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Quantifying the detection rate of the widely used quantitative RT-PCR (RT-qPCR) test for severe acute respiratory syndrome coronavirus 2 and its dependence on patient demographic characteristics and disease progression is key in designing epidemiologic strategies. Analyzing 843,917 test results of 521,696 patients, a “positivity period” was defined for each patient between diagnosis of coronavirus disease 2019 and the last positive test result. The fraction of positive test results within this period was then used to estimate detection rate. Regression analyses were used to determine associations of detection with time of sampling after diagnosis, patient demographic characteristics, and viral RNA copy number based on RT-qPCR cycle threshold values of the next positive test result. The overall detection rate in tests performed within 14 days after diagnosis was 83.1%. This rate was higher at days 0 to 5 after diagnosis (89.3%). Furthermore, detection rate was strongly associated with demographic characteristics, with an odds ratio of 0.58 (95% CI, 0.53 to 0.63) for women over men and 0.74 (95% CI, 0.72 to 0.75) for patients 10 years younger. Finally, the detection rate with the Allplex 2019-nCoV RT-qPCR kit was associated, at the single-patient level, with viral RNA copy number (P value

Background Although BNT162b2 vaccine-efficacy analyses have been published, the effectiveness of the vaccine in preventing coronavirus disease 2019 given confirmed exposure has not been previously demonstrated, even though it has policy implications, such as the need for self-quarantine when exposure has occurred. Methods In a retrospective cohort study, we used data collected between 20 December 2020 and 17 March 2021 from the second largest healthcare provider in Israel to analyze the probability of an additional household infection occurring within 10 days after an index infection. In model 1, vaccine effectiveness was described for Fully Vaccinated individuals (7 or more days from second dose) vs either Unvaccinated individuals or those Recently Vaccinated Once (0–7 days from the first dose, presumably still unprotected). Secondary analyses included correction for differing testing rates. In model 2, we conducted a separate analysis of households comprised of only adults with the same vaccination status. Results A total of 173 569 households were included, of which 6351 had an index infection (mean [standard deviation] age, 58.9 [13.5] years); 50% were women. Adjusted vaccine effectiveness of Fully Vaccinated compared with Unvaccinated participants was 80.3% (95% confidence interval [CI], 73.5–85.4) and 82.0% (95% CI, 75.6–86.8) compared with those Recently Vaccinated Once. Conclusions The BNT162b2 vaccine is effective in high-risk real-life exposure scenarios, but the protection afforded in these settings is lower than that previously described. Individuals with a confirmed significant exposure to severe acute respiratory syndrome are still at risk of being infected even if fully vaccinated.

The short-term effectiveness of a two-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine was widely demonstrated. However, long term effectiveness is still unknown. Leveraging the centralized computerized database of Maccabi Healthcare Services (MHS), we assessed the correlation between time-from-vaccine and incidence of breakthrough infection between June 1 and July 27, the date of analysis. After controlling for potential confounders as age and comorbidities, we found a significant 1.51 fold (95% CI, 1.38–1.66) increased risk for infection for early vaccinees compared to those vaccinated later that was similar across all ages groups. The increased risk reached 2.26- fold (95% CI, 1.80–3.01) when comparing those who were vaccinated in January to those vaccinated in April. This preliminary finding of vaccine waning as a factor of time from vaccince should prompt further investigations into long-term protection against different strains., The duration of effectiveness of SARS-CoV-2 vaccination is not yet known. Here, the authors present preliminary evidence of BNT162b2 vaccine waning across all age groups above 16, with a higher incidence of infection in people who received their second dose early in 2021 compared to later in the year.

Celiac disease clinical presentation is constantly changing. We set to determine the prevalence of elevated transaminases in newly diagnosed celiac patients and to evaluate this sub-group of patients for associated clinical and laboratory findings and assess their natural course of disease following therapeutic diet initiation. We conducted a prospective-observational study of all newly diagnosed pediatric celiac patients, between August 2016 and April 2018, in a pediatric gastroenterology clinic. Clinical data, anthropometrics, and blood test results were recorded at diagnosis and at 3, 6, and 12 months, respectively, of follow-up. We compared patients with normal and elevated transaminases at diagnosis. ALT threshold was set at 24 U/l. Of 125 newly diagnosed celiac patients, 31 (24.8%) had elevated ALT at diagnosis; two (1.6%) with over 3 × ULN. Patients with elevated ALT at diagnosis were significantly younger (mean age 5.5 (SD 3.4) vs. 7.3 (SD 3.7) years, p

Deployment of the BNT162b2 mRNA Covid-19 Vaccine in Israel began in December 2020.This is a retrospective analysis of serological data, describing SARS-CoV-2 anti-S IgG kinetics in 116 Israeli healthcare workers administrated the BNT162b2 vaccine.Seroconversion occurred by day 14 in all individuals, with IgG levels peaking approximately 30 days post inoculation.This study demonstrated the kinetics of the antibody response post vaccination with BNT162b2. The robustness of seroconversion was observed, alongside a statistically significant difference in IgG levels between employees over and younger 50 years of afge. Further research is required in order to examine the antibody kinetics overtime, as well as whether the age-dependent difference persists.

Purpose: Understanding the normal range of laboratory values as pertained to different age groups and males or females is paramount in health care delivery. We aimed to assess the distribution of glucose levels by age and sex in the general population of children using a large-scale population-based cohort.Methods: A retrospective study with real-world de-identified data from a large, state mandated health fund in Israel among children aged 2 to 18 years old between 2006 and 2019. Age, sex, and BMI differences in mean glucose levels were evaluated using 3-way Anova.Results: Study included 130,170 blood samples from 117,411 children, 53.3% were female. After adjusting for age boys had higher glucose levels than girls, with a mean of 89.21 ±8.66 mg/dL vs. 87.59 ±8.35 (p

Few data describing pre-diagnosis changes in patients with inflammatory bowel disease (IBD) exist. We aimed to determine if there is a pattern of change in use of health resources, medications and laboratory results in the years preceding diagnosis.This retrospective study used electronic medical records of Maccabi Health Services (MHS). Patients with IBD ≥ 16 years of age and minimum of 5-years follow-up were identified by entry into the MHS IBD registry and included in the analysis. Demographic, clinical, medication and laboratory data were collected. Generalized estimating equation model was applied to study trends and compare between years.This study included 5643 patients with IBD. Of these, 3039 (53.8%) had Crohn's disease (CD), 2322 (41.1%) had ulcerative colitis (UC) and 282 (5%) had indeterminate colitis (IC). Laboratory parameters including white blood cells, platelets and C-reactive protein showed significant increases while haemoglobin and mean cell volume showed significant decreases in mean values in the 2 years prior to diagnosis with stable values prior to that (p 0.0001). Parameters such as creatinine, total protein and albumin showed significant, progressive decreases in mean values starting 5 years prior to diagnosis (p 0.0001). Patients with CD had distinct laboratory trends when compared with patients with UC.Changes in laboratory parameters, healthcare service and medication use occur during the 5-year period before IBD diagnosis. These data can have future clinical applicability by developing a composite score and referral algorithm introducing red flags into primary care visits and appropriate referral for specialist care.

