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1.
J Bone Jt Infect ; 9(1): 87-97, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601005

RESUMO

Introduction: The BIOFIRE Joint Infection (JI) Panel is a diagnostic tool that uses multiplex-PCR testing to detect microorganisms in synovial fluid specimens from patients suspected of having septic arthritis (SA) on native joints or prosthetic joint infections (PJIs). Methods: A study was conducted across 34 clinical sites in 19 European and Middle Eastern countries from March 2021 to June 2022 to assess the effectiveness of the BIOFIRE JI Panel. Results: A total of 1527 samples were collected from patients suspected of SA or PJI, with an overall agreement of 88.4 % and 85 % respectively between the JI Panel and synovial fluid cultures (SFCs). The JI Panel detected more positive samples and microorganisms than SFC, with a notable difference on Staphylococcus aureus, Streptococcus species, Enterococcus faecalis, Kingella kingae, Neisseria gonorrhoeae, and anaerobic bacteria. The study found that the BIOFIRE JI Panel has a high utility in the real-world clinical setting for suspected SA and PJI, providing diagnostic results in approximately 1 h. The user experience was positive, implying a potential benefit of rapidity of results' turnover in optimising patient management strategies. Conclusion: The study suggests that the BIOFIRE JI Panel could potentially optimise patient management and antimicrobial therapy, thus highlighting its importance in the clinical setting.

2.
J Clin Virol ; 171: 105648, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38309173

RESUMO

BACKGROUND: Varicella zoster virus (VZV) is among the leading pathogens causing meningitis and encephalitis. While VZV-PCR-positive CSF is considered a gold-standard for diagnosis, it is not-uncommon to detect VZV-DNA in CSF of patients with other acute or chronic illness. Our goal was to determine the clinical relevance of VZV-PCR-positive CSF when investigating patients with neurological symptoms. METHODS: In this retrospective cohort from the largest hospital in Israel, we collected demographic, clinical and laboratory data of patients with VZV-PCR-positive CSF, analyzing the significance of various parameters. RESULTS: During a 5-years study, 125 patient-unique VZV-PCR-positive CSFs were recorded, in which only 9 alternative diagnoses were noted. The commonest symptoms were headache (N = 104, 83 %) and rash (N = 96, 76 %). PCR-cycle-threshold (Ct), a surrogate of viral burden, did not significantly vary across the clinical manifestations; however, patients with rash and Ct<35 were prone to develop stroke in the following year (N = 6, 7 %). Empiric nucleoside-analogue treatment was not associated with a better outcome compared to treatment administered upon a positive-PCR result. DISCUSSION: Our findings suggest that in patients with neurological symptoms, detection of VZV-DNA in CSF renders VZV the probable culprit. Nevertheless, a systematic evaluation of treatment and follow-up algorithms of patients with suspected or proved VZV meningitis and encephalitis is needed. The benefits of a prompt treatment should be weighed against the potential complications of nucleoside-analogue. Conversely, the propensity for stroke in patients with higher viral-burden, necessitates further studies assessing VZV causal role, directing additional workup, treatment and monitoring policy.


Assuntos
Encefalite , Exantema , Herpes Zoster , Meningite , Acidente Vascular Cerebral , Humanos , Herpesvirus Humano 3/genética , Relevância Clínica , Estudos Retrospectivos , Nucleosídeos , DNA Viral/líquido cefalorraquidiano , Reação em Cadeia da Polimerase , Acidente Vascular Cerebral/complicações , Herpes Zoster/diagnóstico , Líquido Cefalorraquidiano
3.
Pediatr Neurol ; 153: 68-76, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38335916

