Persistent COVID-19 in Immunocompromised Patients - Israeli Society of Infectious Diseases Consensus Statement on Diagnosis and Management.

BACKGROUND: Immunocompromised patients with impaired humoral immunity are at risk for persistent COVID-19 (pCOVID), a protracted symptomatic disease with active viral replication. OBJECTIVES: To establish a national consensus statement on the diagnosis, treatment, management, isolation, and prevention of pCOVID in adults. SOURCES: We base our suggestions on the available literature, our own experience and clinical reasoning. CONTENT: Literature on the treatment of pCOVID is scarce and consists of few case-reports and case series. The available studies provide low-quality evidence for monoclonal antibodies, convalescent plasma, anti-viral drugs, and immunomodulators. Different combination therapies are described. Continuous viral replication and anti-viral treatment may lead to the development of mutations that confer resistance to therapy. IMPLICATIONS: To reduce the risk of resistance and improve outcomes, we suggest treating pCOVID with a combination of antibody-based therapy and two anti-viral drugs for a duration of five to ten days. Immunomodulatory therapy can be added in patients with an inflammatory clinical picture. In case of treatment failure or relapse, prolonged anti-viral treatment can be considered. For the prevention of pCOVID we suggest active and passive vaccination, as well as early initiation of treatment for acute COVID-19. Additional research on pCOVID treatment is urgently needed.

Use of Fourier-transform infrared spectroscopy for real-time outbreak investigation of OXA-48-producing Escherichia coli.

BACKGROUND: Efficient infection control during carbapenem-resistant Enterobacterales outbreaks demands rapid and simple techniques for outbreak investigations. WGS, the current gold standard for outbreak identification, is expensive, time-consuming and requires a high level of expertise. Fourier-transform infrared (FTIR) spectroscopy (IR Biotyper) is a rapid typing method based on infrared radiation applied to samples, which provides a highly specific absorption spectrum. OBJECTIVES: To investigate an outbreak of OXA-48-producing Escherichia coli in real-time using FTIR and subsequently compare the results with WGS. METHODS: Twenty-one isolates were collected during a nosocomial outbreak, and identification and antibiotic susceptibilities were confirmed by VITEK®2. FTIR was conducted for all isolates, and nine representative isolates were sequenced. RESULTS: FTIR was able to correctly determine the clonal relatedness of the isolates and to identify the outbreak cluster, as confirmed by WGS. By WGS, isolates in the main FTIR cluster belonged to the same MLST type and core-genome MLST type, and they harboured similar plasmids and resistance genes, whereas the singletons external to the FTIR cluster had different genetic content. CONCLUSIONS: FTIR can operate as a rapid, efficient and reliable first-line tool for outbreak investigations during a real-time ongoing E. coli outbreak, which can contribute to limiting the spread of pathogens.

Dual Oxygenation in the Treatment of Hypoxemic Respiratory Failure: A Retrospective Cohort Study.

BACKGROUND: At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, many patients presented with acute hypoxemic respiratory failure, requiring ventilatory support. One treatment method was the addition of a reservoir mask to a high flow nasal cannula (HFNC) (dual oxygenation). OBJECTIVES: To evaluate the clinical outcomes of combining reservoir mask on top of a high-flow nasal cannula. METHODS: A retrospective cohort of adult patients who were admitted due to COVID-19 during the first year of the pandemic to Rambam Health Care Campus. The primary endpoint was 30-day mortality. Secondary endpoints were incidence of invasive positive pressure ventilation initiation and admission to the intensive care unit (ICU). Patients who received positive pressure ventilation for reasons other than hypoxemic respiratory failure or who were transferred to another facility while still on HFNC were excluded. RESULTS: The final analysis included 333 patients; 166 were treated with dual oxygenation and 167 with HFNC only (controls). No significant differences in baseline characteristics were noted between the groups. The dual oxygenation group was slightly older (69.2 ± 14.8 years vs. 65.6 ± 15.5 years, P = 0.034). The 30-day mortality (24.1% vs. 36.5%, P = 0.013), rates of invasive positive pressure ventilation (47% vs. 59.3%, P = 0.024), and ICU admissions (41.6% vs. 52.7%, P = 0.042) were all significantly lower in the dual oxygenation group. CONCLUSIONS: The addition of reservoir masks to HFNC may improve the oxygenation and overall prognosis in patients with severe hypoxemia due to COVID-19.