ObjectivesThere are paucity of studies examining naturally acquired immunity against SARS-CoV-2 in children and adolescents, though they are generally the last group to be afforded the vaccine, and a significant portion of them are still unvaccinated. This study examined the duration of protection conferred by a previous SARS-CoV-2 infection amongst children and adolescents.DesignA retrospective study, applying two complementary approaches: a matched test-negative case control design and a retrospective cohort design.SettingNationally centralized database of Maccabi Healthcare Services, an Israeli national health fund that covers 2.5 million people.ParticipantsThe study population included between 293,743 and 458,959 individuals (depending on the model), 5-18 years of age, who were unvaccinated SARS-CoV-2 naïve persons or unvaccinated convalescent patients.Main outcomes and measuresAnalyses focused on the period of July 1 to December 13, 2021, a Delta-dominant period in Israel. We evaluated three SARS-CoV-2-related outcomes: (1) documented PCR confirmed infection or reinfection, (2) COVID-19 and (3) severe COVID-19.ResultsOverall, children and adolescents who were previously infected acquired durable protection against reinfection (symptomatic or not) with SARS-CoV-2 for at least 18 months. Importantly, no COVID-19 related deaths were recorded in either the SARS-CoV-2 naïve group or the previously infected group. Effectiveness of naturally-acquired immunity against a recurrent infection reached 89.2% (95% CI: 84.7%-92.4%) three to six months after first infection, mildly declining to 82.5% (95% CI, 79.1%-85.3%) nine months to one year after infection, then remaining rather steady for children and adolescents for up to 18 months, with a slight non-significant waning trend. Additionally, we found that ages 5-11 exhibited no significant waning of naturally acquired protection throughout the outcome period, whereas waning protection in the 12-18 age group was more prominent, but still mild.ConclusionsChildren and adolescents who were previously infected with SARS-CoV-2 remain protected against reinfection to a high degree for 18 months. Policy decision makers should consider when and if convalescent children and adolescents should be vaccinated. Nonetheless, further research is needed to examine naturally acquired immunity against emerging variants, including the Omicron.

Purpose: To assess the distribution of glucose levels by age and sex in healthy children using a large-scale population-based cohort.Methods: A retrospective study with real-world de-identified data from a large, state mandated health fund in Israel among healthy children aged 2 to 18 years old between 2006 and 2019. Age, sex, and BMI differences in mean glucose levels were evaluated using 3-way Anova.Results: Study included 130,170 blood samples from 117,411 children, 53.3% were female. After adjusting for ager boys had higher glucose levels than girls, with a mean of 89.21 ±8.66 mg/dL vs. 87.59 ±8.35 (p

Little is known about the effect of prematurity on later development of celiac disease (CD). We conducted a retrospective analysis of real-world data examining the association between very low birth weight (VLBW) prematurity and later development of CD autoimmunity (CDA) in 3580 infants born between years 2000 and 2012 and their matched controls. At a median of 12 years, VLBW prematurity was negatively associated with later development of CDA with a cumulative prevalence of 5.9 per 1000 versus 10.3 per 1000 (P = 0.02), though more former VLBW premature infants were ever tested for CDA (48.5% vs 37.4%, P < 0.001). The odds ratio for developing CDA among children born preterm at VLBW was 0.57 (95% confidence interval (CI) 0.35-0.92) as compared with matched controls. There was no difference in clinical characteristics of CDA between both groups. In conclusion, VLBW preterm infants present a decreased risk for the development of CDA during childhood and adolescence.

IMPORTANCE: Pregnant women were excluded from the BNT162b2 messenger RNA (mRNA) COVID-19 vaccine (Pfizer-BioNTech) preauthorization trial. Therefore, observational data on vaccine safety for prenatally exposed newborns are critical to inform recommendations on maternal immunization. OBJECTIVE: To examine whether BNT162b2 mRNA vaccination during pregnancy is associated with adverse neonatal and early infant outcomes among the newborns. DESIGN, SETTING, AND PARTICIPANTS: Population-based cohort study comprising all singleton live births in March through September 2021, within a large state-mandated health care organization in Israel, followed up until October 31, 2021. EXPOSURE: Maternal BNT162b2 mRNA vaccination during pregnancy. MAIN OUTCOMES AND MEASURES: Risk ratios (RR) of preterm birth, small birth weight for gestational age (SGA), congenital malformations, all-cause hospitalizations, and infant death. Stabilized inverse probability weighting was used to adjust for maternal age, timing of conception, parity, socioeconomic status, population subgroup, and maternal influenza immunization status. RESULTS: The cohort included 24 288 eligible newborns (49% female, 96% born at ≥37 weeks’ gestation), of whom 16 697 were exposed (n = 2134 and n = 9364 in the first and second trimesters, respectively) to maternal vaccination in utero. Median (IQR) follow-up after birth was 126 days (76-179) among exposed and 152 days (88-209) among unexposed newborns. No substantial differences were observed in preterm birth rates between exposed and unexposed newborns (RR = 0.95; 95% CI, 0.83-1.10) or SGA (RR = 0.97; 95% CI, 0.87-1.08). No significant differences were observed in the incidence of all-cause neonatal hospitalizations (RR = 0.99; 95% CI, 0.88-1.12), postneonatal hospitalizations after birth (RR = 0.95; 95% CI, 0.84-1.07), congenital anomalies (RR = 0.69; 95% CI, 0.44-1.04), or infant mortality over the study period (RR = 0.84; 95% CI, 0.43-1.72). CONCLUSIONS AND RELEVANCE: This large population-based study found no evident differences between newborns of women who received BNT162b2 mRNA vaccination during pregnancy, vs those of women who were not vaccinated, and contributes to current evidence in establishing the safety of prenatal vaccine exposure to the newborns. Interpretation of study findings is limited by the observational design.

