The association of medical, social, and normative factors with the implementation of end-of-life care practices.

BACKGROUND: End-of-life (EoL) care practices (EoLCP) are procedures carried out at the EoL and bear directly on this stage in the patient's life. Public support of these practices in Israel is far from uniform. Previous studies show that while ∼30% of participants support artificial respiration or feeding of terminally ill patients, 66% support analgesic treatment, even at the risk of shortening life. This study aimed to create a typology of six end-of-life care practices in Israel and assess the association of medical, social, and normative factors with the implementation of those practices. These practices included mechanical ventilation, artificial feeding, deep sedation, providing information to the patient and family caregivers, including family caregivers in EoL decision-making, and opting for death at home. METHODS: This cross-sectional study was performed as an online survey of 605 adults aged 50 or more in Israel, of which ~ 50% (n = 297) reported supporting a dying terminally ill relative in the last 3 years. Participants were requested to provide their account of the EoL process of their relative dying from a terminal illness in several aspects, as well as the EoL care practices utilized by them. RESULTS: The accounts of the 297 interviewees who supported a dying relative reveal a varied EoL typology. The utilization of end-of-life care practices was associated with the socio-normative beliefs of family caregivers but not with their socioeconomic status. Strong correlations were found between family caregiver support for three key practices (mechanical ventilation, artificial feeding, and family involvement in EoL) and the actual utilization of these practices in the care of dying patients. CONCLUSIONS: The findings portray an important image of equity in the utilization of EoLCP in Israel, as the use of these practices was not associated with socioeconomic status. At the same time, the study found substantial diversity in family caregivers' preferences regarding EoL care practices use not related to socioeconomic status. We believe that differences in preferences that do not lead to problems with equity or other important societal values should be respected. Accordingly, policymakers and health system leaders should resist calls for legislation that would impose uniform EoL practices for all Israelis. Instead, they should take concrete steps to preserve and enhance the widespread current practice of practitioners to adapt EoL care to the varied needs and preferences of Israeli families and cultural, social, and religious subgroups. These steps should include providing frameworks and tools for family caregivers to support their loved ones close to their deaths, such as educational programs, seminars, supportive care before and during the end of life of their loved ones, etc.

Humoral Immunity of Unvaccinated COVID-19 Recovered vs. Naïve BNT162b2 Vaccinated Individuals: A Prospective Longitudinal Study.

To study the differences in the immune response to SARS-CoV-2 infection compared to the response to vaccination, we characterized the humoral immune kinetics of these situations. In this prospective longitudinal study, we followed unvaccinated COVID-19-recovered individuals (n = 130) and naïve, two-dose BNT162b2-vaccinated individuals (n = 372) who were age- and BMI-matched for six months during the first pandemic year. Anti-RBD-IgG, neutralizing antibodies (NAbs), and avidity were assessed monthly. For recovered patients, data on symptoms and the severity of the disease were collected. Anti-RBD-IgG and NAbs titers at peak were higher after vaccination vs. after infection, but the decline was steeper (peak log IgG: 3.08 vs. 1.81, peak log NAbs: 5.93 vs. 5.04, slopes: -0.54 vs. -0.26). Peak anti-RBD-IgG and NAbs were higher in recovered individuals with BMI > 30 and in older individuals compared to individuals with BMI < 30, younger population. Of the recovered, 42 (36%) experienced long-COVID symptoms. Avidity was initially higher in vaccinated individuals compared with recovered individuals, though with time, it increased in recovered individuals but not among vaccinated individuals. Here, we show that while the initial antibody titers, neutralization, and avidity are lower in SARS-CoV-2-recovered individuals, they persist for a longer duration. These results suggest differential protection against COVID-19 in recovered-unvaccinated vs. naïve-vaccinated individuals.

Polarization in public attitudes toward end-of-life decisions in Israel - A cross-sectional study.

OBJECTIVES: End-of-life (EoL) processes are a complex socio-normative and ethical phenomenon. This study aimed to generate a database of public opinion in Israel concerning EoL processes and decisions and to identify differences in attitudes across subgroups in the population, particularly based on experience as a family caregiver of a dying patient. METHODS: This cross-sectional study was performed in late March 2022. The study utilized an online sample of 605 adults over the age of 50 including those who accompanied a loved one to their death in the last 3 years. Participants were requested to provide their opinions and attitudes on several aspects of EoL decisions, including truth-telling, medically assisted dying, EoL procedures, pre-death actions, and family caregivers' engagement. RESULTS: While only 27% and ∼30% of participants support artificial respiration or feeding (respectively) of terminally ill patients, 66% support analgesic treatment, even at the risk of shortening life. The data show an association between religiosity and agreement with life-extending procedures. For example, while 83% of seculars support medically assisted dying, only 59% and 26% of traditional and religious respondents support it. However, no statistically significant differences were observed in support of family involvement in EoL process in any sociodemographic variable. SIGNIFICANCE OF RESULTS: The results of this study suggest that the Israeli public is relatively polarized on several issues about EoL processes, specifically patient autonomy and medically assisted dying. Yet, at the same time, there is a consensus among the Israeli public about certain EoL elements, particularly the importance of family caregivers in the EoL decision-making process.