Identification and control of two outbreaks of unrelated New Delhi metallo-ß-lactamase-producing carbapenem-resistant Escherichia coli traced to the same endoscope defect.

We report 2 outbreaks of genetically unrelated carbapenem-resistant New Delhi metallo-ß-lactamase-producing Escherichia coli caused by contaminated duodenoscopes. Using endoscopes with disposable end caps, adherence to the manufacturer's reprocessing instructions, routine audits, and manufacturer evaluation are critical in preventing such outbreaks.

Immunogenicity and SARS-CoV-2 Infection following the Fourth BNT162b2 Booster Dose among Health Care Workers.

INTRODUCTION: The fourth SARS-CoV-2 vaccine dose was found to protect against infection and more importantly against severe disease and death. It was also shown that the risk of symptomatic or severe disease was related to the antibody levels after vaccination or infection, with lower protection against the BA.4 BA.5 Omicron variants. The aim of our study was to assess the impact of the fourth dose on infection and perception of illness seriousness among healthcare workers (HCWs) at a tertiary health care campus in Haifa, Israel, and to investigate the possible protective effect of antibody levels against infection. METHODS: We conducted a prospective cohort study among fully vaccinated HCWs and retired employees at Rambam Healthcare Campus (RHCC), a tertiary hospital in northern Israel. Participants underwent serial serological tests at 1, 3, 6, 9, 12 and 18 months following the second BNT162b2 vaccine dose. Only a part of the participants chose to receive the fourth vaccine. A multivariable logistic regression was conducted to test the adjusted association between vaccination, and the risk of infection with SARS-CoV-2. Kaplan-Meier SARS-CoV-2 free "survival" analysis was conducted to compare the waning effect of the first and second, third and fourth vaccines. Receiver Operating Characteristic (ROC) curve was plotted for different values of the sixth serology to identify workers at risk for disease. RESULTS: Disease occurrence was more frequent among females, people age 40-50 years old and those with background chronic lung disease. The fourth vaccine was found to have better protection against infection, compared to the third vaccine; however, it also had a faster waning immunity compared to the third vaccine dose. Antibody titer of 955 AU/mL was found as a cutoff protecting from infection. CONCLUSIONS: We found that the fourth vaccine dose had a protective effect, but shorter than the third vaccine dose. Cutoff point of 955 AU/mL was recognized for protection from illness. The decision to vaccinate the population with a booster dose should consider other factors, including the spread of disease at the point, chronic comorbidities and age, especially during shortage of vaccine supply.

Risk factors for acquisition of carbapenemase-producing versus non-carbapenemase-producing enterobacterales: a case-control study.

OBJECTIVES: We aimed to assess the association between carbapenem-resistant Enterobacterales (CRE) colonization pressure and carbapenem exposure and acquisition of carbapenemase-producing Enterobacterales (CPE) and non-carbapenemase-producing carbapenem-resistant Enterobacterales (non-CP-CRE). METHODS: We conducted a parallel 1:2 matched case-control study at Rambam Health Care Campus, Israel, from January 2014 to June 2017. The cases included all adults who acquired CPE or non-CP-CRE in hospital. The controls were hospitalized patients who were negative for CRE on screening and matched by age, hospitalization division and the number of hospitalization days 90 days prior to CRE screening. The exposures of interest were high CRE colonization pressure, defined as a higher-than-median proportion of CRE carriers in the concurrent patient's department before acquisition, and carbapenem exposure, assessed as days of treatment. Conditional logistic regression was used for analyses of CPE and non-CP-CRE. RESULTS: In total, 1058 patients were included: 278 CPE and 75 non-CP-CRE cases, matched to 556 and 149 controls, respectively. High CRE colonization pressure was associated with CPE acquisition (adjusted odds ratio [aOR], 2.6; 95% CI, 1.69-4.02); however, the duration of carbapenem treatment was not (aOR, 1.004; 95% CI, 0.98-1.03; 1-day increment). The duration of carbapenem treatment was significantly associated with non-CP-CRE acquisition (aOR per day, 1.07; 95% CI, 1.03-1.11). A source patient was identified significantly more frequently in epidemiological acquisition investigations of CPE than in those of non-CP-CRE (107/240, 44.6% vs. 18/64, 28.1%, respectively; p 0.017). CONCLUSIONS: CPE acquisition was associated with horizontal transmission, whereas non-CP-CRE was associated with carbapenem exposure. Differences in the drivers of acquisition mandate tailored infection prevention efforts.

