Immune and behavioral correlates of protection against symptomatic post-vaccination SARS-CoV-2 infection.

Introduction: We sought to determine pre-infection correlates of protection against SARS-CoV-2 post-vaccine inzfections (PVI) acquired during the first Omicron wave in the United States. Methods: Serum and saliva samples from 176 vaccinated adults were collected from October to December of 2021, immediately before the Omicron wave, and assessed for SARS-CoV-2 Spike-specific IgG and IgA binding antibodies (bAb). Sera were also assessed for bAb using commercial assays, and for neutralization activity against several SARS-CoV-2 variants. PVI duration and severity, as well as risk and precautionary behaviors, were assessed by questionnaires. Results: Serum anti-Spike IgG levels assessed by research assay, neutralization titers against Omicron subvariants, and low home risk scores correlated with protection against PVIs after multivariable regression analysis. Commercial assays did not perform as well as research assay, likely due to their lower dynamic range. Discussion: In the 32 participants that developed PVI, anti-Spike IgG bAbs correlated with lower disease severity and shorter duration of illness.

Antibiotics for UTI Prevention After Intradetrusor OnabotulinumtoxinA Injections.

IMPORTANCE: Urinary tract infections (UTIs) occur in 8.6% to 48.1% of patients after intradetrusor onabotulinumtoxinA injections. OBJECTIVE: The objective of this study was to evaluate both choice and duration of antibiotic prophylaxis on the incidence of UTI within 30 days after in-office onabotulinumtoxinA injections. STUDY DESIGN: We included a single-site, retrospective cohort of 305 patients with overactive bladder or bladder pain syndrome receiving postprocedure prophylactic antibiotics for in-office, 100-unit intradetrusor onabotulinumtoxinA injections from 2019 to 2023. Categories of antibiotic prophylaxis compared included (1) nitrofurantoin 100 mg twice daily for 3 days, (2) nitrofurantoin 100 mg twice daily for 5 days, (3) trimethoprim-sulfamethoxazole 160 mg/800 mg twice daily for 3 days, and (4) "other regimens." Primary outcome was incidence of UTI within 30 days. Variables were compared via χ2 test. Crude/adjusted odds were estimated using binary logistic regression. RESULTS: Incidence of UTI was 10.4% for 3-day nitrofurantoin, 20.5% for 5-day nitrofurantoin, 7.4% for 3-day trimethoprim-sulfamethoxazole, and 25.7% among "other regimens" (P = 0.023). Differences among primary regimens were substantial but not statistically significant: 3-day trimethoprim-sulfamethoxazole had 31% lower odds of UTI versus 3-day nitrofurantoin (odds ratio [OR], 0.689; P = 0.518). Compared with 3-day nitrofurantoin regimen, the 5-day nitrofurantoin regimen had twice the odds of UTI (OR, 2.22; P = 0.088). Those receiving "other regimens" had nearly 3 times the odds of UTI (OR, 2.98; P = 0.018). Results were similar adjusting for age and race. Overall urinary retention rate was 1.97%. CONCLUSIONS: Prophylactic antibiotic choice and duration of treatment potentially affect UTI incidence after in-office, intradetrusor onabotulinumtoxinA injections. Nitrofurantoin and trimethoprim-sulfamethoxazole for 3 days have the lowest UTI incidence.

Suicidal Behaviors Among Active-Duty US Service Members: Data from the 2018 Health-Related Behaviors Survey.