The aim of this real-life, big data population-based study was to evaluate differences in symptomatic presentation of children infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) between the third and fourth waves of the pandemic in Israel, dominated by the Alpha and Delta variants, respectively. Our cohort included all children and adolescents, members of the second-largest Health Maintenance Organisation in Israel that had positive real-time polymerase chain reaction (RT-PCR) test during the third and fourth waves of the pandemic (December 1, 2020 - April 30, 2021, and June 1, 2021 - October 10, 2021, respectively). A total of 32,485 and 44,130 children and adolescents in the third and fourth waves were included in the final analysis. The rate of children with symptomatic disease among patients with documented SARS-CoV-2 infection was higher in the fourth wave compared to the third wave (49.9% vs. 37.5%). The most commonly reported symptom and the only symptom that substantially differed between waves was fever, with 33% of SARS-CoV-2 infected children in the fourth wave vs. 13.6% in the third wave. Preschool children had the lowest prevalence of febrile illness compared to other age groups.Conclusion: Children and adolescents infected during the fourth wave of the pandemic in Israel, a Delta-dominant period, had a significantly higher rate of symptomatic febrile illness than the Alpha-dominant period. This phenomenon occurred across all age groups.

The aim of this real-life, big data population-based study was to evaluate differences in symptomatic presentation of children infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) between the third and fourth waves of the pandemic in Israel, dominated by the Alpha and Delta variants, respectively. Our cohort included all children and adolescents, members of the second-largest Health Maintenance Organization in Israel that had positive real-time polymerase chain reaction (RT-PCR) test during the third and fourth waves of the pandemic (December 1, 2020, to April 30, 2021, and June 1, 2021, to October 10, 2021, respectively). A total of 32,485 and 44,130 children and adolescents in the third and fourth waves were included in the final analysis. The rate of children with symptomatic disease among patients with documented SARS-CoV-2 infection was higher in the fourth wave compared to the third wave (49.9% vs. 37.5%). The most commonly reported symptom and the only symptom that substantially differed between waves was fever, with 33% of SARS-CoV-2 infected children in the fourth wave vs. 13.6% in the third wave. Preschool children had the lowest prevalence of febrile illness compared to other age groups.Children and adolescents infected during the fourth wave of the pandemic in Israel, a Delta-dominant period, had a significantly higher rate of symptomatic febrile illness than the Alpha-dominant period. This phenomenon occurred across all age groups.• There are differences in COVID-19 severity among adults and children during different waves of the pandemic. • There is a paucity of data regarding symptomatic characteristics in children in large-scale cohorts aside from hospital settings.• In a time period dominated by the Delta variant, there were substantially more children with symptomatic disease and febrile illness compared to a period dominated by the alpha variant. • Preschool children had the lowest rate of febrile illness among all age groups.

Background Waning of protection against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) conferred by 2 doses of the BNT162b2 vaccine begins shortly after inoculation and becomes substantial within 4 months. With that, the impact of prior infection on incident SARS-CoV-2 reinfection is unclear. Therefore, we examined the long-term protection of naturally acquired immunity (protection conferred by previous infection) compared to vaccine-induced immunity. Methods A retrospective observational study of 124 500 persons, compared 2 groups: (1) SARS-CoV-2-naive individuals who received a 2-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 vaccine, and (2) previously infected individuals who have not been vaccinated. Two multivariate logistic regression models were applied, evaluating four SARS-CoV-2-related outcomes—infection, symptomatic disease (coronavirus disease 2019 [COVID-19]), hospitalization, and death—between 1 June and 14 August 2021, when the Delta variant was dominant in Israel. Results SARS-CoV-2-naive vaccinees had a 13.06-fold (95% confidence interval [CI], 8.08–21.11) increased risk for breakthrough infection with the Delta variant compared to unvaccinated-previously-infected individuals, when the first event (infection or vaccination) occurred during January and February of 2021. The increased risk was significant for symptomatic disease as well. When allowing the infection to occur at any time between March 2020 and February 2021, evidence of waning naturally acquired immunity was demonstrated, although SARS-CoV-2 naive vaccinees still had a 5.96-fold (95% CI: 4.85–7.33) increased risk for breakthrough infection and a 7.13-fold (95% CI: 5.51–9.21) increased risk for symptomatic disease. Conclusions Naturally acquired immunity confers stronger protection against infection and symptomatic disease caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 2-dose vaccine-indued immunity.

To describe trends and correlates of acid-suppressant therapy usage during the first year of life.A population-based cohort in a large state-mandated health fund in Israel, including members born between 2005 and 2020, was conducted. Acid-suppressant therapy initiation was defined by any purchase within the first year of life. The association between acid-suppressant therapy initiation with medical and sociodemographic characteristics was assessed via logistic regression.Among 595 860 children, acid-suppressant therapy was initiated in 22 412 (37.6 per 1000). The incidence rate increased by 2.8-fold from 18.2 per 1000 in 2005 to 51.0 per 1000 in 2020, furthermore the median age at initiation decreased. Primary care providers accounted for 74.8% of prescribing physicians in 2005 vs 96.1% in 2020, whereas the prevalence of prescribing gastroenterologists decreased from 18.8% to 2.8%. Preterm birth and small weight per gestational age were associated with acid-suppressant therapy usage, with an aOR of 4.23 (95% CI 3.59-4.99), 3.05 (95% CI 2.72-3.42), and 1.65 (95% CI 1.58-1.74) for extreme, very, and moderate preterm vs term birth and aOR 1.22 (95% CI 1.16-1.28) for small weight per gestational age. Birth order was inversely associated with acid-suppressant therapy initiation, with aOR 0.62 (95% CI 0.60-0.65) for third born vs firstborns. High socioeconomic status was linearly associated with initiation, with aOR 1.12 (95% CI 1.11-1.12) per 1-point increase on a 10-point score.Our analysis demonstrates a substantial increase in early life exposure to acid-suppressant therapy during recent years in Israel. Correlates for initiation in early life were identified to define a population for intervention to reduce potential unnecessary use.