Hospitalized Patients With Severe Coronavirus Disease 2019 During the Omicron Wave in Israel: Benefits of a Fourth Vaccine Dose.

BACKGROUND: Waning immunity and an increased incidence of coronavirus disease 2019 (COVID-19) during the Omicron outbreak led the Israeli Ministry of Health to recommend a fourth vaccine dose for high-risk individuals. In this study, we assessed its effect for hospitalized patients with severe breakthrough COVID-19. METHODS: In this multicenter cohort study of hospitalized adults with severe COVID-19 in Israel, from 15 to 31 January 2022, cases were divided according to the number of vaccinations received. Poor outcome was defined as mechanical ventilation or in-hospital death and was compared between 3- and 4-dose vaccinees using logistic regression. RESULTS: Included were 1049 patients, median age 80 years. Among them, 394 were unvaccinated, 386 and 88 had received 3 or 4 doses, respectively. The 3-dose group was older, included more males, and immunosuppressed patients but with similar outcomes, 49% vs 51% compared with unvaccinated patients (P = .72). Patients who received 4 doses were similarly older and immunosuppressed but had better outcomes compared with unvaccinated patients, 34% vs 51% (P < .01). We examined independent predictors for poor outcome in patients who received either 3 or 4 doses a median of 161 days or 14 days before diagnosis, respectively. Receipt of the fourth dose was associated with protection (odds ratio, 0.51; 95% confidence interval, .3-.87), as was remdesivir. Male sex, chronic renal failure, and dementia were associated with poor outcomes. CONCLUSIONS: Among hospitalized patients with severe breakthrough COVID-19, a recent fourth dose was associated with significant protection against mechanical ventilation or death compared with 3 doses.

Six-Year Surveillance of Acquired Bloodstream Infection in a Pediatric Intensive Care Unit in Israel.

OBJECTIVES: We studied profile of the bloodstream infections (BSI) in the pediatric intensive care unit (PICU) and identified predictors of mortality. METHODS: The study collected data from hospital records for children younger than 18-years who developed BSI during their PICU stay between 2014 and 2019. RESULTS: In 114 patients, 136 PICU-acquired BSIs with 152 pathogens were documented. The incidence of BSI was 47.12/1,000 PICU admissions and 7.95/1000 PICU hospital days. Gram-negative rods accounted for 75% of isolates, Gram-positive cocci accounted for 21.7% of isolates, and fungi accounted for 3.3% of isolated pathogens. ICU mortality was observed in 25 (21.9%) patients with a BSI compared to 94 (3.1%) patients without a BSI (P<0.001). Hemodynamic instability (P=0.014, OR 4.10, CI 1.33-12.66), higher blood urea nitrogen (BUN) (P=0.044), and lower albumin levels (P=0.029) were associated with increased risk of ICU mortality. CONCLUSION: BSI in the PICU is associated with increased mortality. Early identification and management of risk factors independently associated with poor clinical outcomes in these patients should be aimed to ensure improved survival.

Evaluation of Pediatric Screening for Resistant Pathogens in an Israeli Tertiary Center.

BACKGROUND: Antibiotic resistance is a worldwide problem associated with increased morbidity and mortality. OBJECTIVES: To evaluate multidrug resistant (MDR) bacteria carriage in selected populations. METHODS: Data were collected from all patients under 18 years who met our internal guidelines from 2015-2016. They were screened for carbapenem-resistant Enterobacteriaceae (CRE), extended spectrum beta-actamase (ESBL), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE). Indications for screening were non-resident non-Israeli patients (from the Palestinian Authority, Syria, and foreign patients), internal transfers from intensive care units, admission to high-risk departments, recent carriage of MDR bacteria, transfer from other hospitals, and recent hospitalization. Data were analyzed for MDR bacteria from at least one screening site (rectal, nasal, axillary, groin, throat). All data were analyzed per patient and per sample. RESULTS: During the study period 185/2632 positive screening sets (7%) were obtained from 725 patients. Of these, 165 patients (22.7%) were positive for at least one pathogen. Significantly fewer Israeli residents (120/615, 19.5%) tested positive compared to non-Israeli residents (45/110, 40.9%; P < 0.001). Past MDR bacteria carriage was the only significant screening indication (25/61, 41%; P < 0.001). CRE, VRE, MRSA, and ESBL prevalence rates were 0.6% (5/771), 0.5% (3/560) 0.5%, 4.2% (37/888), and 33.7% (139/413), respectively. Among non-ESBL carriers, MRSA was predominant with 38 positive cultures (n=34). CONCLUSIONS: Non-Israeli non-residents and patients with previous positive MDR screening are at higher risk for MDR bacteria. Indications used to identify high-risk patients for drug resistant pathogens were efficacious. More effort is needed to reduce excessive sampling.

