IMPORTANCEDespite the high 3-dose vaccination rate among health care workers (HCWs) in Israel, a high rate of SARS-CoV-2 breakthrough infections in this group was observed during the Omicron wave. As a result, the Israeli Ministry of Health decided to recommend a fourth vaccine dose to medical staff. OBJECTIVE To evaluate the benefit of a fourth BNT162b2 vaccine dose on the breakthrough infection rate among HCWs. DESIGN, SETTING, AND PARTICIPANTS This multicenter cohort study was performed in January 2022, the first month of the 4-dose vaccination campaign, during a surge of the Omicron variant wave. All health care workers at 11 general hospitals in Israel who had been vaccinated with 3 doses up to September 30, 2021, and had not contracted COVID-19 before the vaccination campaign were included. EXPOSURES Vaccination with a fourth dose of the BNT162b2 vaccine during January 2022. MAIN OUTCOMES AND MEASURES Breakthrough COVID-19 infections in 4-dose recipients vs 3-dose recipients measured by a polymerase chain reaction test result positive for SARS-CoV-2. Health care workers were tested based on symptoms or exposure. RESULTS A total of 29 611 Israeli HCWs (19 381 [65%] female; mean [SD] age, 44 [12] years) had received 3 vaccine doses between August and September 2021; of these, 5331 (18%) received the fourth dose in January 2022 and were not infected by the first week after vaccination. Overall breakthrough infection rates were 368 of 5331 (7%) in the 4-dose group and 4802 of 24280 (20%)in the 3-dose group (relative risk, 0.35; 95% CI, 0.32-0.39). Similar reductions were found in a matched analysis by the exact day of receiving the third vaccine (relative risk, 0.61; 95% CI, 0.54-0.71) and in a time-dependent Cox proportional hazards regression model (adjusted hazard ratio, 0.56; 95% CI, 0.50-0.63). In both groups, no severe disease or death occurred. CONCLUSIONS AND RELEVANCEIn this cohort study, the fourth BNT162b2 vaccine dose resulted in a reduced breakthrough infection rate among hospital staff. This reduction was lower than that observed after the third dose; nevertheless, considering the high infectivity of the Omicron variant, which led to critical medical staff shortages, a fourth vaccine dose should be considered to mitigate the infection rate among HCWs.

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In low-dose test, using a 2.5 cm plastic tube ensures completeness of the intravenous adrenocorticotropic hormone injection dosage and provides equivalent cortisol responses.

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Introduction: Infections are a major cause of morbidity and mortality in patients with multiple myeloma (MM) and of these, one of the most frequent is gastroenteritis. This can be explained by immunoparesis, a known manifestation of MM and immunosuppression due to multiple lines of treatment. Other causes of diarrhea such as drugs or gastro-intestinal infiltration by plasma cells should also be excluded. Immunoglobulin A(IgA) is a major immunoglobulin on mucosal surface and defends the bowel from pathogens invasion. Data exists in literature about the protective role of IgA against Shiga toxin. Early isolation of pathogen and correct therapeutic intervention are important and can be lifesaving for MM myeloma patients. Until recently, diagnostic clinical laboratories utilized different methodologies to detect bacterial, parasitic, and viral causes of gastroenteritis. These tests have a number of disadvantages, including poor sensitivity, potentially long turnaround times, and complicated workflows. In addition, there are limited or almost no testing methods routinely available for most strains of Escherichia coli causing diarrhea. The Film Array GI Panel, is a relatively new method introduced recently, which provides comprehensive, simultaneous detection of 22 different enteric pathogens on stool specimens with a turnaround time as short as 1 hour . Because of its high cost it is not used routinely in all patients presenting to the emergency room with acute diarrhea. Here we summarize our real-life experience, using the BioFire PCR-Arrayfor 4 patients with relapsed /refractory MM who were admitted to our medical center with an acute presentation of gastroenteritis Methods: The Infectious Diseases Unit at our medical centre decided to introduce a strategic approach of the use of BioFire PCR-Array for the examination of stool samples, in immunocompromised patients who present to the emergency room with acute diarrhea. The panel used includes the following 22 pathogens: Campylobacter spp., Clostridium difficile(toxin A/B), Plesiomonas shigelloides, Salmonella spp., Vibriospp., Vibrio cholerae, Yersinia enterocolitica, enteroaggregative E. coli, enteropathogenic E. coli, enterotoxigenic E. coli, Shiga-like toxin-producing E. coli (stx1 and stx2) (including specific detection of E. coli O157), Shigella spp./enteroinvasive E. coli, Cryptosporidium spp., Cyclospora cayetanensis, Entamoeba histolytica, Giardia lamblia, adenovirus F 40/41, astrovirus, norovirus GI/GII, rotavirus A, and sapovirus. The assay is sent on the first day of patient admission, and results are reported to the Infectious Diseases Unit within one hour. Here we summarize the results obtained in four patients with MM treated at the Hemato-Oncology Unit in Bnai Zion Medical Centre , Haifa , who were hospitalized in 2018 due to acute diarrhea and had positive PCR-Biofire results; Results: All patients examined had relapsed/refractory MM and had received 2-5 treatment lines for MM. Two of the four patients had neutropenia on admission, two had low IgG level, three had low IgM level and all four had low IgA levels. Of the four patients with MM and acute diarrhea, evaluated by BioFire Film Array, one had two episodes of acute diarrhea on different occasions and was evaluated twice. Five pathogens were detected by BioFire FilmArray, STEC (Shiga-like toxin producing E. coli) was the most common bacteria encountered and was detected 3 times: EPEC (Enteropathogenic E. coli) and ETEC (Entertoxogenic E. coli) were detected one time each. Careful review of the literature did not identify any previous case report of patients with multiple myeloma who had Shiga-like toxin producing E. coli. All patients received antibiotics-Azithromycin and improved. Conclusion: In our experience using the PCR- Biofire assay we show that this approach is feasible and can be used safely to tailor therapy in immunocompromised patients. In all cases, E.Coli was found, most frequently STEC (Shiga-like toxin producing E. coli). Using this approach enable us to identify new pathogens causing diarrhea in immunocompromised patients, extremely quickly. These preliminary results reveal the need for more clinical experience using the Biofire FilmArray as a diagnostic test for patients with MM and other haematological malignancies, who present acutely with severe diarrhea. Disclosures Tadmor: NOVARTIS: Consultancy; ABBVIE: Consultancy; JNJ: Consultancy; PFIEZER: Consultancy; ROCHE: Research Funding. Polliack:ABBVIE: Consultancy; ROCHE: Research Funding.