Primary Dose Research Articles

Assessment of Anti-SARS-CoV-2 antibody levels among university students vaccinated with different COVID-19 primary and booster doses — fall 2021, Wisconsin

BackgroundUniversity students commonly received COVID-19 vaccinations before returning to U.S. campuses in the Fall of 2021. Given likely immunologic variation among students based on differences in type of primary series and/or booster dose vaccine received, we conducted serologic investigations in September and December 2021 on a large university campus in Wisconsin to assess anti-SARS-CoV-2 antibody levels.MethodsWe collected blood samples, demographic information, and COVID-19 illness and vaccination history from a convenience sample of students. Sera were analyzed for both anti-spike (anti-S) and anti-nucleocapsid (anti-N) antibody levels using World Health Organization standardized binding antibody units per milliliter (BAU/mL). Levels were compared across categorical primary COVID-19 vaccine series received and binary COVID-19 mRNA booster status. The association between anti-S levels and time since most recent vaccination dose was estimated by mixed-effects linear regression.ResultsIn total, 356 students participated, of whom 219 (61.5%) had received a primary vaccine series of Pfizer-BioNTech or Moderna mRNA vaccines and 85 (23.9%) had received vaccines from Sinovac or Sinopharm. Median anti-S levels were significantly higher for mRNA primary vaccine series recipients (2.90 and 2.86 log [BAU/mL], respectively), compared with those who received Sinopharm or Sinovac vaccines (1.63 and 1.95 log [BAU/mL], respectively). Sinopharm and Sinovac vaccine recipients were associated with a significantly faster anti-S decline over time, compared with mRNA vaccine recipients (P <.001). By December, 48/172 (27.9%) participants reported receiving an mRNA COVID-19 vaccine booster, which reduced the anti-S antibody discrepancies between primary series vaccine types.ConclusionsOur work supports the benefit of heterologous boosting against COVID-19. COVID-19 mRNA vaccine booster doses were associated with increases in anti-SARS-CoV-2 antibody levels; following an mRNA booster dose, students with both mRNA and non-mRNA primary series receipt were associated with comparable levels of anti-S IgG.

Assessment of mRNA Vaccine Immunogenicity in Solid Organ Transplant Recipients.

Background and Objectives: Solid organ transplant (SOT) recipients have a higher risk of suffering from severe Coronavirus (COVID-19) compared to the general population. Studies have shown impaired immunogenicity of mRNA vaccines in this high-risk population; thus, SOT recipients have been prioritized globally for primary and booster doses. Materials and Methods: We analyzed 144 SOT recipients who had previously received two doses of BNT162b2 or mRNA1273 vaccine, and who were subsequently vaccinated with a booster dose of the mRNA1273 vaccine. Humoral and cellular immune responses were measured 1 and 3 months after the second dose, and 1 month after the third dose. Results: One month after the second dose, 33.6% (45/134) of patients displayed a positive antibody response with a median (25th, 75th) antibody titer of 9 (7, 161) AU/mL. Three months after the second dose, 41.8% (56/134) tested positive with a median (25th, 75th) antibody titer of 18 (7, 251) AU/mL. After the booster dose, the seropositivity rate increased to 69.4% (93/134), with a median (25th, 75th) titer of 966 (10, 8027) AU/mL. The specific SARS-CoV-2 T-cell response was assessed in 44 randomly selected recipients 3 months after the second dose, and 11.4% (5/44) of them had a positive response. Following the third dose, 42% (21/50) tested positive. Side effects after the third dose were mild, with pain at the injection site being the most frequent adverse effect, reported by 73.4% of the recipients. Conclusion: Our study shows a mild delayed increase in antibody titer, three months after primary vaccination compared to one month after. It also shows a robust augmentation of humoral and specific T-cell responses after the booster dose, as well as the safety and tolerability of the mRNA vaccines in SOT recipients.

Risk of myocarditis and pericarditis following coronavirus disease 2019 messenger RNA Vaccination-A nationwide study.