RESUMO

BACKGROUND: Coronavirus disease-associated central nervous system complications (CNS-C) in hospitalized children, especially during the Omicron wave, and in comparison with influenza associated CNS-C, are not well understood. METHODS: The study population included 755 children aged <18 years hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at Sheba Medical Center, during March 2020 to July 2022. A comparative cohort consisted of 314 pediatric patients with influenza during the 2018-2019 and 2019-2020 influenza seasons. RESULTS: Overall, 5.8% (n = 44) of patients exhibited CNS-C. Seizures at presentation occurred in 33 patients with COVID-19 (4.4%), with 2.6% (n = 20) experiencing nonfebrile seizures, 1.1% (n = 8) febrile seizures, and 0.7% (n = 5) status epilepticus. More patients with CNS-C experienced seizures during the Omicron wave versus the pre-Omicron period (77.8% vs 41.2%, P = 0.03). Fewer patients were admitted to the intensive care unit in the Omicron wave (7.4%) versus prior waves (7.4% vs 41.2%, P = 0.02). Fewer patients with SARS-CoV-2 experienced CNS-C (5.8%) versus patients with influenza (9.9%), P = 0.03. More patients with SARS-CoV-2 experienced nonfebrile seizures (2.6% vs 0.6%, P = 0.06), whereas more patients with influenza experienced febrile seizures (7.3% vs 1.1%, P < 0.01). CONCLUSIONS: The Omicron wave was characterized by more seizures and fewer intensive-care-unit admissions than previous waves. Pediatric patients with SARS-CoV-2 experienced fewer CNS-C and more nonfebrile seizures compared with patients with influenza.


Assuntos
COVID-19 , Doenças do Sistema Nervoso Central , Influenza Humana , Convulsões Febris , Humanos , Criança , SARS-CoV-2 , COVID-19/complicações , COVID-19/epidemiologia , Israel/epidemiologia , Influenza Humana/complicações , Influenza Humana/epidemiologia , Pandemias , Sistema Nervoso Central
4.
Sci Rep ; 14(1): 1430, 2024 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-38228695

RESUMO

During the Covid-19 pandemic, accurate PCR tests were augmented by the cheap, rapid, and logistically convenient, yet less sensitive antigen tests. In Israel, a testing policy shift was implemented due to limited availability of PCR tests during the Omicron surge. Thus, both PCR and antigen tests were used, as this was the only alternative for mass testing and surveillance at the time. Yet, evidence-based surveillance requires a robust understanding of the expected consequences of changing the testing policy. Using 41,065 paired tests performed by trained staff between January and April 2022 in Israel, we estimate how the sensitivity of antigen tests changes as a function of Ct value and other key covariates. The results reveal a logarithmic relationship between antigen detection probability and viral load, as quantified by Ct-values of the PCR tests. Further analysis shows a statistically significant association with an odds ratio of approximately 0.76 with each unit of Ct-value. The analysis suggests that in spite of their compromised sensitivity, antigen tests are a natural solution for routine use, while PCR tests should be considered in situations where a false negative result could have serious consequences. These findings are the foundations of policies that will utilize the strengths of the different tests, and achieve enhanced hybrid surveillance.


Assuntos
COVID-19 , Humanos , COVID-19/diagnóstico , COVID-19/epidemiologia , Pandemias , Saúde Pública , Israel/epidemiologia , Reação em Cadeia da Polimerase , Sensibilidade e Especificidade , Teste para COVID-19
5.
Diagn Microbiol Infect Dis ; 108(2): 116121, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37984111

RESUMO

Microbiological services consolidation has increased the usage of preservative-containing urine tubes, potentially inhibiting pathogens in low-volume pediatric urine samples, yielding false-negative results. Our study demonstrates comparable growth with 1 ml versus the recommended 3 ml urine, following different shipping intervals. We advocate for regulators to consider similar large-scale validations, ensuring results' consistency.