Studies have shown decreased response to coronavirus disease 2019 (COVID-19) vaccinations in some populations. In addition, it is possible that vaccine-triggered immune activation could trigger immune dysregulation and thus exacerbate inflammatory bowel diseases (IBD). In this population-based study we used the epi-Israeli IBD Research Nucleus validated cohort to explore the effectiveness of COVID-19 vaccination in IBD and to assess its effect on disease outcomes.We included all IBD patients insured in 2 of the 4 Israeli health maintenance organizations, covering 35% of the population. Patients receiving 2 Pfizer-BioNTech BNT162b2 vaccine doses between December 2020 and June 2021 were individually matched to non-IBD controls. To assess IBD outcomes, we matched vaccinated to unvaccinated IBD patients, and response was analyzed per medical treatment.In total, 12,109 IBD patients received 2 vaccine doses, of whom 4946 were matched to non-IBD controls (mean age, 51 ± 16 years; median follow-up, 22 weeks; interquartile range, 4-24). Fifteen patients in each group (0.3%) developed COVID-19 after vaccination (odds ratio, 1; 95% confidence interval, 0.49-2.05; P = 1.0). Patients on tumor necrosis factor (TNF) inhibitors and/or corticosteroids did not have a higher incidence of infection. To explore IBD outcomes, 707 vaccinated IBD patients were compared with unvaccinated IBD patients by stringent matching (median follow-up, 14 weeks; interquartile range, 2.3-20.4). The risk of exacerbation was 29% in the vaccinated patients compared with 26% in unvaccinated patients (P = .3).COVID-19 vaccine effectiveness in IBD patients is comparable with that in non-IBD controls and is not influenced by treatment with TNF inhibitors or corticosteroids. The IBD exacerbation rate did not differ between vaccinated and unvaccinated patients.

Beyond their substantial protection of individual vaccinees, coronavirus disease 2019 (COVID-19) vaccines might reduce viral load in breakthrough infection and thereby further suppress onward transmission. In this analysis of a real-world dataset of positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test results after inoculation with the BNT162b2 messenger RNA vaccine, we found that the viral load was substantially reduced for infections occurring 12–37 d after the first dose of vaccine. These reduced viral loads hint at a potentially lower infectiousness, further contributing to vaccine effect on virus spread. Breakthrough infections of SARS-CoV-2 occurring 12 or more days after the first dose of the BNT162b2 mRNA vaccine were associated with lower viral loads than those found in unvaccinated individuals, suggesting that the vaccine might reduce infectiousness.

BackgroundReports of waning vaccine-induced immunity against COVID-19 have begun to surface. With that, the comparable long-term protection conferred by previous infection with SARS-CoV-2 remains unclear.MethodsWe conducted a retrospective observational study comparing three groups: (1)SARS-CoV-2-naïve individuals who received a two-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 vaccine, (2)previously infected individuals who have not been vaccinated, and (3)previously infectedandsingle dose vaccinated individuals. Three multivariate logistic regression models were applied. In all models we evaluated four outcomes: SARS-CoV-2 infection, symptomatic disease, COVID-19-related hospitalization and death. The follow-up period of June 1 to August 14, 2021, when the Delta variant was dominant in Israel.ResultsSARS-CoV-2-naïve vaccinees had a 13.06-fold (95% CI, 8.08 to 21.11) increased risk for breakthrough infection with the Delta variant compared to those previously infected, when the first event (infection or vaccination) occurred during January and February of 2021. The increased risk was significant (PConclusionsThis study demonstrated that natural immunity confers longer lasting and stronger protection against infection, symptomatic disease and hospitalization caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 two-dose vaccine-induced immunity. Individuals who were both previously infected with SARS-CoV-2 and given a single dose of the vaccine gained additional protection against the Delta variant.

Background Red blood cell distribution width (RDW) has been assessed during COVID-19 patient hospitalization, however, further research should be done to evaluate RDW from routine community blood tests, before infection, as a risk factor for COVID-19 related hospitalization and mortality. Patients and methods RDW was measured as a predictor along with age, sex, chronic illnesses, and BMI in logistic regressions to predict hospitalization and mortality. Hospitalization and mortality odds ratios (ORs) were estimated with 95% confidence intervals (CI). RDW was evaluated separately as continuous and discrete (High RDW ≥ 14.5) variables. Results Four thousand one hundred and sixty-eight patients were included in this study, where 824 patients (19.8%) had a high RDW value ≥14.5% (High RDW: 64.7% were female, mean age 58 years [±22] vs. Normal RDW: 60.2% female, mean age 46 years [±19]). Eight hundred and twenty-nine patients had a hospitalization, where the median time between positive PCR and hospital entry was 5 [IQR 1–18] days. Models were analyzed with RDW (continuous) and adjusted for age, sex, comorbidities, and BMI suggested an OR of 1.242 [95% CI = 1.187–2.688] for hospitalization and an OR of 2.911 [95% CI = 1.928–4.395] for mortality (p

The short-term effectiveness of a two-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine was widely demonstrated. However, long term effectiveness is still unknown. A nationwide vaccination campaign was initiated early in Israel, allowing for a real-world evaluation of the interaction between protection and time-from-vaccine. The Delta (B.1.617.2) variant became the dominant strain in Israel in June 2021, as Israel is currently experiencing a new surge of cases. Leveraging the centralized computerized database of Maccabi Healthcare Services (MHS), we assessed the correlation between time-from-vaccine and incidence of breakthrough infection. We found that the risk for infection was significantly higher for early vaccinees compared to those vaccinated later. This preliminary finding should prompt further investigagions into long-term protection against different strains, and prospective clinical trials to examine the effect of a booster vaccine against breakthrough infection.

The role of a positive family history in pediatric inflammatory bowel disease (IBD) in the era of biologic therapy has not been elucidated. We retrospectively reviewed the medical records of children with IBD and retrieved demographic and clinical characteristics, including the presence of a positive family history of IBD, IBD phenotype, disease course, and therapy. Overall, 325 children (age range at diagnosis 11-15 years) were included, of whom 82 (25.2%) had a positive family history. Children diagnosed during 2016-2020 had a higher frequency of positive family history compared to those diagnosed during 2010-2015 (31.8% versus 20.7%, respectively, p = 0.024). Children with a positive family history had a higher risk for a stricturing phenotype than those with a negative family history (11.3% versus 2.8%, respectively, p = 0.052). They more often received nutritional therapy (53.7% versus 36.6%, p = 0.007) and less often received corticosteroids (36.6% versus 52.7%, p = 0.012). More children with a negative family history needed intensification of biologic therapy (p = 0.041).Conclusion: The rate of a positive family history of IBD in the pediatric IBD population is increasing. A positive family history may have some impact upon IBD phenotype but none on IBD outcome. What is Known: •Familial clustering of inflammatory bowel disease (IBD) has been reported in 5%-15% of IBD patients. •The investigation of the impact of a positive family history upon IBD characteristics and severity revealed conflicting results. What is New: •In this cohort of 325 children with IBD, 25.2% had a positive family history. •The rate of a positive family history of IBD in the pediatric IBD population is increasing. •A positive family history may have some impact upon IBD phenotype but none on IBD outcome.

