pain. Anticipating differences in COVID-19 vaccination symptoms allow for the development of tailored education and resources for self-management and care. Citation Format: Iqra Siddiqui, Ana Maria Lopez, FNU Nikita. Assessing COVID-19 vaccination status and symptoms in persons with a history of cancer [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B030.

Vaccine coverage and timeliness among children of adolescent mothers: A community-based study in the Eastern Cape, South Africa

BackgroundChildren born to adolescent mothers are more vulnerable to infant mortality and morbidity than those born to adult mothers. HIV-exposed children have lower antibody protection against vaccine-preventable diseases at birth compared to unexposed children. In South Africa, 17 % of adolescent girls aged 15–19 years are mothers, yet vaccination coverage and timeliness among their children is underreported. MethodsThis study estimated age-appropriate vaccination coverage and timeliness among children (n = 1080) of adolescent mothers (n = 1015) in the Eastern Cape, South Africa. Mother-child dyads were recruited through healthcare and community-based sampling strategies. Vaccination data were abstracted from 1013 home-based child health records (2017–2019). Coverage is reported for Diphtheria-Tetanus-Pertussis 3rd dose (DTP3), under-1 vaccination among children over 12 months (n = 613) and measles 2nd dose (MCV2) among children over 24 months (n = 382) using proportions with 95 % confidence intervals (95 %CI). Timeliness is defined as receiving each vaccination within 4 weeks of recommended age. Findings are disaggregated by maternal HIV-status. ResultsOverall, 27.3 % of adolescent mothers were living with HIV. Coverage of DTP3 was 85.6 % (95 %CI: 82.6–88.3 %), under-1 coverage was 53.2 % (95 %CI: 49.1–57.2 %), and MCV2 coverage was 62.3 % (95 %CI: 57.2–67.2 %). Vaccination coverage was lower among children of adolescent mothers living with HIV (AMLHIV) than unexposed children (DTP3 80.3 % vs 88.2 % p-value: 0.01; under-1 46.5 % vs 56.4 % p-value: 0.02; MCV2 55.4 % vs 67.1 % p-value: 0.02). Timeliness of vaccinations declined over time from 98.0 % at birth, 70.7 % at 14 weeks, 71.9 % at 9 months and 37.3 % at 18 months. ConclusionVaccination coverage among children of adolescent mothers in the Eastern Cape are below national targets. Children of AMLHIV had lower coverage than HIV-unexposed children. Further research is needed to identify risk factors associated with incomplete and delayed vaccinations among this group, particularly among HIV-exposed children. Enhanced vaccination campaigns may be required for children of adolescent mothers.

Evaluation of the Informative Value of the Results of Soil Observations in a Stationary Experiment

The effective and potential fertility of leached chernozem was evaluated in a field stationary experiment at the Central Experimental Field of the Kurgan Research Institute and the application of 2 crop cultivation technologies. In the first part of the experiment, the corn–wheat–wheat–oat crop rotation was studied during annual plowing, in the second – permanent wheat after a stubble background. The first technology was characterized by higher effective fertility, a large number of plant residues, due to which its advantage was manifested in terms of humus content. The positive effect of fertilizers on the indicators of potential soil fertility was manifested when applying the 2nd and 3rd doses of nitrogen against the background of the use of phosphorus.

SARS-COV-2 breakthrough infection and its covariates among healthcare providers of a hospital in Bangladesh during the omicron wave