Third BNT162b2 Vaccine Booster Dose against SARS-CoV-2-Induced Antibody Response among Healthcare Workers.

This study assessed humoral response to the third BNT162b2 dose among healthcare workers (HCW). This prospective cohort study of HCW tested for anti-spike antibodies (LIAISON SARS-CoV-2 S1/S2 IgG assay) at 1, 3, 6, 9, and 12 months after receiving the second BNT162b2 vaccine dose (tests 1, 2, 3, 4, and 5, respectively). A third (booster) vaccination dose was introduced before test 4. Linear regression model was used to determine the humoral response following vaccine doses. For each serology test, changes in log-transformed antibody concentrations over time, adjusted for age, sex, underlying diseases, steroid treatment, and smoking were described using the general linear mix model. Serology tests were performed at 3, 6, 9, and 12 months after the second vaccine dose in 1113, 1058, 986, and 939 participants, respectively. The third dose was received by 964 participants before the 9-month tests, 797 of whom participated in the 9- and 12-month serology tests. A significant inverse correlation was noted between time from third dose and antibody concentrations (Spearman correlation −0.395; p < 0.001). Age (p < 0.0001; CI 95% −0.005−−0.004), heart disease (p < 0.0001; CI 95% −0.177−−0.052), immunodeficiency (p < 0.0001; CI 95% 0.251−−0.106), and smoking (p < 0.0001; CI 95% −0.122−−0.040) were significantly associated with decreased antibody concentrations. Female sex (p = 0.03; CI 95% 0.013−0.066) was associated with increased antibody concentrations. The third booster dose had a better effect on immunogenicity, with higher antibody concentrations among tested HCW. Heart disease, smoking, and other known risk factors were associated with decreased antibody concentrations.

SARS-CoV-2 and seasonal influenza: similarities and disparities.

This report describes the differences in disease severity and clinical presentation between hospitalized patients with coronavirus disease 2019 (COVID-19) and others with seasonal influenza. A total of 136 influenza and 152 COVID-19 patients were included. Patients with influenza more frequently had dyspnea (p = 0.004), hypoxemia (p < 0.001), underlying diseases (p = 0.046), and elevated liver enzymes (p = 0.028). In contrast, patients with COVID-19 were overweight (p < 0.001), lymphopenic (p < 0.001), had elevated CRP (p = 0.011), and radiological abnormalities (p < 0.001). Patients with influenza were more severely ill on admission (NEWS > 5) (p < 0.001). However, length of hospital stay, ventilatory support, and 30-day-mortality were similar. Despite differences in clinical presentation and disease severity between influenza and COVID-19 patients, both groups had similar clinical outcomes.

Association between IgG antibody levels and adverse events after first and second Bnt162b2 mRNA vaccine doses.

OBJECTIVES: This study sought to correlate the SARS-CoV-2 IgG antibody response level to the BNT162b2 (Pfizer BioNTech) mRNA vaccine after the first and second doses with the reported adverse events. METHODS: This cohort study examined the adverse events profiles of people vaccinated with BNT162b2 in our institute between late 2020 and May 2021. Adverse events, age, and sex were reported using an electronic questionnaire, and their SARS-CoV-2 IgG antibody levels were retrieved from the hospital database. RESULTS: Between 20 December 2020 and 31 May 2021, the adverse events questionnaire was completed by 9700 individuals who received the first vaccine dose and 8321 who received the second dose. After the first and second doses, the average antibody levels were 62.34 AU/mL (mean 4-373) and 188.19 AU/mL (mean 20-392), respectively. All of the adverse events, except local pain, were more common after the second vaccine dose. Multivariate analysis showed that after the first vaccine dose, female sex and younger age (but not IgG titres) were associated with a higher probability of adverse events (OR 2.377, 95% CI, 1.607-3.515, p = 0.000; OR 0.959, 95% CI, 0.944-0.977, p £0.000; OR 1.002, 95% CI, 0.995-1.008, p £0.601; respectively); however, all three parameters were associated with the incidence of adverse events after the second dose (OR 2.332, 95% CI, 1.636-3.322, p = 0.000; OR 0.984, 95% CI, 0.970-0.999, p £0.039; OR 1.004, 95% CI, 1.001-1.007, p £0.022; respectively). DISCUSSION: Adverse events are significantly more common after the second BNT162b2 vaccine dose than after the first dose. We found an association between sex, age, and SARS-CoV-2 IgG antibody titre with the incidence of adverse events.

