Booster Effect Research Articles

Association of a third vaccination with antibody levels and side reactions in essential workers: A prospective cohort study.

To evaluate the relationship between the change of titer and adverse events after the third vaccination for COVID-19 among healthcare workers. This was a prospective cohort study, and the follow-up period was from December 2021 to November 2023. A total of 392 healthcare workers aged over 20years who worked at the facility and wished to have vaccine antibody titers measured participated in this study. A third dose of BNT162b2 COVID-19 vaccine was administered to healthcare workers working at the hospital, and we evaluated the changes in antibody titers before and after the vaccine, as well as adverse reactions after vaccination. The primary endpoints were adverse reactions within 7days after the third dose of COVID-19 vaccine and the rate of increase in COVID-19 vaccine antibody titer at 4weeks. A total of 392 people participated in the study, of whom 358 participants had their antibody titers measured before and after the booster vaccination. The overall IgG geometric mean was 609 U/mL (561-663) before booster vaccination and increased to 18,735 U/mL (17,509-20,049) at 4weeks after vaccination (p<0.001). Multivariate analysis showed no statistically significant relationship between the primary endpoints, such as a change in antibody titer due to the presence of fever after vaccination or a change in antibody titer due to swelling at the vaccination site. Factors affecting the rate of increase in antibody titer, evaluated as secondary endpoints, were suggested to be age (1.02 (95% confidence interval (CI): 1.01-1.03)) and hypertension (0.66 (95% CI: 0.47-0.93)). In relation to the booster effect of the third dose of COVID-19 vaccination, there was no statistically significant difference in the presence of fever or use of antipyretic or other drugs.

Effectiveness of mRNA Vaccine Booster against SARS-CoV-2 Infection and COVID-19 in the Adult Population during the First Three Months of the Omicron Wave in Sicily.

In Italy, the administration of the COVID-19 vaccine booster dose started on 27 September 2021, supported by clinical trials corroborating its efficacy. Given the paucity of real-world effectiveness data, this study aims to estimate the vaccine effectiveness of the booster dose against SARS-CoV-2 infection, severe disease, and death in the adult Sicilian population. This retrospective cohort study was carried out from 1 January to 31 March 2022 and included all residents in Sicily aged ≥ 18 years without previous SARS-CoV-2 infection and with a complete mRNA vaccine primary cycle. The cohort was split into two groups (booster and primary cycle) matched by age, gender, vaccine type, and month of completion of the primary vaccination cycle. 913,382 subjects were observed in the study: 456,690 (50%) were vaccinated with two doses and 456,692 (50%) with three doses. There were 43,299 cases of SARS-CoV-2 among the two-doses vaccinees (9.5%) and 10,262 (2.2%) among the three-doses counterpart. Vaccine effectiveness in the booster cohort was 76.5% and 74.4% against SARS-CoV-2 infection, 85.7% and 79.7% against severe disease, and 84.1% and 73.1% against intubation or death, for BNT162b2 and mRNA-1273, respectively. This study confirmed the remarkable efficacy profile of the SARS-CoV-2 vaccine booster dose against infection, severe disease, and death attributable to the virus. Overall, the results of this study provide important real-world data to support the continued roll-out of the COVID-19 booster dose and have the potential to inform public health policy and guide decisions on vaccination strategies in countries around the world.

COVID-19 vaccine and booster hesitation around the world: A literature review.

The development of COVID-19 vaccines has helped limit the extent of the pandemic, which over the past 2 years has claimed the lived of millions of people. The Moderna and Pfizer COVID-19 vaccines were the first to be manufactured using mRNA technology. Since then, other manufacturers have built their own vaccines which utilize adenovirus vector, whole inactivated coronavirus, and protein subunit methods. Given the continued mutation of the SARS-CoV-2 virus, a booster of the COVID-19 vaccine offers additional protection for citizens, especially those with comorbid conditions. However, uptake of the vaccine and booster has faced hurdles. This literature review aims to analyze the acceptance of the COVID-19 booster among different populations throughout the world. Keywords searched include "COVID-19 vaccine rates OR COVID-19 booster rates," "COVID-19 vaccine hesitancy," "COVID-19 booster hesitancy," "reasons against COVID-19 vaccine," "reasons for COVID-19 vaccine," and "COVID-19 vaccine acceptance" (for each country). Research articles indexed in PubMed, University of Illinois Urbana-Champaign Library, and Google Scholar were included. Despite the proven effectiveness of the COVID-19 booster, vaccine hesitancy is still causing suboptimal compliance to the primary vaccine and booster, thus slowing down control of the pandemic. Reasons for vaccine hesitancy differ by country and acceptance is affected by misinformation, political circumstances, and cultural values. Among the most common reasons found are distrust in the government, a lack of safety information, and fear of side effects. Uptake of the COVID-19 vaccine has also been delayed in low and middle income countries due to resource allocation and as a result, these countries have fallen behind vaccination benchmarks. The future of COVID-19 vaccination is unknown, but vaccine mandates and additional booster doses are a possibility. Determining the ethical impact that these policies could have will allow for the best implementation.