Assuntos
Automação Laboratorial , Manejo de Espécimes , Humanos , Criança , Manejo de Espécimes/métodos , Ácidos Bóricos/farmacologia , Urina/microbiologia
7.
Pediatr Infect Dis J ; 43(3): e108-e110, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38134367

RESUMO

Despite appropriate disinfection, sample contamination during in-and-out urinary catheterization is not uncommon, yielding false-positive and "mixed-culture" interpretations. We implemented a "midstream-like" catheterization technique, and cultured both first- and second-voided urine fractions. Second-fraction cultures exhibited less contaminants and "mixed-culture" interpretations and were better aligned with pyuria, thereby enhancing diagnostic accuracy and minimizing the risk of clinical misdiagnosis and unwarranted antibiotic use.


Assuntos
Bacteriúria , Piúria , Infecções Urinárias , Humanos , Criança , Bacteriúria/diagnóstico , Cateteres Urinários , Piúria/diagnóstico , Cateterismo Urinário , Desinfecção , Infecções Urinárias/diagnóstico
8.
Open Forum Infect Dis ; 10(10): ofad464, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37808896

RESUMO

We report 8 cases of persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia in patients previously treated with anti-CD20 monoclonal antibodies. Polymerase chain reaction of nasopharyngeal swabs for SARS-CoV-2 was negative in most cases; viral cell cultures confirmed that viable SARS-Co-2 virus was present. Four patients were treated with anti-SARS-CoV-2 hyperimmune globulins with rapid resolution of disease.

9.
Microorganisms ; 11(9)2023 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-37764056

RESUMO

Invasive meningococcal disease (IMD) is a devastating disease with significant mortality and long-term morbidity. The COVID-19 pandemic and containment measures have affected the epidemiology of infectious pathogens. This study's aim was to assess IMD trends in Israel prior to and during the COVID-19 pandemic. The Neisseria meningitidis invasive infection is a notifiable disease in Israel. Laboratory analysis includes serogrouping and molecular characterization. The overall national IMD incidence rate (1998-2022) was 0.8/100,000 population. The IMD incidence rates declined during the pandemic years (0.3/100,000 in 2020-2022 vs. 0.9/100,000 in 1998-2019). The number of notified IMD cases declined by 65% in 2020-2022. The case fatality rate among laboratory-confirmed IMD cases was 9% (47/521, 2007-2022). Mortality risk markers included cases' age (older) and socio-economic status (lower). Overall, most Neisseria meningitidis isolates were of serogroup B (62.6%), and the most prevalent clonal complex (CC) was CC32 (24.2%). Serogroup B prevailed in cases aged 0-9 years (74.5%) and less in cases aged 10 years and above (39%). Neisseria meningitidis serogroups and CC distribution altered recently with a decline in serogroup B fraction, an increase in serogroup Y, and a decline in CC32. Ongoing IMD surveillance is necessary to assess trends in circulating strains and support decision-making on meningococcal vaccination programs.

10.
Diagn Microbiol Infect Dis ; 107(2): 116033, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37549634

RESUMO

We report the off-label use of a commercial gastrointestinal protozoa multiplex-PCR panel for bronchoalveolar lavage samples, detecting respiratory cryptosporidiosis in 2 immunocompromised pediatric patients. We suggest that implying this readily available assay in cases in which systemic cryptosporidiosis is suspected, may widen our understanding regarding this rarely reported syndrome.


Assuntos
Criptosporidiose , Humanos , Criança , Criptosporidiose/diagnóstico , Hospedeiro Imunocomprometido , Reação em Cadeia da Polimerase Multiplex
11.
J Antimicrob Chemother ; 78(9): 2306-2314, 2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-37527397