Background: This study aimed to 1) determine the prevalence of past-year suicidal ideation (SI) and attempts (SA) among active-duty SMs; 2) determine whether differences exist by age, sex, and race; and 3) assess whether prevalence estimates vary by risk profiles of mental health conditions and substance use. Methods: Data were from the 2018 Health-Related Behavior Survey (HRBS), a cross-sectional survey of active-duty SMs (n = 17,166). We used the logistic model to identify the factors of SI and SA and latent class analysis (LCA) to identify the risk profiles. Results: Among active duty SMs, 8.26% had SI and 1.25% had SA in the past year. Gender and age have been shown to influence how race might contribute to suicidal behaviors. Mental health conditions were associated with higher odds of SI and SA, as were younger ages; LGB identity; being separated, divorced, or widowed; use of e-cigarettes, dual use of e-cigarettes and cigarettes, or drugs; and history of deployment of less than 12 months. Frequencies of cigarette and e-cigarette use were also associated with SI and SA, indicating the odds were increasing by 0.3% for every additional cigarette or e-cigarette used. Five risk profiles were identified: class 1 (illegal drug use), class 2 (mental health needs with tobacco and alcohol use), class 3 (mental health conditions only), class 4 ("low risk" SMs with low levels of illegal drug use, mental health visits, tobacco use, and alcohol use), and class 5 (alcohol use). Compared to class 4 ("low risk"), all other risk profiles were associated with increased odds of suicidal behaviors. Conclusion: Despite the resources and increased access provided for mental health support, the prevalence of SI among active-duty SMs is greater than in the general population of the same age, likely due to additional military exposures and stressors.

The effect of geographic origin and destination on congenital heart disease outcomes: a retrospective cohort study.

BACKGROUND: Congenital heart disease (CHD) is a common and significant birth defect, frequently requiring surgical intervention. For beneficiaries of the Department of Defense, a new diagnosis of CHD may occur while living at rural duty stations. Choice of tertiary care center becomes a function of geography, referring provider recommendations, and patient preference. METHODS: Using billing data from the Military Health System over a 5-year period, outcomes for beneficiaries age < 10 years undergoing CHD surgery were compared by patient origin (rural versus urban residence) and the distance to treatment (patient's home and the treating tertiary care center). These beneficiaries include children of active duty, activated reserves, and federally activated National Guard service members. Analysis of the outcomes were adjusted for procedure complexity risk. Treatment centers were further stratified by annual case volume and whether they publicly reported results in the society of thoracic surgery (STS) outcomes database. RESULTS: While increasing distance was associated with the cost of admission, there was no associated risk of inpatient mortality, one year mortality, or increased length of stay. Likewise, rural origination was not significantly associated with target outcomes. Patients traveled farther for STS-reporting centers (STS-pr), particularly high-volume centers. Such high-volume centers (> 50 high complexity cases annually) demonstrated decreased one year mortality, but increased cost and length of stay. CONCLUSIONS: Together, these findings contribute to the national conversation of rural community medicine versus regionalized subspecialty care; separation of patients between rural areas and more urban locations for initial CHD surgical care does not increase their mortality risk. In fact, traveling to high volume centers may have an associated mortality benefit.

Determination of Lethality Curve for Cobalt-60 Gamma-Radiation Source in Rhesus Macaques Using Subject-Based Supportive Care.

Well-characterized and validated animal models are required for the development of medical countermeasures (MCMs) for acute radiation syndrome to mitigate injury due to high doses of total- or partial-body irradiation. Animal models used in MCM development must reflect a radiation dose- and time-dependent relationship, clinical presentation, and pathogenesis of organ injuries in humans. The objective of the current study was to develop the lethality curve for the Armed Forces Radiobiology Research Institute high level cobalt-60 gamma-radiation source in nonhuman primates (NHPs) after total-body irradiation. A dose-response relationship was determined using NHPs (rhesus macaques, N = 36, N = 6/radiation dose) irradiated with 6 doses in the range of 6.0 to 8.5 Gy, with 0.5 Gy increments at a dose rate of 0.6 Gy/min. Animals were provided subject-based supportive care including blood transfusions and were monitored for 60 days postirradiation. Survival was the primary endpoint of the study and the secondary endpoint included hematopoietic recovery. The lethality curve suggested LD30/60, LD50/60, and LD70/60 values as 5.71, 6.78, and 7.84 Gy, respectively. The results of this study will be valuable to provide specific doses for various lethalities of 60Co-gamma radiation to test radiation countermeasures in rhesus macaques using subject-based supportive care including blood transfusion.

Chronic Traumatic Encephalopathy in the Brains of Military Personnel.