Hospitalised patients with breakthrough COVID-19 following vaccination during two distinct waves in Israel, January to August 2021: a multicentre comparative cohort study.

BackgroundChanging patterns of vaccine breakthrough can clarify vaccine effectiveness.AimTo compare breakthrough infections during a SARS-CoV-2 Delta wave vs unvaccinated inpatients, and an earlier Alpha wave.MethodsIn an observational multicentre cohort study in Israel, hospitalised COVID-19 patients were divided into three cohorts: breakthrough infections in Comirnaty-vaccinated patients (VD; Jun-Aug 2021) and unvaccinated cases during the Delta wave (ND) and breakthrough infections during an earlier Alpha wave (VA; Jan-Apr 2021). Primary outcome was death or ventilation.ResultsWe included 343 VD, 162 ND and 172 VA patients. VD were more likely older (OR: 1.06; 95% CI: 1.05-1.08), men (OR: 1.6; 95% CI: 1.0-2.5) and immunosuppressed (OR: 2.5; 95% CI: 1.1-5.5) vs ND. Median time between second vaccine dose and admission was 179 days (IQR: 166-187) in VD vs 41 days (IQR: 28-57.5) in VA. VD patients were less likely to be men (OR: 0.6; 95% CI: 0.4-0.9), immunosuppressed (OR: 0.3; 95% CI: 0.2-0.5) or have congestive heart failure (OR: 0.6; 95% CI: 0.3-0.9) vs VA. The outcome was similar between all cohorts and affected by age and immunosuppression and not by vaccination, variant or time from vaccination.ConclusionsVaccination was protective during the Delta variant wave, as suggested by older age and greater immunosuppression in vaccinated breakthrough vs unvaccinated inpatients. Nevertheless, compared with an earlier post-vaccination period, breakthrough infections 6 months post-vaccination occurred in healthier patients. Thus, waning immunity increased vulnerability during the Delta wave, which suggests boosters as a countermeasure.

COVID-19: Healthcare Workers May Be at Greater Risk Outside Their Work Environment-A Retrospective Observational Study.

BACKGROUND: With the availability of coronavirus disease 2019 (COVID-19) vaccine, concerns have been raised regarding pre-vaccination seroprevalence in healthcare workers (HCW). This study examines the seroprevalence of HCW at an Israeli tertiary medical center before first BNT162b2 vaccination. METHODS: This was a retrospective observational study. Before vaccination, HCW at our center were offered serological testing. Data on their epidemiological, workplace, and quarantine history were collected. The SARS-CoV-2 IgG assay was performed pre-vaccination. RESULTS: A total of 4,519 (82.5%) of the HCW were tested. Of these, 210 were seropositive; 101 had no known history of COVID-19. Of the 101 asymptomatic HCW, only 3 (3%) had worked at COVID-19 departments, and 70 (69.3%) had not been previously quarantined. Positive serology was similarly distributed across age groups, and about 40% had no children. Nearly half of the HCW tested were administrative and service staff. Overall, seropositive tests were associated with having no children (OR 1.42, 95% CI 1.06-1.89; P=0.0218), history of having been quarantined without proof of disease (OR 6.04, 95% CI 4.55-8.01; P<0.001), and Arab ethnicity (OR 3.36, 95% CI 2.54-4.43; P<0.001). Seropositivity was also more prevalent in members of the administration compared to other sectors, medical and paramedical, who are exposed to patients in their daily work (OR 1.365, 95% CI 1.02-1.82; P=0.04). CONCLUSIONS: The low percentage of asymptomatic COVID-19 among our HCW may reflect the high compliance to personal protective equipment use despite treating hundreds of COVID-19 patients. The relatively high number of childless seropositive HCW could reflect misconceptions regarding children as a main source of infection, leading to carelessness regarding the need for appropriate out-of-hospital protection.