IntroductionBreakthrough infection by SARS-COV-2 virus among vaccinated individuals has been reported from all over the world and it has created a substantial challenge in designing strategies to live with the virus in the post-pandemic era. Factors affecting the extent and nature of breakthrough infection are still not fully understood and those are known to vary depending on host and agent factors. Health Care Workers (HCWs), especially in hospital settings, are front-liners in combating the epidemic and, consequently, they are more vulnerable to breakthrough infection by SARS-COV-2. Like most of the countries of the world, Bangladesh went through several waves of COVID-19 and the last (3rd wave) was the widespread Omicron wave during the winter of 2022. HCWs in Bangladesh have been disproportionately affected by the virus. Under this context, the aim of the present study was to explore breakthrough infection (BTI) and its host-related covariates among HCWs of a COVID-dedicated city-based hospital during the Omicron wave in Bangladesh. Materials and methodsAn observational cross-sectional study was conducted on 267 HCWs of the Narayanganj Tertiary (300-bed) hospital during February–March 2022 which coincided with the terminal part of the 3rd wave. Data were collected by trained Field Assistants using Interviewer-administered Data Collection Forms with Questionnaires as instruments. Previous COVID-19 status (any time after the onset of the pandemic and within last 3 months) was explored by the history of specific symptoms as well as by the confirmatory rtPCR test reports from DGHS approved laboratories Anti-nucleocapsid antibody (Anti-N-Ab) in venous blood samples, assayed by a chemiluminescent ELISA technique, was used as a seroprevalence-based marker of breakthrough infection during the preceding few months. Data were analyzed by bivariate as well as multivariate statistics using the IBM-SPSS software. ResultsThe median age (range) of the HCWs was 38 (21–65) years; Body Mass Index (BMI, kg/m2) 25 (15–49); and Waist-Hip Ratio (WHR) was 0.92 (0.46–1.21). The male subjects had significantly higher median age (p = 0.01) and higher WHR (p = 0.001) as compared to the female subjects. As per the BMI category, subjects with overweight and obesity constituted 83.3 % of the male subjects as compared to 61.6 % of the female subjects (p = 0.001). The time lapse between receiving of 3rd dose and blood sampling was significantly higher among females compared to males (median days 60 vs 49, p < 0.02) indicating earlier vaccination with 1st booster dose among females. A proportion of 51.85 % male and 49.68 % female subjects showed Anti-N-Ab positivity; there was no significant difference between the gender groups. Also, there was no significant difference among male and female subjects regarding the Ab levels. On Spearman correlation analysis, a tendency of association of WHR with Ab level was observed among the male subjects; however, the association did not show statistical significance (p = 0.09). On binary logistic regression Ab positivity was found to be independently associated with WHR (p = 0.03), and prior SARS-COV-2 infection within the last 3 months (p = 0.02) among males. When all the subjects were considered together, COVID symptom positivity during the last 3 months (p = 0.067) and receiving the 1st booster dose (p = 0.07) showed a tendency of association with Ab positivity. On multiple regression analysis, Ab levels showed a negative association with WHR (p = 0.035) among males. ConclusionsMore than 50 % of the vaccinated hospital-based HCWs in Bangladesh suffered from BTI during the winter of 2022 when the Omicron wave (the 3rd wave) of COVID-19 was at its peak. The data also indicate that overweight and obesity are major host-related risk factors underlying BTI. Inadequate coverage by a booster dose seems to be another determinant of BTI and the level of immune response in this population.

COVID-19 vaccination in patients with classic and variant hairy cell leukemia

AbstractPatients with the B-cell malignancy hairy cell leukemia (HCL) and the poorer-prognosis variant HCLv often receive anti-CD20 monoclonal antibodies (mAbs), which kill normal B cells, impairing humoral immunity. We measured COVID-19 antibodies after doses of COVID-19 vaccine in patients with HCL (n = 415) and HCLv (n = 32). After the second COVID-19 vaccine dose, spike antibody level most strongly correlated with normal B-cell levels (r = 0.365, P < .0001), followed by CD4+ T-cell count (r = 0.244, P = .0002), and was less related to immunoglobulin G level (r = 0.101, P = .14). Spike antibody also correlated with normal B cells after the third to fifth vaccine doses and with CD4+ count after the third dose. Normal B-cells were undetectable in 87% of patients within 6 months after the last dose of anti-CD20 mAb and were lower than in patients at 6 to 12 months (P = .0003), which, in turn, were lower than at 12 to 18 months (P = .0002). Infection with COVID-19 became more common after use of the third vaccine dose; spike antibody levels were higher in patients with prior infection (positive vs negative nucleocapsid antibodies; P < .0001). Spike antibodies decreased faster after ibrutinib or anti-CD20 mAb. We conclude that decreased levels of normal B cells in patients with HCL/HCLv, due to disease and/or anti-CD20 therapy, are associated with lower COVID-19 vaccination efficiency and such patients may not respond well to vaccines. The associated studies were registered at www.ClinicalTrials.gov as #NCT01087333 (HCL/HCLv) and #NCT04362865 (COVID-19).