BACKGROUND: Persistent neuropsychiatric sequelae may develop in military personnel who are exposed to combat; such sequelae have been attributed in some cases to chronic traumatic encephalopathy (CTE). Only limited data regarding CTE in the brains of military service members are available. METHODS: We performed neuropathological examinations for the presence of CTE in 225 consecutive brains from a brain bank dedicated to the study of deceased service members. In addition, we reviewed information obtained retrospectively regarding the decedents' histories of blast exposure, contact sports, other types of traumatic brain injury (TBI), and neuropsychiatric disorders. RESULTS: Neuropathological findings of CTE were present in 10 of the 225 brains (4.4%) we examined; half the CTE cases had only a single pathognomonic lesion. Of the 45 brains from decedents who had a history of blast exposure, 3 had CTE, as compared with 7 of 180 brains from those without a history of blast exposure (relative risk, 1.71; 95% confidence interval [CI], 0.46 to 6.37); 3 of 21 brains from decedents with TBI from an injury during military service caused by the head striking a physical object without associated blast exposure (military impact TBI) had CTE, as compared with 7 of 204 without this exposure (relative risk, 4.16; 95% CI, 1.16 to 14.91). All brains with CTE were from decedents who had participated in contact sports; 10 of 60 contact-sports participants had CTE, as compared with 0 of 165 who had not participated in contact sports (point estimate of relative risk not computable; 95% CI, 6.16 to infinity). CTE was present in 8 of 44 brains from decedents with non-sports-related TBI in civilian life, as compared with 2 of 181 brains from those without such exposure in civilian life (relative risk, 16.45; 95% CI, 3.62 to 74.79). CONCLUSIONS: Evidence of CTE was infrequently found in a series of brains from military personnel and was usually reflected by minimal neuropathologic changes. Risk ratios for CTE were numerically higher among decedents who had contact-sports exposure and other exposures to TBI in civilian life than among those who had blast exposure or other military TBI, but the small number of CTE cases and wide confidence intervals preclude causal conclusions. (Funded by the Department of Defense-Uniformed Services University Brain Tissue Repository and Neuropathology Program and the Henry M. Jackson Foundation for the Advancement of Military Medicine.).

The Effects of Berry Extracts on Oxidative Stress in Cultured Cardiomyocytes and Microglial Cells: A Potential Cardioprotective and Neuroprotective Mechanism.

Oxidative stress is a key underlying factor in cognitive decline and atherosclerosis. Oxidative stress occurs at the cellular level with an imbalance between reactive oxygen species and reactive nitrogen species and a deficiency in antioxidants. Mounting evidence suggests that berry flavonoids may promote cellular health by exerting antioxidant properties. Black currant and various berry extracts were tested in microglia (BV-2) and cardiomyocyte (HL-1) cell lines to study their biological effects. The principal ingredients in black currant and cranberry extract-delphinidin 3-rutinoside (D3R) and cyanidin 3-glucoside (C3G), were also assessed. A menadione-induced oxidative stressor was used, and its output was quantified to detect oxidative stress (CellROXTM). Black currant extract had similar antioxidant effects as N-acetylcysteine (NAC) in HL-1 cells with regard to cellular protection, whereas cranberry extract was ineffective. In contrast, cranberry extract was comparable in effectiveness to black currant extract in BV-2 cells. D3R and C3G also reduced oxidative stress similarly to whole berry extracts, which indicates that these ingredients may confer the antioxidant effects of berries. Black currant and cranberry extracts inhibit oxidative stress in microglial and cardiomyocyte cell lines. Black currant extract was more effective in reducing oxidative stress in the HL-1 cells, whereas cranberry extract was comparable in reducing oxidative stress in the BV-2 cells. The results suggest that berry flavonoids exert neuro- and cardioprotective effects.

Examining cognitive-behavioral therapy change mechanisms for decreasing depression, weight, and insulin resistance in adolescent girls at risk for type 2 diabetes.

