National Weekly SARS-CoV-2 RT-PCR Screening of All Workers in Long-Term Care Facilities Associated with Decrease in Resident Mortality Rate.

INTRODUCTION: Outbreaks of COVID-19 in long-term care facilities (LTCFs) have resulted mainly from disease transmission by asymptomatic health care workers. This study examines whether routine screening tests carried out on health care workers can help in reducing COVID-19 outbreaks, morbidity, and mortality of LTCF residents. METHODS: The study followed a weekly, nationwide, government-funded screening program of LTCF personnel for SARS-CoV-2, by using reverse transcription polymerase chain reaction as the main testing technology. It included all residents and employees in Israeli LTCFs who were screened weekly during the second wave of COVID-19, during the period of time between July 13, 2020, and November 21, 2020. RESULTS: During the study period, 1,107 LTCFs were screened on a weekly basis, including 62,159 HCWs and 100,046 residents. The program screened a median of 55,282 (range 16,249, min 45,910, max 62,159) employees per week, 0.05-1.5% of which were positive for SARS-CoV-2. LTCF mortality in the first wave accounted for 45.3% of all COVID-19 deaths recorded nationally (252 of 556), and in the second wave, this ratio was reduced to 30.3% (709 of 2,337) representing a reduction of 33.8% in expected mortality (p < 0.001). A significant reduction was detected also in hospitalization rate (13.59 vs. 11.41%, p < 0.001) and elder (≥75 years old) mortality rate (52.89 vs. 41.42%, p < 0.001). 214 outbreaks in the second wave were avoided by early identification of SARS-CoV-2 positive HCWs and successful prevention of subsequent infections in the facility. CONCLUSION: Routine weekly SARS-CoV-2 RT-PCR testing of LTCF employees was associated with reduced national LTCF residents' hospitalizations and mortality rate.

Anxiety in the face of the first wave of the spread of COVID-19 in Israel: Psychosocial determinants of a "Panic-to-complacency-continuum".

BACKGROUND AND METHODS: Based on an established ongoing prospective-longitudinal study examining anxiety in response to COVID-19, a representative sample of 1018 Jewish-Israeli adults were recruited online. A baseline assessment was employed two days prior to the first spread of COVID-19, followed by six weekly assessments. Three classes of general anxiety and virus-specific anxiety were identified: (1) "Panic" (a very high and stable anxiety throughout the spread), (2) "Complacency" (a very low and stable anxiety throughout the spread), and (3) "Threat-Sensitivity" (a linear increase, plateauing at the 5th wave). For general-anxiety only, a fourth, "Balanced," class was identified, exhibiting a stable, middle-level of anxiety. We tested theory-based, baseline, social-cognitive predictors of these classes: self-criticism, perceived social support, and perceptions/attitudes towards the Israeli Ministry of Health. We also controlled for trait anxiety. Multinomial regression analyses in the context of General Mixture Modeling were utilized. RESULTS: Baseline virus-specific anxiety linearly predicted emerging virus-specific anxiety classes. Virus-specific panic has higher trait anxiety than the other two classes. The general anxiety panic class was over-represented by women and exhibited higher baseline general anxiety and self-criticism than all other classes, and higher baseline virus-specific anxiety along with lower perceived support and less positive perceptions of the ministry of health than two of the three other classes. CONCLUSIONS: Preexisting anxiety shapes subsequent anxious responses to the spread of COVID-19. The general-anxiety panic class may be markedly demoralized, requiring targeted public-health interventions.

Association between SARS-CoV-2 infection and the physical fitness of young-adult cadets: a retrospective case-control study.