RESUMO

BACKGROUND: Antimicrobial resistance is common in Nocardia species but data regarding the molecular mechanisms beyond their resistance traits are limited. Our study aimed to determine the species distribution, the antimicrobial susceptibility profiles, and investigate the associations between the resistance traits and their genotypic determinants. METHODS: The study included 138 clinical strains of Nocardia from nine Israeli microbiology laboratories. MIC values of 12 antimicrobial agents were determined using broth microdilution. WGS was performed on 129 isolates of the eight predominant species. Bioinformatic analysis included phylogeny and determination of antimicrobial resistance genes and mutations. RESULTS: Among the isolates, Nocardia cyriacigeorgica was the most common species (36%), followed by Nocardia farcinica (16%), Nocardia wallacei (13%), Nocardia abscessus (9%) and Nocardia brasiliensis (8%). Linezolid was active against all isolates, followed by trimethoprim/sulfamethoxazole (93%) and amikacin (91%). Resistance to other antibiotics was species-specific, often associated with the presence of resistance genes or mutations: (1) aph(2″) in N. farcinica and N. wallacei (resistance to tobramycin); (ii) blaAST-1 in N. cyriacigeorgica and Nocardia neocaledoniensis (resistance to amoxicillin/clavulanate); (iii) blaFAR-1 in N. farcinica (resistance to ceftriaxone); (iv) Ser83Ala substitution in the gyrA gene in four species (resistance to ciprofloxacin); and (v) the 16S rRNA m1A1408 methyltransferase in N. wallacei isolates (correlating with amikacin resistance). CONCLUSIONS: Our study provides a comprehensive understanding of Nocardia species diversity, antibiotic resistance patterns, and the molecular basis of antimicrobial resistance. Resistance appears to follow species-related patterns, suggesting a lesser role for de novo evolution or transmission of antimicrobial resistance.


Assuntos
Anti-Infecciosos , Nocardiose , Nocardia , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Amicacina , RNA Ribossômico 16S/genética , Nocardiose/tratamento farmacológico , Nocardiose/microbiologia , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana/genética , Nocardia/genética , Anti-Infecciosos/farmacologia
12.
J Clin Virol ; 165: 105522, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37331097

RESUMO

BACKGROUND: Enteroviruses (EV) comprise the single most common cause of aseptic meningitis with variable geographical and temporal epidemiology. While EV-PCR in CSF is considered a gold standard for diagnosis, it is not-uncommon to use stool EV as a surrogate. Our aim was to assess the clinical significance of EV-PCR-positive CSF and stool in the investigation of patients with neurological symptoms. METHODS: In this retrospective study from Sheba Medical centre, the largest tertiary hospital in Israel, we collected demographic, clinical and laboratory data of patients with EV-PCR-positive between 2016 and 2020. A comparison between various combinations of EV-PCR-positive CSF and stool was conducted. Data regarding EV strain-type and cycle threshold (Ct) were crossed with clinical symptoms and temporal kinetics. RESULTS: Between 2016-2020, 448 CSF samples with positive EV-PCR were recorded from unique patients, the vast majority of which were diagnosed with meningitis (98%, 443/448). Unlike the diverse strain types of EV background activity, meningitis-related EV showed a clear epidemic pattern. In comparison with the EV CSF+/Stool+ group, the EV CSF-/Stool+ group had frequently more alternative pathogens detected and a higher stool Ct-value. Clinically, EV CSF-/Stool+ patients were less febrile and more lethargic and convulsive. DISCUSSION: The comparison of the EV CSF+/Stool+ and CSF-/Stool+ groups suggests that putative diagnosis of EV meningitis is prudent in the febrile, non-lethargic non-convulsive patients with an EV-PCR-positive stool. Otherwise, the detection of stool EV only, in a non-epidemic setup, especially with a high Ct-value, may be incidental and mandate a continuous diagnostic effort for an alternative culprit.


Assuntos
Infecções por Enterovirus , Enterovirus , Meningite Asséptica , Meningite Viral , Humanos , Lactente , Estudos Retrospectivos , Infecções por Enterovirus/diagnóstico , Infecções por Enterovirus/epidemiologia , Enterovirus/genética , Meningite Viral/epidemiologia , Reação em Cadeia da Polimerase , Meningite Asséptica/diagnóstico
13.
Emerg Infect Dis ; 29(7): 1297-1301, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37347492

RESUMO

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.


