Vaccine-induced and hybrid immunity to SARS-CoV-2 after three or four doses of BNT162b2 - results from 22 months follow-up of a healthcare workers cohort, Israel, 2020-2022.

OBJECTIVES: SARS-CoV-2 remains a global health concern 3 years after its emergence. Safe and effective vaccines mitigate the pandemic impact, but the optimal schedule remains unclear, especially in a context where a high proportion of the population is infected. METHODS: We periodically measured anti-spike SARS-CoV-2 immunoglobulin (Ig)G titers using a quantitative assay in an Israeli healthcare worker cohort who all received at least two BNT162b2 doses and either received further doses and/or were subsequently infected up to 22 months after dose two, and compared geometric mean concentrations according to number of doses received and infection status using analysis of variance. RESULTS: Among the 993 included participants, infection after dose two led to higher geometric mean concentration IgG titers than a third dose (4285 vs 2845 arbitrary unit/ml 1-2 months after infection/vaccination, P = 0.03). In 16-18 months after dose two, those infected and those who received three or four vaccine doses all had IgG geometric mean concentration levels above 500 arbitrary unit/ml with no significant differences among groups (P = 0.6). IgG levels plateaued 16-22 months after dose two. CONCLUSION: Three BNT162b2 doses provide long-term immunogenicity comparable to breakthrough infection after dose two. Dose four transiently increases IgG levels and may be especially important for providing additional protection to vulnerable individuals during periods of increased transmission risk.

Antibody-Mediated Immunogenicity Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Following Priming, Boosting, and Hybrid Immunity: Insights From 11 Months of Follow-up of a Healthcare Worker Cohort in Israel, December 2020-October 2021.

BACKGROUND: We determined circulating anti-S severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) antibody titers in a vaccinated healthcare workers (HCWs) cohort from Northern Israel in the 11 months following primary vaccination according to age, ethnicity, and previous infection status. METHODS: All consenting HCWs were invited to have their IgG levels measured before vaccination and at 6 subsequent timepoints using a quantitative S1/S2 IgG assay. All HCWs with suspected coronavirus disease 2019 (COVID-19) were polymerase chain reaction (PCR) tested. We described trends in circulating IgG geometric mean concentration (GMC) by age, ethnicity, timing of boosting, and previous infection status and compared strata using Kruskall-Wallis tests. RESULTS: Among 985 vaccinated HCWs, IgG titers between 1 month post 2nd dose to pre-boosting gradually decreased in all age groups. Younger or previously infected individuals had higher initial post-vaccination IgG levels (P < .001 in both cases); differences substantially decreased or disappeared at 7-9 months, before boosting. The proportion of individuals infected prior to initiating vaccination and re-infected after dose 1 was comparable to the proportion of breakthrough infection post-dose 2 in those not previously infected (4.2 vs 4.7%). Pre-infection IgG levels in the 40 participants with breakthrough infection after dose 2 were similar to levels measured at the same timepoint in vaccinated HCWs who remained uninfected (P > .3). Post-dose3 IgG levels were more than 10-fold those 1 month post-dose 2. CONCLUSIONS: Immunity waned in all age groups and previously infected individuals, reversed by boosting. IgG titers decrease and reinfections in individuals with hybrid immunity (infection + vaccination) suggests they may also require further doses. Our study also highlights the difficulty in determining protective IgG levels.

Cycle threshold responses in SARS-COV2 PCR tests depend on the method by which the samples were obtained and require strict global standardization.

PURPOSE: Since 2020, a SARS-COV2 epidemic has been raging worldwide. The cycle of the PCR test in which the virus is detected is called cycle threshold (CT). The method of obtaining the sample is not detailed in any published study and is based on general guidelines of the CDC. Our contention is that the manner in which the sample is obtained has a dramatic effect on CT values. METHODS: For each person suspected of having Covid-19 who arrives at the emergency room, two swabs are taken in succession, one according to CDC guidelines and the other according to "Ziv" guidelines. The Ziv method sample collection guidelines determine the depth of penetration, the number of rotations of the swab, and their direction. Each double sample was sent for analysis. RESULTS: Analysis of the CT results of the sample to results methods and of the Seegene platform clearly found (p = 0.003 and p = 0.001, respectively) that more rigorous sample collection yielded lower CT values. CONCLUSION: The method of obtaining the samples had a dramatic effect on CT results. Any publication that includes CT results, and certainly studies that discuss CT kinetics, must describe in detail the method by which the samples were obtained. In places where it is also important to detect the onset of illness (airports, hospitals, schools, etc.), it is important to use the Ziv method to reduce the risk of false negatives.