OBJECTIVES: To determine the association of symptomatic and asymptomatic mild COVID-19 and the SARS-CoV-2 viral load with the physical fitness of army cadets. DESIGN: A retrospective case-control study. SETTING: Officers' Training School of the Israel Defense Forces. PARTICIPANTS: The study included all cadets (age, 20.22±1.17 years) in the combatant (n=597; 514 males, 83 females; 33 infected, all males) and non-combatant (n=611; 238 males, 373 females; 91 infected, 57 females, 34 males) training courses between 1 August 2020 and 28 February 2021. COVID-19 outbreaks occurred in September 2020 (non-combatants) and January 2021(combatants). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measures were the aerobic (3000 m race) and anaerobic (combatant/non-combatant-specific) physical fitness mean score differences (MSDs) between the start and end of the respective training courses in infected and non-infected cadets. Secondary outcome measures included aerobic MSD associations with various COVID-19 symptoms and SARS-CoV-2 viral loads. RESULTS: SARS-CoV-2 infection led to declined non-combatant and combatant aerobic fitness MSD (14.53±47.80 vs -19.19±60.89 s; p<0.001 and -2.72±21.74 vs -23.63±30.92 s; p<0.001), but not anaerobic. The aerobic physical fitness MSD decreased in symptomatic cadets (14.69±44.87 s) and increased in asymptomatic cadets (-3.79±31.07 s), but the difference was statistically insignificant (p=0.07). Symptomatic cadets with fever (24.70±50.95 vs -0.37±33.87 s; p=0.008) and headache (21.85±43.17 vs 1.69±39.54 s; p=0.043) had more positive aerobic physical fitness MSD than asymptomatic cadets. The aerobic fitness decline was negatively associated with viral load assessed by the RNA-dependent RNA polymerase (n=61; r = -0.329; p=0.010), envelope (n=56; r = -0.385; p=0.002) and nucleus (n=65; r = -0.340; p=0.010) genes. CONCLUSIONS: SARS-CoV-2 infection was associated with a lingering decline in aerobic, but not anaerobic, fitness in symptomatic and asymptomatic young adults, suggesting possible directions for individualised symptom-dependent and severity-dependent rehabilitation plans' optimisation.

The role of time-varying viral shedding in modelling environmental surveillance for public health: revisiting the 2013 poliovirus outbreak in Israel.

Environmental pathogen surveillance is a sensitive tool that can detect early-stage outbreaks, and it is being used to track poliovirus and other pathogens. However, interpretation of longitudinal environmental surveillance signals is difficult because the relationship between infection incidence and viral load in wastewater depends on time-varying shedding intensity. We developed a mathematical model of time-varying poliovirus shedding intensity consistent with expert opinion across a range of immunization states. Incorporating this shedding model into an infectious disease transmission model, we analysed quantitative, polymerase chain reaction data from seven sites during the 2013 Israeli poliovirus outbreak. Compared to a constant shedding model, our time-varying shedding model estimated a slower peak (four weeks later), with more of the population reached by a vaccination campaign before infection and a lower cumulative incidence. We also estimated the population shed virus for an average of 29 days (95% CI 28-31), longer than expert opinion had suggested for a population that was purported to have received three or more inactivated polio vaccine (IPV) doses. One explanation is that IPV may not substantially affect shedding duration. Using realistic models of time-varying shedding coupled with longitudinal environmental surveillance may improve our understanding of outbreak dynamics of poliovirus, SARS-CoV-2, or other pathogens.

A Non-Randomized Controlled Trial for Reducing Postpartum Depression in Low-Income Minority Women at Community-Based Women's Health Clinics.

OBJECTIVE: To analyze an intervention that delivered tailored clinic staff training on postpartum depression (PPD) followed by awareness raising and social support aimed at lowering PPD among low-income Bedouin women in southern Israel. METHODS: We conducted a non-randomized controlled trial at two women's health clinics. The study included 332 of the 384 eligible women recruited at baseline (intervention = 169, control = 163), who completed two face-to-face interviews, one at 26-38 weeks of pregnancy (Time 1) and one 2-4 months postpartum (Time 2). PPD was measured by the Edinburgh Postnatal Depression Scale (EPDS) and dichotomized using a ≥ 10 score cutoff. We calculated EPDS change (rate difference of dichotomous EPDS from Time 1 to Time 2) (no change, positive change, or negative change), and compared EPDS changes in a control clinic vs. an intervention clinic. RESULTS: The intervention group showed a greater decrease in dichotomous EPDS ≥ 10 between times 1 and 2 (38.5% to 17.2%) than the control group (31.9% to 29.4%, PV = 0.008). Multinomial logistic regression showed that high PPD awareness significantly contributed to positive EPDS change in the intervention group (PV = 0.003) and high social support significantly protected against negative EPDS change in both groups, intervention (PV = 0.001) and control (PV = 0.003). CONCLUSIONS: In low-income women, an intervention focusing on increasing PPD awareness and social support following staff training was associated with reduced EPDS and positive EPDS change following the intervention. Similar interventions should be implemented in women's clinics during pregnancy. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov NCT02862444.