Vaccination with Tozimameran Induces T-Cell Activation, but Not Senescent or Exhaustive Alterations, in Kidney Transplant Recipients.

Multiple vaccinations have potential inimical effects on the immune system aging process. We examined whether response to SARS-CoV-2 vaccination with Tozinameran is associated with immunosenescence and immunoexhaustion in kidney transplant recipients (KTRs). In this prospective observational study, we observed 39 adult kidney transplant recipients (KTRs) who had no pre-existing anti-SARS-CoV-2 antibodies and were on stable immunosuppression. CD4+ and CD8+ T-cell subpopulations [comprising CD45RA+CCR7+ (naïve), CD45RA-CCR7+ (T-central memory, TCM), CD45RA-CCR7- (T-effector memory, TEM) and CD45RA+CCR7- (T-effector memory re-expressing CD45RA, TEMRA, senescent), CD28- (senescent) and PD1+ (exhausted)] were evaluated at 2 time points: T1 (48 h prior to the 3rd), and T2 (3 weeks following the 3rd Tozinameran dose administration). At each time point, patients were separated into Humoral and/or Cellular Responders and Non-Responders. From T1 to T2, CD4+TCM and CD8+TEM were increased, while naïve CD4+ and CD8+ proportions were reduced in the whole cohort of patients, more prominently among responders. At T2, responders compared to non-responders had higher CD8+CD28+ [227.15 (166) vs. 131.44 (121) cells/µL, p: 0.036], lower CD4+CD28- T-lymphocyte numbers [59.65 (66) cells/µL vs. 161.19 (92) cells/µL, p: 0.026] and percentages [6.1 (5.5)% vs. 20.7 (25)%, p: 0.04]. In KTRs, response to vaccination is not associated with an expansion of senescent and exhausted T-cell concentrations, but rather with a switch from naïve to differentiated-activated T-cell forms.

Equal Maintenance of Anti-SARS-CoV-2 Antibody Levels Induced by Heterologous and Homologous Regimens of the BNT162b2, ChAdOx1, CoronaVac and Ad26.COV2.S Vaccines: A Longitudinal Study Up to the 4th Dose of Booster.

Several technological approaches have been used to develop vaccines against COVID-19, including those based on inactivated viruses, viral vectors, and mRNA. This study aimed to monitor the maintenance of anti-SARS-CoV-2 antibodies in individuals from Brazil according to the primary vaccination regimen, as follows: BNT162b2 (group 1; 22) and ChAdOx1 (group 2; 18). Everyone received BNT162b2 in the first booster while in the second booster CoronaVac, Ad26.COV2.S, or BNT162b2. Blood samples were collected from 2021 to 2023 to analyze specific RBD (ELISA) and neutralizing antibodies (PRNT50). We observed a progressive increase in anti-RBD and neutralizing antibodies in each subsequent dose, remaining at high titers until the end of follow-up. Group 1 had higher anti-RBD antibody titers than group 2 after beginning the primary regimen, with significant differences after the 2nd and 3rd doses. Group 2 showed a more expressive increase after the first booster with BNT162B2 (heterologous booster). Group 2 also presented high levels of neutralizing antibodies against the Gamma and Delta variants until five months after the second booster. In conclusion, the circulating levels of anti-RBD and neutralizing antibodies against the two variants of SARS-CoV-2 were durable even five months after the 4th dose, suggesting that periodic booster vaccinations (homologous or heterologous) induced long-lasting immunity.

