Candida lusitaniae Fungemia in Children: A multicenter case series of emerging pathogen.

Candida lusitaniae fungemia is a serious infection that is rarely reported in children. The aim of this study is to describe a case series of C. lusitaniae fungemia and review previous publications regarding this rare pathogen. This is a multicenter case series of children diagnosed with C. lusitaniae fungemia. A total of 18 cases that occurred over a 15-year period in five tertiary hospitals were included. Additionally, a review of the literature regarding C. lusitaniae fungemia in children was performed. A total of 18 cases were enrolled; 11/18 (61%) were males, with a mean age of 2.3 years. All patients had severe underlying diseases and risk factors for opportunistic infection, most commonly prematurity and malignancies. More than one-third of cases occurred during the last 2 years of the study period. All isolates were susceptible to all tested antifungals. The survival rate following the acute infection was 94%, whereas the survival rate of 14 previously published cases was 71%, with the most common underlying diseases being CGD and malignancies. Candida lusitaniae fungemia is not a common event in the pediatric population, occurring exclusively in children with severe underlying diseases and significant risk factors. This cohort revealed better clinical outcomes than previously reported. All tested isolates were susceptible to all antifungal agents; variability in susceptibility as previously reported was not found in this study. The allegedly higher rate of infection in recent years is in need of further investigation in larger prospective studies in order to conclude if a real trend is at play.

Candida lusitaniae fungemia is a serious infection rarely reported in children. This cohort revealed better clinical outcomes than previously reported. All tested isolates were susceptible to all antifungal agents. The higher rate of infection in recent years is in need of further investigation.

Nationwide Outbreak of Candida auris Infections Driven by COVID-19 Hospitalizations, Israel, 2021-2022

We report an outbreak of Candida auris across multiple healthcare facilities in Israel. For the period of May 2014-May 2022, a total of 209 patients with C. auris infection or colonization were identified. The C. auris incidence rate increased 30-fold in 2021 (p = 0.00015), corresponding in time with surges of COVID-19-related hospitalization. Multilocus sequence typing revealed hospital-level outbreaks with distinct clones. A clade III clone, imported into Israel in 2016, accounted for 48.8% of typed isolates after January 2021 and was more frequently resistant to fluconazole (100% vs. 63%; p = 0.00017) and voriconazole (74% vs. 5.2%; p<0.0001) than were non-clade III isolates. A total of 23% of patients had COVID-19, and 78% received mechanical ventilation. At the hospital level, outbreaks initially involved mechanically ventilated patients in specialized COVID-19 units and then spread sequentially to ventilated non-COVID-19 patients and nonventilated patients.

Revaccination of children with acute lymphoblastic leukemia following completion of chemotherapy.

BACKGROUND: Intensive chemotherapy for acute lymphoblastic leukemia (ALL) may affect the immune system and potentially the immune memory causing antibodies provided by vaccination to disappear. There are disagreements regarding the guidelines for posttreatment immunization strategy. METHODS: Ninety-six children (aged 1-18 years at diagnosis) who completed chemotherapy for ALL were recruited. Antibody levels in the patient's serum against measles, varicella, polio, pertussis, hepatitis A, and hepatitis B were tested after completion of chemotherapy in patients who were fully vaccinated against these agents. Children who did not have positive serology to specific agents were revaccinated with a single dose accordingly. Antibody concentrations were measured again at least 4 weeks after revaccination. RESULTS: Positive antibody levels varied between the different agents. The highest percentage of positive serology was against polio (87%) and the lowest against pertussis (4%) (p < .001). There were significant differences between patients with high risk (HR) and non-HR ALL regarding serology status for some vaccines. After revaccination, the levels of response to each booster dose were significantly different: 100% after booster dose for varicella and polio, and only 34% after pertussis booster. CONCLUSIONS: Loss of humoral protection for vaccine preventable diseases is a common finding among patients with ALL. Revaccination with one dose of vaccine after completion of chemotherapy achieved seroconversion in 34-100% of the patients depending on the type of vaccine. We recommend this revaccination schedule to all children who completed ALL therapy and were previously fully vaccinated.

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.

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.

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.

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.

Invasive Fungal Diseases in Hospitalized Patients with COVID-19 in Israel: A Multicenter Cohort Study.

Highly variable estimates of COVID-19-associated fungal diseases (IFDs) have been reported. We aimed to determine the incidence of clinically important fungal diseases in hospitalized COVID-19 patients during the first year of the pandemic. We performed a multicenter survey of IFDs among patients hospitalized with COVID-19 in 13 hospitals in Israel between February 2020 and May 2021. COVID-19-associated pulmonary mold disease (PMD) and invasive candidiasis (IC) were defined using ECMM/ISHAM and EORTC/MSG criteria, respectively. Overall rates of IC and PMD among patients with critical COVID-19 were 10.86 and 10.20 per 1000 admissions, respectively, with significant variability among medical centers. PMD rates were significantly lower in centers where galactomannan was a send-out test versus centers with on-site testing (p = 0.035). The 30-day mortality rate was 67.5% for IC and 57.5% for PMD. Treatment with an echinocandin for IC or an extended-spectrum azole for PMD was associated with significantly lower mortality rates (adjusted hazard ratio [95% confidence interval], 0.26 [0.07-0.91] and 0.23 [0.093-0.57], respectively). In this multicenter national survey, variable rates of PMD were associated with on-site galactomannan testing, suggesting under-detection in sites lacking this capacity. COVID-19-related IFDs were associated with high mortality rates, which were reduced with appropriate antifungal therapy.