Assuntos
COVID-19 , Candidíase Invasiva , Humanos , Candida/genética , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida auris , Israel/epidemiologia , COVID-19/epidemiologia , Candidíase Invasiva/tratamento farmacológico , Surtos de Doenças , Hospitalização , Testes de Sensibilidade Microbiana
14.
Infect Dis Ther ; 12(5): 1437-1443, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37129850

RESUMO

INTRODUCTION: Microbiological diagnosis is central for adequate treatment of bone and joint infections. Culture-based methods have a limited diagnostic sensitivity and a long turnaround time (TAT). The objective of this study was to compare the diagnostic performance of BioFire Joint Infection Panel Investigational Use Only version (hereafter BioFire)-a sample-to-result multiplex PCR panel-with culture-based methods and 16S ribosomal RNA (rRNA) PCR and sequencing, when available. METHODS: This study presents a retrospective analysis of a prospective validation study of the BioFire panel. Specimens were obtained from consecutive patients evaluated for suspected bone and joint infections and processed using culture, BioFire, and 16S rRNA PCR and sequencing. Final clinical diagnosis was used as the reference for definition of infection. RESULTS: Samples, including synovial fluid, bone and periarticular tissue, were obtained from 57 patients, 39 of whom were finally diagnosed with a bone or joint infection. Cultures were positive in 27/39 infected patients and in 3/18 uninfected patients (sensitivity 69%, specificity 83%). BioFire was positive in 22/39 infected patients and in none of the uninfected patients (sensitivity 56%, specificity 100%). Sensitivity for PCR panel organisms was 92% (22/24) and sensitivity for organisms identified by any microbiological modality was 69% (22/32). Gram stain results were positive in 13/39 infected patients and in none of the uninfected patients (sensitivity 33%, specificity 100%). 16S rRNA was positive in 20/28 infected patients and in 0/12 uninfected patients (sensitivity 71%, specificity 100%). Net machine time for BioFire-1 h-was shorter than the mean TAT for Gram stain results, which was 4 h. CONCLUSION: BioFire offered equivalent diagnostic performance with superior TAT for bone and joint infections, compared with conventional methods.

15.
Artigo em Inglês | MEDLINE | ID: mdl-37174146

RESUMO

Non-typhoidal salmonellosis (NTS) is one of the most common foodborne diseases worldwide. In this study, we aimed to analyze trends in the epidemiology of NTS in the last decade in Israel. Laboratory-confirmed cases of NTS at eight sentinel laboratories were reported to the Israel Sentinel Laboratory-Based Surveillance Network, integrated with the serotype identification performed at the Salmonella National Reference Laboratory of the Ministry of Health. The decrease in NTS incidence since 1999 continued between 2010 and 2014 (16.1 per 100,000 in 2014) and was interrupted by a rise between 2015 and 2017 (39.1 per 100,000 in 2017) associated with outbreaks of Salmonella Enteritidis. The incidence of NTS dropped again thereafter (21.4 per 100,000 in 2021). The 0-4 age group was the most affected by NTS (55.5% of the cases) throughout the surveillance period. The age-adjusted incidence rates were consistently high in the summer months (June-September) and low in the winter months (December-February). The overall decrease in the incidence of NTS in Israel since 1999 was temporarily interrupted in the last decade by country-wide outbreaks involving emerging or re-emerging Salmonella serotypes. Control measures should be enhanced for all risk points of food chain transmission of Salmonella spp. to further reduce the NTS morbidity in Israel.