Standardization of a Developmental Milestone Scale Using Data From Children in Israel.

Importance: Routine developmental screening tests for children are used worldwide for early detection of developmental delays. However, assessment of developmental milestone norms lacks strong normative data, and there are inconsistencies among different screening tools. Objective: To establish milestone norms and build an updated developmental scale. Design, Setting, and Participants: This is a cross-sectional, population-based study conducted between 2014 and 2020. Developmental assessments were conducted by trained public health nurses, documented in national maternal child health clinics, known as Tipat Halav, which serve all children in Israel. Participants included all children born between January 2014 and September 2020, who were followed at the maternal child health clinics from birth to age 6 years. Exclusion criteria were preterm birth, missing gestational age, low birth weight (<2.5 kg), abnormal weight measurement (<3% according to standardized child growth charts), abnormal head circumference measurement (<3% or >97% according to standardized child growth charts), and visits without developmental data or without the child's age. Data analysis was performed from September 2020 to June 2021. Exposures: In total, 59 milestones in 4 developmental domains were evaluated, and the achievement rate per child's age was calculated for each milestone. Main Outcomes and Measures: A contemporary developmental scale, the Tipat Halav Israel Screening (THIS) Developmental Scale, was built, presenting the 75%, 90%, and 95% achievement rates for each milestone. The THIS scale was compared with other commonly used screening tests, including the Denver Developmental Screening Test II (Denver II), the Alberta Infant Motor Scale (AIMS), and the Centers for Disease Control and Prevention (CDC) Developmental Assessment. Results: A total of 839 574 children were followed in the maternal child health clinics between January 2014 and September 2020 in Israel, and 195 616 children were excluded. A total of 3 774 517 developmental assessments were performed for the remaining 643 958 children aged 0 to 6 years (319 562 female children [49.6%]), resulting in the establishment of new developmental norms. In terms of the comparable milestones, THIS milestones had a match of 18 of 27 (67%) with the Denver II, 7 of 7 (100%) with AIMS, and 10 of 19 (53%) with the CDC Developmental Assessment. The remaining unmatched milestones were achieved earlier in the THIS scale compared with other screening tools. Conclusions and Relevance: The THIS developmental scale is based on the largest population evaluated to date for developmental performance, representing the heterogeneous, multicultural population comprising this cohort. It is recommended for further evaluation worldwide.

Genomic Epidemiology of Clinical Brucella melitensis Isolates from Southern Israel.

Brucellosis, a zoonosis mainly transmitted by consumption of unpasteurized dairy products, is endemic in Southern Israel, mainly among the Bedouin Arab population. However, the genomic epidemiology of B. melitensis in this region has not yet been elucidated. A cohort of brucellosis cases (n = 118) diagnosed between 2017-2019 was studied using whole-genome sequencing (WGS). Phylogenetic analyses utilized core genome MLST (cgMLST) for all local isolates and core genome SNPs for 347 human-associated B. melitensis genomes, including Israeli and publicly available sequences. Israeli isolates formed two main clusters, presenting a notable diversity, with no clear dominance of a specific strain. On a global scale, the Israeli genomes clustered according to their geographical location, in proximity to genomes originating from the Middle East, and formed the largest cluster in the tree, suggesting relatively high conservation. Our study unveils the genomic epidemiology of B. melitensis in Southern Israel, implicating that rather than a common source, the transmission pattern of brucellosis among Bedouin communities is complex, predominantly local, and household-based. Further, genomic surveillance of B. melitensis is expected to inform future public health and veterinary interventions and clinical care.