OBJECTIVE: Depression in adolescence is linked to risk for type 2 diabetes (T2D). In this secondary data analysis of a randomized controlled trial comparing cognitive-behavioral therapy (CBT) to a control program to ameliorate insulin resistance via reducing depression symptoms, we examine which CBT change mechanisms (e.g., behavioral activation, cognitive restructuring) contributed to decreased depression and subsequent improvements in body mass index (BMI), percent body fat, and insulin resistance. METHODS: Girls 12-17y with overweight/obesity and family history of T2D were randomized to six-week group CBT (n = 61) or health education (HealthEd; n = 58). At baseline and post-treatment, adolescents completed questionnaires assessing activities, thoughts, and depression symptoms. At baseline, post-treatment, and one-year, BMI was calculated and insulin outcomes were derived from two-hour oral glucose tolerance testing. At baseline and one-year, percent body fat was assessed with dual-energy x-ray absorptiometry. Indirect effects of CBT components were tested on one-year changes in BMI, percent body fat, and insulin indices through decreases in depression symptoms during treatment. Intervention was tested as a moderator. RESULTS: In CBT, but not HealthEd, there was an indirect effect of increased physical activity during treatment on decreased one-year BMI via reductions in depression symptoms during treatment. Also, there were conditional indirect effects in CBT of increased pleasantness of physical and social activity during treatment on decreased one-year BMI via decreased depression symptoms during treatment. CONCLUSION: Behavioral activation may be a useful intervention to decrease depression and reduce excess weight gain in the targeted prevention of T2D in at-risk adolescent girls. NCT01425905, clinicaltrials.gov.

Perceptions of care following initiation of do-not-resuscitate orders.

PURPOSE: Documenting do-not-resuscitate (DNR) status in the surgical intensive care unit (ICU) can be controversial; some providers believe that DNR orders change care. This survey evaluates current perceptions. MATERIALS AND METHODS: IRB approved survey consisting of 31 validated questions divided into 3 factors (1. palliation, 2. active treatment, and 3. trust/communication). Individual questions were compared using Fisher's exact-tests and factors were compared via t-tests. RESULTS: Both surgical and ICU staff believe care decreases after DNR order initiation (43%). More surgical staff report decreased care aggressiveness versus ICU staff (63% vs 25%, p < 0.005 and Factor 2, 25.8 versus 29.8, p < 0.001), and felt that electrical cardioversion outside of the setting of ACLS would not be performed (57% vs 24%, p < 0.005). CONCLUSIONS: Surgical staff expressed more concern about care after DNR status than their ICU counterparts. Determining whether care actually changes clinically warrants further investigation.

Examination of the Interaction between Parental Military-Status and Race among Non-Hispanic Black and Non-Hispanic White Adolescents with Overweight/Obesity.

OBJECTIVES: Adolescent military-dependents experience distinct risk and protective factors, which may necessitate additional clinical considerations. In civilian youth, overweight/obesity is associated with eating, internalizing, and externalizing difficulties, with some studies reporting more difficulties among non-Hispanic White (vs. non-Hispanic Black) youth. It is unknown if these disparities exist among adolescent military-dependents, or between civilian and military-dependent youth. METHODS: Non-Hispanic Black (187 civilian, 38 military-dependent) and non-Hispanic White (205 civilian, 84 military-dependent) adolescents with overweight/obesity (14.7 ± 1.6 years; 73.9% girls; body mass index adjusted for age and sex 1.9 ± 0.5) completed a disordered-eating interview; parents completed a measure assessing their child's internalizing and externalizing difficulties. Multiple linear regressions examined parental military-status as a moderator of the relationship of participant race with eating, internalizing, and externalizing difficulties. RESULTS: White civilian youth with overweight/obesity reported significantly greater disordered-eating than their Black peers (p < .001); there were no other significant racial differences. In all regressions, parental military-status significantly moderated the association between race and each dependent variable (ps < .047). Black military-dependents (vs. civilians) reported more disordered-eating and internalizing difficulties (ps = .01). White military-dependents (vs. civilians) reported fewer externalizing difficulties (p = .01). CONCLUSIONS: Black adolescent military-dependents with overweight/obesity may experience more eating and internalizing difficulties (vs. civilians), a pattern not observed among White participants. Future work should examine if being a military-dependent and a historically marginalized racial group member accounts for these findings. Such data may inform providers of youth with intersecting minority identities.

Prospective Assessment of Symptoms to Evaluate Asymptomatic SARS-CoV-2 Infections in a Cohort of Health Care Workers.