ObjectivesCeliac disease clinical presentation is constantly changing. We set to determine the prevalence of elevated transaminases in newly diagnosed celiac patients, and to evaluate this sub-group of patients for associated clinical and laboratory findings and assess their natural course of disease following therapeutic diet initiation.MethodsWe conducted a prospective-observational study of all newly-diagnosed pediatric celiac patients, between August 2016 – April 2018, in a pediatric gastroenterology clinic. Clinical data, anthropometrics and blood test results were recorded at diagnosis and at three, six and twelve months of follow-up. We compared patients with normal and elevated transaminases at diagnosis. ALT threshold was set at 24 U/l.ResultsOf 125 newly-diagnosed celiac patients, 31 (24.8%) had elevated ALT at diagnosis; two (1.6%) with over 3xULN. Patients with elevated ALT at diagnosis were significantly younger (mean age 5.5 (SD- 3.4) vs 7.3 (SD- 3.7) years, p

Key Points Question Is 1 dose of the BNT162b2 COVID-19 mRNA vaccine associated with protection against infection with SARS-CoV-2 and symptomatic COVID-19 in real-world settings? Findings In this comparative effectiveness study of 503 875 individuals who received 1 dose of the BNT162b2 vaccine, the first dose of the vaccine was associated with an approximately 51% reduction in the risk of SARS-CoV-2 infections at 13 to 24 days after immunization compared with 1 to 12 days after vaccination. The first dose was associated with 54% effectiveness against symptomatic COVID-19. Meaning The results of this study agree with vaccine efficacy as reported in the phase III randomized clinical trial after 1 dose., This comparative effectiveness study examines the effectiveness associated with 1 dose of the BNT162b2 COVID-19 vaccine in a real-world setting., Importance The BNT162b2 vaccine showed high efficacy against COVID-19 in a phase III randomized clinical trial. A vaccine effectiveness evaluation in a real-world setting is needed. Objective To assess the short-term effectiveness of the first dose of the BNT162b2-vaccine against SARS-CoV-2 infection 13 to 24 days after immunization in a real-world setting. Design, Setting, and Participants This comparative effectiveness study used data from a 2.6 million-member state-mandated health care system in Israel. Participants included all individuals aged 16 years and older who received 1 dose of the BNT162b2 vaccine between December 19, 2020, and January 15, 2021. Data were analyzed in March 2021. Exposure Receipt of 1 dose of the BNT162b2 vaccine. Main Outcomes and Measures Information was collected regarding medical history and positive SARS-CoV-2 polymerase chain reaction test and COVID-19 symptoms from 1 day after first vaccine to January 17, 2021. Daily and cumulative infection rates in days 13 to 24 were compared with days 1 to 12 after the first dose using Kaplan-Meier survival analysis and generalized linear models. Results Data for 503 875 individuals (mean [SD] age, 59.7 [14.7] years; 263 228 [52.4%] women) were analyzed, of whom 351 897 had follow-up data for days 13 to 24. The cumulative incidence of SARS-CoV-2 infection was 2484 individuals (0.57%) during days 1 through 12 and 614 individuals (0.27%) in days 13 through 24. The weighted mean (SE) daily incidence of SARS-CoV-2 infection in days 1 through 12 was 43.41 (12.07) infections per 100 000 population and 21.08 (6.16) infections per 100 000 population in days 13 through 24, a relative risk reduction (RRR) of 51.4% (95% CI, 16.3%-71.8%). The decrease in incidence was evident from day 18 after the first dose. Similar RRRs were calculated in individuals aged 60 years or older (44.5%; 95% CI, 4.1%-67.9%), those younger than 60 years (50.2%; 95% CI, 14.1%-71.2%), women (50.0%; 95% CI, 13.5%-71.0%), and men (52.1%; 95% CI, 17.3%-72.2%). Findings were similar in subpopulations (eg, ultraorthodox Jewish: RRR, 53.5% [95% CI, 19.2%-73.2%]) and patients with various comorbidities (eg, cardiovascular diseases: RRR, 47.2% [95% CI, 7.8%-69.8%]). Vaccine effectiveness against symptomatic COVID-19 was 54.4% (95% CI, 21.4%-73.6%). Conclusions and Relevance In this comparative effectiveness study of a single dose of the BNT162b2 vaccine, results were comparable to that of the phase III randomized clinical trial.

Background Pathophysiological mechanisms active in inflammatory bowel disease (IBD), such as mucosal barrier repair, innate and adaptive immune responses, intestinal motility and gut microbiome, all exhibit diurnal variations. Chronic disruption of the molecular clock augments inflammatory response. We have shown that newly diagnosed, naïve to treatment, young IBD patients showed reduced clock gene expression in both inflamed and non-inflamed intestinal tissues and in peripheral White blood cells (WBCs). This reduction correlated with disease activity1. Our aim in the current study was to determine whether certain clock genes correlate with disease activity scores or inflammatory markers in Crohn’s disease (CD) vs. ulcerative colitis (UC). Methods Fourteen CD and 11 UC patients, 8–22 years old, were recruited. Patients were evaluated upon diagnosis and during medical treatment. Disease activity scores, C-reactive protein (CRP) and faecal calprotectin (Fcal) levels were measured and WBC were analysed for clock gene (CLOCK, BMAL1, CRY1, CRY2, PER1 and PER2) expression. Clock gene expression levels were correlated to disease activity scores (clinically active vs. remission), CRP levels (5 mg/l) and Fcal levels (250 μg/mg) in CD (21 samples) and UC patients (20 samples). Results In UC, CLOCK (p < 0.025), CRY1 (p < 0.033) and PER1 (p < 0.038) showed decreased expression when Fcal levels were >>250 μg/mg. When compared with the clinical status only BMAL1 showed reduced expression (p < 0.019). CRP levels showed no correlation with clock gene expression. In CD, CRP as well as the clinical status correlated with clock gene expression. Whereas CLOCK was reduced (p < 0.019), PER2 was induced (p < 0.005) when CRP levels were >5 mg/dl. Furthermore, CLOCK (p < 0.0005), PER1 (0.017) and PER2 (0.044) were reduced in CD patients with an active disease. However, Fcal did not correlate with clock gene expression. Conclusion Altered levels of certain clock genes were demonstrated in young CD and UC patients in relapse vs. remission and correlated with Fcal in UC patients and clinical status as well as CRP levels in CD patients. Reference