An extended interval between the two primary doses may reduce the risk of myocarditis/pericarditis after COVID-19mRNA vaccination. Taiwan has implemented a two-dose regimen with a 12-week interval for adolescents. Here we present nationwide data of myocarditis/pericarditis following COVID-19 vaccinations. Data on adverse events of myocarditis/pericarditis were from the Taiwan Vaccine Adverse Events Reporting System between March 22, 2021, and February 9, 2022. The reporting rates according to sex, age, and vaccine type were calculated. We investigated the rates among young individuals under different two-dose intervals and among those who received two doses of different vaccines. Among 204 cases who met the case definition of myocarditis/pericarditis, 75 cases occurred after the first dose and 129 after the second. The rate of myocarditis/pericarditis after COVID-19 vaccination varied across sex and age groups and was highest after the second dose in males aged 12-17 years (126.79 cases per million vaccinees) for the BNT162b2 vaccine and in males aged 18-24 years (93.84 cases per million vaccinees) for the mRNA-1273 vaccine. The data did not suggest an association between longer between-dose interval and lower rate of myocarditis/pericarditis among males and females aged 18-24 or 25-29 years who received two doses of the BNT162b2 or mRNA-1273 vaccine. Rates of myocarditis/pericarditis in males and females aged 18-49 years after receiving ChAdOx1-S - mRNA-1273 vaccination was significantly higher than after ChAdOx1-S - ChAdOx1-S vaccination. Myocarditis and pericarditis are rare following mRNA vaccination, with higher risk occurring in young males after the second dose.

Небезпечні хлорити у питній воді: утворення та видалення при використанні діоксиду хлору в технології водопідготовки

The aim of the work was to study the features of the formation and removal of toxic chlorites at the treatment facilities of the Dnipro water pipeline in Kiev, where chlorine dioxide is used in water treatment technology, and the influence of priority natural and technological factors on these processes. Materials and methods. The studies were carried out in 2021-2022. at the Dnipro waterworks in Kyiv, where chlorine dioxide is used instead of chlorine in water treatment technology. We have analyzed the data of water studies for the content of dioxide and chlorites, carried out at the treatment facilities by the laboratory of the Dnipro water pipeline in order to establish the features of the formation and efficiency of chlorite removal when using the applied water treatment technology. Also, selective studies of chlorine dioxide and chlorites in the water supply were carried out by titrimetric and photometric methods, the results of which coincide with the data obtained on the water supply using the ion chromatography method. Main results. A positive hygienic assessment of the modern new technology for the preparation of drinking water from surface sources using chlorine dioxide instead of chlorine gas is given. It is shown that with high purifying and disinfecting effects of water treatment with chlorine dioxide, its by-products, in particular, toxic chlorites, are constantly formed in it, the levels of which are directly dependent on the doses of chlorine dioxide used, which vary according to the seasons of the year. In general, the primary dose of chlorine dioxide and chlorites in the water after CWR, entering the water supply networks, is reduced by 89.3-92.0% for chlorine dioxide, and by 76.2-85.6% for chlorites. At the same time, the concentration of chlorine dioxide in disinfected water is always within the normal range - at least 0.1 mg / dm3, and chlorites often exceed the national hygienic standard (0.2 mg / dm3), but does not go beyond the standard recommended by WHO (0.7 mg/dm3). The highest concentrations of chlorites are formed in water in summer (on average 0.35 mg/dm3) in accordance with the increased doses of chlorine dioxide during this period (on average 2.51 mg/dm3), and the lowest in winter (on average 0.17 mg/dm3). Conclusions. As a result of the study, it was found that the process of treating natural water with chlorine dioxide is accompanied by the formation of its by-products in water, mainly toxic chlorites, the levels of which depend on the doses of chlorine dioxide used and are the lowest in winter and the highest in summer. After coagulation treatment of the source water with aluminum sulfate and ferric chloride (ratio 10:4-5), settling and filtering the level of chlorites in water (LCW) is intensively reduced, but not always reach the standard values. In summer, the maximum levels of chlorites in water with LCW can be higher than the national hygienic standard (0.2 mg/dm3) and range up to 0.7 mg/dm3, which corresponds to the WHO recommended standard for this substance in drinking water. The issue of revising the national standard for chlorites in water from 0.2 mg/dm3 to 0.7 mg/dm3 after appropriate scientific justification is being raised.