Pediatric Hospitalizations After School Reopening During the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Alpha (B.1.1.7) Variant Spread: A Multicenter Cross-sectional Study in Israel.

This multicenter, cross-sectional study provides evidence on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated emergency department visits and hospitalizations in pediatric wards and intensive care units after school reopening during the SARS-CoV-2 Alpha (B.1.1.7) variant spread in Israel. Study findings suggest that school reopening was not followed by an increase in SARS-CoV-2-related pediatric morbidity.

Effectiveness of BNT162b2 mRNA Coronavirus Disease 2019 (COVID-19) Vaccine Against Acquisition of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Among Healthcare Workers in Long-Term Care Facilities: A Prospective Cohort Study.

BACKGROUND: We assessed vaccine effectiveness (VE) of BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) acquisition among healthcare workers (HCWs) of long-term care facilities (LTCFs). METHODS: This prospective study, in the framework of the "Senior Shield" program in Israel, included routine weekly nasopharyngeal SARS-CoV-2 RT-PCR testing from all LTCF HCWs since July 2020. All residents and 75% of HCWs were immunized between December 2020 and January 2021. The analysis was limited to HCWs adhering to routine testing. Fully vaccinated (14+ days after second dose; n = 6960) and unvaccinated (n = 2202) HCWs were simultaneously followed until SARS-CoV-2 acquisition or end of follow-up, 11 April 2021. Hazard ratios (HRs) for vaccination versus no vaccination were calculated (Cox proportional hazards regression models, adjusting for sociodemographics and residential-area COVID-19 incidence). VE was calculated as (1- HR) × 100. RT-PCR cycle threshold (Ct) values were compared between vaccinated and unvaccinated HCWs. RESULTS: At >14 days post-second dose, 40 vaccinated HCWs acquired SARS-CoV-2 (median follow-up, 66 days; cumulative incidence, 0.6%) versus 84 unvaccinated HCWs (median follow-up, 43 days; cumulative incidence, 5.1%) (HR, .11; 95% CI, .07-.17; unadjusted VE, 89%; 95% CI, 83-93%). Adjusted VE >7 and >14 days post-second dose were similar. The median PCR Ct targeting the ORF1ab gene among 20 vaccinated and 40 unvaccinated HCWs was 32.0 versus 26.7, respectively (P value  = .008). CONCLUSIONS: VE following 2 doses of BNT162b2 against SARS-CoV-2 acquisition in LTCF HCWs was high. The lower viral loads among SARS-CoV-2-positive HCWs suggest further reduction in transmission.

Changes in General and Virus-Specific Anxiety During the Spread of COVID-19 in Israel: A 7-Wave Longitudinal Study.

We compared 3 hypothetical trajectories of change in both general and coronavirus disease 2019 (COVID-19)-specific anxiety during the first wave of the spread in the state of Israel: panic (very high anxiety, either from the outset or rapidly increasing), complacency (stable and low anxiety), and threat-sensitive (a moderate, linear increase compatible with the increase in threat). A representative sample of 1,018 Jewish-Israeli adults was recruited online. A baseline assessment commenced 2 days prior to the identification of the first case, followed by 6 weekly assessments. Latent mixture modeling analyses revealed the presence of 3 trajectories: 1) "threat-sensitivity" (29% and 66%, for general and virus-specific anxiety, respectively), 2) panic (12% and 25%), and 3) complacency (29% and 9%). For general anxiety only, a fourth class representing a stable mid-level anxiety was identified ("balanced": 30%). For general anxiety, women and the initially anxious-both generally and specifically from the spread of the virus-were more likely to belong to the panic class. Men and older participants were more likely to belong to the complacency class. Findings indicate a marked heterogeneity in anxiety responses to the first wave of the spread of COVID-19, including a large group evincing a "balanced" response.

Low and High Ambient Temperatures during Pregnancy and Birth Weight among 624,940 Singleton Term Births in Israel (2010-2014): An Investigation of Potential Windows of Susceptibility.