SARS-CoV-2 immunogenicity in individuals infected before and after COVID-19 vaccination: Israel, January-March 2021.

Between December 2020 and March 2021, we measured anti-SARS-CoV-2 IgG titres among 725 Israeli hospital workers vaccinated against COVID-19. Infection post-dose 1 vaccination did not increase IgG titres, and individuals infected post-dose 1 had IgG levels comparable to never-infected individuals who received a single dose, lower than fully vaccinated, never-infected individuals. This suggests dose 2, currently not offered to those infected post-dose 1, may be required in these individuals. Larger studies should confirm whether individuals infected post-dose 1 need the second.

Impact of age, ethnicity, sex and prior infection status on immunogenicity following a single dose of the BNT162b2 mRNA COVID-19 vaccine: real-world evidence from healthcare workers, Israel, December 2020 to January 2021.

The BNT162b2 mRNA COVID-19 vaccine showed high efficacy in clinical trials but observational data from populations not included in trials are needed. We describe immunogenicity 21 days post-dose 1 among 514 Israeli healthcare workers by age, ethnicity, sex and prior COVID-19 infection. Immunogenicity was similar by ethnicity and sex but decreased with age. Those with prior infection had antibody titres one magnitude order higher than naïve individuals regardless of the presence of detectable IgG antibodies pre-vaccination.

Hospital Operation During a Disaster - Hospital Multi-Component Emergency Center (HMCEC).

A hospital's operating modes can be divided into three main levels of operation: routine, mass-casualty, and interim states that require procedures and resources beyond the routine capacity.Regardless of the nature of the event and the needs, the medical staff has to be prepared for a sudden increase in demand for service that could overwhelm the functional capacity and safety standards of the hospital.In any sort of an emergency event, the hospital has to fulfill two goals: First is to be able to sustain itself against the sudden rise in demand for medical support; the aid given depends on the nature of the disaster. The second goal is to continue supporting the essential routine duties for patients already hospitalized and for others arriving at the hospital regardless of the disaster.The aim of this paper is to describe the principles and the methods for hospital operation in case of a disaster-level event. The paper describes the structure and methods for handling prolonged disaster-level events and the adjustments that can be made in the case of lower intensity events.

Humanitarian medical aid to the Syrian people: Ethical implications and dilemmas.

Medical professionals providing humanitarian aid in times of crisis face complicated ethical and clinical challenges. Today, humanitarian aid is given in accordance with existing guidelines developed by international humanitarian organizations and defined by international law. This paper considers the ethical aspects and frameworks of an atypical humanitarian project, namely one that provides medical support through an Israeli civilian hospital to Syrian Civil War casualties. We explore new ethical questions in this unique situation that pose a serious challenge for the medical community and conventional ethical norms, a challenge Israeli medical staff meet on a daily basis. Before discussing the ethical challenges, we give a description of the project and its unique status.

Smoking Behavior Change During Compulsory Military Service in Israel, 1987-2011.

INTRODUCTION: Smoking in military settings is of major concern. We aimed to assess the association between personal, family, and military factors and smoking behavior change during compulsory military service in Israel. METHODS: Participants were soldiers recruited between 1987 and 2008 who were interviewed at recruitment and reinterviewed at discharge (1987-2011) (total: 29 189; males:15 136; females:14 053). The primary outcome variables were smoking initiation during service among nonsmokers at recruitment, and cessation during service among smokers at recruitment. We examined potential predictors of change, and trends by calendar year. RESULTS: Smoking prevalence increased by 39.4% during military service (recruitment: 26.2%, discharge: 36.5%). 18.4% of nonsmoking recruits initiated smoking, and 12.4% of smoking recruits quit smoking between recruitment and discharge. There was no observed trend in initiation between 1987 and 2011. The strongest predictor of smoking initiation among nonsmokers at recruitment was smoking history (former vs. never-smoker, odds ratio (OR) [95% confidence interval [CI]]: males: 5.63 [4.63,6.85], females: 6.76 [5.27, 8.68]. Other variables had smaller effects on initiation. Females were less likely to initiate smoking than males (OR [CI]): 0.75 [0.69,0.81]. Both males and females with high military fitness levels were more likely to initiate smoking. Among women, those with lower education, with fathers with lower education, of lower socioeconomic status, and ever-users of contraceptives were more likely to initiate smoking. Cessation among males modestly increased over the years (OR [CI]): 1.03 [1.01,1.05]. CONCLUSIONS: Smoking increased substantially during mandatory military service in Israel. Former smokers were at greatly increased risk of initiation and should be targeted for relapse prevention. Military service represents a golden opportunity for tobacco control. IMPLICATIONS: Military tobacco control policy is an important contributor to longevity among service personnel, and population-wide mortality in countries with compulsory service. The increased smoking prevalence among military personnel, and increases in smoking during military service should act as a wake-up call to governments and health systems in countries lacking strong military tobacco control policies. The substantial progress in military tobacco control in the United States, which includes strong antitobacco policies for prevention of smoking initiation, aid to smokers to quit smoking, and protection of nonsmokers from tobacco smoke, should be emulated by others. Former smokers and others at high risk should be targeted for relapse prevention. The closed environment of military service provides a golden opportunity for tobacco control.

