Association between COVID-19 Vaccination and SARS-CoV-2 Infection among Household Contacts of Infected Individuals: A Prospective Household Study in England.

BACKGROUND: We investigated whether COVID-19 vaccination reduced SARS-CoV-2 infection risk among adult household contacts of COVID-19 index cases during the Alpha, Delta, and Omicron waves in England. METHODS: Between February 2021 and February 2022, SARS-CoV-2 RT-PCR nasal swabs were collected from COVID-19-confirmed index cases aged ≥20 years and their household contacts at enrolment and three and seven days thereafter. Generalized Estimating Equations models were fitted with SARS-CoV-2 positivity as the outcome and household contacts' vaccination status as the main exposure while adjusting for confounders. RESULTS: SARS-CoV-2 infection was confirmed in 238/472 household contacts (50.4%) aged ≥20 years. The adjusted relative risk (95% confidence interval) of infection in vaccinated versus unvaccinated household contacts was 0.50 (0.35-0.72) and 0.69 (0.53-0.90) for receipt of two doses 8-90 and >90 days ago, respectively, and 0.34 (0.23-0.50) for vaccination with three doses 8-151 days ago. Primary vaccination protected household contacts against infection during the Alpha and Delta waves, but only three doses protected during the Omicron wave. Vaccination with three doses in the index case independently reduced contacts' infection risk: 0.45 (0.23-0.89). CONCLUSIONS: Vaccination of household contacts reduces their risk of infection under conditions of household exposure though, for Omicron, only after a booster dose.

Characterization of Antibiotic Treatment among Children Aged 0-59 Months Hospitalized for Acute Bacterial Gastroenteritis in Israel.

BACKGROUND: We examined the extent and correlates of appropriate antibiotic use among children hospitalized with bacterial acute gastroenteritis (AGE) in Israel, a high-income country setting. METHODS: Data were collected from children aged 0-59 months who participated in active hospital-based surveillance of AGE undertaken during 2007-2015. Bacterial AGE was defined as having a positive stool culture for Salmonella, Shigella, Campylobacter, or dysentery. Appropriate antibiotic use was defined as the administration of ciprofloxacin, azithromycin, or third-generation cephalosporins during hospitalization or at discharge. RESULTS: Overall, 550 children had bacterial AGE; of those, 369 (67.1% [95% CI 63.1-70.9]) received antibiotics, mostly azithromycin (61.8%) and third-generation cephalosporins (37.9%). Appropriate antibiotic treatment was given to 318/550 (57.8% [95% CI 53.7-61.9]). Children aged 0-11 months vs. 24-49 months were more likely to receive appropriate antibiotic treatment (OR = 1.90 [95% CI 1.09-3.33]). Having dysentery (OR = 5.30 [95% CI 3.35-8.39]), performing blood culture (OR = 1.59 [95% CI 1.02-2.48]), and C-reactive protein (CRP) levels (OR = 1.01 [95% CI 1.01-1.02]) were positively associated with receiving appropriate antibiotic treatment. CONCLUSIONS: Most children with bacterial AGE received appropriate antibiotic treatment, which correlated with young age, dysentery, CRP level, and performing blood culture, suggesting more severe illness, thus supporting the clinical decisions of physicians.

Descemet membrane endothelial keratoplasty compared with ultrathin Descemet stripping automated endothelial keratoplasty: a meta-analysis.

AIMS: This study aims to compare the clinical outcome of Descemet membrane endothelial keratoplasty (DMEK) and ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) in patients with corneal endothelial dysfunction due to Fuchs' endothelial dystrophy or pseudophakic bullous keratopathy. METHODS: We conducted a meta-analysis using a literature search of Embase, PubMed, Cochrane CENTRAL, ClinicalTrials.gov and WHO ICTRP databases. We included randomised controlled trials (RCTs) and cohort studies that compared DMEK and UT-DSAEK (graft<130 µm), with a follow-up of ≥12 months, published until 20 February 2022. We used the Revised Cochrane risk-of-bias tool for RCTs and the Risk of Bias in Non-Randomised Studies-of Interventions system for cohort studies. RESULTS: Out of 144 records, 8 studies (3 RCTs, 2 fellow-eye studies and 3 cohort studies) were included, encompassing 376 eyes, (N=187 DMEK vs N=189 UT-DSAEK). The 12-month logarithm of the minimum angle of resolution best-corrected visual acuity (BCVA) was better post-DMEK (mean difference -0.06 (95% CI -0.10 to -0.02)), but with higher rebubbling risk: OR 2.76 (95% CI 1.46 to 5.22). Heterogeneity was significant I2=57%. Findings were consistent when excluding retrospective studies, including only studies with low risk of bias or RCTs only. An analysis of studies with mean DSAEK grafts <70 µm showed no significant difference in BCVA between the procedures. Publication bias was found in the BCVA analysis (Egger's test p=0.023). CONCLUSIONS: Post-DMEK BCVA is superior to post-UT-DSAEK when using <130 µm grafts. DSAEK grafts <70 µm may not significantly differ from DMEK. The higher risk of rebubbling with DMEK necessitates an appropriate selection of patients. PROSPERO REGISTRATION NUMBER: CRD42022340805.