BACKGROUND: Exposure to heat during pregnancy has been associated with reduced fetal growth. Less is known about associations with cold and the potential for critical time windows of exposure. OBJECTIVES: We aimed to evaluate, in a national retrospective cohort, critical windows of susceptibility during pregnancy to extreme temperatures (low and high) and fetal growth, among 624,940 singleton term births in Israel during the period 2010-2014. METHODS: Temperature exposures were estimated using a spatially refined gridded climate data set with a 1-h and 1-km2 resolution. Percentiles of temperature were categorized by climatic zone for the entire pregnancy and by trimesters and weeks. Generalized additive models with the distributed lag nonlinear model framework were used to estimate unadjusted and adjusted associations between percentiles and categories of temperature and fetal growth markers: term [births after 36 weeks of gestational age (GA)] mean birth weight and term low birth weight (tLBW, term infants with birth weight below 2,500g). RESULTS: After adjustment, extreme temperatures (percentiles) during the entire pregnancy were associated with a lower mean birth weight {≤10th vs. 41st-50th percentile: -56g [95% confidence interval (CI): -63g, -50g)]; >90th vs. 41st-50th percentile: -65g; 95% CI: -72g, -58g}. Similar inverse U-shaped patterns were observed for all trimesters, with stronger associations for heat than for cold and for exposures during the third trimester. For heat, results suggest critical windows between 3-9 and 19-34 GA-weeks, with the strongest association estimated at 3 GA-weeks (temperature >90th vs. 41st-50th percentiles: -3.8g; 95% CI: -7.1g, -0.4g). For cold, there was a consistent trend of null associations early in pregnancy and stronger inverse associations over time, with the strongest association at 36 GA-week (≤10th vs. 41st-50th percentiles: -2.9g; 95% CI: -6.5g, 0.7g). For tLBW, U-shape patterns were estimated for the entire pregnancy and third trimester exposures, as well as nonsignificant associations with heat for 29-36 GA-weeks. Generally, the patterns of associations with temperatures during the entire pregnancy were consistent when stratified by urbanicity and geocoding hierarchy, when estimated for daily minimum and maximum temperatures, when exposures were classified based on temperature distributions in 49 natural regions, and when estimated for all live births. DISCUSSION: Findings from our study of term live births in Israel (2010-2014) suggest that exposure to extreme temperatures, especially heat, during specific time windows may result in reduced fetal growth. https://doi.org/10.1289/EHP8117.

Inferring Numbers of Wild Poliovirus Excretors Using Quantitative Environmental Surveillance.

Response to and monitoring of viral outbreaks can be efficiently focused when rapid, quantitative, kinetic information provides the location and the number of infected individuals. Environmental surveillance traditionally provides information on location of populations with contagious, infected individuals since infectious poliovirus is excreted whether infections are asymptomatic or symptomatic. Here, we describe development of rapid (1 week turnaround time, TAT), quantitative RT-PCR of poliovirus RNA extracted directly from concentrated environmental surveillance samples to infer the number of infected individuals excreting poliovirus. The quantitation method was validated using data from vaccination with bivalent oral polio vaccine (bOPV). The method was then applied to infer the weekly number of excreters in a large, sustained, asymptomatic outbreak of wild type 1 poliovirus in Israel (2013) in a population where >90% of the individuals received three doses of inactivated polio vaccine (IPV). Evidence-based intervention strategies were based on the short TAT for direct quantitative detection. Furthermore, a TAT shorter than the duration of poliovirus excretion allowed resampling of infected individuals. Finally, the method documented absence of infections after successful intervention of the asymptomatic outbreak. The methodologies described here can be applied to outbreaks of other excreted viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), where there are (1) significant numbers of asymptomatic infections; (2) long incubation times during which infectious virus is excreted; and (3) limited resources, facilities, and manpower that restrict the number of individuals who can be tested and re-tested.

The role of caloric intake in the association of high salt intake with high blood pressure.