[ACADEMY AND PUBLIC HOSPITALS - MUTUALLY BENEFICIAL AND SYNERGISTIC RELATIONSHIP].

Modern medicine deals with the combined quality of the profession and the medical service. The first rule of medicine is Primum non nocere" (first, do no harm). However, the essence of this unique profession cannot be confined by this basic message phrased by negation, but should be based on the principle of doing one's best to save the patient's life and to cure him. In this academic and dynamic profession, the physician keeps asking himself frequently whether the provided treatment is the best one possible. The internal need to answer this question and the concomitant curiosity, create the necessary critical integration between the physician and the researcher. Medical research is essential for the promotion of the profession, and it is a vital tool that leads to excellence in healthcare services. Throughout recent years the hospitals in Israel's Northern District, from Nazareth and Nahariya to Ziv, are in a continuous process of development and advancement with the aim to provide modern and available medical services of the highest quality to the residents of the area, tourists, IDF soldiers and even for those who arrive from across the border. This growth and development is reflected in the provision of new services, alongside the improvement of existing resources, and is based on collaboration between experienced and new staff transferred from various regions in Israel. The Medical Faculty of Bar Ilan University in Safed plays a significant and dominant part in this change. The affiliation of the hospitals to the faculty, the establishment of new research laboratories in hospitals, additional educational services for students, such as the pathology laboratory in Ziv, and, of course, the medical students studying in different departments - all of these constitute a thriving engine for the academy, combining teaching with promotion of research. Researchers and physicians from the hospitals are integrated in the medical school, in teaching, research and mentoring students. Department directors and senior physicians create an atmosphere of learning, among others, for the population of interns and trainees who are integrated in teaching and in the new research laboratories. The administrations of the hospitals and the faculty cooperate and work in synergy in order to promote the physicians and the researchers who are already working in the region and to attract new professionals to join them. The new academic climate is also the product of cooperation with regional colleges, Safed and Tel-Hai, as well as the work of MIGAL Galilee Research Institute and the support provided by the Ministry of Health and the Ministry for the Development of the Negev and Galilee. We strive to attract the faculty graduates to stay in the region, and to build a high-quality professional future for the essential medical services in the Israel's Northern District.

Seroprevalence of measles, mumps and rubella among young adults, after 20 years of universal 2-dose MMR vaccination in Israel.

Evidence-based vaccination policy is important for the global and local efforts of achieving control over measles. In 2007, the first Israeli birth cohort to be twice vaccinated during childhood with Measles-Mumps-Rubella vaccine reached adulthood. In parallel, Israel experienced its largest measles outbreak since 1994. We aimed to assess the seroprevalence of measles IgG antibodies and concordance with rubella and mumps seroprevalence among young Israeli adults born 1988-9 in comparison to previous birth cohorts, in order to inform evidence based prevention policy. We conducted a seroprevalence study of IgG antibodies among 439 Israeli adults born in 1988-9, based on a representative sample of sera collected at age 18-19 upon recruitment to mandatory military service in 2007. In total, 85.7% were seropositive for measles as compared with 95.6% in the 1996 recruitment (P < 0.001). The absolute decline was significant both for males (8.8%, P = 0.001) and females (12.1%, P < 0.001). There were no significant differences in seropositivity by gender, years of education, country of birth or smoking status. Rubella seropositivity among measles seropositives was 90.4%, significantly (P < 0.001) higher than 72.1% among measles seronegatives. Mumps seropositivity among measles seropositives was 87.0%, significantly (P < 0.001) higher than 62.3% among measles seronegatives. Results were similar for Israeli-born only. Our findings indicate that measles seroprevalence decreased after the last change in vaccination policy and reach sub-optimal level. Until global eradication is reached, a proactive vaccination program to supplement routine childhood vaccination program should be considered in Israel and in other countries.