Assuntos
Infecções por Salmonella , Humanos , Israel/epidemiologia , Infecções por Salmonella/epidemiologia , Salmonella , Sorogrupo , Surtos de Doenças
16.
JAMA Netw Open ; 6(5): e2314757, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37219906

RESUMO

Importance: A correlation between antibody levels and risk of infection has been demonstrated for the wild-type, Alpha, and Delta SARS-COV-2 variants. High rates of breakthrough infections by the Omicron variant emphasized the need to investigate whether the humoral response elicited by mRNA vaccines is also associated with reduced risk of Omicron infection and disease. Objective: To investigate whether the high antibody levels in individuals who have received at least 3 doses of an mRNA vaccine are associated with reduced risk of Omicron infection and disease. Design, Setting, and Participants: This prospective cohort study used serial real time-polymerase chain reaction (RT-PCR) and serological test data from January and May 2022 to assess the association of preinfection immunoglobin G (IgG) and neutralizing antibody titers with incidence of Omicron variant infection, incidence of symptomatic disease, and infectivity. Participants included health care workers who had received 3 or 4 doses of an mRNA COVID-19 vaccine. Data were analyzed from May to August 2022. Exposures: Levels of SARS-CoV-2 anti-receptor binding domain IgG and neutralizing antibodies. Main Outcomes and Measures: The main outcomes were incidence of Omicron infection, incidence of symptomatic disease, and infectivity. Outcomes were measured using SARS-COV-2 PCR and antigen testing and daily online surveys regarding symptomatic disease. Results: This study included 3 cohorts for 3 different analyses: 2310 participants were included in the protection from infection analysis (4689 exposure events; median [IQR] age, 50 [40-60] years; 3590 [76.6%] among female health care workers), 667 participants (median [IQR] age, 46.28 (37.44,54.8); 516 [77.4%] female) in the symptomatic disease analysis, and 532 participants (median [IQR] age, 48 [39-56] years; 403 [75.8%] female) in the infectivity analysis. Lower odds of infection were observed for each 10-fold increase in preinfection IgG (odds ratio [OR], 0.71; 95% CI, 0.56-0.90) and for each 2-fold increase in neutralizing antibody titers (OR, 0.89; 95% CI, 0.83-0.95). The odds of substantial symptomatic disease were reduced for each 10-fold increase in IgG levels (OR, 0.48; 95% CI, 0.29-0.78) and for each 2-fold increase in neutralizing antibodies levels (OR, 0.86; 95% CI, 0.76-0.96). Infectivity, assessed by mean cycle threshold value, was not significantly decreased with increasing IgG or neutralizing antibodies titers. Conclusions and Relevance: In this cohort study of vaccinated health care workers, IgG and neutralizing antibody titer levels were associated with protection against infection with the Omicron variant and against symptomatic disease.


Assuntos
COVID-19 , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Israel , Vacinas contra COVID-19 , Estudos de Coortes , Estudos Prospectivos , SARS-CoV-2 , Anticorpos Neutralizantes , Pessoal de Saúde , Imunoglobulina G
18.
Clin Microbiol Infect ; 29(7): 918-923, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36921715

RESUMO

OBJECTIVES: The capability of the SARS-CoV-2 Omicron variant to escape immunity conferred by mRNA vaccines has led to the development of Omicron-adapted vaccines. In this study, we aimed to compare the immune response with the ancestral strain and with the BA.1 Omicron variant after administration of the original vaccine and the Omicron-adapted vaccine. METHODS: This is an ongoing phase 3, double-blinded randomized controlled trial, comparing the original BNT161b2 vaccine, monovalent Omicron BA.1-adapted BNT161b2 vaccine, and bivalent combinations. Each vaccine was given at a 30 µg and 60 µg dose. Primary outcomes considered included neutralization titers of SARS-CoV-2 ancestral strain and Omicron BA.1. Exploratory endpoints included neutralization titers for Omicron BA.5, and the incidence of COVID-19 cases. RESULTS: Overall, 122 individuals (22, 19, 20, 20, 20, 20, and 21 in each arm) completed a 90-day follow-up. Three months after vaccination, adjusting for baseline levels, neutralizing antibody titers were 0.63 (95% CI: 0.3-1.32) and 0.54 (0.24-1.2) for monovalent/60 µg, 0.9 (0.42-1.92) and 2.69 (1.17-6.17) times for monovalent-Omi.BA.1/30 µg, 1.28 (0.6-2.75) and 2.79 (1.21-6.41) times for monovalent-Omi.BA.1/60 µg, 0.96 (0.46-1.97) and 2.07 (0.93-4.58) times for bivalent-Omi.BA.1/30 µg, and 0.79 (0.38-1.63) and 1.95 (0.88-4.32) times for bivalent-Omi.BA.1/60 µg when compared with BNT162b2/30 µg against the ancestral strain and BA.1 variant, respectively. DISCUSSION: BA.1-adapted mRNA vaccines lead to a stronger neutralizing antibody response against the Omicron BA.1 sub-variant.