Effectiveness of mRNA boosters after homologous primary series with BNT162b2 or ChAdOx1 against symptomatic infection and severe COVID-19 in Brazil and Scotland: A test-negative design case-control study.

Brazil and Scotland have used mRNA boosters in their respective populations since September 2021, with Omicron's emergence accelerating their booster program. Despite this, both countries have reported substantial recent increases in Coronavirus Disease 2019 (COVID-19) cases. The duration of the protection conferred by the booster dose against symptomatic Omicron cases and severe outcomes is unclear. Using a test-negative design, we analyzed national databases to estimate the vaccine effectiveness (VE) of a primary series (with ChAdOx1 or BNT162b2) plus an mRNA vaccine booster (with BNT162b2 or mRNA-1273) against symptomatic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes (hospitalization or death) during the period of Omicron dominance in Brazil and Scotland compared to unvaccinated individuals. Additional analyses included stratification by age group (18 to 49, 50 to 64, ≥65). All individuals aged 18 years or older who reported acute respiratory illness symptoms and tested for SARS-CoV-2 infection between January 1, 2022, and April 23, 2022, in Brazil and Scotland were eligible for the study. At 14 to 29 days after the mRNA booster, the VE against symptomatic SARS-CoV-2 infection of ChAdOx1 plus BNT162b2 booster was 51.6%, (95% confidence interval (CI): [51.0, 52.2], p < 0.001) in Brazil and 67.1% (95% CI [65.5, 68.5], p < 0.001) in Scotland. At ≥4 months, protection against symptomatic infection waned to 4.2% (95% CI [0.7, 7.6], p = 0.02) in Brazil and 37.4% (95% CI [33.8, 40.9], p < 0.001) in Scotland. VE against severe outcomes in Brazil was 93.5% (95% CI [93.0, 94.0], p < 0.001) at 14 to 29 days post-booster, decreasing to 82.3% (95% CI [79.7, 84.7], p < 0.001) and 98.3% (95% CI [87.3, 99.8], p < 0.001) to 77.8% (95% CI [51.4, 89.9], p < 0.001) in Scotland for the same periods. Similar results were obtained with the primary series of BNT162b2 plus homologous booster. Potential limitations of this study were that we assumed that all cases included in the analysis were due to the Omicron variant based on the period of dominance and the limited follow-up time since the booster dose. We observed that mRNA boosters after a primary vaccination course with either mRNA or viral-vector vaccines provided modest, short-lived protection against symptomatic infection with Omicron but substantial and more sustained protection against severe COVID-19 outcomes for at least 3 months.

Willingness of college students to receive COVID-19 heterologous vaccination in Taizhou, China

ABSTRACT This study aimed to determine the willingness of college students to choose COVID-19 heterologous vaccination and its associated influencing factors in Taizhou, China. A population-based, self-administered online questionnaire was conducted from March 15 to 17, 2022. Of the 2,463 participants who had received the invitation, 1,821 responded to the survey (response rate = 73.9%). Only 14% (86/614) of those willing to receive a booster would chose a heterologous vaccination; the perception of better effectiveness of a COVID-19 heterologous vaccination booster was the significant factor (X2 = 22.671, p < .001). Additionally, female college students’older age (χ2 = 7.523, P = .023), major of medical (χ2 = 6.294, P = .012), and better perceived effectiveness of COVID-19 heterologous vaccination booster (χ2 = 22.659, P < .001), were more willing to receive heterologous booster doses. Chinese college students have a strong willingness to receive booster shots, but the percentage of those willing to receive a heterologous vaccine is only 14.0%, and the lack of understanding of its effectiveness is an important factor in the low proportion of heterologous vaccine selection. Health education, public health awareness, and the disclosure of heterologous vaccine information can help improve the public’s understanding of heterologous vaccines and provide them with more choices.