ESCMID guidelines on testing for SARS-CoV-2 in asymptomatic individuals to prevent transmission in the health care setting.

SCOPE: This guideline addresses the indications for direct testing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in asymptomatic individuals in health care facilities, with the aim to prevent SARS-CoV-2 transmissions in these settings. The benefit of testing asymptomatic individuals to create a safe environment for patients and health care workers must be weighed against potential unintended consequences, including delaying necessary treatments owing to false positive results and lower quality of care owing to strict isolation measures. METHODS: A total of nine PICOs (population, intervention, comparison, outcome) on the topic of testing asymptomatic individuals was selected by the panel members. Subsequently, a literature search for existing guidelines and systematic reviews was performed on PubMed, Epistemonikos, and RecMap using relevant filters available in each database. Data on article/recommendation type, setting, target population, intervention, and quality of the evidence were extracted. Credibility of the systematic reviews was evaluated using the AMSTAR tool, and level of agreement with available recommendation was evaluated with the AGREE II score. Because the evidence available from systematic reviews was deemed insufficiently updated to formulate relevant recommendations, an additional search targeting relevant guidance documents from major public health institutions and original studies was performed. Provisional recommendations were discussed via web conferences until agreement was reached, and final recommendations were formulated according to the GRADE approach. RECOMMENDATIONS: Recommendations were formulated regarding systematic testing in asymptomatic individuals upon admission to a health care setting, during hospital stay, before elective procedures, and before scheduled nonsurgical procedures. Moreover, recommendations regarding testing of asymptomatic visitors, personal caregivers, and health care workers in health care facilities were presented. Recommendations also were given on contact tracing in asymptomatic patients or health care workers and the possibility of a negative screening test to shorten the quarantine period. Furthermore, if applicable, recommendations were specified to transmission rate and vaccination coverage.

The Changing Epidemiology of Carbapenemase-Producing Enterobacterales.

OBJECTIVE: Israeli hospitals were confronted with a major national outbreak of carbapenemase-producing Enterobacterales (CPE) starting in 2006, caused predominantly by monoclonal Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae. Our hospital, Rambam Health Care Campus (RHCC), was one of the medical centers affected by this outbreak. We aimed to investigate the changing epidemiology of CPE at RHCC since 2006. METHODS: This was a retrospective observational cohort study performed in Northern Israel (Haifa) at RHCC, which is a primary tertiary acute care academic hospital. The study included all patients who had acquired CPE at RHCC between January 2005 and December 2020. RESULTS: The proportion of patients infected with K. pneumoniae dropped from 100% of all CPE in the first years to 28% (37/134) in 2020. In 2014, the carbapenemase in 94% of all CPE patients (89/95) was KPC. This decreased to 56% in 2020, while New Delhi metallo-ß-lactamase (NDM) and OXA-48 carbapenemases increased from 4% and 2% to 29% (39/134) and 12.7% (17/134) of CPE, respectively. CONCLUSIONS: The CPE epidemic evolved from KPC-producing K. pneumoniae to involve different Enterobacterales and carbapenemases. Our results are a microcosm of the current global epidemiology attesting to globalization in bacteriology. The results have implications for infection control and antibiotic treatment of CPE infections.

NonTuberculous Mycobacteria Blood Stream Infection in Pediatric and Adult Patients: 15 Years Surveillance.

BACKGROUND: Nontuberculous Mycobacteria (NTM) are rare causes of bloodstream infection (BSI). This study addresses the management and prognosis of NTM BSI and the differences between adult and pediatric patients. METHODS: We retrospectively reviewed the medical charts of patients at any age with NTM BSI, from January 1, 2005, to June 30, 2020. Data on demographics, underlying conditions, clinical manifestations, NTM species, antibiotic treatments and outcomes were retrieved. RESULTS: Positive blood cultures for NTM were detected in 43 patients, 30 children and 13 adults. Median age: 10.37 years (IQR 6.692-39.864). Thirty-seven (86%) patients had an active malignant disease. Fever was the chief sign in 23 (53.5%) patients and pulmonary manifestations in 14 (32.6%). Rapidly growing NTM comprised 39 (90.7%) of the isolates. Central venous catheter (CVC) was documented in 39 (90.7%) cases, 31 (79.5%) of which were removed as part of treatment. Antibiotic treatment directed against NTM was documented in 26 (60.5%) patients. CVC was removed in 7/17 patients who were not treated with antibiotics. Relapse occurred in 3 cases; no 30-days mortality was reported. Children and adults had similar clinical characteristics. However, children had a higher rate of CVC at the time of bacteremia and a higher chance to receive treatment. CONCLUSION: NTM BSI was seen mainly in oncologic patients with CVC. Children and adults had a similar disease course and outcome. Relapse was rare and NTM-related mortality was not reported.