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.

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.

Invasive Fusariosis in Pediatric Hematology/Oncology and Stem Cell Transplant Patients: A Report from the Israeli Society of Pediatric Hematology-Oncology.

Invasive Fusarium species infections in immunocompromised patients occur predominantly in those with hematological malignancies. Survival rates of 20−40% were reported in adults, but data in children are limited. Our retrospective, nationwide multicenter study of invasive fusariosis in pediatric hematology/oncology and stem cell transplant (SCT) patients identified twenty-two cases. Underlying conditions included hematological malignancies (n = 16; 73%), solid tumors (n = 2), and non-malignant hematological conditions (n = 4). Nineteen patients (86%) were neutropenic, nine (41%) were SCT recipients, and seven (32%) received corticosteroids. Sixteen patients (73%) had disseminated fusariosis, five had local infection, and one had isolated fungemia. Fifteen patients (68%) had skin involvement and eight (36%) had a bloodstream infection. Four patients (18%) presented with osteoarticular involvement and four with pulmonary involvement. Nineteen patients (86%) received combination antifungal therapy upfront and three (14%) received single-agent treatment. Ninety-day probability of survival was 77%: four of the five deaths were attributed to fusariosis, all in patients with relapsed/refractory acute leukemias. Ninety-day probability of survival for patients with relapsed/refractory underlying malignancy was 33% vs. 94% in others (p < 0.001). Survival rates in this largest pediatric population-based study were strikingly higher than those reported in adults, demonstrating that invasive fusariosis is a life-threatening but salvageable condition in immunosuppressed children.

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.

Single BNT162b2 vaccine dose produces seroconversion in under 60 s cohort.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has led to worldwide vaccination development efforts. In December 2020 the Pfizer BNT162b2 vaccine was approved in the United States. This study describes the first BNT162b2 vaccine dose effect on a large cohort. METHODS: This retrospective study examined first vaccine dose effect on serology and investigated the associations between seroconversion and age or sex. RESULTS: Serological blood tests were performed on 1898 participants following first vaccine dose; 81% were tested on day 21, before receiving the second dose (mean age 47.5 ± 12.45; median 47.7, range 18-90). Positive serology was found in 92.7% of day 21 tests. Overall positivity was 86.8%, with rates increasing from 2.5% within 1-14 days to 89.8% (14-20 days), 92.7% (21 days), and 95.9% (>21 days). Mean antibody levels 21 days after first dose were 64.3 ± 33.01 AU/ml, (range 15-373 AU/ml, median 61 AU/ml). Seropositivity was greater in females than males (88.3%. vs 83.3% respectively, p < 0.001; OR1.515; 95% CI 1.152-1.994). Older age > 60 years was associated with decreased likelihood of seropositivity (p < 0.001; OR 0.926; 95% CI 0.911-0.940). Longer time between first vaccination and serology tests was associated with increased likelihood for seropositivity (p < 0.001; OR 1.350; 95% CI 1.298-1.404). CONCLUSIONS: The high seroconversion rate following first BNT162b2 dose among individuals < 60 may justify delayed delivery of the second dose, potentially help relieve the worldwide vaccination supply shortage, enable vaccination of twice this population within a shorter period, and ultimately reduce COVID-19 contagion.

Six-Month Efficacy and Toxicity Profile of BNT162b2 Vaccine in Cancer Patients with Solid Tumors.

We had previously reported short-term efficacy, immunogenicity, and safety of the BNT162b2 vaccine among cancer patients with solid tumors. We aimed to evaluate these outcomes at six months postvaccination. The study cohort comprised patients who were on treatment during vaccination and throughout six months postvaccination. Serologic tests were performed after second vaccination and six months afterward. An age-matched cohort of health care workers served as controls. Documentation of COVID-19 infection, blood tests, and imaging studies during the study period was reviewed. Participants included 154 patients and 135 controls. Six months postvaccination, 122 (79%) patients were seropositive compared with 114 (84%) controls (P = 0.32). Serology titer dramatically decreased in a similar manner in both cohorts. No COVID-19 cases were documented in controls, and one case occurred in patient cohort. All previously reported adverse effects resolved. Taken together, the pattern of immunogenicity, efficacy, and safety of BNT162b2 in patients with cancer with solid tumors at six months postvaccination resembles that of the general population. SIGNIFICANCE: Evidence regarding efficacy and safety of COVID-19 vaccines in patients with cancer indicate a favorable short-term profile. Immunomodulation due to anticancer treatments may affect immunity and immunogenicity of patients with cancer to the BNT162b2 vaccine over time. Our study sheds light on these long-term outcomes and portrays a trend that resembles the general population.This article is highlighted in the In This Issue feature, p. 2355.