Antibody production capacity after COVID-19 vaccination in immune-mediated neuromuscular diseases under immunotherapy

The post-vaccination antibody response in patients with immune-mediated neuromuscular diseases under immuno-suppressive therapy has not been sufficiently verified. The Japanese Society of Neurology has stated that coronavirus disease 2019 (COVID-19) vaccination should be given priority in patients with immunotherapy-associated neuromuscular diseases; however, data on antibody production to a novel mRNA vaccine are scarce in these patients. In this study, we aimed to measure residual antibody titers after the second dose and produced antibodies after the third dose of SARS-CoV-2 mRNA vaccine in 25 patients with neuromuscular diseases under immuno-suppressive therapy (disease group). We compared the disease group antibody titers with those of 829 healthy employees in our hospital (control group). The disease group included 17 patients with myasthenia gravis, 4 with multiple sclerosis, 3 with inflammatory muscle disease, and 1 with chronic inflammatory demyelinating polyneuropathies. Seven cases of the disease group showed negative antibody levels (<15.0s/co) before the third vaccination, and antibody titers in the positive cases ranged from 16.9 to 4,589.0s/co. Three of the seven antibody-negative cases turned positive after the third vaccination, and all but one of the antibody-positive cases showed a booster effect, with antibody titers after the third dose ranging from 245.1 to 85,374.0s/co (1.0 to 885.0 times higher than those before vaccination). Although the immune response in the disease group was modest compared to the control group, in which antibody titers after the third vaccination ranged from 67.8 to 150,000s/co (0.9 to 5,402.1 times higher than those before vaccination), the result indicated that a constant immune response was achieved under immuno-suppressive therapy. Even in the control group, three participants tested negative for residual antibody before the third inoculation, and four of the antibody-positive participants (27.7-24,054.0s/co) lacked a booster effect after the third vaccination.

SARS-CoV-2 booster effect and waning immunity in hemodialysis patients: A cohort study.

SARS-CoV-2 booster effect and waning immunity in hemodialysis patients: A cohort study.

Effectiveness of Bivalent Boosters Over Nine and Half Months

Effectiveness of Bivalent Boosters Over Nine and Half Months

Effectiveness of Heterologous COVID-19 Vaccine Booster in Korean Elderly Population, 2022.

We conducted a cohort study to assess vaccine effectiveness (VE) of coronavirus disease 2019 vaccine combinations on severe acute respiratory syndrome coronavirus 2 critical infection and death among elderly population in Korea. From January to August 2022, VE against death for 4 doses mRNA recipients was 96.1%, whereas 1-dose viral vector + 3-dose mRNA recipients had VE of 90.8%.

Safety and immunogenicity of sequential administration of PCV13 followed by PPSV23 in pneumococcal vaccine-naïve adults aged ≥ 65 years: Comparison of booster effects based on intervals of 0.5 and 1.0 year

ObjectiveAn open-label study was conducted to compare the safety and immunogenicity of a sequential administration of 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) between an interval of 0.5 (0.5-y) and 1 year (1.0-y) in adults aged ≥ 65 years. MethodsPneumococcal vaccine-naïve adults aged ≥ 65 years (n = 129) received a sequential administration with an interval of 0.5-y or 1.0-y or received a single administration of PPSV23 (single PPSV23). We evaluated the immunogenicity before and 1 month after each vaccination and at 0.5-y intervals for 2 years. The primary endpoint was the increase in geometric mean fold rises (GMFRs) of immunoglobulin G (IgG) or opsonophagocytic activity (OPA) for eight common serotypes one month after one dose of PPSV23. The secondary endpoint was the safety profile for one dose of PPSV23. ResultsOne month after administration of PPSV23, the GMFRs of IgG considerably increased for five of eight serotypes in the 1.0-y interval group, whereas the GMFRs of IgG considerably increased for two serotypes in the 0.5-y interval group. Furthermore, GMFRs of OPA markedly increased for all eight serotypes in the 1.0-y interval group, while GMFRs of OPA markedly increased for four serotypes in the 0.5-y interval group. At 2 years after initial vaccination, GMFRs of IgG or OPA were higher for all serotypes, except for serotype 3, than those in the single PPSV23 group irrespective of intervals. No significant difference was found in the frequencies of local reactions of all grades between the two intervals. ConclusionsThe 1.0-y interval provided better booster effects induced by PPSV23 than those of the 0.5-y interval in a sequential administration in pneumococcal vaccine-naïve adults aged ≥ 65 years. No difference was found in the safety profile between both intervals.