Quality of life and severity of symptoms among patients with various degrees of reflux esophagitis: a prospective study.

Gastro-esophageal reflux disease (GERD) can cause erosive esophagitis (EE) and compromise the quality of life (QoL). We examined differences in symptom severity and QoL according to EE severity grade. A follow-up study was conducted among GERD patients at the Nazareth Hospital in Israel. Patients underwent a baseline gastroscopy in 2014-2020 during which the EE grade was determined using the Los Angeles classification. Follow-up telephone interviews were conducted during 2019-2020 with a mean time interval of 18.9 months (SD = 14.9) after the baseline gastroscopy to assess GERD symptoms using the Reflux disease questionnaire (RDQ) and QoL using the GERD QoL questionnaire. The patients were interviewed in their native language (Arabic or Hebrew). Overall, 149 (66.4% males) patients were included; 50 had EE grades C/D and 99 had grades A/B. The mean age at baseline and follow-up was 44.6 years (SD = 15.1) and 46.2 years (SD = 14.9), respectively. Cronbach's alpha was 0.928 and 0.855 for the RDQ and QoL questionnaires, respectively. Patients with EE C/D grades had more severe symptoms than patients with EE A/B grades (P = 0.05), especially in regurgitation scores (P = 0.03). Females had more severe symptoms (overall) than males (adjusted OR = 2.34; 95% CI 1.12-4.90). Patients with the more severe esophagitis EE C/D group (adjusted OR = 1.98; 95% CI 0.93-4.24) and those who used PPIs treatment (adjusted OR = 2.19; 95% CI 0.95-5.01) reported more severe GERD symptoms. The number of schooling years was significantly associated with better QoL score (beta coefficient 1.33, P = 0.005) but not EE grade or GERD symptoms. Follow-up endoscopy conducted among 22 patients with EE grades C/D showed that 13 (59.1%) of these patients had normal endoscopic findings, 6 patients (27.3%) had a grade A EE, 1 patient (4.5%) had grade B, and 2 (9.1%) remained with grade C EE. The Arabic and Hebrew versions of the RDQ and QoL questionnaires were highly reliable. GERD symptoms severity was more profound among patients with more severe esophagitis. No significant association between EE grade and QoL; this negative result might be due to the improvement in esophagitis endoscopic findings among patients with C/D grade.

Relationships of the gut microbiome with cognitive development among healthy school-age children.

Background: The gut microbiome might play a role in neurodevelopment, however, evidence remains elusive. We aimed to examine the relationship between the intestinal microbiome and cognitive development of school-age children. Methods: This cross-sectional study included healthy Israeli Arab children from different socioeconomic status (SES). The microbiome was characterized in fecal samples by implementing 16S rRNA gene sequencing. Cognitive function was measured using Stanford-Binet test, yielding full-scale Intelligence Quotient (FSIQ) score. Sociodemographics and anthropometric and hemoglobin measurements were obtained. Multivariate models were implemented to assess adjusted associations between the gut microbiome and FSIQ score, while controlling for age, sex, SES, physical growth, and hemoglobin levels. Results: Overall, 165 children (41.2% females) aged 6-9 years were enrolled. SES score was strongly related to both FSIQ score and the gut microbiome. Measures of α-diversity were significantly associated with FSIQ score, demonstrating a more diverse, even, and rich microbiome with increased FSIQ score. Significant differences in fecal bacterial composition were found; FSIQ score explained the highest variance in bacterial ß-diversity, followed by SES score. Several taxonomic differences were significantly associated with FSIQ score, including Prevotella, Dialister, Sutterella, Ruminococcus callidus, and Bacteroides uniformis. Conclusions: We demonstrated significant independent associations between the gut microbiome and cognitive development in school-age children.

Predictors of reinfection with pre-Omicron and Omicron variants of concern among individuals who recovered from COVID-19 in the first year of the pandemic.