BACKGROUND: The frequency of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is unclear and may be influenced by how symptoms are evaluated. In this study, we sought to determine the frequency of asymptomatic SARS-CoV-2 infections in a prospective cohort of health care workers (HCWs). METHODS: A prospective cohort of HCWs, confirmed negative for SARS-CoV-2 exposure upon enrollment, were evaluated for SARS-CoV-2 infection by monthly analysis of SARS-CoV-2 antibodies as well as referral for polymerase chain reaction testing whenever they exhibited symptoms of coronavirus disease 2019 (COVID-19). Participants completed the standardized and validated FLU-PRO Plus symptom questionnaire scoring viral respiratory disease symptom intensity and frequency at least twice monthly during baseline periods of health and each day they had any symptoms that were different from their baseline. RESULTS: Two hundred sixty-three participants were enrolled between August 25 and December 31, 2020. Through February 28, 2021, 12 participants were diagnosed with SARS-CoV-2 infection. Symptom analysis demonstrated that all 12 had at least mild symptoms of COVID-19, compared with baseline health, near or at time of infection. CONCLUSIONS: These results suggest that asymptomatic SARS-CoV-2 infection in unvaccinated, immunocompetent adults is less common than previously reported. While infectious inoculum doses and patient factors may have played a role in the clinical manifestations of SARS-CoV-2 infections in this cohort, we suspect that the high rate of symptomatic disease was due primarily to participant attentiveness to symptoms and collection of symptoms in a standardized, prospective fashion. These results have implications for studies that estimate SARS-CoV-2 infection prevalence and for public health measures to control the spread of this virus.

Durability of Antibody Response and Frequency of SARS-CoV-2 Infection 6 Months after COVID-19 Vaccination in Healthcare Workers.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies decay but persist 6 months postvaccination; lower levels of neutralizing titers persist against Delta than wild-type virus. Of 227 vaccinated healthcare workers tested, only 2 experienced outpatient symptomatic breakthrough infections, despite 59/227 exhibiting serologic evidence of SARS-CoV-2 infection, defined as presence of nucleocapsid protein antibodies.

Adverse Effects and Antibody Titers in Response to the BNT162b2 mRNA COVID-19 Vaccine in a Prospective Study of Healthcare Workers.

BACKGROUND: The relationship between postvaccination symptoms and strength of antibody responses is unclear. The goal of this study was to determine whether adverse effects caused by vaccination with the Pfizer/BioNTech BNT162b2 vaccine are associated with the magnitude of vaccine-induced antibody levels. METHODS: We conducted a single-center, observational cohort study consisting of generally healthy adult participants that were not severely immunocompromised, had no history of coronavirus disease 2019, and were seronegative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein before vaccination. Severity of vaccine-associated symptoms was obtained through participant-completed questionnaires. Testing for immunoglobulin G antibodies against SARS-CoV-2 spike protein and receptor-binding domain was conducted using microsphere-based multiplex immunoassays performed on serum samples collected at monthly visits. Neutralizing antibody titers were determined by microneutralization assays. RESULTS: Two hundred six participants were evaluated (69.4% female, median age 41.5 years old). We found no correlation between vaccine-associated symptom severity scores and vaccine-induced antibody titers 1 month after vaccination. We also observed that (1) postvaccination symptoms were inversely correlated with age and weight and more common in women, (2) systemic symptoms were more frequent after the second vaccination, (3) high symptom scores after first vaccination were predictive of high symptom scores after second vaccination, and (4) older age was associated with lower titers. CONCLUSIONS: Lack of postvaccination symptoms after receipt of the BNT162b2 vaccine does not equate to lack of vaccine-induced antibodies 1 month after vaccination.

Distribution of Triatoma dimidiata sensu lato (Reduviidae: Triatominae) and Risk Factors Associated with Household Invasion in Northern Belize, Central America.