Correlates of protection against COVID-19 infection and intensity of symptomatic disease in vaccinated individuals exposed to SARS-CoV-2 in households in Israel (ICoFS): a prospective cohort study.

BACKGROUND: Identifying COVID-19 correlates of protection and immunity thresholds is important for policy makers and vaccine development. We aimed to identify correlates of protection of BNT162b2 (Pfizer-BioNTech) vaccination against COVID-19. METHODS: In this prospective cohort study, households within a radius of 40 km of the Sheba Medical Center in Israel in which a new SARS-CoV-2 infection (defined as the index case) was detected within the previous 24 h were approached between July 25 and Nov 15, 2021. We included adults (aged >18 years) who had received one or two vaccine doses, had an initial negative SARS-CoV-2 PCR and no previous infection reported, and had a valid IgG and neutralising antibody result. The exposure of interest was baseline immune status, including IgG antibody concentration, neutralising antibody titre, and T-cell activation. The outcomes of interest were PCR-positive SARS-CoV-2 infection between day 2 and day 21 of follow-up and intensity of disease symptoms (self-reported via a telephone questionnaire) among participants who had a confirmed infection. Multivariable logistic and ordered logit ordinal regressions were used for the adjusted analysis. To identify immunological thresholds for clinical protection, we estimated the conditional probability of infection and moderate or severe disease for individuals with pre-exposure IgG and neutralising antibody concentrations above each value observed in the study data. FINDINGS: From 16 675 detected index cases in the study region, 5718 household members agreed to participate, 1461 of whom were eligible to be included in our study. 333 (22·8%) of 1461 household members who were not infected with SARS-CoV-2 at baseline were infected within 21 days of follow-up. The baseline (pre-exposure) IgG and neutralising antibodies were higher in participants who remained uninfected than in those who became infected (geometric mean IgG antibody concentration 168·2 binding antibody units [BAU] per mL [95% CI 158·3-178·7] vs 130·5 BAU/mL [118·3-143·8] and geometric mean neutralising antibody titre 197·5 [181·9-214·4] vs 136 ·7 [120·3-155·4]). Increasing IgG and neutralising antibody concentrations were also significantly associated with a reduced probability of increasing disease severity. Odds of infection were significantly reduced each time baseline IgG antibody concentration increased by a factor of ten (odds ratio [OR] 0·43 [95% CI 0·26-0·70]) and each time baseline neutralising antibody titre increased by a factor of two (0·82 [0·74-0·92]). In our cohort, the probability of infection if IgG antibody concentrations were higher than 500 BAU/mL was 11% and the probability of moderate disease severity was 1%; the probability of infection if neutralising antibody titres were above or equal to 1024 was 8% and the probability of moderate disease severity was 2%. T-cell activation rates were not significantly associated with reduced probability of infection (OR 1·04, 95% CI 0·83-1·30). INTERPRETATION: Both IgG and neutralising antibodies are correlates of protection against SARS-CoV-2 infection. Our data suggest that IgG concentrations higher than 500 BAU/mL and neutralising antibody titres of 1024 or more are thresholds for immunological protection from SARS-CoV-2 delta variant infection. Potentially, updated protective thresholds against emerging variants of concern could be calculated, which could support decision makers on administration of new vaccination strategies and on the optimal period between vaccine doses. FUNDING: Israeli Ministry of Health.

Superior immunogenicity and effectiveness of the third compared to the second BNT162b2 vaccine dose.

As the effectiveness of a two-dose messenger RNA (mRNA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine regimen decreases with time, a third dose has been recommended. Here, we assessed immunogenicity, vaccine effectiveness and safety of the third BNT162b2 vaccine dose in a prospective cohort study of 12,413 healthcare workers (HCWs). Anti-RBD immunoglobulin G (IgG) levels were increased 1.7-fold after a third dose compared with following the second dose. Increased avidity from 61.1% (95% confidence interval (CI), 56.1-66.7) to 96.3% (95% CI, 94.2-98.5) resulted in a 6.1-fold increase in neutralization titer. Peri-infection humoral markers of 13 third-dose Delta variant of concern (VOC) breakthrough cases were lower compared with 52 matched controls. Vaccine effectiveness of the third dose relative to two doses was 85.6% (95% CI, 79.2-90.1). No serious adverse effects were reported. These results suggest that the third dose is superior to the second dose in both quantity and quality of IgG antibodies and safely boosts protection from infection.

Real World Performance of SARS-CoV-2 Antigen Rapid Diagnostic Tests in Various Clinical Settings.