Homologous but not heterologous COVID-19 vaccine booster elicits IgG4+ B-cells and enhanced Omicron subvariant binding

Booster vaccinations are recommended to improve protection against severe disease from SARS-CoV-2 infection. With primary vaccinations involving various adenoviral vector and mRNA-based formulations, it remains unclear if these differentially affect the immune response to booster doses. We examined the effects of homologous (mRNA/mRNA) and heterologous (adenoviral vector/mRNA) vaccination on antibody and memory B cell (Bmem) responses against ancestral and Omicron subvariants. Healthy adults who received primary BNT162b2 (mRNA) or ChAdOx1 (vector) vaccination were sampled 1-month and 6-months after their 2nd and 3rd dose (homologous or heterologous) vaccination. Recombinant spike receptor-binding domain (RBD) proteins from ancestral, Omicron BA.2 and BA.5 variants were produced for ELISA-based serology, and tetramerized for immunophenotyping of RBD-specific Bmem. Dose 3 boosters significantly increased ancestral RBD-specific plasma IgG and Bmem in both cohorts. Up to 80% of ancestral RBD-specific Bmem expressed IgG1+. IgG4+ Bmem were detectable after primary mRNA vaccination, and expanded significantly to 5–20% after dose 3, whereas heterologous boosting did not elicit IgG4+ Bmem. Recognition of Omicron BA.2 and BA.5 by ancestral RBD-specific plasma IgG increased from 20% to 60% after the 3rd dose in both cohorts. Reactivity of ancestral RBD-specific Bmem to Omicron BA.2 and BA.5 increased following a homologous booster from 40% to 60%, but not after a heterologous booster. A 3rd mRNA dose generates similarly robust serological and Bmem responses in homologous and heterologous vaccination groups. The expansion of IgG4+ Bmem after mRNA priming might result from the unique vaccine formulation or dosing schedule affecting the Bmem response duration and antibody maturation.

Pharmacokinetics of piperaquine and its association with intermittent malaria preventive therapy outcomes during pregnancy

BackgroundDihydroartemisinin-piperaquine (DHP) recently showed superior effectiveness over sulfadoxine-pyrimethamine for malaria intermittent preventive treatment in pregnancy (IPTp). We investigated day 7 piperaquine pharmacokinetics and its therapeutic efficacy in preventing malaria during pregnancy.MethodsMalaria-free (mRDT) pregnant women (n = 400) who received monthly IPTp-DHP were enrolled and followed till delivery. Day 7 Plasma piperaquine concentrations were determined after each IPTp dose using UPLC/MS/MS. IPTp outcomes (symptomatic malaria and parasitemia during pregnancy, placental malaria, and maternal malaria at delivery) were monitored. Linear mixed model and Cox regression were used to assess predictors of day 7 piperaquine concentration and treatment outcome, respectively.ResultsThe incidences of symptomatic malaria and parasitemia during pregnancy per 100 person-year at risk were 2 and 33, respectively. The prevalence of histopathologically confirmed placental malaria and maternal malaria at delivery were 3% and 9.8%, respectively. Repeated monthly IPTp-DHP resulted in significantly increased day 7 plasma piperaquine concentration (p < 0.001). Following the 1st, 2nd, and 3rd monthly IPTp-DHP doses, the proportions of women with day 7 piperaquine concentration below the therapeutic threshold (< 30 ng/mL) were 6.1%, 4.1% and 3.6%, respectively. Factors such as maternal age, body weight and trimester were not significant predictors of day 7 piperaquine concentration. However, having a low day 7 piperaquine plasma concentration (< 30 ng/mL) was significantly associated with a higher risk of parasitemia during pregnancy (p = 0.004).ConclusionLower day 7 piperaquine plasma concentration is a risk factor for parasitemia during pregnancy. Single plasma sampling at day 7 can be used to monitor piperaquine effectiveness during IPTp-DHP.Trial registrationRegistered 09/12/2016, PACTR201612001901313.