Safety of the BNT162b2 COVID-19 Vaccine in Children Aged 5 to 17 Years

Active monitoring of health outcomes after COVID-19 vaccination offers early detection of rare outcomes that may not be identified in prelicensure trials. To conduct near-real-time monitoring of health outcomes following BNT162b2 COVID-19 vaccination in the US pediatric population aged 5 to 17 years. This population-based study was conducted under a public health surveillance mandate from the US Food and Drug Administration. Participants aged 5 to 17 years were included if they received BNT162b2 COVID-19 vaccination through mid 2022 and had continuous enrollment in a medical health insurance plan from the start of an outcome-specific clean window until the COVID-19 vaccination. Surveillance of 20 prespecified health outcomes was conducted in near real time within a cohort of vaccinated individuals from the earliest Emergency Use Authorization date for the BNT162b2 vaccination (December 11, 2020) and was expanded as more pediatric age groups received authorization through May and June 2022. All 20 health outcomes were monitored descriptively, 13 of which additionally underwent sequential testing. For these 13 health outcomes, the increased risk of each outcome after vaccination was compared with a historical baseline with adjustments for repeated looks at the data as well as a claims processing delay. A sequential testing approach was used, which declared a safety signal when the log likelihood ratio comparing the observed rate ratio against the null hypothesis exceeded a critical value. Exposure was defined as receipt of a BNT162b2 COVID-19 vaccine dose. The primary analysis assessed primary series doses together (dose 1 + dose 2), and dose-specific secondary analyses were conducted. Follow-up time was censored for death, disenrollment, end of the outcome-specific risk window, end of the study period, or a receipt of a subsequent vaccine dose. Twenty prespecified health outcomes: 13 were assessed using sequential testing and 7 were monitored descriptively because of a lack of historical comparator data. This study included 3 017 352 enrollees aged 5 to 17 years. Of the enrollees across all 3 databases, 1 510 817 (50.1%) were males, 1 506 499 (49.9%) were females, and 2 867 436 (95.0%) lived in an urban area. In the primary sequential analyses, a safety signal was observed only for myocarditis or pericarditis after primary series vaccination with BNT162b2 in the age group 12 to 17 years across all 3 databases. No safety signals were observed for the 12 other outcomes assessed using sequential testing. Among 20 health outcomes that were monitored in near real time, a safety signal was identified for only myocarditis or pericarditis. Consistent with other published reports, these results provide additional evidence that COVID-19 vaccines are safe in children.

Chapter 14: TBE-Prevention: Vaccines and Immunoglobulins

Worldwide there are 6 different TBE vaccines – two from Western Europe, three from Russia and one from China. The two western European vaccines and one of the Russian vaccines have an adult and a pediatric formulation. The products names are FSME IMMUN and FSME-IMMUN Junior; Encepur adults and Encepur children, Klesch-E-Vac, EnceVir and EnceVir Neo, Dry lyophilized TBE Moscow and Sen Tai Bao All TBE vaccines except the one from China have similar but not identical immunization schedules with primary immunization (&gt;3 doses) and regular booster vaccinations. For FSME-IMMUN, Encepur and EnceVir rapid immunization schedules are also licensed. The Chinese vaccine is given with 2 primary doses 2 weeks apart followed by annual boosters. All vaccines induce significant immune responses. In the absence of a formal correlate of protection, the presence of neutralizing antibodies is used as a surrogate marker for protection. Recent clinical studies show long-term seropersistence of TBE antibodies after the first booster vaccination (dose 4) with the two European vaccines. An effectiveness of approximately 99% (years 2000–2006) and 98.7% (years 2000-2011) was calculated for regularly vaccinated persons in Austria, a country with established high vaccination uptake. Whereas in Western Europe post-exposure prophylaxis with immunoglobulins was discontinued in the late 1990s, in the highly endemic regions of Russia it continues to be common practice. Both – FSME-IMMUN and Encepur are well tolerated with a well-established safety profile. TBE-Moscow and EnceVir appear to be somewhat more reactogenic.

Serological Response to SARS-CoV-2 after COVID-19 Vaccination in Lung Cancer Patients: Short Review.

In comparison to the general population, lung cancer patients are more likely to suffer from severe Coronavirus disease (COVID-19) and associated mortality. Considering this increased risk, and in order to prevent symptoms and severe disease, patients with lung cancer have been prioritized for COVID-19 vaccination primary and booster doses. Despite this, the pivotal clinical trials did not include these patients, which leaves open questions regarding vaccine efficacy and humoral immune response. This review outlines the findings of recent investigations into the humoral responses of lung cancer patients to COVID-19 vaccination, particularly the primary doses and first boost.

Antidepressants for pain management in adults with chronic pain: a network meta-analysis.

Antidepressants for pain management in adults with chronic pain: a network meta-analysis.

Pneumococcal carriage following PCV13 delivered as one primary and one booster dose (1+1) compared to two primary doses and a booster (2+1) in UK infants.

In January 2020 the UK changed from a 2+1 schedule for 13-valent pneumococcal conjugate vaccine (PCV13) to a 1+1 schedule (doses at 3 and 12months) based on a randomized immunogenicity trial comparing the two schedules. Carriage prevalence measured at the time of booster and 6months later in 191 of the 213 study infants was 57% (109/191) and 60% (114/190) respectively. There were eight episodes of vaccine-type (VT) or vaccine-related 6C carriage in the 2+1 and six in the 1+1 group; ≥4-fold rises in serotype-specific IgG in 71 children with paired post-booster and follow up blood samples at 21-33months of age were found in 20% (7/35) of the 2+1 and 15% (6/41) of the 1+1 group. VTs identified in carriage and inferred from serology were similar comprising 3, 19A and 19F. Dropping a priming dose from the 2+1 PCV 13 schedule did not increase VT carriage in the study cohort. Ongoing population level carriage studies will be important to confirm this.