OBJECTIVE: To assess the validity of Antigen rapid diagnostic tests (Ag-RDT) for SARS-CoV-2 as decision support tool in various hospital-based clinical settings. DESIGN: Retrospective cohort study among symptomatic and asymptomatic patients and Healthcare workers (HCW). SETTING: A large tertiary teaching medical center serving as a major COVID-19 hospitalizing facility. PARTICIPANTS AND METHODS: Ag-RDTs' performance was assessed in three clinical settings: 1. Symptomatic patients and HCW presenting at the Emergency Departments 2. Asymptomatic patients screened upon hospitalization 3. HCW of all sectors tested at the HCW clinic following exposure. RESULTS: We obtained 5172 samples from 4595 individuals, who had both Ag-RDT and quantitative real-time PCR (qRT-PCR) results available. Of these, 485 samples were positive by qRT-PCR. The positive percent agreement (PPA) of Ag-RDT was greater for lower cycle threshold (Ct) values, reaching 93% in cases where Ct-value was <25 and 85% where Ct-value was <30. PPA was similar between symptomatic and asymptomatic individuals. We observed a significant correlation between Ct-value and time from infection onset (p<0.001). CONCLUSIONS: Ag-RDT are highly sensitive to the infectious stage of COVID-19 manifested by either high viral load (lower Ct) or proximity to infection, whether patient is symptomatic or asymptomatic. Thus, this simple-to-use and inexpensive detection method can be used as a decision support tool in various in-hospital clinical settings, assisting patient flow and maintaining sufficient hospital staffing.

Coronavirus disease 2019 (COVID-19) vaccination uptake among healthcare workers.

OBJECTIVE: To assess reasons for noncompliance with COVID-19 vaccination among healthcare workers (HCWs). DESIGN: Cohort observational and surveillance study. SETTING: Sheba Medical Center, a 1,600-bed tertiary-care medical center in Israel. PARTICIPANTS: The study included 10,888 HCWs including all employees, students, and volunteers. INTERVENTION: The BNT162b2 mRNA COVID-19 vaccine was offered to all HCWs of the hospital. Noncompliance was assessed, and pre-rollout and post-rollout surveys were conducted. Data regarding uptake of the vaccine as well as demographic data and compliance with prior influenza vaccination were collected, and 2 surveys were distributed. The survey before the rollout pertained to the intention to receive the vaccine, and the survey after the rollout pertained to all unvaccinated HCWs regarding causes of hesitancy. RESULTS: In the pre-rollout survey, 1,673 (47%) of 3,563 HCWs declared their intent to receive the vaccine. Overall, 8,108 (79%) HCWs received the COVID-19 vaccine within 40 days of rollout. In a multivariate logistic regression model, the factors that were significant predictors of vaccine uptake were male sex, age 40-59 years, occupation (paramedical professionals and doctors), high socioeconomic level, and compliance with flu vaccine. Among 425 unvaccinated HCWs who answered the second survey, the most common cause for hesitancy was the risk during pregnancy (31%). CONCLUSIONS: Although vaccine uptake among HCWs was higher than expected, relatively low uptake was observed among young women and those from lower socioeconomic levels and educational backgrounds. Concerns regarding vaccine safety during pregnancy were common and more data about vaccine safety, especially during pregnancy, might improve compliance.

Effect of ethnicity, country of origin and workplace on health behaviors and health perception among nurses: Cross-sectional study.

PURPOSE: The study aimed to (1) examine health behaviors and perceived health among nurses; (2) analyze the effect of nurses' personal and work characteristics on these variables; and (3) explore the relationship between health behaviors and nurses' health perception. DESIGN AND METHODS: A cross-sectional study was conducted among nurses working in health care organizations (HCOs) across Israel. An email with the online questionnaire was sent to nurses working in 19 HCOs across Israel during September-December 2018. FINDINGS: Of 18,120 nurses employed, 3542 completed the survey. Mean age was 44.8 years, 91% were female), 64.6% were hospital nurses and 52.8% were clinical staff nurses. Two-thirds of nurses did not achieve the physical activity (PA) target; the majority reported unfavorable eating habits; 66% slept less than 7 h at night and 15% smoke. Hospital nurses working night shifts reported the least favorable health behaviors. Non-Jewish nurses had less eating habits compared with Jewish nurses. Nurses born in the Former Soviet Union perceived their health as significantly worse than that of the other respondents. Binomial logistic regression demonstrated that, age, Israeli origin, achieving the PA target, having food breaks during work, consuming a Mediterranean diet, sleeping at least 7 h, undergoing screening tests as recommended, and not smoking predicted better health perception among nurses. CONCLUSIONS: Nurses, particularly hospital-based, non-Jewish and immigrants from the Soviet Union, demonstrated unfavorable health behaviors that may negatively affect their wellbeing and health perception. CLINICAL RELEVANCE: Interventions aimed at improving the health promoting mindset of nurses have the potential to improve their health and wellbeing and to enable them to become role models and health educators for patients and their families.