Vaccination Status Against the Hepatitis B Virus of the Patients Visiting a Tertiary Care Dental Hospital

Abstract: Objective To assess the vaccination status for Hepatitis B virus among patients attending a tertiary care dental hospital in Multan, aiming to identify gaps and opportunities for improvement in vaccination coverage. Methods This cross-sectional questionnaire study conducted at Multan Dental College from June 2023 to Feb 2023 included patients attending the dental OPD. 181 participants completed the questionnaire regarding vaccination status. Ethical approval and informed consent were obtained from Multan Dental Hospital. Results Among 181 participants, 98 (54.14%) were males and 83 (45.86%) were females. Regarding age groups, 36 (19.9%) were 16-20 years old, 69 (38.12%) were 21-25 years old, 54 (29.83%) were 26-30 years old, and 22 (12.15%) were 31 years old or above. Out of 181 participants, 51 (28.17%) were non-vaccinated, while 130 (71.83%) were vaccinated. Among the vaccinated, 47 (26%) received the 1st dose, 36 (19.9%) received the 2nd and 3rd doses each, and 11 (6.07%) received the Booster dose. The majority (58.82%) of non-vaccinated individuals cited multiple reasons for not receiving immunization, including vaccine unavailability and busy schedules. Additionally, 9.8% lacked awareness of the vaccination, while others mentioned injection phobia and lack of motivation Conclusion The study emphasizes the challenge of incomplete vaccination among patients, which necessitates coordinated efforts by public health officials. Implementing AI-powered reminder systems could effectively address this issue, improving vaccination rates and public health outcomes.

Self-controlled risk interval study of rotavirus vaccine safety: Findings and implications.

The self-controlled case series (SCCS) is often used to monitor vaccine safety. The evaluation of intussusception after the rotavirus vaccine is complicated because the baseline rate varies with age. Time-varying baseline risk adjustments with data from unexposed cohorts are utilised. Self-controlled risk interval (SCRI), with a shorter observation period, can also mitigate the problem by studying a control period close to the risk period. An Indian rotavirus vaccine has previously been studied using SCCS. The risk of intussusception in the high-risk windows (21 days after vaccination) was comparable to the background risk. The aim was to re-analyse data of an existing SCCS study using alternate statistical methods to examine vaccine safety. We examined the mean age of intussusception in the vaccinated and the unvaccinated. We performed an SCRI analysis of the surveillance data from the SCCS study, limiting the observation period to 180 days. We analysed the time-to-intussusception from the last vaccination. Finally, we performed an SCCS analysis, excluding unvaccinated cases from the analysis. We found that the mean age of intussusception was significantly lower in the vaccinated (205 days) compared to the unvaccinated (223 days) (p-value 0.0026). The Incident Risk Ratio (IRR) on SCRI analysis was 1.62 (95% CI 1.07-2.44). There were significantly more intussusceptions in the first 30 days after vaccination compared to the next 30-day window. (92 vs 63 p-value = 0.009). We found that excluding unvaccinated infants from the SCCS analysis demonstrated significantly increased risk for the risk period 1-21 days after the 3rd dose (IRR 2.47, 95% CI 1.70-3.59). The risks of intussusception were missed in traditional SCCS analysis using unvaccinated infants as controls. Traditional risk adjustments using data from unexposed cohorts in SCCS may not be appropriate for investigating the risk of intussusception where vaccination lowers the mean age of intussusception.