Immunogenicity and safety of homologous and heterologous booster vaccination of ChAdOx1 nCoV-19 (COVISHIELD™) and BBV152 (COVAXIN®): a non-inferiority phase 4, participant and observer-blinded, randomised study.

Primary SARS-CoV-2 vaccination has been shown to wane with time and provide lower protection from disease with new viral variants, prompting the WHO to recommend the administration of booster doses. We determined the safety and immunogenicity of homologous or heterologous boosters with ChAdOx1 nCoV-19 (COVISHIELD™) or BBV152 (COVAXIN®), the two vaccines used widely for primary immunization in India, in participants who had already received two primary doses of these vaccines. Participants primed with two doses each of COVISHIELD™ or COVAXIN® 12-36 weeks previously, were randomised to receive either COVISHIELD™ or COVAXIN® booster in a 1:1 ratio. The primary outcome was day 28 post-booster anti-spike IgG seropositivity and secondary outcomes were anti-spike IgG levels and assessment of safety and reactogenicity. The results of 90 days intention-to-treat analysis are presented. This trial is registered with ISRCTN (CTRI/2021/08/035648). In the COVISHIELD™ primed group with 200 participants, the seropositivity 28 days post booster in the heterologous COVAXIN® arm was 99% and non-inferior to the homologous COVISHIELD™ arm, which was also 99% (difference 0%; 95% CI:-2.8% to 2.7%). The geometric mean concentration (GMC) of anti-spike antibodies following heterologous COVAXIN® boost on day 28 was 36,190.78 AU/mL (95% CI: 30,526.64-42,905.88) while the GMC following homologous COVISHIELD™ boost was 97,445.09 AU/mL (82,626.97-114,920.7). In the COVAXIN® primed group with 204 participants, the seropositivity 28 days post booster in the heterologous COVISHIELD™ arm was 100% and non inferior to the homologous COVAXIN® arm which was 96% (difference 4%, 95% CI: 0.2%-7.8%). The GMC following heterologous COVISHIELD™ boost was 241,681.6 AU/mL (95% CI: 201,380.2-290,048.3) compared to homologous COVAXIN® boost, which was 48,473.94 AU/mL (95% CI: 38,529.56-60,984.95). The day 28 geometric mean ratio (GMR) of the anti-spike IgG between the heterologous and homologous boosted arms was 0.42 (95% CI: 0.34-0.52) in the COVISHIELD™ primed group and 5.11 (95% CI: 3.83-6.81) in the COVAXIN® primed group. There were no related serious adverse events reported in any group. Homologous and heterologous boosting with COVISHIELD™ or COVAXIN® in COVISHIELD™ or COVAXIN® primed individuals are immunogenic and safe. A heterologous boost with COVISHIELD™ after COVAXIN® prime offers the best immune response among the four combinations evaluated. Azim Premji Foundation and Bill and Melinda Gates Foundation.

Persistence of immune responses after heterologous and homologous third COVID-19 vaccine dose schedules in the UK: eight-month analyses of the COV-BOOST trial

COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose in June 2021. Monovalent messenger RNA (mRNA) COVID-19 vaccines were subsequently widely used for the third and fourth-dose vaccination campaigns in high-income countries. Real-world vaccine effectiveness against symptomatic infections following third doses declined during the Omicron wave. This report compares the immunogenicity and kinetics of responses to third doses of vaccines from day (D) 28 to D242 following third doses in seven study arms. The trial initially included ten experimental vaccine arms (seven full-dose, three half-dose) delivered at three groups of six sites. Participants in each site group were randomised to three or four experimental vaccines, or MenACWY control. The trial was stratified such that half of participants had previously received two primary doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd) and half had received two doses of BNT162b2 (Pfizer-BioNtech, hereafter referred to as BNT). The D242 follow-up was done in seven arms (five full-dose, two half-dose). The BNT vaccine was used as the reference as it was the most commonly deployed third-dose vaccine in clinical practice in high-income countries. The primary analysis was conducted using all randomised and baseline seronegative participants who were SARS-CoV-2 naïve during the study and who had not received a further COVID-19 vaccine for any reason since third dose randomisation. Among the 817 participants included in this report, the median age was 72 years (IQR: 55-78) with 50.7% being female. The decay rates of anti-spike IgG between vaccines are different among both populations who received initial doses of ChAd/ChAd and BNT/BNT. In the population that previously received ChAd/ChAd, mRNA vaccines had the highest titre at D242 following their vaccine dose although Ad26. COV2. S (Janssen; hereafter referred to as Ad26) showed slower decay. For people who received BNT/BNT as their initial doses, a slower decay was also seen in the Ad26 and ChAd arms. The anti-spike IgG became significantly higher in the Ad26 arm compared to the BNT arm as early as 3 months following vaccination. Similar decay rates were seen between BNT and half-BNT; the geometric mean ratios ranged from 0.76 to 0.94 at different time points. The difference in decay rates between vaccines was similar for wild-type live virus-neutralising antibodies and that seen for anti-spike IgG. For cellular responses, the persistence was similar between study arms. Heterologous third doses with viral vector vaccines following two doses of mRNA achieve more durable humoral responses compared with three doses of mRNA vaccines. Lower doses of mRNA vaccines could be considered for future booster campaigns.