Early Immunogenicity and Safety of the Third Dose of BNT162b2 Messenger RNA Coronavirus Disease 2019 Vaccine Among Adults Older Than 60 Years: Real-World Experience.

BACKGROUND: Despite high vaccine coverage, an increase in breakthrough coronavirus disease 2019 (COVID-19) infections, prompted administration of a third BNT162b2 dose to people aged >60 years in Israel since July 2021. Here, we report real-world immunogenicity following third dose. METHODS: Overall, 208 healthcare workers aged >60 years were included. Paired pre- and post-second and/or third dose immunoglobulin G (IgG) and neutralizing antibody titers were compared. A subpopulation of low responders to the second dose was also tested for T-cell activation. For 25 paired serum samples, we tested neutralization of wild-type vs neutralization of Delta and Lambda variants, pre- and post-third dose. Active surveillance of vaccine adverse events was conducted through surveys. RESULTS: A pronounced immune response was observed following the third dose, including a 33-fold and 51-fold increase in IgG and neutralizing antibody, respectively. The neutralizing antibody levels post-third dose were 9.34 times higher than post-second dose (geometric mean titer, 2598 [95% confidence interval {CI}, 2085-3237] vs 207 [95% CI, 126-339]). Nine previously low responders had a significant antibody increase post-third dose, and 7 of 9 showed increase in T-cell activation. Additionally, sera obtained post-third dose highly and comparably neutralized the wild-type and Delta and Lambda variants. Of 1056 responders to the adverse-event survey, none had serious events. CONCLUSIONS: We demonstrate a rapid and broad immune response to the third BNT162b2 dose in individuals >60 years of age.

Waning Immune Humoral Response to BNT162b2 Covid-19 Vaccine over 6 Months.

BACKGROUND: Despite high vaccine coverage and effectiveness, the incidence of symptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been increasing in Israel. Whether the increasing incidence of infection is due to waning immunity after the receipt of two doses of the BNT162b2 vaccine is unclear. METHODS: We conducted a 6-month longitudinal prospective study involving vaccinated health care workers who were tested monthly for the presence of anti-spike IgG and neutralizing antibodies. Linear mixed models were used to assess the dynamics of antibody levels and to determine predictors of antibody levels at 6 months. RESULTS: The study included 4868 participants, with 3808 being included in the linear mixed-model analyses. The level of IgG antibodies decreased at a consistent rate, whereas the neutralizing antibody level decreased rapidly for the first 3 months with a relatively slow decrease thereafter. Although IgG antibody levels were highly correlated with neutralizing antibody titers (Spearman's rank correlation between 0.68 and 0.75), the regression relationship between the IgG and neutralizing antibody levels depended on the time since receipt of the second vaccine dose. Six months after receipt of the second dose, neutralizing antibody titers were substantially lower among men than among women (ratio of means, 0.64; 95% confidence interval [CI], 0.55 to 0.75), lower among persons 65 years of age or older than among those 18 to less than 45 years of age (ratio of means, 0.58; 95% CI, 0.48 to 0.70), and lower among participants with immunosuppression than among those without immunosuppression (ratio of means, 0.30; 95% CI, 0.20 to 0.46). CONCLUSIONS: Six months after receipt of the second dose of the BNT162b2 vaccine, humoral response was substantially decreased, especially among men, among persons 65 years of age or older, and among persons with immunosuppression.

Decreased infectivity following BNT162b2 vaccination: A prospective cohort study in Israel.

BACKGROUND: BNT162b2 was shown to be 92% effective in preventing COVID-19. Prioritizing vaccine rollout, and achievement of herd immunity depend on SARS-CoV-2 transmission reduction. The vaccine's effect on infectivity is thus a critical priority. METHODS: Among all 9650 HCW of a large tertiary medical center in Israel, we calculated the prevalence of positive SARS-CoV-2 qRT-PCR cases with asymptomatic presentation, tested following known or presumed exposure and the infectious subset (N-gene-Ct-value<30) of these. Additionally, infection incidence rates were calculated for symptomatic cases and infectious (Ct<30) cases. Vaccine effectiveness within three months of vaccine rollout was measured as one minus the relative risk or rate ratio, respectively. To further assess infectiousness, we compared the mean Ct-value and the proportion of infections with a positive SARS-CoV-2 antigen test of vaccinated vs. unvaccinated. The correlation between IgG levels within the week before detection and Ct level was assessed. FINDINGS: Reduced prevalence among fully vaccinated HCW was observed for (i) infections detected due to exposure, with asymptomatic presentation (VE(i)=65.1%, 95%CI 45-79%), (ii) the presumed infectious (Ct<30) subset of these (VE(ii)=69.6%, 95%CI 43-84%) (iii) never-symptomatic infections (VE(iii)=72.3%, 95%CI 48-86%), and (iv) the presumed infectious (Ct<30) subset (VE(iv)=83.0%, 95%CI 51-94%).Incidence of (v) symptomatic and (vi) symptomatic-infectious cases was significantly lower among fully vaccinated vs. unvaccinated individuals (VE(v)= 89.7%, 95%CI 84-94%, VE(vi)=88.1%, 95%CI 80-95%).The mean Ct-value was significantly higher in vaccinated vs. unvaccinated (27.3±1.2 vs. 22.2±1.0, p<0.001) and the proportion of positive SARS-CoV-2 antigen tests was also significantly lower among vaccinated vs. unvaccinated PCR-positive HCW (80% vs. 31%, p<0.001). Lower infectivity was correlated with higher IgG concentrations (R=0.36, p=0.01). INTERPRETATION: These results suggest that BNT162b2 is moderately to highly effective in reducing infectivity, via preventing infection and through reducing viral shedding. FUNDING: Sheba Medical Center, Israel.