OBJECTIVES: The predictors of SARS-CoV-2 reinfection are unclear. We examined predictors of reinfection with pre-Omicron and Omicron variants among COVID-19-recovered individuals. METHODS: Randomly selected COVID-19-recovered patients (N = 1004) who donated convalescent plasma during 2020 were interviewed between August 2021 and March 2022 regarding COVID-19 vaccination and laboratory-proven reinfection. The sera from 224 (22.3%) participants were tested for antispike (anti-S) immunoglobulin G and neutralizing antibodies. RESULTS: The participants' median age was 31.1 years (78.6% males). The overall reinfection incidence rate was 12.8%; 2.7% versus 21.6% for the pre-Omicron (mostly Delta) versus Omicron variants. Negative associations were found between fever during the first illness and pre-Omicron reinfection: relative risk 0.29 (95% confidence interval 0.09-0.94), high anti-N level at first illness and Omicron reinfection: 0.53 (0.33-0.85), and overall reinfection: 0.56 (0.37-0.84), as well as between subsequent COVID-19 vaccination with the BNT162b2 vaccine and pre-Omicron 0.15 (0.07-0.32), Omicron 0.48 (0.25-0.45), and overall reinfections 0.38 (0.25-0.58). These variables significantly correlated with immunoglobulin G anti-S follow-up levels. High pre-existing anti-S binding and neutralizing antibody levels against the SARS-CoV-2 Wuhan and Alpha strains predicted protection against Omicron reinfections. CONCLUSION: Strong immune responses after the first COVID-19 infection and subsequent vaccination with the BNT162b2 vaccine provided cross-protection against reinfections with the Delta and Omicron variants.

Multicenter Surveillance of Antimicrobial Resistance among Gram-Negative Bacteria Isolated from Bloodstream Infections in Ghana.

BACKGROUND: Antimicrobial resistance (AMR) in Gram-negative bacteria-causing bloodstream infections (BSIs), such as Klebsiella pneumoniae and non-typhoidal Salmonella (NTS), is a major public health concern. Nonetheless, AMR surveillance remains scarce in sub-Saharan Africa, where BSI treatment is largely empirical. The aim of the study was to determine the distribution and AMR patterns of BSI-causing NTS, K. pneumoniae, and other Gram-negative bacteria in Ghana. METHODS: A cross-sectional study was conducted between April and December 2021 at eleven sentinel health facilities across Ghana as part of a pilot study on the feasibility and implementation of the human sector AMR surveillance harmonized protocol in sub-Saharan Africa. Gram-negative bacteria recovered from blood specimens of febrile patients were identified using MALDI-TOF and evaluated for antimicrobial resistance using the BD Phoenix M50 analyzer and Kirby-Bauer disc diffusion. The Department of Medical Microbiology at the University of Ghana served as the reference laboratory. RESULTS: Out of 334 Gram-negative blood isolates, there were 18 (5.4%) NTS, 85 (25.5%) K. pneumoniae, 88 (26.4%) Escherichia coli, 40 (12.0%) Acinetobacter baumannii, 25 (7.5%) Pseudomonas aeruginosa, and 77 (23.1%) other Gram-negative bacteria. As a composite, the isolates displayed high resistance to the antibiotics tested-amoxicillin (89.3%), tetracycline (76.1%), trimethoprim-sulfamethoxazole (71.5%), and chloramphenicol (59.7%). Resistance to third-generation cephalosporins [ceftriaxone (73.7%), cefotaxime (77.8%), and ceftazidime (56.3%)] and fluoroquinolones [ciprofloxacin (55.3%)] was also high; 88% of the isolates were multidrug resistant, and the rate of extended-spectrum beta-lactamase (ESBL) production was 44.6%. Antibiotic resistance in K. pneumoniae followed the pattern of all Gram-negative isolates. Antibiotic resistance was lower in NTS blood isolates, ranging between 16.7-38.9% resistance to the tested antibiotics. Resistance rates of 38.9%, 22.2%, and 27.8% were found for cefotaxime, ceftriaxone, and ceftazidime, respectively, and 27.8% and 23.8% for ciprofloxacin and azithromycin, respectively, which are used in the treatment of invasive NTS. The prevalence of multidrug resistance in NTS isolates was 38.9%. CONCLUSIONS: Multicenter AMR surveillance of Gram-negative blood isolates from febrile patients was well-received in Ghana, and the implementation of a harmonized protocol was feasible. High resistance and multidrug resistance to first- or second-choice antibiotics, including penicillins, third-generation cephalosporins, and fluoroquinolones, were found, implying that these antibiotics might have limited effectiveness in BSI treatment in the country. Continuation of AMR surveillance in Gram-negative blood isolates is essential for a better understanding of the extent of AMR in these pathogens and to guide clinical practice and policymaking.

The development and validation of screening tools for semi-automated surveillance of surgical site infection following various surgeries.