Focal versus craniospinal radiation for disseminated atypical teratoid/rhabdoid tumor following favorable response to systemic therapy.

Radiotherapy (RT) is associated with improved survival in atypical teratoid/rhabdoid tumor (ATRT); however, optimal RT delivery is unknown. A meta-analysis was conducted for disseminated (M+) ATRT receiving focal or craniospinal radiation (CSI). After abstract screening, 25 studies (1995-2020) contained necessary patient, disease, and radiation treatment information (N=96). All abstract, full text, and data capture were independently double-reviewed. The corresponding author was contacted for cases of insufficient information. Response to pre-radiation chemotherapy (N=57) was categorized as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). Univariate and multivariate statistics were performed to investigate survival correlation. Patients with M4 disease were excluded. The 2- and 4-year overall survival (OS) was 63.8% and 45.7%, respectively, with a median follow-up of 2years (range 0.3-13.5). The median age was 2years (range 0.2-19.5), and 96% received chemotherapy. On univariate analysis, gross total resection (GTR, p=.0007), pre-radiation chemotherapy response (p<.001), and high-dose chemotherapy with stem cell recuse (HDSCT, p=.002) correlated with survival. On multivariate analysis, pre-radiation chemotherapy response (p=.02) and GTR (p=.012) retained survival significance as compared to a trend for HDSCT (p=.072). Comparisons of focal RT (vs. CSI) and greater than or equal to 5400cGy primary dose were nonsignificant. Following CR or PR, a statistical trend favored focal radiation (p=.089) over CSI. Chemotherapy response prior to RT and GTR correlated with improved survival on multivariate analysis for ATRT M+ receiving RT. No benefit was observed for CSI compared to focal RT among all patients and following favorable chemotherapy response, inviting further study of focal RT for ATRT M+.

Effect of immunization during pregnancy and pre-existing immunity on diphtheria-tetanus-acellular pertussis vaccine responses in infants

ABSTRACT Immunization during pregnancy (IP) against pertussis is recommended in many countries to protect infants. Although maternal antibodies can influence the infants’ antibody responses to primary vaccinations, their effect on the development of functional antibodies and B cells remain poorly studied. We investigated the maternal immune response to IP and the effect of IP and pre-existing antibodies on infants’ primary vaccine responses in an open-label, non-randomized trial. Forty-seven mothers received tetanus-diphtheria-acellular pertussis (Tdap) vaccine during pregnancy, and 22 mothers were included as controls. Sixty-nine infants received primary doses of DTaP at three and five months of age. Geometric mean concentrations of antibodies to pertussis toxin, filamentous haemagglutinin, pertactin, diphtheria, and tetanus toxins, pertussis toxin neutralizing antibodies (PTNAs), and plasma and memory B-cell frequencies were studied at delivery, and at three, five and six months. Levels of antibodies, PTNAs, and frequencies of memory B-cells were significantly increased at delivery and up to six months after in mothers with IP compared to those without IP (all p < 0.05, except for PT-specific memory B-cells). In vaccinated pregnant women, high pre-existing antibody levels were positively correlated with higher antibody responses after IP. IP blunted the infants’ antibody and plasma B-cell responses to all vaccine antigens, except for tetanus toxin. This blunting effect was the strongest in infants with high concentrations of maternal antibodies. In conclusion, IP resulted in significantly higher concentrations of antibodies in infants up to three months of age (all p < 0.05); but was associated with blunting of various infants’ vaccine responses.