BNT162b2 COVID-19 vaccine and correlates of humoral immune responses and dynamics: a prospective, single-centre, longitudinal cohort study in health-care workers.

BACKGROUND: Concurrent with the Pfizer-BioNTech BNT162b2 COVID-19 vaccine roll-out in Israel initiated on Dec 19, 2020, we assessed the early antibody responses and antibody kinetics after each vaccine dose in health-care workers of different ages and sexes, and with different comorbidities. METHODS: We did a prospective, single-centre, longitudinal cohort study at the Sheba Medical Centre (Tel-Hashomer, Israel). Eligible participants were health-care workers at the centre who had a negative anti-SARS-CoV-2 IgG assay before receiving the first dose of the intramuscular vaccine, and at least one serological antibody test after the first dose of the vaccine. Health-care workers with a positive SARS-CoV-2 PCR test before vaccination, a positive anti-SARS-CoV-2 IgG serology test before vaccination, or infection with COVID-19 after vaccination were excluded from the study. Participants were followed up weekly for 5 weeks after the first vaccine dose; a second dose was given at week 3. Serum samples were obtained at baseline and at each weekly follow-up, and antibodies were tested at 1-2 weeks after the first vaccine dose, at week 3 with the administration of the second vaccine dose, and at weeks 4-5 (ie, 1-2 weeks after the second vaccine dose). Participants with comorbidities were approached to participate in an enriched comorbidities subgroup, and at least two neutralising assays were done during the 5 weeks of follow-up in those individuals. IgG assays were done for the entire study population, whereas IgM, IgA, and neutralising antibody assays were done only in the enriched comorbidities subgroup. Concentrations of IgG greater than 0·62 sample-to-cutoff (s/co) ratio and of IgA greater than 1·1 s/co, and titres of neutralising antibodies greater than 10 were considered positive. Scatter plot and correlation analyses, logistic and linear regression analyses, and linear mixed models were used to investigate the longitudinal antibody responses. FINDINGS: Between Dec 19, 2020, and Jan 30, 2021, we obtained 4026 serum samples from 2607 eligible, vaccinated participants. 342 individuals were included in the enriched comorbidities subgroup. The first vaccine dose elicited positive IgG and neutralising antibody responses at week 3 in 707 (88·0%) of 803 individuals, and 264 (71·0%) of 372 individuals, respectively, which were rapidly increased at week 4 (ie, 1 week after the second vaccine dose) in 1011 (98·4%) of 1027 and 357 (96·5%) of 370 individuals, respectively. Over 4 weeks of follow-up after vaccination, a high correlation (r=0·92) was detected between IgG against the receptor-binding domain and neutralising antibody titres. First-dose induced IgG response was significantly lower in individuals aged 66 years and older (ratio of means 0·25, 95% CI 0·19-0·31) and immunosuppressed individuals (0·21, 0·14-0·31) compared with individuals aged 18·00-45·99 years and individuals with no immunosuppression, respectively. This disparity was partly abrogated following the second dose. Overall, endpoint regression analysis showed that lower antibody concentrations were consistently associated with male sex (ratio of means 0·84, 95% CI 0·80-0·89), older age (ie, ≥66 years; 0·64, 0·58-0·71), immunosuppression (0·44, 0·33-0·58), and other specific comorbidities: diabetes (0·88, 0·79-0·98), hypertension (0·90, 0·82-0·98), heart disease (0·86, 0·75-1·00), and autoimmune diseases (0·82, 0·73-0·92). INTERPRETATION: BNT162b2 vaccine induces a robust and rapid antibody response. The significant correlation between receptor-binding domain IgG antibodies and neutralisation titres suggests that IgG antibodies might serve as a correlate of neutralisation. The second vaccine dose is particularly important for older and immunosuppressed individuals, highlighting the need for timely second vaccinations and potentially a revaluation of the long gap between doses in some countries. Antibody responses were reduced in susceptible populations and therefore they might be more prone to breakthrough infections. FUNDING: Sheba Medical Center, Israel Ministry of Health.