18-month longitudinal SARS COV-2 neutralizing antibody dynamics in haemodialysis patients receiving heterologous 3-dose vaccination (AZD-1222- AZD-1222- BNT162b2) in a lower middle income setting

BackgroundPatients with chronic kidney disease on haemodialysis (HD) were given priority COVID-19 vaccination due to increased disease risk. The immune response to COVID-19 vaccination in patients on HD was diminished compared to healthy individuals in 2-dose studies. This study aimed to evaluate seroconversion rate, neutralizing antibody (nAB) levels and longitudinal antibody dynamics to 3-dose heterologous vaccination against COVID-19 in a cohort of HD patients compared to healthy controls and assess patient factors associated with antibody levels.MethodsThis study was a case–control longitudinal evaluation of nAB dynamics in 74 HD patients compared to 37 healthy controls in a low/middle income setting. Corresponding samples were obtained from the two cohorts at time-points (TP) 1–1-month post 2nd dose of AZD1222 vaccine, TP2- 4 months post 2nd dose, TP4- 2 weeks post 3rd dose with BNT162b2 vaccine, TP5-5 months post 3rd dose and TP6-12 months post 3rd dose. Additional data is available at TP0- pre 2nd dose and TP3- 6 months post 2nd dose in HC and HD cohorts respectively. Anti-SARS-CoV-2 nAB were detected using Genscript cPassTM pseudoviral neutralization kit. Demographic and clinical details were obtained using an interviewer administered questionnaire.ResultsCohorts were gender matched while mean age of the HD cohort was 54.1yrs (vs HCs mean age, 42.6yrs, p < 0.05). Percentage seroconverted and mean/median antibody level (MAB) in the HD cohort vs HCs at each sampling point were, TP1-83.7% vs 100% (p < 0.05), MAB-450 IU/ml vs 1940 IU/ml (p < 0.0001); TP2-71.4% vs 100%, (p < 0.001), MAB- 235 IU/ml vs 453 IU/ml, (p < 0.05); TP4-95.2% vs 100% (p > 0.05), MAB-1029 IU/ml vs 1538 IU/ml (p < 0.0001); TP5-100% vs 100%, MAB-1542 IU/ml vs 1741IU/ml (p > 0.05); TP6-100% vs 100%, MAB-1961 IU/ml vs 2911 IU/ml (p > 0.05). At TP2, patients aged < 60 years (p < 0.001) were associated with maintaining seropositivity compared to patients > 60 years.ConclusionTwo dose vaccination of haemodialysis patients provided poor nAB levels which improved markedly following 3rd dose vaccination, the effect of which was long- lasting with high nAB levels in both patients and controls detectable at 1 year follow-up.

Relative and Temporal Efficacy of the First and Second Covid 19 Booster Vaccine (3rd And 4th Dose) to Prevent Symptomatic Infection from December 2021 to October 2023 in a General Medicine Office in Toledo (Spain)

Background: The effectiveness of COVID-19 vaccines in preventing serious infection and death is established, but their protection against infection is less certain. Additionally, their effectiveness diminishes over time. Furthermore, the evolution of the effectiveness of different booster doses of the vaccine against COVID-19, to prevent symptomatic infection in real life during the pandemic and the subsequent endemic, is not clearly documented. Objective: To compare the effectiveness of the 3rd and 4th vaccine boosters against COVID-19 in preventing symptomatic COVID-19 infection during both the pandemic and the subsequent endemic phase. Methodology: A comparative secondary analysis of the vaccine’s effectiveness against symptomatic COVID-19 infection (calculated as: 1 – (COVID-19 cases with vaccine doses / COVID-19 cases without vaccine dose) × 100) based on a prospective study from December 2021 to October 2023 in a general medicine office was conducted. The first booster dose was administered with monovalent mRNA vaccines, and the second booster with bivalent mRNA vaccines. Results: From December 2021 to February 2022, the effectiveness of the primer vaccine booster was 60% when administered &gt;= 15 days versus &lt;15 days before infection, and 36% when administered &gt;= 29 days versus &lt; 29 days before infection. From October 2022 to February 2023, the effectiveness of the vaccine’s 4th dose was 84%. From October 2022 to October 2023, the effectiveness of the 4th dose of bivalent mRNA vaccine in preventing reinfections was 30%. Conclusion: In the general practice setting in Toledo, Spain, the effectiveness of the first booster with mRNA vaccines against SARS-CoV-2 primary infection and symptomatic COVID-19 waned over time, but protection remained high with the second bivalent booster. However, the booster vaccine’s effectiveness is more modest in preventing symptomatic reinfections. Overall, completing the booster vaccination is worthwhile.