Omicron BA.1 breakthrough infections in inactivated COVID-19 vaccine recipients induced distinct pattern of antibody and T cell responses to different Omicron sublineages

ABSTRACT The adaptive immunity against SARS-CoV-2 prototype strain and Omicron sublineages induced by BA.1 breakthrough infection in vaccinees of inactivated COVID-19 vaccines have not been well characterized. Here, we report that BA.1 breakthrough infection induced mucosal sIgA and resulted in higher IgG titers against prototype strain and Omicron sublineages in vaccinees than in vaccine naïve-infected individuals. BA.1 breakthrough infection boosted antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis to prototype strain and BA.1, BA.1.1, BA.2, BA.2.12.1, and BA.2.75 but not BA.4/5 and induced neutralization against prototype strain and BA.1, BA.1.1, BA.2, BA.2.12.1, BA.2.75, and BA.4/5 but not BF.7, BQ.1, and XBB. In total, BA.1 breakthrough infection individuals produced less extensive sIgA, plasma IgG and NAb responses against Omicron sublineages compared with those against prototype strain. Further, BA.1 breakthrough infection induced recall B cell response to prototype strain and Omicron variant, primarily targeting memory B cells producing conserved epitopes. Memory T cell responses against Omicron is largely preserved. Individuals with vaccine booster did not induce more beneficial immune responses to Omicron sublineages upon BA.1 breakthrough infection than those with primary vaccine dose only. The breakthrough infection individuals produced stronger adaptive immunity than those of inactivated vaccine-healthy individuals. These data have important implications for understanding the vaccine effectiveness and adaptive immunity to breakthrough infection in individuals fully immunized with inactivated vaccines. Omicron sublineages, especially for those emerged after BA.4/5 strain, evade NAb responses induced by BA.1 breakthrough infection. It is urgent to optimize the vaccine immunogen design and formulations to SARS-CoV-2 variants.

Impact of Risk Factors and Long Term Survival Analysis of Patients With Primary Refractory Hodgkin Lymphoma Who Underwent High Dose Chemotherapy and Autologous Stem Cell Transplant

Patients with primary refractory Hodgkin lymphoma (ref-HL) can still be salvaged with high dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT). Outcome of patients with ref-HL is poorer than those with relapsed HL, but most studies have included patients with both relapsed and refractory diseases, and separate analyses or studies on patients with ref-HL are limited. This study aimed to evaluate the outcomes of HDC auto-SCT and impact of various prognostic factors on patients with ref-HL both at the time of primary treatment failure and also on subsequent survival at the time of failure post HDC auto-SCT. This was a retrospective, single-institution, cohort analysis using HDC and auto-SCT database, approved by the Institutional Research Advisory Counsel and Ethics Committee for identifying patients. We used Fine and Gray competing risk analysis method, regression model for outcome analysis and Kaplan-Meier method (KM) for survival. Two hundred consecutive ref-HL patients underwent HDC auto-SCT between 1996 to 2019. Median age was 22.75 years, median follow-up 106 months. Post auto-SCT, disease status was complete remission (CR), partial remission, and progressive disease in 122 (61%), 22 (11%), and 47 (23.5%) patients, respectively. KM median progression-free survival (PFS) after auto-SCT was 43.9 months (5:10 years, 49.3%:45.5%). Median overall survival (OS) was 168.6 months (5:10 years, 61.2%:56.2%). Eighty-five patients (44.5%) died - 69 (34.5%) due to disease. For both PFS and OS, multivariate analysis identified similar adverse factors. For PFS, stage III-IV at relapse (HR=1.65, P=0.045), mediastinal involvement (HR=2.01, P=0.009), and no CR after salvage chemotherapy (HR=2.2, P=0.001) as adverse factors. PFS with 0-1 (not reached), 2 (40.8), 3 adverse factors (5.4 months) were significant (p<0.001). For OS, stage III-IV at relapse (HR=1.68, P=0.045), mediastinal involvement (HR=2.52, P=0.007), and no CR after salvage chemotherapy (HR=2.15, P=0.004) were significant. OS with 0-1 (not reached), 2 (148.5) 3 adverse factors (34.4 months) were significant (p<0.001). Median OS after auto-SCT failure was 23.6 months; patients received post auto-SCT brentuximab/second SCT (not reached), other treatments (22.5 months), and supportive care (8.4) (p<0.001). OS with five risk factors, present at HDC auto-SCT failure, (stage III-IV, failure <12 months, tumor >5 cm, B-symptoms, low albumin) showed that 0-1:2:3-5 risk factors had 152:30.9:9.45 months OS (p<0.001). Ref-HL patients have encouraging survival after HDC auto-SCT and can even be salvaged after auto-SCT failure. Based on prognostic factors, survival prediction is possible. Patients who fail to respond to HDC auto-SCT may benefit from newer treatments strategies and may qualify for enrollment in clinical trials.