To date, Triatoma dimidiata sensu lato [Reduviidae: Triatominae (Latreille 1811)] remains the sole vector species associated with Chagas disease transmission reported from Belize. Human infection data are limited for Belize and the disease transmission dynamics have not been thoroughly investigated, yet the likelihood of autochthonous transmission is supported by the widespread collection of infected vectors from within local households. Here, we report updated infection rates of the vector population and infestation rates for villages in north and central Belize. Overall, 275 households were enrolled in an ongoing vector surveillance program. Of the 41 insects collected, 25 were PCR positive for T. cruzi, indicating an infection rate as high as 60%. To further characterize the epidemiological risk of human-vector contact, determinants of household invasion were modeled. Local households were surveyed and characterized with respect to over 25 key factors that may be associated with household infestation by T. dimidiata s.l. While final models were not strongly predictive with respect to the risk factors that were surveyed, likely due to the low number of collection observations, the presence of domestic/peri-domestic dogs, nearby light sources, and household structure materials could be the focus of continued risk assessments. In northern Belize, this vector survey lends support to T. dimidiata s.l. inhabiting sylvatic settings as opposed to the classical paradigm of domiciliated vector populations. This designation has strong implications for the local level of human exposure risk which can help guide vector surveillance and control resources.

Effects of captopril against radiation injuries in the Göttingen minipig model of hematopoietic-acute radiation syndrome.

Our laboratory has demonstrated that captopril, an angiotensin converting enzyme inhibitor, mitigates hematopoietic injury following total body irradiation in mice. Improved survival in mice is correlated with improved recovery of mature blood cells and bone marrow, reduction of radiation-induced inflammation, and suppression of radiation coagulopathy. Here we investigated the effects of captopril treatment against radiation injuries in the Göttingen mini pig model of Hematopoietic-Acute Radiation Syndrome (H-ARS). Minipigs were given captopril orally (0.96 mg/kg) twice daily for 12 days following total body irradiation (60Co 1.79 Gy, 0.42-0.48 Gy/min). Blood was drawn over a time course following irradiation, and tissue samples were collected at euthanasia (32-35 days post-irradiation). We observed improved survival with captopril treatment, with survival rates of 62.5% in vehicle treated and 87.5% in captopril treated group. Additionally, captopril significantly improved recovery of peripheral blood mononuclear cells, and a trend toward improvement in recovery of red blood cells and platelets. Captopril significantly reduced radiation-induced expression of cytokines erythropoietin and granulocyte-macrophage colony-stimulating factor and suppressed radiation-induced acute-phase inflammatory response cytokine serum amyloid protein A. Using quantitative-RT-PCR to monitor bone marrow recovery, we observed significant suppression of radiation-induced expression of redox stress genes and improved hematopoietic cytokine expression. Our findings suggest that captopril activities in the Göttingen minipig model of hematopoietic-acute radiation syndrome reflect findings in the murine model.

Identifying Nontraditional Epidemic Disease Risk Factors Associated with Major Health Events from World Health Organization and World Bank Open Data.

Health events emerge from host, community, environment, and pathogen factors-forecasting epidemics is a complex task. We describe an exploratory analysis to identify economic risk factors that could aid epidemic risk assessment. A line list was constructed using the World Health Organization Disease Outbreak News (2016-2018) and economic indicators from the World Bank. Poisson regression employing forward imputations was used to establish relationships with the frequency with which countries reported public health events. Economic indicators demonstrated strong performance appropriate for further assessment in surveillance programming. In our analysis, three economic indicators were significantly associated to event reporting: how much the country's urban population changed, its average forest area, and a novel economic indicator we developed that assessed how much the gross domestic product changed per capita. Other economic indicators performed less well: changes in total, female, urban, and rural population sizes; population density; net migration; change in per cent forest area; total forest area; and another novel indicator, change in percent of trade as a fraction of the total economy. We then undertook a further analysis of the start of the current COVID-19 pandemic that revealed similar associations, but confounding by global disease burden is likely. Continued development of forecasting approaches capturing information relevant to whole-of-society factors (e.g., economic factors as assessed in our study) could improve the risk management process through earlier hazard identification and inform strategic decision processes in multisectoral strategies to preventing, detecting, and responding to pandemic-threat events.

Adverse effects and antibody titers in response to the BNT162b2 mRNA COVID-19 vaccine in a prospective study of healthcare workers.