Vaccine Free, Natural Broad ‘Immune Booster’ Effect Following 24 Months of Severe COVID-19 Infection could be Correlated to Massive Cytokine Storm and High C-Reactive Protein Level

As of Nov. 12, 2022, 6.61 million people or 0.084% of the world’s population have died from COVID that originated from China and then mutated into multiple variants and subvariants. The total number of documented cases around the world has been 635 million; almost 8% of the world’s population was confirmed positive cases for COVID with a mortality rate of almost 1%. Those, who were confirmed positive and survived, had a range of symptoms ranging from mild to severe. Those with underlying conditions like diabetes, hypertension and genetic or acquired immunodeficiencies had more severe symptoms and some required hospitalization and even care in an ICU. We are reporting a stringently recorded such severe case confirmed positive for COVID on Nov. 12, 2020 and optimally treated to clear COVID when tested on Dec. 12, 2020 and then was in rehab to receive care from speech therapist, occupational therapist and a physical therapist followed by a team of specialists to monitor any long COVID. The case has had no reinfection, never subsequently tested positive and never received any vaccine against COVID. The antibody level was monitored subsequently for 22 months and astonishingly the antibody levels against spike protein of COVID have been higher than the previous measurements. We conclude that there is phenomenal long lasting natural “booster effect” being reported for the first time, following any viral infection.

Real-world Evidence of COVID-19 Vaccines Effectiveness in Solid-organ Transplant Recipient Population in Colombia: A Study Nested in the Esperanza Cohort.

Solid-organ transplant recipients (SOTRs) have a higher risk of coronavirus disease 2019 (COVID-19) complications and death and a less powerful and lasting response to vaccines and to natural infection. In Colombia, this population was prioritized in the National Vaccination Plan against COVID-19 and received vaccines from different platforms. The aim of this study was to estimate the effectiveness of the complete vaccination schedule and of the vaccine booster for COVID-19 administered to SOTRs in Colombia. A nested-cohort was assembled within the population-based ESPERANZA cohort and included the subset of 16 y and older SOTRs (n = 6963); the follow-up period spanned March 11, 2021, to May 11, 2022. The vaccine effectiveness was estimated with Cox proportional-hazards models so that the overall effectiveness of the complete vaccination schedule, the vaccine booster, each used vaccine, and the homologous and heterologous schedules were estimated, adjusting by the main confounders. The overall effectiveness of being fully vaccinated was 73.7% (95% confidence interval [CI], 68.9%-77.0%) to prevent COVID-19 infection, 83.7% (95% CI, 78.7%-87.5%) to prevent hospitalization, and 92.1% (95% CI, 88.8%-94.4%) to prevent death due to COVID-19. Similarly, the effectiveness of the vaccine booster was 76.7% (95% CI, 70.6%-81.5%), 86.9% (95% CI, 79.4%-91.6%), and 94.5% (95% CI, 89.8%-97.1%) to prevent confirmed COVID-19 infection, hospitalization, and death due to COVID-19, respectively. In both cases, there were no statistically significant differences across age groups. Findings from this work show a high protection of vaccination against infection, hospitalization, and death due to COVID-19 in SOTRs, which increases with the vaccine booster.

Infections, Hospitalizations, and Deaths Among US Nursing Home Residents With vs Without a SARS-CoV-2 Vaccine Booster