Background: Surveillance of surgical site infections (SSIs) is essential for better prevention. We developed a screening method for SSIs in adults. Methods: The training dataset included data from patients who underwent orthopedic surgeries (N = 1,090), colorectal surgeries (N = 817), and abdominal hysterectomies (N = 523) during 2015-2018. The gold standard for the validation of the screening tool was the presence of SSI as determined by a trained infection control practitioner, via manual full medical record review, using the US Center for Disease Control and Prevention criteria. Using multivariable regression models, we identified the correlates of SSI. Patients who had at least one of these correlates were classified as likely to having SSI and those who did not have any of the correlates were classified as unlikely to have SSI. We calculated the sensitivity and specificity of this tool compared to the gold standard and applied the tool to a validation dataset (N = 1,310, years 2019-2020). Results: SSI was diagnosed by an infection control specialist in 8.2, 5.2, and 31.2% of the patients in the training dataset who underwent hysterectomies, orthopedic surgeries and colorectal surgeries, respectively, vs. 6.2, 6.6, and 25.5%, respectively, in the validation dataset. The correlates of SSI after abdominal hysterectomy were prolonged hospitalization, ordering wound or blood culture, emergency room visit and reoperation; in orthopedic surgery, emergency room visit, wound culture, reoperation, and documentation of SSI, and in colorectal surgeries prolonged hospitalization, readmission, and ordering wound or blood cultures. Area under the curve was >90%. The sensitivity and specificity (95% CI) of the screening tool were 98% (88-100) and 58% (53-62), for abdominal hysterectomy, 91% (81-96) and 82% (80-84) in orthopedic surgeries and 96% (90-98) and 62% (58-66) in colorectal surgeries. The corresponding values for the validation dataset were 89% (67-97) and 75% (69-80) in abdominal hysterectomy; 85% (72-93) and 83% (80-86) in orthopedic surgeries and 98% (93-99) and 59% (53-64) in colorectal surgeries. The number of files needed to be fully reviewed declined by 61-66. Conclusion: The presented semi-automated simple screening tool for SSI surveillance had good sensitivity and specificity and it has great potential of reducing workload and improving SSI surveillance.

Threshold protective levels of serum IgG to Shigella lipopolysaccharide: re-analysis of Shigella vaccine trials data.

OBJECTIVES: Establishing a correlate of protection is essential for the development and licensure of Shigella vaccines. We examined potential threshold levels of serum IgG to Shigella lipopolysaccharide (LPS) that could predict protection against shigellosis. METHODS: We performed new analyses of serologic and vaccine efficacy (VE) data from two randomized vaccine-controlled trials of the Shigella sonnei-Pseudomonas aeruginosa recombinant exoprotein A (rEPA) conjugate conducted in young adults and children aged 1-4 years in Israel. Adults received either S. sonnei-rEPA (n = 183) or control vaccines (n = 277). Children received the S. sonnei-rEPA conjugate (n = 1384) or S. flexneri 2a-rEPA conjugate (n = 1315). VE against culture-proven shigellosis was determined. Sera were tested for IgG anti-S. sonnei LPS antibodies. We assessed the association of various levels of IgG anti-S. sonnei LPS antibodies with S. sonnei shigellosis risk using logistic regression models and the reverse cumulative distribution of IgG levels. RESULTS: Among adults, four vaccinees and 23 controls developed S. sonnei shigellosis; the VE was 74% (95% CI, 28-100%). A threshold of ≥1:1600 IgG anti-S. sonnei LPS titre was associated with a reduced risk of S. sonnei shigellosis and a predicted VE of 73.6% (95% CI, 65-80%). The IgG anti-S. sonnei LPS correlated with serum bactericidal titres. In children, a population-based level of 4.5 ELISA Units (EU) corresponding to 1:1072 titre, predicted VE of 63%, versus 71% observed VE in children aged 3-4 years. The predicted VE in children aged 2-4 years was 49%, consistent with the 52% observed VE. CONCLUSION: Serum IgG anti-S. sonnei LPS threshold levels can predict the degree of VE and can be used for the evaluation of new vaccine candidates.

Associations of early-life exposures and socioeconomic status with cognitive development at preadolescence.