Low HBV knowledge is associated with low HBV vaccination uptake in general adult population despite incentivization of HBV vaccination

BackgroundHepatitis B virus (HBV) vaccination in Vietnamese adults remains low and unequally distributed. We conducted a study on HBV-naïve adults living in Ho Chi Minh City, Viet Nam, to determine barriers associated with HBV vaccination uptake after removing the financial barrier by providing free coupons for HBV vaccination.MethodsAfter being screened for HBsAg, anti-HBs, and anti-HBc, 284 HBV-naïve study participants aged 18 and over (i.e., negative for HBsAg, anti-HBs, and anti-HBc total) were provided free 3-dose HBV vaccine coupons. Next, study participants’ receipt of 1st, 2nd, and 3rd doses of HBV vaccine was documented at a pre-specified study healthcare facility, where HBV vaccines were distributed at no cost to the participants. Upon study entry, participants answered questionnaires on sociodemographics, knowledge of HBV and HBV vaccination, and related social and behavioral factors. The proportions of three doses of HBV vaccine uptake and their confidence intervals were analyzed. Associations of HBV vaccine initiation with exposures at study entry were evaluated using modified Poisson regression.Results98.9% (281 of 284) of study participants had complete data and were included in the analysis. The proportion of participants obtaining the 1st, 2nd, and 3rd doses of HBV vaccine was 11.7% (95% Confidence Interval [95% CI] 8.0-15.5%), 10.7% (95%CI 7.1–14.3%), and 8.9% (95%CI 5.6–12.2%), respectively. On the other hand, participants were more likely to initiate the 1st dose if they had adequate knowledge of transmission (adjusted relative risk [aRR] = 2.58, 95% CI 1.12–5.92), adequate knowledge of severity (aRR = 6.75, 95%CI 3.38–13.48), and annual health-checking seeking behavior (aRR = 2.04, 95%CI 1.07–3.87).ConclusionWe documented a low HBV vaccination uptake despite incentivization. However, increased vaccine initiation was associated with better HBV knowledge and annual health check-up adherence. When considering expanding HBV vaccination to the general adult population, we should appreciate that HBV knowledge is an independent predictor of vaccine uptake.

Development of antibody levels and subsequent decline in individuals with vaccine induced and hybrid immunity to SARS-CoV-2

ObjectivesThis study aimed to compare antibody trajectories among individuals with SARS-CoV-2 hybrid and vaccine-induced immunity. MethodsDanish adults receiving three doses of BTN162b2 or mRNA-1237 were included prior to first vaccination (Day 0). SARS-CoV-2 anti-spike IgG levels were assessed before each vaccine dose, at Day 90, Day 180, 28 days after 3rd vaccination (Day 251), Day 365, and prior to 4th vaccination (Day 535). SARS-CoV-2 PCR results were extracted from the national microbiology database. Mixed-effect multivariable linear regression investigated the impact of hybrid-immunity (stratified into 4 groups: no hybrid immunity, PCR+ prior to 3rd dose, PCR+ after 3rd dose and before Day 365, PCR+ after Day 365) on anti-spike IgG trajectories. ResultsA total of 4,936 individuals were included, 47% developed hybrid-immunity. Anti-spike IgG increases were observed in all groups at Day 251, with the highest levels in those PCR+ prior to 3rd dose (Geometric Mean; 535,647AU/mL vs. 374,665AU/mL with no hybrid-immunity, P<0.0001). Further increases were observed in participants who developed hybrid immunity after their 3rd dose. Anti-spike IgG levels declined from Day 251-535 in individuals without hybrid-immunity and in those who developed hybrid-immunity prior to their 3rd dose, with lower rate of decline in those with hybrid-immunity. ConclusionHybrid-immunity results in higher and more durable antibody trajectories in vaccinated individuals.