A SARS-CoV-2 vaccine booster dose has been recommended for all nursing home residents. However, data on the effectiveness of an mRNA vaccine booster in preventing infection, hospitalization, and death in this vulnerable population are lacking. To evaluate the association between receipt of a SARS-CoV-2 mRNA vaccine booster and prevention of infection, hospitalization, or death among nursing home residents. This cohort study emulated sequentially nested target trials for vaccination using data from 2 large multistate US nursing home systems: Genesis HealthCare, a community nursing home operator (system 1) and Veterans Health Administration community living centers (VHA CLCs; system 2). The cohort included long-term (≥100 days) nursing home residents (10 949 residents from 202 community nursing homes and 4321 residents from 128 VHA CLCs) who completed a 2-dose series of an mRNA vaccine (either BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]) and were eligible for a booster dose between September 22 and November 30, 2021. Residents were followed up until March 8, 2022. Receipt of a third mRNA vaccine dose, defined as a booster dose (boosted group), or nonreceipt of a booster dose (unboosted group) on an eligible target trial date. If participants in the unboosted group received a booster dose on a later target trial date, they were included in the booster group for that target trial; thus, participants could be included in both the boosted and unboosted groups. Test-confirmed SARS-CoV-2 infection, hospitalization, or death was followed up to 12 weeks after booster vaccination. The primary measure of estimated vaccine effectiveness was the ratio of cumulative incidences in the boosted group vs the unboosted group at week 12, adjusted with inverse probability weights for treatment and censoring. System 1 included 202 community nursing homes; among 8332 boosted residents (5325 [63.9%] female; 6685 [80.2%] White) vs 10 886 unboosted residents (6865 [63.1%] female; 8651 [79.5%] White), the median age was 78 (IQR, 68-87) years vs 78 (IQR, 68-86) years. System 2 included 128 VHA CLCs; among 3289 boosted residents (3157 [96.0%] male; 1950 [59.3%] White) vs 4317 unboosted residents (4151 [96.2%] male; 2434 [56.4%] White), the median age was 74 (IQR, 70-80) vs 74 (IQR, 69-80) years. Booster vaccination was associated with reductions in SARS-CoV-2 infections of 37.7% (95% CI, 25.4%-44.2%) in system 1 and 57.7% (95% CI, 43.5%-67.8%) in system 2. For hospitalization, reductions of 74.4% (95% CI, 44.6%-86.2%) in system 1 and 64.1% (95% CI, 41.3%-76.0%) in system 2 were observed. Estimated vaccine effectiveness for death associated with SARS-CoV-2 was 87.9% (95% CI, 75.9%-93.9%) in system 1; however, although a reduction in death was observed in system 2 (46.6%; 95% CI, -34.6% to 94.8%), this reduction was not statistically significant. A total of 45 SARS-CoV-2-associated deaths occurred in system 1 and 18 deaths occurred in system 2. For the combined end point of SARS-CoV-2-associated hospitalization or death, boosted residents in system 1 had an 80.3% (95% CI, 65.7%-88.5%) reduction, and boosted residents in system 2 had a 63.8% (95% CI, 41.4%-76.1%) reduction. In this study, during a period in which both the Delta and Omicron variants were circulating, SARS-CoV-2 booster vaccination was associated with significant reductions in SARS-CoV-2 infections, hospitalizations, and the combined end point of hospitalization or death among residents of 2 US nursing home systems. These findings suggest that administration of vaccine boosters to nursing home residents may have an important role in preventing COVID-19-associated morbidity and mortality.

Association between primary or booster COVID-19 mRNA vaccination and Omicron lineage BA.1 SARS-CoV-2 infection in people with a prior SARS-CoV-2 infection: A test-negative case-control analysis.