Serologic Status and Toxic Effects of the SARS-CoV-2 BNT162b2 Vaccine in Patients Undergoing Treatment for Cancer.

Importance: The efficacy and safety profile of SARS-CoV-2 vaccines have been acquired from phase 3 studies; however, patients with cancer were not represented in these trials. Owing to the recommendation to prioritize high-risk populations for vaccination, further data are warranted. Objective: To evaluate the use and safety of the BNT162b2 vaccine in patients undergoing treatment for cancer. Design, Setting, and Participants: In January 2021, mass SARS-CoV-2 vaccination of high-risk populations, including patients with cancer, was initiated in Israel. This cohort study prospectively enrolled and followed up patients with cancer and healthy participants between January 15 and March 14, 2021. The study was conducted at the Division of Oncology of Rambam Health Care Campus, the major tertiary (referral) medical center of northern Israel. Participants included 232 patients with cancer who were receiving active treatment after the first and second doses of the BNT162b2 vaccine and 261 healthy, age-matched health care workers who served as controls. Exposures: Serum samples were collected after each vaccine dose and in cases of seronegativity. Questionnaires regarding sociodemographic characteristics and adverse reactions were administered at serum collection. A regulatory agencies-approved assay was used to assess IgG at all time points. Patients' electronic medical records were reviewed for documentation of COVID-19 infection and results of blood cell counts, liver enzyme levels, and imaging studies. Main Outcomes and Measures: Seroconversion rate after the first and second doses of the BNT162b2 vaccine and documented COVID-19 infection. Results: Of the 232 patients undergoing treatment for cancer, 132 were men (57%); mean (SD) age was 66 (12.09) years. After the first dose of BNT162b2 vaccine, 29% (n = 25) patients were seropositive compared with 84% (n = 220) of the controls (P < .001). After the second dose, the seropositive rate reached 86% (n = 187) in the patients. Testing rate ratios per 1000 person-days after the first dose were 12.5 (95% CI, 3.4-45.7) for the patients and 48.5 (95% CI, 37.2-63.2) for the controls. Patients undergoing chemotherapy showed reduced immunogenicity (odds ratio, 0.41; 95% CI, 0.17-0.98). In seronegative patients, the rate of documented absolute leukopenia reached 39%. No COVID-19 cases were documented throughout the study period; however, 2 cases in the patient cohort were noted immediately after the first dose. Reported adverse events were similar to data in former trials comprising mostly healthy individuals. Conclusions and Relevance: In this cohort study, the SARS-CoV-2 BNT162b2 vaccine appeared to be safe and achieve satisfactory serologic status in patients with cancer. There was a pronounced lag in antibody production compared with the rate in noncancer controls; however, seroconversion occurred in most patients after the second dose. Future real-world data are warranted to determine the long-term efficacy of the vaccine with regard to type of anticancer treatment.

COVID-19 in a Subset of Hospitalized Children in Israel.

BACKGROUND: Most pediatric coronavirus disease 2019 (COVID-19) is mild. We assessed nationally severe COVID-19, including pediatric inflammatory multisystem syndrome (PIMS), in hospitalized children. METHODS: An ongoing, prospective, national surveillance was conducted from March 2020 through March 2021, at 20 hospitals treating children <18 years across Israel (~75% of Israeli hospitals). RESULTS: Overall, 1007 cases (439 outpatients and 568 hospitalized) identified represent 0.35% of pediatric COVID-19 nationwide (n = 291 628). Of hospitalized cases, 464 (82%), 48 (8%), and 56 (10%) had mild, moderate/severe, and PIMS disease, respectively. The mean ± SD age was 5.6 ± 6.4 years. In mild, moderate/severe, and PIMS disease, 55%, 23%, and 4% of patients were <1 year old, respectively. Obesity was reported in 1%, 4%, and 13% of patients, respectively (P < .001). The most common symptom was fever in 67%, 60%, and 100%, respectively, whereas respiratory symptoms were documented in 33%, 41%, and 38% of patients, respectively. Lymphopenia was recorded in 25%, 60%, and 86% of cases, respectively. PIMS diagnosis was mainly serology-based (in 59%). Gastrointestinal symptoms, cardiovascular involvement, rash, and conjunctivitis were noted in 82%, 61%, 57%, and 34% of PIMS episodes, respectively. Elevated C-reactive protein (100%), ferritin, troponin, D-dimer, low albumin, and thrombocytopenia were common in PIMS. Echocardiography revealed pathological findings in 33% of patients. PIMS mainstay treatment included corticosteroids (77%) and intravenous immunoglobulin (53%). No mortality was recorded. CONCLUSIONS: At a national level, pediatric COVID-19 is mild, even in hospitalized cases, with only a third presenting with respiratory involvement. PIMS is rare, but necessitates a high index of suspicion, and with suitable treatment prognosis is favorable.