Abstract 2821: Mitigation of radiation-induced colon injuries in mice by oral sepiapterin (PTC923)

Abstract The rectum is the primary dose limiting structure for radiation therapy (RT) in treating prostate cancer. Two clinical forms of rectal injury have been described: early and late. Early injury typically develops during RT and occurs to some degree in most patients. The condition is usually self-limiting, but can predispose patients to the development of late injury. Late rectal injury occurs in up to 25% of patients months to years after pelvic RT and is more concerning, since it can be irreversible and can have a major impact on a patient’s lifestyle. Development of new pharmacologic approaches to eliminate the risk of RT-dependent rectal injury remains an important goal. Although detailed mechanisms underlying normal tissue toxicities vary from tissue to tissue, the central underlying mechanism is abnormal wound healing involving endothelial dysfunction (ED) and subsequently fibrosis. Regardless of its cause, ED is characterized by an “uncoupled” endothelial NOS (eNOS) activity that generates superoxide (O2 -) and peroxynitrite (ONOO-) rather than NO. One mechanism for uncoupling in inflammatory conditions is oxidation of the reduced cofactor tetrahydrobiopterin (BH4). The product of uncoupling, ONOO-, oxidizes BH4, initiating a feed forward mechanism to sustain uncoupling. Oral treatment with sepiapterin (PTC923), a tetrahydrobiopterin precursor, decreased infiltrating inflammatory cells and cytokine levels in mice with colitis. We therefore tested whether a synthetic PTC923 might mitigate radiation-induced colon injuries. C57L/J wild-type 6-8-week-old males mice received 13.5 Gy total-body irradiation (TBI). Starting from 24 h post-irradiation, mice were treated once daily with 1 mg/kg PTC923 for six days by oral gavage. Colon injuries were accessed on 6th day after IR by colonoscopy and scored by using distal-proximal endoscopic colitis scoring system (D-PECS). The system has a core inflammatory component of four non-co-linear parameters and decimal units to notable lesions or complications. Relative expression of cytokines IL-1β, IL-6, IL-17α, and TGF-β1 in colon endothelial cells were measured by RT-PCR 8 days after IR. According with D-PECS estimation, post-irradiation colon injury was significantly reduced by PTC923 treatment: on the 6th day after TBI mice demonstrated D-PECS score 5.8±1.48 vs 1.6±0.55 D-PECS score for animals received PTC923 treatment after TBI (p-value=0.00). Increase of cytokines IL-6 and TGF-β1 in the colon endothelium after TBI was effectively blocked by PTC923 treatment (IL-6: IR+Vehicle = 4.31±1.31 fold increase vs IR+PTC923 = 1.29±0.37 fold increase (p-value=0.0016); TGF-β1: IR+Vehicle = 5.18±0.66 fold increase vs IR+PTC923 = 2.01±0.75 fold increase (p-value=0.00029)). In conclusion, these findings support the proposal that oral treatment with sepiapterin is a potential mitigator of colon injury caused by RT. Citation Format: Vasily A. Yakovlev, Christopher S. Rabender, Ross B. Mikkelsen. Mitigation of radiation-induced colon injuries in mice by oral sepiapterin (PTC923) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2821.

Editor's Choice – Estimated Radiation Dose to the Operator During Endovascular Aneurysm Repair

To estimate operator organ doses from fluoroscopically guided infrarenal endovascular aneurysm repair (EVAR) procedures, using the detailed exposure information contained in radiation dose structured reports. Conversion factors relating kerma area product (PKA) to primary operator organ doses were calculated using Monte Carlo methods for 91 beam angles and seven x-ray spectra typical of clinical practice. A computer program was written, which selects the appropriate conversion factor for each exposure listed in a structured report and multiplies it by the respective PKA. This system was used to estimate operator doses for 81 EVAR procedures for which structured reports were available. The impact of different shielding scenarios and variations in operator position was also investigated. Without any shielding, the median estimated effective dose was 113 μSv (interquartile range [IQR] 71, 252 μSv). The highest median organ doses were for the colon (154 μSv, IQR 81, 343) and stomach (133 μSv, IQR 76, 307). These dose estimates represent all exposures, including fluoroscopy and non-fluoroscopic digital acquisitions. With minimal shielding provided by 0.25 mm of Pb covering the torso and upper legs, the effective dose was reduced by a factor of around 6. With additional shielding from ceiling and table shields, a 25 to 50 fold reduction in dose is achievable. Estimated doses were highest where the primary beam was pointed directly away from the operator. The models suggest that with optimal use of shielding, operator doses can be reduced to levels equivalent to one to two days of natural background exposure and well below statutory dose limits.