The benefit of primary and booster vaccination in people who experienced a prior Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection remains unclear. The objective of this study was to estimate the effectiveness of primary (two-dose series) and booster (third dose) mRNA vaccination against Omicron (lineage BA.1) infection among people with a prior documented infection. We conducted a test-negative case-control study of reverse transcription PCRs (RT-PCRs) analyzed with the TaqPath (Thermo Fisher Scientific) assay and recorded in the Yale New Haven Health system from November 1, 2021, to April 30, 2022. Overall, 11,307 cases (positive TaqPath analyzed RT-PCRs with S-gene target failure [SGTF]) and 130,041 controls (negative TaqPath analyzed RT-PCRs) were included (median age: cases: 35 years, controls: 39 years). Among cases and controls, 5.9% and 8.1% had a documented prior infection (positive SARS-CoV-2 test record ≥90 days prior to the included test), respectively. We estimated the effectiveness of primary and booster vaccination relative to SGTF-defined Omicron (lineage BA.1) variant infection using a logistic regression adjusted for date of test, age, sex, race/ethnicity, insurance, comorbidities, social venerability index, municipality, and healthcare utilization. The effectiveness of primary vaccination 14 to 149 days after the second dose was 41.0% (95% confidence interval (CI): 14.1% to 59.4%, p 0.006) and 27.1% (95% CI: 18.7% to 34.6%, p < 0.001) for people with and without a documented prior infection, respectively. The effectiveness of booster vaccination (≥14 days after booster dose) was 47.1% (95% CI: 22.4% to 63.9%, p 0.001) and 54.1% (95% CI: 49.2% to 58.4%, p < 0.001) in people with and without a documented prior infection, respectively. To test whether booster vaccination reduced the risk of infection beyond that of the primary series, we compared the odds of infection among boosted (≥14 days after booster dose) and booster-eligible people (≥150 days after second dose). The odds ratio (OR) comparing boosted and booster-eligible people with a documented prior infection was 0.79 (95% CI: 0.54 to 1.16, p 0.222), whereas the OR comparing boosted and booster-eligible people without a documented prior infection was 0.54 (95% CI: 0.49 to 0.59, p < 0.001). This study's limitations include the risk of residual confounding, the use of data from a single system, and the reliance on TaqPath analyzed RT-PCR results. In this study, we observed that primary vaccination provided significant but limited protection against Omicron (lineage BA.1) infection among people with and without a documented prior infection. While booster vaccination was associated with additional protection against Omicron BA.1 infection in people without a documented prior infection, it was not found to be associated with additional protection among people with a documented prior infection. These findings support primary vaccination in people regardless of documented prior infection status but suggest that infection history may impact the relative benefit of booster doses.

Determinants of the willingness of medical staff to vaccinate their children with a booster dose of the COVID-19 vaccine in Taizhou, China

ABSTRACT The study aimed to determine the willingness of medical staff to have their children vaccinated with a COVID-19 booster in Taizhou, China. From March 21 to April 19, 2022, an online questionnaire survey was conducted to assess the willingness of medical staff to vaccinate their children with a booster dose of the COVID-19 vaccine. Of the 1,252 medical staff in a tertiary grade hospital in Taizhou who were invited to answer the structured questionnaire, 514 (41.1%) samples had valid information for further data analysis. Four hundred thirty-seven medical staff (85.0%) were willing to have their children receive vaccine boosters. After adjustments for confounding factors, the opinion (‘Do you think your child needs a booster vaccination against COVID-19?’) (yes vs. no, OR = 6.91, 95% CI: 3.29–14.54), the viewpoint (‘What are your thoughts the effectiveness of COVID-19 vaccine boosters for children?’ (≥12 vs. <12, OR = 13.81, 95% CI: 4.03-), and the attitude (‘Your attitude to whether your child is boosting the Covid-19 vaccine?’) (yes vs. no, OR = 4.66, 95% CI: 2.30–9.44) were significantly associated with their willingness to have their children receive a COVID-19 vaccine booster. A moderate percentage of the respondents expressed willingness to have their children receive booster vaccines. The findings implied that factors affecting medical staffs’ willingness to vaccinate their children with a COVID-19 vaccine booster included viewpoint, opinion, and attitudes.

SARS-CoV-2-Spike Antibody and T-Cell Responses Elicited by a Homologous Third mRNA COVID-19 Dose in Hemodialysis and Kidney Transplant Recipients.

The effect of a third vaccine dose (3D) of homologous mRNA vaccine on blood levels of SARS-CoV-2-receptor binding domain (RBD)-total antibodies was assessed in 40 hemodialysis patients (HD) and 21 kidney transplant recipients (KTR) at a median of 46 days after 3D. Anti-RBD antibodies were detected in 39/40 HD and 19/21 KTR. Overall, 3D boosted anti-RBD antibody levels (median: 58-fold increase). Neutralizing antibodies (NtAb) against the Wuhan-Hu-1, Delta, and Omicron variants were detected in 14, 13, and 11 out of 14 HD patients, and in 5, 5, and 4 out of 8 KTR patients, respectively. The median fold increase in NtAb titers in HD patients was 77, 28, and 5 and 56, 37, and 9 in KTR patients for each respective variant. SARS-CoV-2-S S-IFN-γ-producing CD8+ and CD4+ T-cell responses were detected in the majority of HD (35 and 36/37, respectively) and all KTR (16/16) patients at 3D. Overall, the administration of 3D boosted T-cell levels in both population groups. In conclusion, a homologous mRNA COVID-19 vaccine 3D exerts a booster effect on anti-RBD antibodies, NtAb binding to Wuhan-Hu-1, Delta, and Omicron variants, and SARS-CoV-2-S-IFN-γ-producing T cells in both HD and KTR patients. The magnitude of the effect was more marked in HD than KTR patients.