BACKGROUND: The long-term relations of socioeconomic status (SES) and early-life exposures with cognitive development at preadolescence are not fully understood, especially in low SES populations. We examined associations of SES and early-life exposures including feeding practices, physical growth and infections with cognitive development among preadolescents from underprivileged communities. METHODS: A prospective study was conducted among 146 healthy children from two relatively low SES Arab villages in Israel, who were recruited at age 1-9 weeks and followed until age 18 months. Information was obtained on their feeding practices, health status and growth indicators. Cognitive development at age 10-12 years was assessed using the Wechsler Intelligence Scale, including the full-scale intelligence quotient (FSIQ) and scores of four cognitive domains. Multiple linear regression models were performed. RESULTS: Nearly all the children (98%) were breastfed in infancy. Bivariate correlations were found of SES, growth indices and rates of diarrheal and respiratory illnesses in infancy, but not of feeding practices, with cognitive scores. In multivariable models, SES was positively (p < 0.001) associated with all the cognitive domains (beta coefficient ranges 4.3 to 8.2). Birthweight was positively associated with FSIQ (p = 0.039) and the perceptual reasoning index (p = 0.002). Weight for age Z score at age 10-14 months was positively associated with the verbal comprehension index (p = 0.003). The rate of respiratory illnesses was negatively associated with the perceptual reasoning index (p = 0.05). CONCLUSION: SES is strongly associated with cognitive development even in relatively low SES communities. Birthweight, weight indicators and respiratory illness in infancy might affect cognitive development through preadolescence.

Review of Israel's action and response during the COVID-19 pandemic and tabletop exercise for the evaluation of readiness and resilience-lessons learned 2020-2021.

Background: Reevaluating response plans is essential to ensuring consistent readiness and resilience to the COVID-19 pandemic. The "During Action Review" and Tabletop (DART) methodology provides a retrospective and prospective assessment to inform the adaptive response. Israel introduced COVID-19 vaccinations in December 2020 and was the first country to implement booster vaccination to address waning immunity and surges caused by new variants. We assessed Israel's readiness and resilience related to COVID-19 response while capturing the pre-vaccination and vaccination periods. Methods: A DART analysis was conducted between December 2020 and August 2021 among experts involved in the management of the COVID-19 pandemic in Israel. During the retrospective stage, a role-based questionnaire and discussions were undertaken in a participant-led review of the response, focusing on epidemiology and surveillance, risk communication, and vaccines. The prospective stage included tabletop exercises to evaluate short to long-term simulated scenarios. Results: Participants emphasized the pivotal role of Israel globally by sharing experiences with the pandemic, and vaccination. Perceived strengths included multi-sectoral collaboration between the Ministry of Health, healthcare providers, academia, military, and others, stretching capacities, expanding laboratory workload, and establishing/maintaining surveillance. The vaccine prioritization plan and strong infrastructure, including computerized databases, enabled real-life assessment of vaccine uptake and impact. Challenges included the need to change case definitions early on and insufficient staffing. Quarantine of patients and contacts was particularly challenging among underprivileged communities. Risk communication approaches need to focus more on creating norms in behavior. Trust issues and limited cooperation were noted, especially among ethnic and religious minorities. To ensure readiness and resiliency, participants recommended establishing a nationally deployed system for bringing in and acting upon feedback from the field, especially concerning risk communication and vaccines. Conclusion: Our study appraised strengths and weaknesses of the COVID-19 pandemic response in Israel and led to concrete recommendations for adjusting responses and future similar events. An efficient response comprised multi-sectoral collaboration, policy design, infrastructure, care delivery, and mitigation measures, including vaccines, while risk communication, trust issues, and limited cooperation with minority groups were perceived as areas for action and intervention.

Comparison between School-Age Children with and without Obesity in Nutritional and Inflammation Biomarkers.

Childhood obesity is a major health problem. We examined differences between children with obesity and normal weight in nutritional and inflammation biomarkers. A cross-sectional study was conducted among healthy children aged 10-12 years from Arab villages in Israel. Parents were interviewed regarding sociodemographic and children's health status. Body weight and height measurements were performed and weight categories were defined using the 2007 WHO growth curves. Blood samples were tested for complete blood count, levels of iron, ferritin, lipids, uric acid, and C-reactive protein (CRP). Overall, 146 children (59.0% males, mean age = 11.3 [SD = 0.5]) were enrolled. In total 43.8%, 14.1% and 42.3% of the participants had normal weight, overweight and obesity, respectively. A multivariable logistic regression model showed that children with overweight and obesity had lower iron, and HDL-C levels than children with normal weight. Levels of CRP, uric acid, LDL-C and lymphocytes were higher among children with overweight and obesity. In conclusion, our findings highlight the worse metabolic and nutritional status in overweight and obese children. Such markers play a role in metabolic syndrome, thus suggesting that metabolic syndrome might start in childhood.

Epidemiological and Clinical Characteristics of Non-Typhoidal Salmonella Bloodstream Infections in Central Israel: A Case-Control Study.