Health literacy and post-vaccination COVID-19 prevention behavior in the community: a crosssectional study in Indonesia

Background: The government has made vaccination the primary strategy to control the COVID-19 pandemic. However, the public still needs to implement COVID-19 prevention behavior even though they have been vaccinated because COVID-19 infection with or without symptoms can still occur. Health literacy is the basis for behavior change. Purpose: This study aimed to determine the relationship between health literacy and post-vaccination COVID-19 prevention behavior of the community in the work area of ​​the Patrang Public Health Center, Jember Regency. Methods: A descriptive correlation study with a cross-sectional approach was performed in May 2022. The sample in this study was 435 selected by purposive sampling with the inclusion criteria of those aged &gt;17 years old and receiving a full primary dose of vaccination. The data were collected using the Health Literacy Survey Coronavirus Disease Questionnaire 22 (HLS-COVID-Q22) and COVID-19 prevention behavior questionnaire. The data were analyzed by Spearman with a significance level of 0.05. Results: The results showed that the majority of health literacy was inadequate health literacy (43,2%), and the post-vaccination COVID-19 prevention behavior was in the moderate category (42.7%). There was a significant moderate positive correlation between health literacy and post-vaccination COVID-19 prevention behavior (p &lt; 0.001; r = 0.513). Conclusion: The higher the health literacy, the better the post-vaccination COVID-19 prevention behavior. The nurse was importance to provide health education by paying attention to the health literacy ability. Focusing on improving health literacy is an important strategy to enhance COVID-19 prevention behavior and reduce transmission of the coronavirus.

Factors associated with the Severity of COVID-19 patients in Bac Ninh and Nghe An Provinces: A Hospital-based Case-control Study in 2022

Background: It is crucial to study characteristics and determine associated factors with the severity of COVID-19 while the pandemic has been complicated yet. We aimed to describe the characteristics and determine associated factors with the severe state of disease among COVID-19 hospitalized patients within six first months in 2022. Methods: A case – control study was conducted among 3.242 COVID-19 patients in two provincial hospitals in Bac Ninh and Nghe An from January to June 2022. Cases were defined as severe or critical COVID-19 patients and controls were COVID-19 patients who were classified into the mild group during 24-first-hour admission. We used an online research health record to collect patient’s information. Multivariable logistic regression was utilized to explore and decide associated factors with the severity of COVID-19 among participants. Results: The percentage of patients who were classified into the severe disease group at admission time was 20.0%. Respiratory symptoms (70.3%) and fatigue (30.6%) were the most common ones recorded when patients were admitted to the ward. Older age, male, pre-comorbidities such as diabetes, chronic cardiovascular or pulmonary disease increased the likelihood to have severe COVID-19 disease. D-dimer ≥ 500 ng/ml, aspartate aminotransferase enzyme (AST) &gt; 37 U/L, the percentage of lymphocytes in blood &lt; 20%, and C-reactive protein (CRP) ≥ 5 mg/l were identified as prognostic factors for severity within 24-first-hour admission. Two primary doses of the COVID-19 vaccine and boosted doses significantly decreased the chance to have severe COVID-19. Conclusions: Our findings highlighted that it is important to monitor patients and early diagnoses with the help of prognostic factors. Moreover, widely supplying two primary and boosted doses of the COVID-19 vaccine for people, especially for the high-risk population is necessary.

A population-based assessment of myocarditis after messenger RNA COVID-19 booster vaccination among adult recipients

ObjectivesWe aimed to estimate the rate of myocarditis after the messenger RNA (mRNA) COVID-19 booster vaccination by vaccine type, age, and sex. MethodsWe used data from the British Columbia COVID-19 Cohort, a population-based cohort surveillance platform. The exposure was a booster dose of an mRNA vaccine. The outcome was diagnosis of myocarditis during hospitalization or an emergency department visit within 7-21 days of booster vaccination. ResultsThe overall rate of myocarditis was lower for the booster dose (6.41, 95% confidence interval [CI]: 3.50-10.75) than the second dose (17.97, 95% CI: 13.78-23.04); (Rate ratiobooster vs dose-2 = 0.34, 95% CI: 0.17-0.61). This difference was more apparent for the mRNA-1273 vaccine type. After the second dose, the myocarditis rate in males was significantly lower for BNT162b2 than mRNA-1273 overall and among those aged 18-39 years. In contrast, after the booster dose, no significant differences between myocarditis and vaccine type was observed overall or within the specific age groups among males or females. ConclusionMyocarditis after mRNA COVID-19 vaccines is a rare event. A lower absolute risk of myocarditis was observed after a booster dose of mRNA vaccine than the primary series second dose.