BACKGROUND: mRNA COVID-19 vaccines are playing a key role in controlling the COVID-19 pandemic. The relationship between post-vaccination symptoms and strength of antibody responses is unclear. OBJECTIVE: To determine whether adverse effects caused by vaccination with the Pfizer/BioNTech BNT162b2 vaccine are associated with the magnitude of vaccine-induced antibody levels. DESIGN: Single center, prospective, observational cohort study. SETTING: Participants worked at Walter Reed National Military Medical Center and were seen monthly at the Naval Medical Research Center Clinical Trials Center. PARTICIPANTS: Generally healthy adults that were not severely immunocompromised, had no history of COVID-19, and were seronegative for SARS-CoV-2 spike protein prior to vaccination. MEASURES: Severity of vaccine-associated symptoms was obtained through participant completed questionnaires. Testing for IgG antibodies against SARS-CoV-2 spike protein and receptor binding domain was conducted using microsphere-based multiplex immunoassays. RESULTS: 206 participants were evaluated (69.4% female, median age 41.5 years old). We found no correlation between vaccine-associated symptom severity scores and vaccine-induced antibody titers one month after vaccination. We also observed that 1) post-vaccination symptoms were inversely correlated with age and weight and more common in women, 2) systemic symptoms were more frequent after the second vaccination, 3) high symptom scores after first vaccination were predictive of high symptom scores after second vaccination, and 4) older age was associated with lower titers. LIMITATIONS: Study only observes antibody responses and consists of healthy participants. CONCLUSIONS: Lack of post-vaccination symptoms following receipt of the BNT162b2 vaccine does not equate to lack of vaccine-induced antibodies one month after vaccination. This study also suggests that it may be possible to design future mRNA vaccines that confer robust antibody responses with lower frequencies of vaccine-associated symptoms. FUNDING: This study was executed by the Infectious Disease Clinical Research Program (IDCRP), a Department of Defense (DoD) program executed by the Uniformed Services University of the Health Sciences (USUHS) through a cooperative agreement by the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. (HJF). This project has been funded by the Defense Health Program, U.S. DoD, under award HU00012120067. Project funding for JHP was in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The funding bodies have had no role in the study design or the decision to submit the manuscript for publication.

Prospective Assessment of SARS-CoV-2 Seroconversion (PASS) study: an observational cohort study of SARS-CoV-2 infection and vaccination in healthcare workers.

BACKGROUND: SARS-CoV-2 is a recently emerged pandemic coronavirus (CoV) capable of causing severe respiratory illness. However, a significant number of infected people present as asymptomatic or pauci-symptomatic. In this prospective assessment of at-risk healthcare workers (HCWs) we seek to determine whether pre-existing antibody or T cell responses to previous seasonal human coronavirus (HCoV) infections affect immunological or clinical responses to SARS-CoV-2 infection or vaccination. METHODS: A cohort of 300 healthcare workers, confirmed negative for SARS-CoV-2 exposure upon study entry, will be followed for up to 1 year with monthly serology analysis of IgM and IgG antibodies against the spike proteins of SARS-CoV-2 and the four major seasonal human coronavirus - HCoV-OC43, HCoV-HKU1, HCoV-229E, and HCoV-NL63. Participants will complete monthly questionnaires that ask about Coronavirus Disease 2019 (COVID-19) exposure risks, and a standardized, validated symptom questionnaire (scoring viral respiratory disease symptoms, intensity and severity) at least twice monthly and any day when any symptoms manifest. SARS-CoV-2 PCR testing will be performed any time participants develop symptoms consistent with COVID-19. For those individuals that seroconvert and/or test positive by SARS-CoV-2 PCR, or receive the SARS-CoV-2 vaccine, additional studies of T cell activation and cytokine production in response to SARS-CoV-2 peptide pools and analysis of Natural Killer cell numbers and function will be conducted on that participant's cryopreserved baseline peripheral blood mononuclear cells (PBMCs). Following the first year of this study we will further analyze those participants having tested positive for COVID-19, and/or having received an authorized/licensed SARS-CoV-2 vaccine, quarterly (year 2) and semi-annually (years 3 and 4) to investigate immune response longevity. DISCUSSION: This study will determine the frequency of asymptomatic and pauci-symptomatic SARS-CoV-2 infection in a cohort of at-risk healthcare workers. Baseline and longitudinal assays will determine the frequency and magnitude of anti-spike glycoprotein antibodies to the seasonal HCoV-OC43, HCoV-HKU1, HCoV-229E, and HCoV-NL63, and may inform whether pre-existing antibodies to these human coronaviruses are associated with altered COVID-19 disease course. Finally, this study will evaluate whether pre-existing immune responses to seasonal HCoVs affect the magnitude and duration of antibody and T cell responses to SARS-CoV-2 vaccination, adjusting for demographic covariates.