Non-typhoidal Salmonella (NTS) infection continues to be a significant cause of morbidity. In addition to gastroenteritis (GE), NTS may cause bloodstream infections (BSI). Our goals were to characterize the demographics, clinical characteristics and outcome of NTS-BSI in central Israel. The study was a retrospective, case-control study conducted at the Tel Aviv Sourasky Medical Center between 2001−2018. Cases with NTS-BSI were matched by age and compared with two control groups, hospitalized patients with NTS-GE and patients with E. coli BSI. The NTS-BSI group included 34 patients who were compared with 69 and 68 patients in the NTS-GE and E. coli BSI groups, respectively. In the NTS-BSI group, the median age was 59 years, with 20% of patients below 20 years of age. Diarrhea was less common in NTS-BSI patients compared with NTS-GE: 53% vs. 80% (p < 0.01). Compared with NTS-GE patients, NTS-BSI patients had a higher rate of recent antimicrobial use: 21% vs. 5.9%, p = 0.03, respectively. They also had a slightly higher Charlson Comorbidity Index score, and history of past malignancy and steroid use, but these differences were not statistically significant. Antimicrobial treatment was documented in 30/34 of the NTS-BSI patients vs. 55/69 of the NTS-GE patients (p < 0.001). NTS-BSI patients had higher rates of in-hospital death (23% vs. 4%, p < 0.01) and a longer length of stay (8 vs. 4 days, p < 0.001) compared with NTS-GE. There was no significant difference in the outcome compared with the E. coli BSI group. In conclusion, our study found relatively low rates of pediatric cases compared with previous studies in Israel. NTS-BSI patients had slightly higher rates of comorbidities compared with NTS-GE patients, and a similar prognosis to E. coli BSI patients.

Association of BNT162b2 Vaccine Third Dose Receipt With Incidence of SARS-CoV-2 Infection, COVID-19-Related Hospitalization, and Death Among Residents of Long-term Care Facilities, August to October 2021.

Importance: COVID-19 vaccine might be less immunogenic and effective among residents of long-term care facilities (LTCFs). Objective: To examine the association of BNT162b2 third dose (first booster dose) with overall SARS-CoV-2 infection, COVID-19 hospitalizations, and mortality among LTCF residents during a nationwide surge of the Delta variant in Israel. Design, Setting, and Participants: This observational cohort study conducted nationwide COVID-19 surveillance in LTCFs in Israel between August and October 2021. Participants were residents of LTCFs aged 60 years or older. Exposures: Vaccination with the third dose of BNT162b2 vaccine vs receipt of 2 doses at least 5 months earlier, based on self-preference and choice. Main Outcomes and Measures: The cumulative incidences of reverse transcription-polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infection, COVID-19 hospitalizations, and COVID-19-related deaths more than 7 days after vaccination with the third dose were compared between the groups using Kaplan-Meier curves. Hazard ratios (HRs) and 95% CIs were obtained using multivariable Cox regression models. Results: Among 18 611 residents included in the analysis, 12 715 (68.3%) were female, 463 (2.5%) were from the Arab population, 16 976 (91.2%) were from the general Jewish population, and 618 (3.3%) were from the ultraorthodox Jewish population; the mean (SD) age was 81.1 (9.2) years; 16 082 residents received their first booster dose (third dose) and 2529 were vaccinated with 2 doses at least 5 months earlier. The median (IQR) follow-up durations were 66 (60-70) days among 3-dose recipients and 56 (53-62) days among 2-dose-only recipients; 107 residents had SARS-CoV-2 infection after 7 days following vaccination with the booster dose compared with 185 among the 2-dose only group (cumulative incidence: 0.7% vs 7.5%; adjusted HR, 0.11 [95% CI, 0.07-0.15]). The respective adjusted HRs were 0.07 (95% CI, 0.03-0.14) and 0.10 (95% CI, 0.04-0.24) for the associations of vaccination with the third dose with hospitalization for mild-to-moderate COVID-19 and severe illness. Five COVID-19-related deaths occurred among the third dose vaccinees during the follow-up period compared with 22 among the 2-dose-only vaccinees (cumulative rate: 0.04% vs 0.9%; adjusted HR, 0.04 [95% CI, 0.009-0.16]). Conclusions and Relevance: This cohort study found significant inverse associations between vaccination with the third dose of the BNT162b2 vaccine with overall SARS-CoV-2 infection, COVID-19 hospitalizations, severe disease, and COVID-19-related deaths among LTCF residents during a massive surge caused by the Delta variant in Israel.

Comparison in Adherence to Treatment between Patients with Mild-Moderate and Severe Reflux Esophagitis: A Prospective Study.