Covid-19 Breakthrough Infections in Vaccinated Health Care Workers.

BACKGROUND: Despite the high efficacy of the BNT162b2 messenger RNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rare breakthrough infections have been reported, including infections among health care workers. Data are needed to characterize these infections and define correlates of breakthrough and infectivity. METHODS: At the largest medical center in Israel, we identified breakthrough infections by performing extensive evaluations of health care workers who were symptomatic (including mild symptoms) or had known infection exposure. These evaluations included epidemiologic investigations, repeat reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays, antigen-detecting rapid diagnostic testing (Ag-RDT), serologic assays, and genomic sequencing. Correlates of breakthrough infection were assessed in a case-control analysis. We matched patients with breakthrough infection who had antibody titers obtained within a week before SARS-CoV-2 detection (peri-infection period) with four to five uninfected controls and used generalized estimating equations to predict the geometric mean titers among cases and controls and the ratio between the titers in the two groups. We also assessed the correlation between neutralizing antibody titers and N gene cycle threshold (Ct) values with respect to infectivity. RESULTS: Among 1497 fully vaccinated health care workers for whom RT-PCR data were available, 39 SARS-CoV-2 breakthrough infections were documented. Neutralizing antibody titers in case patients during the peri-infection period were lower than those in matched uninfected controls (case-to-control ratio, 0.361; 95% confidence interval, 0.165 to 0.787). Higher peri-infection neutralizing antibody titers were associated with lower infectivity (higher Ct values). Most breakthrough cases were mild or asymptomatic, although 19% had persistent symptoms (>6 weeks). The B.1.1.7 (alpha) variant was found in 85% of samples tested. A total of 74% of case patients had a high viral load (Ct value, <30) at some point during their infection; however, of these patients, only 17 (59%) had a positive result on concurrent Ag-RDT. No secondary infections were documented. CONCLUSIONS: Among fully vaccinated health care workers, the occurrence of breakthrough infections with SARS-CoV-2 was correlated with neutralizing antibody titers during the peri-infection period. Most breakthrough infections were mild or asymptomatic, although persistent symptoms did occur.

Assisted life termination and truth telling to terminally ill patients - a cross-sectional study of public opinions in Israel.

BACKGROUND: End-of-life decisions are highly complex socio-normative and ethical phenomena. The goal of this study was to provide an assessment of public opinions in Israel concerning aspects of end-of-life decisions. METHODS: An online cross sectional study was performed in February 2020. The primary tool including items pertaining to death assistance and truth telling to patients. A sample of 515 participants representative of the adult Israeli population was obtained. RESULTS: The majority of participants (71%) supports telling the entire truth to patients even in harsh conditions. Support for truth telling decreases with affiliation to religion, with as little as 40% support among ultra-orthodox. People with vocational education are the least supportive of truth telling. Concerning doctor assisted death, almost half (49%) of the sample were supportive. Opposition is positively associated with religiosity, with 90% of ultra-orthodox and 58% of religious participants opposing doctor-assisted death, compared to only 18% among seculars. Non-Jews were 3.35 times (95%CI: 1.90, 5.91) more likely to oppose doctor assisted death than Jews (p < .0001). An Interrelationship analysis crossing between attitudes revealed that the largest group (39%) was comprised of participants who support both ("autonomists"). CONCLUSIONS: Israelis are overwhelmingly supportive of truth telling to patients. In contrast, Israeli public opinions on doctor assisted death are divided. For both attitudes, religiousness plays a crucial role as a catalyst for conservatism and opposition to change. Almost a half of the public is also supportive of an autonomist approach that would allow patients to decide on ending their own lives.

The impact of PCV7/13 on the distribution of carried pneumococcal serotypes and on pilus prevalence; 14 years of repeated cross-sectional surveillance.

BACKGROUND: S. pneumoniae carriage by children is a major source of pneumococcal transmission, and the initial step prior to infection. Pilus type 1, reported in ~30% of pneumococcal strains in the pre-vaccine era, contributes to pneumococcal colonization and virulence. In this study, we report the impact of the pneumococcal conjugate vaccine (PCV), PCV7/PCV13 sequential implementation on serotype distribution, and on the prevalence of piliated strains among carried pneumococci during the pre- and post-vaccine eras. METHODS: During 2002-2016, 12 repeated cross-sectional surveillances of nasopharyngeal S. pneumoniae carriage were conducted among 8,473 children <5.5 years old visiting primary care physicians in Central Israel. Seven biannual surveillances in the pre-PCV period, 2 surveillances after PCV7 was licensed but before implementation in the National Immunization Plan, and 3 additional surveillances in the post-PCV period. S. pneumoniae serotype distribution and prevalence of piliated strains were assessed. RESULTS: Carriage of S. pneumoniae was relatively stable (45.4%). The prevalence of serotypes included in PCV13 was 65.7%, in the pre-vaccine period and the pilus was present in 26.4% of isolates. The distribution of serotypes and the pilus prevalence in the pre-PCV period was relatively stable except for a decrease in prevalence of piliated 19F, observed following the first study year. Following PCV7/PCV13 implementation, vaccine type 13 (VT13) strains were nearly eliminated to 3.3% by 2016. Piliated strains, which were primarily of VT13 serotypes, initially followed a similar trend and were nearly eliminated by 2014 (1.7%). Yet, two years later, pilus prevalence re-emerged among non-VT strains to 12.8% of all pneumococci. CONCLUSIONS: Following PCV implementation, a dramatic and rapid decrease in VT strains prevalence was observed with a concomitant increase in non-VT strains. Piliated strains were nearly eliminated, yet re-emerged 7 years following PCV7/PCV13 implementation in various non-VT strains. This suggests that the pilus confers an advantage in colonization.