Comparison of the effects of osmotic pump implantation with subcutaneous injection for administration of drugs after total body irradiation in mice.

The increasing potential for radiation exposure from nuclear accidents or terrorist activities has intensified the need to develop pharmacologic countermeasures against injury from total body irradiation (TBI). Many initial experiments to develop and test these countermeasures utilize murine irradiation models. Yet, the route of drug administration can alter the response to irradiation injury. Studies have demonstrated that cutaneous injuries can exacerbate damage from radiation, and thus surgical implantation of osmotic pumps for drug delivery could adversely affect the survival of mice following TBI. However, daily handling and injections to administer drugs could also have negative consequences. This study compared the effects of subcutaneous needlesticks with surgical implantation of osmotic pumps on morbidity and mortality in a murine model of hematopoietic acute radiation syndrome (H-ARS). C57BL/6 mice were sham irradiated or exposed to a single dose of 7.7 Gy 60Co TBI. Mice were implanted with osmotic pumps containing sterile saline seven days prior to irradiation or received needlesticks for 14 days following irradiation or received no treatment. All irradiated groups exhibited weight loss. Fewer mice with osmotic pumps survived to 30 days post irradiation (37.5%) than mice receiving needlesticks or no treatment (70% and 80%, respectively), although this difference was not statistically significant. However, mice implanted with the pump lost significantly more weight than mice that received needlesticks or no treatment. These data suggest that surgical implantation of a drug-delivery device can adversely affect the outcome in a murine model of H-ARS.

Permanent change of station moves and disordered-eating attitudes and behaviors in prevention-seeking adolescent military-dependents.

OBJECTIVE: Military-dependent youth appear to be at greater risk for disordered-eating than their civilian counterparts. Permanent change of station moves (PCS-moves), typically occurring every 2-3 years, are commonly experienced by adolescent military-dependents. However, the links between PCS-moves and disordered-eating in this population have not been explored. We hypothesized that stress arising from PCS-moves may contribute to the development and/or exacerbation of disordered-eating. METHODS: One-hundred-forty-nine adolescent military-dependents with overweight or obesity (59.7% female; 46.3% non-Hispanic White; 14.4±1.5 years; BMI-z: 1.9±0.4) completed measures before commencing an adulthood obesity and binge-eating disorder prevention trial for adolescents at-risk for both conditions due to BMI percentile ≥85th and loss-of-control (LOC)-eating and/or elevated anxiety symptoms. Disordered-eating attitudes and LOC-eating were assessed by semi-structured interview, and emotional eating was self-reported. Adjusting for relevant covariates, multiple linear regressions examined the unique association of PCS-move frequency with disordered-eating attitudes and disinhibited-eating behaviors. RESULTS: PCS-move frequency was not significantly associated with either LOC-eating frequency (ß = 0.09, p = .27) or emotional eating (ß = -0.04, p = .62). However, PCS-move frequency was positively associated with disordered-eating attitudes (ß = 0.17, p = .04), which appeared to be primarily driven by shape concerns (ß = 0.21, p = .01). DISCUSSION: Findings indicate that frequency of PCS-moves is related to disordered-eating attitudes, but not behaviors. Longitudinal research is needed to understand if PCS-moves prospectively relate to the onset and/or exacerbation of disordered-eating, and the relevance of disordered-eating attitudes as opposed to disinhibited-eating behaviors.