Purpose: Gastro-esophageal reflux disease (GERD) is prevalent and causes erosive esophagitis (EE) with varying degrees of severity (A to D according to the Los Angeles Classification). Adherence to medical therapy is crucial for treatment success. We compared adherence to treatment recommendations between patients with EE grades C/D and A/B. Methods: A follow-up study was conducted during 2019−2020 among GERD patients who underwent a diagnostic gastroscopy 1−4 years earlier. Telephone interviews were conducted with patients diagnosed with severe EE grades C/D (n = 99) and randomly selected patients with mild−moderate EE grades A/B (n = 50). Patients with grades A/B were classified as adherent if they took proton pump inhibitors (PPIs) for 2−3 months as recommended. Patients with grades C/D were classified as adherent if they took medications for a prolonged period (>6 months) and performed a follow-up endoscopy as recommended. Results: The mean age of the participants was 44.6 years (SD = 15.1). The mean duration of PPIs therapy in patients with EE grades A/B was 9.4 months (SD = 8.7). Fourteen (14.2%) patients with EE grades A/B were non-adherent to treatment, compared to 21 (40.8%) patients with EE grades of C/D: adjusted OR = 0.06; CI 95% 0.02−0.18, p < 0.001. Follow-up endoscopy was performed by 44% of EE−C/D patients. Unmarried patients compared to married ones were less adherent (adjusted OR = 0.23; 95% CI 0.08−0.69, p < 0.001). Conclusions: Patients with esophagitis (EE−A/B) were more adherent to medical therapy when compared to patients with more severe esophagitis (EE−C/D).

Association of Receipt of the Fourth BNT162b2 Dose With Omicron Infection and COVID-19 Hospitalizations Among Residents of Long-term Care Facilities.

Importance: The administration of a fourth BNT162b2 COVID-19 vaccine dose was approved in Israel in December 2021 for individuals 60 years or older who were vaccinated with a third dose 4 months previously or earlier to control the substantial surge of the SARS-CoV-2 Omicron variant. Nonetheless, the association between receipt of the fourth dose and protection against infection remains elusive. Objective: To determine the association of the fourth BNT162b2 dose with protection against SARS-CoV-2-related infections, hospitalizations, and deaths during the Omicron surge in long-term care facility (LTCF) residents. Design, Setting, and Participants: This prospective cohort study was conducted in Israel between January 10 and March 31, 2022 and included LTCF residents 60 years or older. Exposures: Vaccination with the fourth dose of BNT162b2 vs 3 doses that were administered 4 months previously or earlier. Main Outcomes and Measures: Cumulative incidences of SARS-CoV-2 infections, hospitalizations, and deaths during the Omicron surge. The follow-up was initiated more than 7 days after receipt of the fourth dose, which was matched to the follow-up initiation date of those who had received 3 doses of vaccine in each facility. We obtained hazard ratios and 95% confidence intervals from multivariable Cox regression models. Results: The data of 43 775 residents (mean [SD] age, 80.1 [9.4] years; 29 679 women [67.8%]) were analyzed, of whom 24 088 (55.0%) and 19 687 (45.0%) received the fourth and third dose (4 months previously or earlier), respectively. The median follow-up time was 73 days (4-dose group: IQR, 6 days; 3-dose group: IQR, 56 days). More than 7 days postvaccination with the fourth dose, SARS-CoV-2 infection was detected among 4058 fourth-dose vs 4370 third-dose recipients (cumulative incidence, 17.6% vs 24.9%). The corresponding incidences of hospitalizations for mild-to-moderate COVID-19, severe illness, and mortality were 0.9% and 2.8%, 0.5% and 1.5%, and 0.2% and 0.5%, respectively. The adjusted protections were 34% (95% CI, 30%-37%), 64% (95% CI, 56%-71%), and 67% (95% CI, 57%-75%) against overall infection, hospitalizations for mild-to-moderate illness, and severe illness, respectively, and 72% (95% CI, 57%-83%) against related deaths. Conclusions and Relevance: The results of this cohort study suggest that receipt of a fourth BNT162b2 dose conferred high protection against COVID-19 hospitalizations and deaths among LTCF residents during a substantial Omicron variant surge, but protection was modest against infection. These findings are relevant to the control of COVID-19 pandemic globally, especially among the population of LTCFs.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Naturally Acquired Immunity versus Vaccine-induced Immunity, Reinfections versus Breakthrough Infections: A Retrospective Cohort Study.

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.

Socioeconomic disparities and household crowding in association with the fecal microbiome of school-age children.