Immunogenicity trends 1 and 3 months after second BNT162B2 vaccination among healthcare workers in Israel.

OBJECTIVES: We evaluated the antibody response to the BNT162B2 vaccine among healthcare workers (HCWs) to identify factors associated with decreased immunogenicity. METHODS: This prospective cohort study included consenting HCWs who completed a questionnaire regarding background illnesses, medications, and post-vaccination allergic reactions or rash. All HCWs were tested for anti-spike antibodies (LIAISON SARS-CoV-2 S1/S2 IgG assay) 1 and 3 months after the second vaccine dose. A multivariate mixed linear model was adjusted to participants' data and fit to predict antibody levels after the second BNT162B2 vaccine dose, based on antibody levels at 1 month and the slope between 3 months and 1 month. Multivariate analyses identified factors associated with lower antibody levels. RESULTS: In total 1506 HCWs were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. Older age was associated with lower mean antibody levels (-1.22 AU/mL, p < 0.001, 95%CI -1.43 to -1.01). In addition, male sex (-22.16 AU/mL, p < 0.001, 95%CI -27.93 to -16.39), underlying condition (-10.86 AU/mL, p 0.007, 95%CI -18.81 to -2.91) and immunosuppressive treatment (-28.57 AU/mL, p 0.002, 95%CI -46.85 to -10.29) were associated with significantly lower mean antibody levels. Allergic reactions after vaccine administration or peri-vaccination glucocorticosteroid treatment were not correlated with antibody levels. CONCLUSIONS: Most HCWs had measurable antibodies at 3 months. Risk factors for lower antibody levels were older age, male sex, underlying condition, and immunosuppressive treatment. These factors may be considered when planning booster doses during vaccine shortages.

Drastic Reduction Inpatient Visits to the Emergency Department in a Hospital in Israel During the COVID-19 Outbreak, Compared to the H1N1 2009.

BACKGROUND: On February 26, 2020, the first case of coronavirus disease 2019 (COVID-19) was detected in Israel. The Ministry of Health (MoH) instructed people to take isolation measures and restrict their movement. Similarly, there was a gradual decrease in the number of visits to our emergency department (ED). OBJECTIVES: To describe the decline in the referrals to the ED and in-hospital beds occupancy during the COVID-19 pandemic and to compare it to the H1N1 2009 pandemic. METHODS: Employing a cross-sectional epidemiologic study, the pattern of visits to the ED during the COVID-19 was compared with the pattern of visits during the 2009 H1N1 pandemic, as well as a year without a pandemic. The data was adjusted to consider changes in population size. The Welch t test for unpaired, unequal samples was used to analyze the data. RESULTS: Within 2 months of the COVID-19 outbreak, the average number of visits to the ED dropped by 30.2% and the hospital occupancy by 29.2% (a minimum of 57%), compared to the same period, the year before. In comparison to the same period during the H1N1 outbreak, we witnessed a significant decline in the number of visits to the ED during the COVID-19 outbreak. CONCLUSION: The behavior of people during the COVID-19 pandemic was different from their behavior during the H1N1 pandemic. People seemed to avoid visiting the ED. The boundary between precaution and panic in the generation of the media could be very thin. Decision-makers must take this into account.

Randomized Trial of Molnupiravir or Placebo in Patients Hospitalized with Covid-19.

Molnupiravir or Placebo in Patients with Covid-19 Molnupiravir is an oral agent, a metabolite of which has activity against SARS-CoV-2. In a controlled phase 2 trial in adults hospitalized for Covid-19 who had symptoms for 10 days or less prior to randomization, patients received placebo (n=75) or varying doses of molnupiravir (n=218) administered twice daily for 5 days. There was no impact of treatment on death. Median time to sustained recovery was 9 days in all groups, with day 29 recovery rates ranging from 81.5 to 85.2%. There were no dose-limiting side effects or adverse events.