BACKGROUND Although 3,000,000 Americans are afflicted with Inflammatory Bowel Disease (IBD) encompassing Crohn’s Disease (CD) and Ulcerative Colitis (UC)1, timely diagnosis is a challenge due to non-specific and overlapping symptoms.2 More than 20% of patients may be initially misdiagnosed3 causing delayed diagnosis and treatment, potentially leading to increased risk of complications2 and irreversible mucosal damage.4 Artificial intelligence (AI) models can alert physicians to patients who would otherwise be misdiagnosed, potentially improving patient outcomes and reducing costs. We aimed to develop PredictAI, a proprietary AI Gradient Boosted Decision Tree based machine learning algorithm and test its accuracy in identifying undiagnosed CD and UC in the primary care setting. METHODS This was a retrospective study of 2,471,267 patients’ electronic medical records (EMR) from Maccabi Healthcare Services in Israel. Sufficient data was available between the years 2010-2020, of which 2 consecutive years (2015-2016) were pre-assigned to the test set. Inclusion criteria were: (i) CD or UC ICD code as defined by Maccabi’s Registry,5 (ii) no other autoimmune disease diagnosis, (iii) at least 4 years of data antedating first suspicion by primary care physician (PCP) of IBD were available. First suspicion was defined as any diagnostic test, procedure, or referral to a specialist, indicating suspicion of IBD. Here we included adult data only. RESULTS Of 2,471,267 patients, 1,214 had a first-time diagnosis of IBD and available antedating data in the years 2015-2016. Of these, PredictAI identified 126, 120, 104, 93 patients 1, 2, 3 and 4 years prior to initial PCP suspicion, respectively. For CD, it predicted 83/229 (36%) of patients 1 year prior to PCP initial suspicion of disease, 70/211 (33%) patients 2 years prior, 60/179 (33%) patients 3 years prior and 56/148 (38%) patients 4 years prior. Discriminatory accuracy area under the curve (AUC) was 76%, 75%, 75% and 78%, 1, 2, 3 and 4 years before initial PCP suspicion, respectively (Figure 1). Corresponding early-identification ratio and discriminatory accuracy for UC was 42/238 (17%, AUC=71%), 50/225 (22%, AUC=70%), 44/187 (23%, AUC=72%) 37/161 (23%, AUC=74%), for 1,2,3 and 4 years before initial PCP suspicion of UC, respectively (Figure 2). Specificity for CD and UC each was above 90%. CONCLUSIONS PredictAI accurately identified CD and UC diagnosis in 17-38% of patients presenting to primary care up to 4 years prior to PCP’s initial suspicion, potentially reducing time to diagnosis.

Background Gastroesophageal reflux disease (GERD) is associated with high utilization of health care services. Diagnostic tests usually are not required to establish GERD diagnosis, but endoscopy is recommended for patients with alarm symptoms such as dysphagia and unintentional weight loss, and those whose symptoms are not relieved by proton pump inhibitors (PPIs) therapy. Evidence on the correlates of utilization of gastroenterology health services among GERD patients is limited. The study aim was to examine associations of patient and physician’s characteristics with high utilization of gastroenterology services. Methods In a cross-sectional study using the database of the second largest integrated care organization in Israel, data of all adult GERD patients (N = 75,219) in 2012–2015 were analyzed. High utilization of services was assessed using two dependent variables analyzed separately: undergoing two or more gastroscopies or having six or more visits to a gastroenterology consultant during the study-period. Results Overall, 11,261 (15.0%) patients had two or more gastroscopies and 23,703 (31.5%) had six or more visits to a gastroenterology consultant. The likelihood of high utilization of gastroscopy increased with age; in immigrants from the Former Soviet Union versus patients who were born in Israel; residents of Jerusalem, the south, the north and Haifa districts versus the center district; in patients with high PPI purchases, and in patients who belonged to clinics in which the physician-manger had no board certification. The correlates were similar for visits to a gastroenterology consultant. Conclusions Patient and physician’s characteristics were related to high utilization of gastroenterology services among GERD patients. The associations with age and country of birth might reflect more severe disease. The regional differences warrant further research and interventions at the district level. Training in gastroenterology of primary care physicians without a board certification is warranted. Electronic supplementary material The online version of this article (10.1186/s13584-019-0335-3) contains supplementary material, which is available to authorized users.

OBJECTIVES: Recommendations for diagnosing and treating eosinophilic esophagitis (EoE) are evolving; however, information on real world clinical practice is lacking. To assess the practices of pediatric gastroenterologists diagnosing and treating EoE and to identify the triggering allergens in European children. METHODS: Retrospective anonymized data were collected from 26 European pediatric gastroenterology centers in 13 countries. Inclusion criteria were: Patients diagnosis with EoE, completed investigations prescribed by the treating physician, and were on stable medical or dietary interventions. RESULTS: In total, 410 patients diagnosed between December 1999 and June 2016 were analyzed, 76.3% boys. The time from symptoms to diagnosis was 12 ± 33.5 months and age at diagnosis was 8.9 ± 4.75 years. The most frequent indications for endoscopy were: dysphagia (38%), gastroesophageal reflux (31.2%), bolus impaction (24.4%), and failure to thrive (10.5%). Approximately 70.3% had failed proton pump inhibitor treatment. The foods found to be causative of EoE by elimination and rechallenge were milk (42%), egg (21.5%), wheat/gluten (10.9%), and peanut (9.9%). Elimination diets were used exclusively in 154 of 410 (37.5%), topical steroids without elimination diets in 52 of 410 (12.6%), both diet and steroids in 183 of 410 (44.6%), systemic steroids in 22 of 410 (5.3%), and esophageal dilation in 7 of 410 (1.7%). Patient refusal, shortage of endoscopy time, and reluctance to perform multiple endoscopies per patient were noted as factors justifying deviation from guidelines. CONCLUSIONS: In this "real world" pediatric European cohort, milk and egg were the most common allergens triggering EoE. Although high-dose proton pump inhibitor trials have increased, attempted PPI treatment is not universal.

Objectives Data regarding women infected with SARS-CoV-2 during early trimesters are scarce. We aimed to assess preterm birth (PTB) and small-for-gestational-age (SGA) rates in a large and unselected cohort by trimester at infection and overall. Design A retrospective cohort study including all women with a positive SARS-CoV-2 RT-PCR test during a non-ectopic singleton pregnancy between February 21st 2020 and July 2nd 2021 (N = 2753). Each infected woman was matched to a non-infected pregnant woman by age, last menstruation date, sector, and socioeconomic status. Methods Logistic regression was conducted to assess the risks of PTB and SGA including an interaction between group and trimester of infection. Multivariable models included underlying diseases, previous abortions and null parity. Subgroup analyses were conducted on symptomatic infected women and matched non-infected women. Results A total of 2753 /2789 (98.7%) eligible women that were infected during pregnancy could be matched, among them, 17.4% and 48.4% were infected during the first and third trimesters, respectively. While first and second trimester infections were not associated with PTB (p>0.8), third trimester infections and in particular after 34 weeks of gestation had a greater risk of PTB with adjusted ORs of 2.76 (95% CI 1.63–4.67) and 7.10 (95% CI 2.44–20.61), respectively. PTB risk was further heightened in symptomatic third trimester infections (OR = 4.28, 95% CI 1.94–9.25). SGA risk was comparable between study groups across all trimesters of infection. Pregnancy loss incidence was similar in both groups (adjusted OR = 1.16; 95% CI 0.90–1.50). Conclusion SARS-CoV-2 infection was associated with increased risk of PTB only among women infected during late pregnancy, particularly among symptomatic women.