The development of the gut microbiome occurs mainly during the first years of life; however, little is known on the role of environmental and socioeconomic exposures, particularly within the household, in shaping the microbial ecology through childhood. We characterized differences in the gut microbiome of school-age healthy children, in association with socioeconomic disparities and household crowding. Stool samples were analyzed from 176 Israeli Arab children aged six to nine years from three villages of different socioeconomic status (SES). Sociodemographic data were collected through interviews with the mothers. We used 16 S rRNA gene sequencing to characterize the gut microbiome, including an inferred analysis of metabolic pathways. Differential analysis was performed using the analysis of the composition of microbiomes (ANCOM), with adjustment for covariates. An analysis of inferred metagenome functions was performed implementing PICRUSt2. Gut microbiome composition differed across the villages, with the largest difference attributed to socioeconomic disparities, with household crowding index being a significant explanatory variable. Living in a low SES village and high household crowding were associated with increased bacterial richness and compositional differences, including an over-representation of Prevotella copri and depleted Bifidobacterium. Secondary bile acid synthesis, d-glutamine and d-glutamate metabolism and Biotin metabolism were decreased in the lower SES village. In summary, residential SES is a strong determinant of the gut microbiome in healthy school-age children, mediated by household crowding and characterized by increased bacterial richness and substantial taxonomic and metabolic differences. Further research is necessary to explore possible implications of SES-related microbiome differences on children's health and development.

The Incidence of SARS-CoV-2 Reinfection in Persons With Naturally Acquired Immunity With and Without Subsequent Receipt of a Single Dose of BNT162b2 Vaccine : A Retrospective Cohort Study.

BACKGROUND: There is insufficient evidence regarding the magnitude and durability of protection conferred by a combined effect of naturally acquired immunity after SARS-CoV-2 infection and vaccine-induced immunity. OBJECTIVE: To compare the incidence rate of SARS-CoV-2 reinfection in previously infected persons to that of previously infected persons who subsequently received a single dose of BNT162b2 messenger RNA vaccine. DESIGN: A retrospective cohort study emulating a randomized controlled target trial through a series of nested trials. SETTING: Nationally centralized database of Maccabi Healthcare Services, Israel. PARTICIPANTS: Persons with documented SARS-CoV-2 infection who did not receive subsequent SARS-CoV-2 vaccination were compared with persons with documented SARS-CoV-2 infection who received a single dose of the BNT162b2 vaccine at least 3 months after infection. INTERVENTION: Forty-one randomized controlled trials were emulated, in which 107 413 Maccabi Healthcare Services' members aged 16 years and older were eligible for at least 1 trial. MEASUREMENTS: SARS-CoV-2-related outcomes of infection, symptomatic disease, hospitalization, and death, between 2 March and 13 December 2021. RESULTS: A statistically significant decreased risk (hazard ratio, 0.18 [95% CI, 0.15 to 0.20]) for reinfection was found among persons who were previously infected and then vaccinated versus those who were previously infected but remained unvaccinated. In addition, there was a decreased risk for symptomatic disease (hazard ratio, 0.24 [CI, 0.20 to 0.29]) among previously infected and vaccinated persons compared with those who were not vaccinated after infection. No COVID-19-related mortality cases were found. LIMITATION: Hybrid protection against non-Delta variants could not be inferred. CONCLUSION: Persons previously infected with SARS-CoV-2 gained additional protection against reinfection and COVID-19 from a subsequent single dose of the BNT162b2 vaccine. Nonetheless, even without a subsequent vaccination, reinfection appeared relatively rare. PRIMARY FUNDING SOURCE: None.

Incidence and risk factors of hospitalisations for respiratory syncytial virus among children aged less than 2 years.

The study aim was to examine the incidence and risk factors of respiratory syncytial virus (RSV) bronchiolitis hospitalisations and disease severity among infants. We compared demographic and health characteristics of children aged 0-23 hospitalised for RSV bronchiolitis (cases, n = 1227) during 2008-2018 and control children (n = 554) of the same age admitted for non-respiratory disease. RSV antigen was detected in nasal swabs by immunochromatography. Multiple logistic regression models were applied. The average annual incidence of hospitalisation for RSV bronchiolitis was 12.6 per 1000 and 1.7 per 1000 (P < 0.001) among infants and toddlers, respectively, with winter seasonality (November-March). The risk of hospitalisation for RSV bronchiolitis increased among children aged 0-5 months (OR 7.66; 95% CI 5.61-10.45) and 6-11 months (OR 12.88, 95% CI 8.48-19.55), compared to those aged 12-23 months. Additional risk factors were living in low vs. higher socio-economic status towns (OR 1.49; 95% CI 1.14-1.95), having chronic medical conditions (OR 2.75; 95% CI 1.61-4.70), birth month (October-January vs. June-September) (OR 2.19; 95% CI 1.60-2.99) and history of stay in neonatal intensive care unit at birth (OR 2.37; 95% CI 1.27-4.41). Male children and those who had pneumonia were more likely to have severe RSV bronchiolitis. In conclusion, the burden of hospitalisations for RSV bronchiolitis is high, especially in young infants. Effective preventive measures such as RSV active vaccines can reduce the risk of hospitalisations for RSV bronchiolitis among these vulnerable groups.