Gestational diabetes risk in a multi-ethnic population.

AIMS: To compare gestational diabetes mellitus (GDM) risk among two ethnic minority groups, with high type-2 diabetes (T2DM) prevalence, as compared to the Jewish population majority group. METHODS: A historical cohort study was conducted using clinical data collected between January 1, 2007, and December 31, 2011. The study sample included 20-45-year-old women; 2938 Ethiopian, 5849 Arab and 5156 non-Ethiopian Jewish women. GDM was defined according to the two-step strategy: step 1: glucose ≥ 140 mg/dl and step 2: using Coustan and Carpenter's diagnostic criteria. GDM risk was tested in a multivariable model, adjusted for age, parity and pre-gestational values of the metabolic syndrome components. RESULTS: Mean body mass index (BMI) values and morbid obesity rates were lowest among Ethiopian women and highest among Arab women. The prevalence of pre-gestational diabetes was significantly higher among Ethiopian (2.7%) and Arab (4.1%) women than among non-Ethiopian Jewish women (1.6%), and GDM screening rates were relatively high (85.5%, 87.2% and 83%, respectively). The proportion of pregnancies complicated with GDM was higher among Ethiopian women (4.3%) but not significantly different between Arab (2.9%) and non-Ethiopian Jewish (2.2%) women. In multivariable analysis, GDM was associated with Ethiopian ancestry (OR, 2.55; 95% CI, 1.60-4.08), adjusted for age, BMI, plasma triglyceride level and parity. Arab ethnicity was not significantly associated with GDM risk in multivariable analysis. CONCLUSIONS: Both Ethiopian and Arab minority ethnicities have a higher risk of T2DM in comparison with other Israeli women, but only Ethiopian origin is an independent risk factor for GDM while Arab ethnicity is not.

Patterns and Predictors of Staphylococcus aureus Carriage during the First Year of Life: a Longitudinal Study.

We sought here to investigate the patterns of Staphylococcus aureus carriage in the first year of life, its determinants, and the dynamics of transmission between mothers and infants. A prospective longitudinal cohort study of S. aureus carriage among mothers and their infants was performed, including monthly screenings from pregnancy/birth through the first year of the infant's life. Medical and lifestyle data were collected. Infant S. aureus carriage was detected from rectal and nasal swabs, and maternal carriage was detected from nasal and vaginal swabs. Multivariate analysis and a nonlinear mixed model (NLMIXED) were used to determine the predictors of carriage and S. aureus persistence. Of the 671 women recruited, 130 women carried S. aureus at recruitment (19.3%); they and their 132 infants were included in the study. A total of 93% of the infants acquired S. aureus sometime during the first year of life; 64% of these infants acquired the maternal strain, mostly (66%) during the first month of life. We observed that 70 women (52.50%) and 17 infants (14%) carried S. aureus persistently. Early acquisition of S. aureus carriage was associated with longer duration of initial carriage and was the most significant predictor of S. aureus persistence, while day care center attendance was negatively associated with persistent carriage. Methicillin-resistant S. aureus was carried by two infants for only 1 month each and not by any of the mothers. Early acquisition of S. aureus, mostly from the mother, is thus an important determinant of carriage persistence in infancy.

Truth-telling and doctor-assisted death as perceived by Israeli physicians.

BACKGROUND: Medicine has undergone substantial changes in the way medical dilemmas are being dealt with. Here we explore the attitude of Israeli physicians to two debatable dilemmas: disclosing the full truth to patients about a poor medical prognosis, and assisting terminally ill patients in ending their lives. METHODS: Attitudes towards medico-ethical dilemmas were examined through a nationwide online survey conducted among members of the Israeli Medical Association, yielding 2926 responses. RESULTS: Close to 60% of the respondents supported doctor-assisted death, while one third rejected it. Half of the respondents opposed disclosure of the full truth about a poor medical prognosis, and the others supported it. Support for truth-telling was higher among younger physicians, and support for doctor-assisted death was higher among females and among physicians practicing in hospitals. One quarter of respondents supported both truth-telling and assisted death, thereby exhibiting respect for patients' autonomy. This approach characterizes younger doctors and is less frequent among general practitioners. Another quarter of the respondents rejected truth-telling, yet supported assisted death, thereby manifesting compassionate pragmatism. This was associated with medical education, being more frequent among doctors educated in Israel, than those educated abroad. All this suggests that both personal attributes and professional experience affect attitudes of physicians to ethical questions. CONCLUSIONS: Examination of attitudes to two debatable medical dilemmas allowed portrayal of the multi-faceted medico-ethical scene in Israel. Moreover, this study, demonstrates that one can probe the ethical atmosphere of a given medical community, at various time points by using a few carefully selected questions.