Background Coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines were shown to be highly efficacious in preventing the disease in randomized controlled trials; nonetheless, evidence on the real-world effectiveness of this vaccine is limited. Study objective was to evaluate the effectiveness of BNT162b2 vaccine in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19-related hospitalization and mortality. Methods This historical cohort study included members of a large health provider in Israel that were vaccinated with at least 1 dose of BNT162b2. The primary outcome was incidence rate of a SARS-CoV-2 infection confirmed with real-time polymerase chain reaction (rt-PCR), between 7 and 27 days after second dose (protection-period), as compared to days 1–7 after the first dose, where no protection by the vaccine is assumed (reference-period). Results Data of 1 178 597 individuals vaccinated with BNT162b2 were analyzed (mean age 47.7 years [SD = 18.1], 48.4% males) of whom 872 454 (74.0%) reached the protection period. Overall, 4514 infections occurred during the reference period compared to 728 during the protection period, yielding a weighted mean daily incidence of 54.8 per 100 000 (95% confidence interval [CI]: 26.1–115.0 per 100 000) and 5.4 per 100 000 (95% CI: 3.5–8.4 per 100 000), respectively. The vaccine effectiveness in preventing infection was 90% (95% CI: 79%–95%) and 94% (95% CI: 88%–97%) against COVID-19. Among immunosuppressed patients, vaccine effectiveness against infection was 71% (95% CI: 37%–87%). The adjusted hazard ratios for hospitalization in those infected were 0.82 (95% CI: .36–1.88), 0.45 (95% CI: .23–.90), and 0.56 (95% CI: .36–.89) in the age groups 16–44, 45–64. and ≥75 years, respectively. Conclusions The effectiveness of the BNT162b2 vaccine is comparable to the one reported in the phase III clinical trial.

Mass vaccination has the potential to curb the current COVID-19 pandemic by protecting vaccinees from the disease and possibly lowering the chance of transmission to unvaccinated individuals. The high effectiveness of the widely-administered BNT162b vaccine in preventing not only the disease but also infection suggests a potential for a population-level effect, critical for disease eradication. However, this putative effect is difficult to observe, especially in light of highly fluctuating spatio-temporal epidemic dynamics. Here, analyzing vaccination records and test results collected during a rapid vaccine rollout for a large population from 223 geographically defined communities, we find that the rates of vaccination in each community are highly correlated with a later decline in infections among a cohort of under 16 years old which are unvaccinated. These results provide observational evidence that vaccination not only protects individual vaccinees but also provides cross-protection to unvaccinated individuals in the community.

Mass vaccination has the potential to curb the current COVID-19 pandemic by protecting individuals who have been vaccinated against the disease and possibly lowering the likelihood of transmission to individuals who have not been vaccinated. The high effectiveness of the widely administered BNT162b vaccine from Pfizer-BioNTech in preventing not only the disease but also infection with SARS-CoV-2 suggests a potential for a population-level effect, which is critical for disease eradication. However, this putative effect is difficult to observe, especially in light of highly fluctuating spatiotemporal epidemic dynamics. Here, by analyzing vaccination records and test results collected during the rapid vaccine rollout in a large population from 177 geographically defined communities, we find that the rates of vaccination in each community are associated with a substantial later decline in infections among a cohort of individuals aged under 16 years, who are unvaccinated. On average, for each 20 percentage points of individuals who are vaccinated in a given population, the positive test fraction for the unvaccinated population decreased approximately twofold. These results provide observational evidence that vaccination not only protects individuals who have been vaccinated but also provides cross-protection to unvaccinated individuals in the community.

Vaccinations are considered the major tool to curb the current SARS-CoV-2 pandemic. A randomized placebo-controlled trial of the Pfizer BNT162b2 vaccine has demonstrated a 95% efficacy in preventing COVID-19 disease. These results are now corroborated with statistical analyses of real-world vaccination rollouts, but resolving vaccine effectiveness across demographic groups and its interaction with comorbidities is challenging. Here, applying a multivariable logistic regression analysis approach to a large patient-level dataset, including SARS-CoV-2 tests, vaccine inoculations and personalized demographics, we model vaccine effectiveness at daily resolution and its interaction with sex, age and comorbidities. Vaccine effectiveness gradually increased post day 12 of inoculation, then plateaued, around 35 days, reaching 95.0% [CI 93.4%-96.3%] for all infections and 99.5% [CI 97.0%-99.9%] for symptomatic infections. While effectiveness was on average uniform for men and women, it declined mildly but significantly with age especially for males. Effectiveness further declined for people with type 2 diabetes, COPD, and immunosuppression, as well as cardiac disease in females. Quantifying real-world vaccine effectiveness, including both biological and behavioral effects, our analysis provides initial measurement of vaccine effectiveness across demographic groups.

With more than 100 million confirmed COVID-19 cases as of March 2021, reinfection is still considered to be rare. In light of increasing reports of reinfected COVID-19 patients, the need to better understand the real risk for reinfection is critical, with potential effects on public health policies aimed at containing the spread of SARS-CoV-2. In this descriptive preliminary report, we conducted a large-scale assessment on the country level of the possible occurrence of COVID-19 reinfection within the members of a large healthcare provider in Israel. Out of 149,735 individuals with a documented positive PCR test between March 2020 and January 2021, 154 had two positive PCR tests at least 100 days apart, reflecting a reinfection proportion of 1 per 1000. Given our strict inclusion criteria, we believe these numbers represent true reinfection incidence in MHS and should be clinically regarded as such.

Beyond their substantial protection of individual vaccinees, it is hoped that the COVID-19 vaccines would reduce viral load in breakthrough infections thereby further suppress onward transmission. Here, analyzing positive SARS-CoV-2 test results following inoculation with the BNT162b2 mRNA vaccine, we find that the viral load is reduced 4-fold for infections occurring 12-28 days after the first dose of vaccine. These reduced viral loads hint to lower infectiousness, further contributing to vaccine impact on virus spread.