[LESSONS FROM PREPAREDNESS OF HOSPITALS TO SNOWSTORMS].

Snowstorms are not a usual scene in Israel, which normally enjoys relatively warm weather, even in the winter. In the last two years we faced three severe snowstorms that had a major impact on the routine daily life in Israel. Roads were blocked, people experienced long electricity power failures, and secondary to slippery conditions, there was more than a threefold increase of orthopedic injuries. These storms confronted hospitals with unique challenges, both medical and logistic. Hospitals must be prepared to cope with the challenge of maintaining continuation of care. We propose four phases of preparedness strategy: at the beginning of the winter, once there is a weather forecast warning, during the storm itself, and returning to norm. This manuscript deals with the lessons learned by two hospitals in Safed and Jerusalem dealing with snowstorms.

Dynamics of pneumococcal acquisition and carriage in young adults during training in confined settings in Israel.

BACKGROUND: Outbreaks and sporadic cases of pneumococcal illness occur among young adults in confined settings. Our aim was to characterize pneumococcal acquisition and carriage among healthy young adults in Israel during military training in confined settings. METHODS: During the years 2007-2008, an observational longitudinal study was conducted in three cohorts of healthy soldiers, during a 7-month basic training period. Epidemiological data, oropharyngeal and nasopharyngeal cultures were sampled on 5 occasions: before and 3, 6, 12 and 24 weeks after start of training. Samples were processed within 2-18 hours. Relatedness of isolates was investigated by capsular typing of all isolates and pulsed-field gel electrophoresis to determine acquisition and transmission. Carriage and acquisition patterns were analyzed and multivariable logistic regression analysis was performed to assess the impact of time on acquisition after mixing, controlling for other covariates. RESULTS: Pneumococci were recovered on 202 of 1872 visits among 742 individuals, including 40 different serotypes. Mean carriage prevalence increased in all visits following training initiation. Acquisition during training was high, as 36.9% of individuals acquired pneumococci at least once during training, and for almost one fourth of the whole population this occurred during the first 6 weeks. Significant clustering was noted. Sharing drinking glass/bottle was found to be a significant and common risk factor for pneumococcal acquisition. CONCLUSIONS: Pneumococcal acquisition is highly frequent when young adults live in close contact in confined settings, especially early after mixing.

Rubella seroprevalence in the first birth cohort reaching fertility age after 20 years of two dose universal vaccination policy in Israel.

BACKGROUND: A national program of a 2-dose universal childhood MMR vaccination policy has been in effect in Israel since 1988. As the 1988 birth cohort reached fertility age, questions regarding immunity against rubella were raised. OBJECTIVE: To assess the seroprevalence of rubella IgG antibodies among young Israeli adults born after 1987 in comparison to previous birth cohorts, in order to determine evidence based policy for prevention of rubella and congenital rubella syndrome. METHODS: We conducted a seroprevalence study of rubella IgG antibodies among 416 Israeli adults (42.5% females) born in 1988-1989, based on a representative sample of sera collected at age 18-19 upon recruitment to mandatory military service in 2007. RESULTS: In total, 87.7% were seropositive (>15 IU/ml) as compared with 84.8% in the 1999 recruitment (P=0.26) and 93.4% in 1987 (P=0.004). Yet there was a difference by gender. The proportion of seropositives among female young adults (92.7%) was significantly lower as compared to those measured in the 1999 (99.2%, P=0.001) and 1987 (99.0%, P=0.006) recruitments. The proportion of seropositives among males (84.1%) was significantly higher as compared to those measured in 1999 (73.0%, P<0.001) but similar to those of 1987 (88.8%, P=0.13). Females born in the FSU were found to be high risk groups as 11.5% were seronegative. CONCLUSIONS: Our findings indicate that despite a successful program of congenital rubella syndrome prevention in Israel, there is a decline in seroprevalence among female young adults, especially immigrants from the FSU. A proactive catch-up program for females, especially for those of higher risk for susceptibility should be considered in Israel and in other countries.