Comparison of early effects of pneumococcal conjugate vaccines: PCV7, PCV10 and PCV13 on Streptococcus pneumoniae nasopharyngeal carriage in a population based study; The Palestinian-Israeli Collaborative Research (PICR).

BACKGROUND: Pneumococcal conjugate vaccines (PCVs), PCV10 and PCV13, are currently used in different countries. We have previously reported the effectiveness of PCV7, following its introduction in Israel and before PCVs were introduced in Palestine. Here, we extended the study and compared the initial impact of PCV10 to that of PCV7/13. METHODS: Four cross-sectional surveys of S. pneumoniae carriage among children <5y through 2009-2014 were preformed among two proximate populations, living under two distinct health authorities, with different vaccination policies. In East-Jerusalem (EJ), PCV7 was implemented in 2009 and replaced by PCV13 in late 2010, while in Palestine (PA), PCV10 was implemented in 2011. RESULTS: A total of 1267 and 2414 children from EJ and PA were screened. In 2014, S. pneumoniae was detected in 30.7% and 28.6% of the children in EJ and PA respectively Implementation of both PCV7 (in EJ) and PCV10 (in PA) did not affect overall S. pneumoniae carriage, but resulted in a significant decrease in the prevalence of vaccine-type strains. In the pre-vaccine era, VT7/VT13 strains consisted 47.0%/62.0% and 41.2%/54.8% of pneumococci in EJ and PA, respectively. A 48.6% and 53.9% decrease in VT7 strains was observed within 3 years of PCV7 implementation in EJ (p = 0.001) and PCV10 in PA (p<0.0001), respectively. These vaccination policies also resulted in ~50% reduction in VT13-added serotypes especially 6A (from 11.0% to 0.0% (EJ) and 9.5% to 4.9% (PA)). Three years after PCV13 implementation in EJ, an additional 67% decrease in VT13 strains was observed, yet an increase in serotype 3 was observed (0.0% to 3.4%, p = 0.056). While the prevalence of VT13 strains decreased significantly during the study period, the overall carriage rate didn't change significantly due to replacement with non-VT13 strains which comprised 89.8% and 70.7% of all pneumococci, in EJ and in PA respectively in the last study year. CONCLUSIONS: Within the first three years following PCV implementation, we observed similar reductions in carriage of VT10 and VT13 strains with either vaccination policies, with no effect on overall carriage. Further follow-up is needed to compare the long-term effects.

Staphylococcus aureus Colonization Induces Strain-Specific Suppression of Interleukin-17.

Staphylococcus aureus is a pathogen that causes significant morbidity and mortality. Nasal carriage is a major source of transmission and of endogenous infection. Persistent carriage is detected in ∼30% of healthy individuals. While Th17 cells have been shown to play a role in S. aureus infection and clearance, the immune response to carriage is not well understood. Here, we evaluate the Th17 response and its potential inhibitors during S. aureus carriage. We recruited 25 volunteers, of whom 11 were persistent carriers. Volunteers' peripheral blood mononuclear cells (PBMCs) were stimulated with either their endogenous strain (a strain isolated from that carrier) or exogenous ones (strains not carried by that volunteer). Changes in Th17 cell frequency and numbers, interleukin-17 (IL-17) mRNA expression, and IL-17 protein abundance were measured by fluorescence-activated cell sorting, real-time PCR, and enzyme-linked immunosorbent assay. Similarly, responses of IL-17 suppressors (regulatory T cells [FOXP3], IL-10, IL-27, and IL-19) were measured. Th17 and IL-17 levels in response to stimulation with endogenous strains were significantly lower than those in response to stimulation with exogenous ones. Of the suppressive cytokines tested, only IL-19 exhibited a stronger response to endogenous than to exogenous strains. Addition of recombinant IL-19 to exogenous-strain-stimulated PBMCs caused decreased IL-17 expression, whereas addition of IL-19 antibodies to endogenous-strain-stimulated cells resulted in an increased IL-17 response. Together, our results suggest that S. aureus carriage induced a tolerogenic response to a carried strain that could be reproduced through the addition of recombinant IL-19 or prevented by the addition of IL-19 antibodies. This differential immune response may play a role in the determination of S. aureus carriage patterns.