BackgroundBNT162b2 vaccines showed high efficacy against COVID-19 in a randomised controlled phase-III trial. A vaccine effectiveness evaluation in real life settings is urgently needed, especially given the global disease surge. Hence, we assessed the short-term effectiveness of the first dose of BNT162b2-vaccine against SARS-CoV-2 infection. Given the BNT162b2 Phase-III results, we hypothesized that the cumulative incidence of SARS-CoV-2 infection among vaccinees will decline after 12 days following immunization compared to the incidence during the preceding days.MethodsWe conducted a retrospective cohort study using data from 2·6 million-member state-mandated health provider in Israel. Study population consisted of all members aged 16 or above years who were vaccinated with BNT162b2-vaccine between December/19/2020 and January/15/2021. We collected information regarding medical history and positive SARS-CoV-2 polymerase chain reaction test from days after first dose to January/17/2021. Daily and cumulative infection rates in days 13-24 were compared to days 1-12 after first dose using Kaplan-Meier survival analysis and generalized linear models.FindingsData of 503,875 individuals (mean age 59·7 years SD=14·7, 47·8% males) were analysed, of whom 351,897 had 13-24 days of follow-up. The cumulative incidence of SARS-CoV-2 infection was 0·57% (n=2484) during days 1-12 and 0·27% (n=614) in days 13-24. A 51·4% relative risk reduction (RRR) was calculated in weighted-average daily incidence of SARS-CoV-2 infection from 43·41-per-100,000(SE=12·07) in days 1-12 to 21·08-per-100,000(SE=6·16) in days 13-24 following immunization. The decrement in incidence was evident from day 18 after first dose. Similar RRRs were calculated in individuals aged 60 or above (44.5%), younger individuals (50.2%), females (50.0%) and males (52.1%). Findings were similar in sub-populations and patients with various comorbidities.ConclusionsWe demonstrated an effectiveness of 51% of BNT162b2 vaccine against SARS-CoV-2 infection 13-24 days after immunization with the first dose. Immunization with the second dose should be continued to attain the anticipated protection.Research in contextEvidence before this studyWe searched PubMed for follow-up studies regarding the effectiveness of BNT162b2 mRNA Covid-19 Vaccine without any language restrictions. The search terms were (BNT162b2 OR mRNA Covid-19 Vaccine) AND (effectiveness OR real-world OR phase IV) until Jan 15, 2021. We found no relevant observational studies among humans. We also assessed Phase II and Phase III clinical trials with BNT162b2 mRNA vaccine.Added value of this studyTo our knowledge, this is the first and largest phase IV study on the effectiveness of the BNT162b2 mRNA COVID-19 vaccine in real-world settings. Our findings showed that the first dose of the vaccine is associated with an approximately 51% reduction in the incidence of PCR-confirmed SARS-CoV-2 infections at 13 to 24 days after immunization compared to the rate during the first 12 days. Similar levels of effectiveness were found across age groups, sex, as well as among individuals residing in Arab or ultra-orthodox Jewish communities that display an increased COVID-19 risk.Implications of all the available evidenceThe study results indicate that in real life the first dose of the new BNT162b2 mRNA COVID-19 vaccine confers around 50% protection against overall SARS-CoV-2 infections (symptomatic or asymptomatic). Together our findings and the 95% efficacy shown in the phase III trial, suggest that the BNT162b2 vaccine should be administered in two doses to achieve maximum protection and impact in terms of disease burden reduction and possibly reducing SARS-CoV-2 transmission. COVID-19 vaccines should be urgently deployed globally.

AIM More normal weight and overweight children are currently diagnosed with celiac disease (CD). We aimed to describe the relation between body mass index (BMI) and the clinical characteristics of paediatric CD and to determine the effect of a gluten-free diet (GFD) on BMI. METHODS Data on all children diagnosed with CD during 7/2010-7/2019 with documented anthropometric data at diagnosis were retrospectively analysed. The children were divided into three groups according to BMI status at diagnosis: underweight, normal weight and overweight (BMIs 85%, respectively). RESULTS Of the 236 children [median age 7.87 (4.91-11) years] included in the study, 24 (10.1%) were underweight at diagnosis and 32 (13.6%) were overweight. Diarrhoea as the presenting symptom was significantly more common in the overweight group (p = 0.012), while short stature was more common in the underweight group (p = 0.002). Following a GFD had no significant effect on the children's BMI during a median follow-up of 15.7 (0-85) months, but there was a significant shift of patients between the BMI categories (p

Background: BNT162b2 vaccines showed high efficacy against COVID-19 in a randomised controlled phase-III trial. A vaccine effectiveness evaluation in real life settings is urgently needed, especially given the global disease surge. Hence, we assessed the short-term effectiveness of the first dose of BNT162b2-vaccine against SARS-CoV-2 infection. Given the BNT162b2 Phase-III results, we hypothesized that the cumulative incidence of SARS-CoV-2 infection among vaccinees will decline after 12 days following immunization compared to the incidence during the preceding days. Methods: We conducted a retrospective cohort study using data from 2·6 million-member state-mandated health provider in Israel. Study population consisted of all members aged 16 or above years who were vaccinated with BNT162b2-vaccine between December/19/2020 and January/15/2021. We collected information regarding medical history and positive SARS-CoV-2 polymerase chain reaction test from days after first dose to January/17/2021. Daily and cumulative infection rates in days 13-24 were compared to days 1-12 after first dose using Kaplan-Meier survival analysis and generalized linear models. Findings: Data of 503,875 individuals (mean age 59·7 years SD=14·7, 47·8% males) were analysed, of whom 351,897 had 13-24 days of follow-up. The cumulative incidence of SARS-CoV-2 infection was 0·57% (n=2484) during days 1-12 and 0·27% (n=614) in days 13-24. A 51·4% relative risk reduction (RRR) was calculated in weighted-average daily incidence of SARS-CoV-2 infection from 43·41-per-100,000(SE=12·07) in days 1-12 to 21·08-per-100,000(SE=6·16) in days 13-24 following immunization. The decrement in incidence was evident from day 18 after first dose. Similar RRRs were calculated in individuals aged 60 or above (44.5%), younger individuals (50.2%), females (50.0%) and males (52.1%). Findings were similar in sub-populations and patients with various comorbidities. Interpretation: We demonstrated an effectiveness of 51% of BNT162b2 vaccine against SARS-CoV-2 infection 13-24 days after immunization with the first dose. Immunization with the second dose should be continued to attain the anticipated protection. Funding: No external funding was available for this study. Declaration of Interests: We declare no competing interests. Ethics Approval Statement: We obtained ethical approval from Maccabi Healthcare Services Ethics Committee.