Patients with chronic lymphocytic leukemia (CLL) have an increased risk for severe COVID-19 disease and mortality. The goal of this study (NCT04746092) was to determine the efficacy of COVID-19 vaccine in patients with CLL. We evaluated humoral immune responses to BNT162b2 mRNA COVID-19 vaccine in patients with CLL and compared responses with those obtained in age-matched healthy controls. Patients received two vaccine doses, 21 days apart, and antibody titers were measured using Elecsys® Anti-SARS-CoV-2S assay after administration of the second dose. In a total of 167 patients with CLL the antibody response rate was 39.5%. A comparison between 52 patients with CLL and 52 sex- and aged-matched healthy controls, revealed a significantly reduced response rate among patients (52% vs 100%, respectively; adjusted odds ratio=0.010, 95% CI 0.001-0.162; p<0.001). Response rate was highest in patients who obtained clinical remission after treatment (79.2%), followed by 55.2% in treatment-naïve and 16% only in patients under treatment at the time of vaccination. In patients treated with either BTK inhibitors or venetoclax ± anti-CD20 antibody, response rates were considerably low (16.0% and 13.6%, respectively). None of the patients exposed to anti-CD20 antibodies <12 months prior to vaccination responded. In a multivariate analysis, the independent predictors of response were younger age, females, lack of currently active treatment, IgG levels ≥550 mg/dL and IgM levels ≥40mg/dL. In conclusion, antibody-mediated response to BNT162b2 mRNA COVID-19 vaccine in patients with CLL is markedly impaired and affected by disease activity and treatment.
Increased resistance among isolates causing bacteremia constitutes a major challenge to medical practitioners and institutions. Variability between institutes is substantial, and requires the individual analysis of local trends. An eight-year (1997-2004) surveillance study of episodes of bacteremia was conducted in an 850-bed university hospital in central Israel. Trends of incidence, resistance, age, and mortality were analyzed. We studied 6,096 patient-unique episodes of bacteremia, of which, 2,722 (45.3%) were nosocomial and 523 (9.2%) involved children less than 18 years of age. The overall incidence of bacteremia episodes has increased over the study years by 39% and the patient mean age by 7.5 years. Gram-negative organisms accounted for 72% of hospital-acquired cases and 69% of community-acquired cases. There was a substantial increase in the incidence of nosocomial episodes, predominantly due to Gram-negative isolates, mainly Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia coli. Increased resistance to broad-spectrum antibiotics was noted among Gram-negative organisms, including quinolones (in K. pneumoniae), imipenem (A. baumannii and P. aeruginosa), piperacillin-tazobactam (K. pneumoniae), and amikacin (A. baumannii and P. aeruginosa). Increased resistance to oxacillin among coagulase-negative staphylococci was also noted. The all-cause mortality rates showed a significant rise. The patient age, intensive care unit (ICU) stay, and hospital acquisition were independently associated with mortality. We describe an increase in the incidence and resistance of Gram-negative organisms causing bacteremia and concomitant ageing of the patients with bacteremia. Similar patterns have been reported from other localities, and are of real concern.
We determined the extent by which mandatory reporting on isolates of Shigella and Salmonella underestimates the burden of diarrhoeal diseases in individuals aged <17 years in Israel and examined paediatricians' knowledge, attitudes and practices related to patient visits with diarrhoeal diseases. Sources of data were a nationwide population-based telephone survey for presence of diarrhoeal diseases, Maccabi Healthcare Services databases and a mail survey among its paediatricians. Monte Carlo simulation and rate estimates for all stages, from visit to physician to reporting on a culture-confirmed case of shigellosis or salmonellosis, were used to determine the underestimation factor. Of 1492 children, 5·7% reported a diarrhoeal episode during the 2 weeks prior to interview. The rate of visiting a physician with and without fever was 86% and 16%, respectively. A stool culture was performed for around 20% of patients and the isolation rates were 7·1% for Shigella and 2·1% for Salmonella. Paediatricians (n=214) ranked very young age of patient and the complaint 'bloody diarrhoea' as the most important determinants. We estimated that one reported isolate of Shigella or Salmonella represented 152 diarrhoeal episodes of all aetiologies. This estimate is important for further assessments of the true burden of diarrhoeal diseases.
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