Since current recommendations call for a substantial reduction in overall sodium consumption, we tested whether or not these recommendations are implemented in common large subpopulations such as those with abnormal weight or hypertension in the current high sodium, high-calorie nutritional environment. In a national representative cross-sectional survey of the community-dwelling subjects aged 25-65 years conducted in Israel between 2015 and 2017, 582 randomly selected subjects completed health and dietary questionnaires, underwent blood pressure and anthropometric measurements and collected 24-h urine specimens, to assess dietary sodium intake. Overall mean 24-h sodium excretion was 3834 mg, more than double the recommended upper intake for adults < 1500 mg/day. Sodium excretion was directly related to caloric intake and blood pressure and linked to the presence of hypertension and overweight/obesity. The highest sodium excretion was seen in overweight/obese hypertensive subjects. This recent national survey shows a high consumption of sodium in the Israeli population and a dose-response association between caloric intake and urinary sodium excretion, independent of BMI and hypertension. Nevertheless, overweight/obese subjects with hypertension consume (excrete) more sodium than other BMI/ blood pressure-related phenotypes and may thus comprise a target subpopulation for future efforts to reduce sodium intake.

Associations Between Prenatal Exposure to Air Pollution and Congenital Hypothyroidism.

Adequate thyroid hormone availability is required for normal brain development. Studies have found associations between prenatal exposure to air pollutants and thyroid hormones in pregnant women and newborns. We aimed to examine associations of trimester-specific residential exposure to common air pollutants with congenital hypothyroidism (CHT). All term infants born in Israel during 2009-2015 were eligible for inclusion. We used data on CHT from the national neonatal screening lab of Israel, and exposure data from spatiotemporal air pollution models. We used multivariable logistic regression models to estimate associations of exposures with CHT, adjusting for ethnicity, socioeconomic status, geographical area, conception season, conception year, gestational age, birth weight, and child sex. To assess residual confounding, we used postnatal exposures to the same pollutants as negative controls. The study population included 696,461 neonates. We found a positive association between third-trimester nitrogen oxide exposure and CHT (per interquartile-range change, odds ratio = 1.23, 95% confidence interval: 1.08, 1.41) and a similar association for nitrogen dioxide. There was no evidence of residual confounding or bias by correlation among exposure periods for these associations.

Regional differences in pediatric asthma hospital admissions: National data from Israel 1996-2017.

BACKGROUND: Asthma is a common chronic childhood illness and frequent cause of hospitalization. A decline in hospital admission rates was noted up to the 1990s, however, trends are not as clear since the turn of the century. This study aimed to assess the rates and regional differences of asthma admissions over more than two decades using the national Ministry of Health database, which registers data from all the hospitals. METHODS: A retrospective cohort study, analysis of all pediatric asthma admissions, for Patients 1-14 years old, between 1996 and 2017 as recorded by the National Hospital Discharge Registry, was performed. Asthma admission rates were calculated per 1000 age adjusted residents, using the number of admission cases as the numerator, and age specific population size as the denominator. RESULTS: The annual asthma hospitalization rate decreased in the entire pediatric population from 2.14 in 1996-0.89 in 2017. Children in the 1-4 year age group comprised most of the hospital admissions, and most of the decline was attributable to this age group. Significant differences in hospitalizations were found between different regions as well as differences in the rate of decline in asthma hospitalizations with the lowest admission rate in the Jerusalem district, highest in Haifa, northern and southern Israeli regions and the greatest rate of decline in the Tel-Aviv district. CONCLUSION: This nationwide study, over more than two decades, shows clear regional differences in the rates of asthma admissions as well as regional differences in the rates of decline.

Parents' malevolent personification of mass vaccination solidifies vaccine hesitancy.

Parental hesitancy to vaccinate their children derails the success of mass vaccination campaigns. We examined the effect of parents' personification of the vaccinating agency on vaccine hesitancy (i.e. negative or positive mind change) in 555 parents in a mass wild poliovirus vaccination campaign. Parents were assessed before and after the campaign on attitudes toward vaccination and the vaccinating agency ("The Israeli MoH is caring" vs "hysteric"). Positive mind change was predicted by a gender and malevolent personification. A negative mind change was predicted by parental anxiety. We conclude that parental hesitancy is influenced by parents' attachment to the vaccinating agency.