State of anti-rubella virus population immunity in the Republic of Belarus and Russian Federation

To confirm a progress towards the rubella elimination, immunization coverage indicators and the results of serological studies are used. At the same time, the most objective method of assessing collective immunity is a serological examination. The purpose of this work was to compare the results of assessing state of population immunity against rubella virus in the Republic of Belarus and the Russian Federation using various vaccines and different approaches to study organization and cohort selection screening and monitoring. 2019 laboratory studies to determine IgG antibodies against rubella virus were carried out by ELISA method of the unified enzyme immunoassay system Ecolab (Russia). The serum study results of 701 subjects aged 245 years from all the 7 regions of the Republic of Belarus (screening study) and 55 082 subjects aged 349 years (monitoring) from 85 regions of the Russian Federation were analyzed. The results were evaluated in three age groups children, adults, total cohort by using a threshold level of 8385% seropositive individuals sufficient to prevent virus transmission. The antigenic composition of the rubella component in the mono- and complex vaccines respectively used in the Russian Federation and the Republic of Belarus is identical, which allows to compare the state of population immunity against rubella virus therein without taking into account an influence of the vaccine strain. Studies have shown that while using varying vaccine preparations and approaches to organization of serological examination, both in the Republic of Belarus and the Russian Federation, rubella virus-specific IgG level was detected at rather high level in all age groups comprising more than 90%. The portion of rubella seropositive subjects in entire country was 95.44% in the Republic of Belarus and 97.14% in the Russian Federation. Moreover, the level of specific antibodies remains high, despite the low incidence rate and absence of booster effect in both countries. The mean group antibody concentration in seropositive patients in all age groups was quite high and exceeded the minimum protective concentration (11 IU/ml) by 10 or more times. The data obtained indicate the legitimacy of using a serological study of collective rubella immunity as a routine or seromonitoring as well as periodic or screening investigation.

The Booster Effect of a Single Quarterly Dose of Hyaluronic Acid in Knee Osteoarthritis: Five-Year Results of a Registry-Based Study.

Objective Viscosupplementation by hyaluronic acid (HA) is well established non-surgical treatment of knee osteoarthritis (KOA). This registry-basedstudy investigated the booster effect of a quarterly intra-articular single knee injection (30mg/2ml) for five years. Methods Sixty patients, including 29 males and 31 females, with a mean ± SD age 61.07 ± 9.15 with Kellgren-Lawrence grade I-III KOA, have been selected from a registry of interventional treatments for musculoskeletal pain conditions. To be eligible, patients had to be treated with a single quarterly intraarticular injection of HA with a follow-up of at least five yearsand assessed with Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Numeric Rating Scale (NRS) at baseline and after each HA injection in the first 24 months and at 36, 48, and 60 months. Results Sixty of 63 patients enrolled in this study completed the 60 months of follow-up.Patients had a marked improvement in knee function and pain, expressed by the significant reduction in WOMAC (T0 48.62±8.95 vs. T11 10.75±4.36; p<0.0001) and NRS scores (6.38±1.06 vs. T11 0.95±0.89 p<0.0001) from the baseline to the end of the follow-up period. Conclusion A quarterly injection of HA provides a rapid, safe, and stable long-term reduction of pain and improvement of function in elderly people with mild to moderate knee osteoarthritis along a five-yearperiod of treatment and follow-up. Further investigations are necessary to confirm these findings.

Booster Effect of a Third mRNA-Based COVID-19 Vaccine Dose in Patients with Myeloid Malignancies

Introduction We have reported that patients with myeloid malignancies were more responsive to the second dose of mRNA-based COVID-19 vaccines than patients with lymphoid malignancies (Mori, et al. Br J Haematol. 2022;197:691.). However, there are very limited data of response for a third vaccine dose in these patients. In this study, we investigated the antibody titers of COVID-19 in patients with myeloid malignancies who received a third mRNA-based COVID-19 vaccine dose (booster). Patients and Methods Previously treated, currently treated, and newly diagnosed myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) patients were included in this study. All patients were vaccinated with at least two doses of mRNA-based COVID-19 vaccine, either BNT162b2 or mRNA-1273, and visited the Blood Disorders Center at Aiiku Hospital during the period from August 17, 2021 to July 15, 2022. We recruited healthcare workers aged 50 years and older who had received at least two doses of BNT162b2 vaccine as healthy controls (HCs). Anti-SARS-CoV-2S immunoassays were performed at 3 months ± 2 weeks, 6 months ± 4 weeks, and 9 months ± 4 weeks after the second vaccine dose. All third doses were administered between the 6-month and the 9-month blood samplings. Individuals who did not received a third dose prior to the 9-month blood sampling were excluded from the booster effect analysis. Individuals with a known history of COVID-19 were excluded from both cohorts of patients and HCs. This study was part of a prospective observation study (UMIN000045267) and was conducted in compliance with ethical principles based on the Helsinki Declaration and the study was approved by the institutional review board of Aiiku Hospital. Results A total 58 patients with myeloid malignancies with a median age of 70.5 (range: 18-88) years including 20 patients with MDS and 38 patients with AML were enrolled. HCs includes 29 individuals with a median age of 55.0 (range: 50-72) years. Fourteen patients were receiving active treatment, one patient had terminated active treatment, 4 patients were treatment-naive, and one patient had not yet been diagnosed at the time of initial vaccination in MDS patients. Thirteen patients were receiving active treatment, 22 patients were under treatment-free observation in complete remission after treatment, and 3 patients had not yet been diagnosed at the time of initial vaccination in AML patients. Seroconversion rates after the second vaccination for HCs, MDS patients, and AML patients were 100%, 100%, and 94.7%. Patients with MDS showed a significantly lower antibody titer after second vaccination than that in HCs or AML patients, and there was no significant difference between the antibody titers after second vaccination in HCs and AML patients (Figure 1). Third vaccination rates were 89.7%, 95.0%, and 89.5% in HCs, MDS patients, and AML patients, and antibody titers increased prominently after booster vaccine, respectively (Figure 1). Furthermore, the antibody titer in MDS patients increased to comparable levels to that in HCs or AML patients after the third vaccine booster (Figure 1). In MDS patients, the median antibody titer before the booster vaccine was significantly lower in patients on active treatment than in patients under treatment-free or treatment-naive (88.0 U/ml vs 1076.5 U/ml, p<0.05) (Figure 2). However, the median antibody titer after the booster vaccine in MDS patients who were receiving active treatment at the time of the third vaccination increased to the comparable levels to that in MDS patients who were under treatment-free or treatment-naive (Figure 2). On the other hand, AML patients on active treatment at the time of third vaccination showed a significantly lower antibody titer after booster vaccination than that in AML patients under treatment-free observation (p<0.01) (Figure 2). In AML patients actively treated with hypomethylating agent (HMA) ± venetoclax at the time of the third dose, the median antibody titer after booster vaccine was significantly lower than in the other patients (HMA; p<0.05, HMA + venetoclax; p<0.05). Conclusion The third dose of mRNA-based COVID-19 vaccine showed the remarkable booster effect in patients with myeloid malignancies. Especially, the booster vaccine brought a significant improvement in response to MDS patients who had shown inferior response after two doses of vaccination, even to patients who were receiving active treatment. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Cross neutralization of SARS-CoV-2 omicron subvariants after repeated doses of COVID-19 mRNA vaccines.

We have measured the humoral response to messenger RNA (mRNA) vaccines in COVID-19 naïve and convalescent individuals. Third doses of mRNA COVID-19 vaccines induced a significant increase in potency and breadth of neutralization against SARS-CoV-2 variants of concern (VoC) including Omicron subvariants BA.1, BA.2, and BA.2.12.1, that were cross-neutralized at comparable levels and less for BA.4/5. This booster effect was especially important in naïve individuals that only after the third dose achieved a level that was comparable with that of vaccinated COVID-19 convalescents except for BA.4/5. Avidity of RBD-binding antibodies was also significantly increased in naïve individuals after the third dose, indicating an association between affinity maturation and cross neutralization of VoC. These results suggest that at least three antigenic stimuli by infection or vaccination with ancestral SARS-CoV-2 sequences are required to induce high avidity cross-neutralizing antibodies. Nevertheless, the circulation of new subvariants such as BA.4/5 with partial resistance to neutralization will have to be closely monitored and eventually consider for future vaccine developments.