Assuntos
COVID-19 , Vacinas , Humanos , Vacina BNT162 , Seguimentos , COVID-19/prevenção & controle , SARS-CoV-2/genética , Vacinas de mRNA , Anticorpos Neutralizantes , Anticorpos Antivirais
19.
Lancet Microbe ; 4(5): e309-e318, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36963419

RESUMO

BACKGROUND: Identifying COVID-19 correlates of protection and immunity thresholds is important for policy makers and vaccine development. We aimed to identify correlates of protection of BNT162b2 (Pfizer-BioNTech) vaccination against COVID-19. METHODS: In this prospective cohort study, households within a radius of 40 km of the Sheba Medical Center in Israel in which a new SARS-CoV-2 infection (defined as the index case) was detected within the previous 24 h were approached between July 25 and Nov 15, 2021. We included adults (aged >18 years) who had received one or two vaccine doses, had an initial negative SARS-CoV-2 PCR and no previous infection reported, and had a valid IgG and neutralising antibody result. The exposure of interest was baseline immune status, including IgG antibody concentration, neutralising antibody titre, and T-cell activation. The outcomes of interest were PCR-positive SARS-CoV-2 infection between day 2 and day 21 of follow-up and intensity of disease symptoms (self-reported via a telephone questionnaire) among participants who had a confirmed infection. Multivariable logistic and ordered logit ordinal regressions were used for the adjusted analysis. To identify immunological thresholds for clinical protection, we estimated the conditional probability of infection and moderate or severe disease for individuals with pre-exposure IgG and neutralising antibody concentrations above each value observed in the study data. FINDINGS: From 16 675 detected index cases in the study region, 5718 household members agreed to participate, 1461 of whom were eligible to be included in our study. 333 (22·8%) of 1461 household members who were not infected with SARS-CoV-2 at baseline were infected within 21 days of follow-up. The baseline (pre-exposure) IgG and neutralising antibodies were higher in participants who remained uninfected than in those who became infected (geometric mean IgG antibody concentration 168·2 binding antibody units [BAU] per mL [95% CI 158·3-178·7] vs 130·5 BAU/mL [118·3-143·8] and geometric mean neutralising antibody titre 197·5 [181·9-214·4] vs 136 ·7 [120·3-155·4]). Increasing IgG and neutralising antibody concentrations were also significantly associated with a reduced probability of increasing disease severity. Odds of infection were significantly reduced each time baseline IgG antibody concentration increased by a factor of ten (odds ratio [OR] 0·43 [95% CI 0·26-0·70]) and each time baseline neutralising antibody titre increased by a factor of two (0·82 [0·74-0·92]). In our cohort, the probability of infection if IgG antibody concentrations were higher than 500 BAU/mL was 11% and the probability of moderate disease severity was 1%; the probability of infection if neutralising antibody titres were above or equal to 1024 was 8% and the probability of moderate disease severity was 2%. T-cell activation rates were not significantly associated with reduced probability of infection (OR 1·04, 95% CI 0·83-1·30). INTERPRETATION: Both IgG and neutralising antibodies are correlates of protection against SARS-CoV-2 infection. Our data suggest that IgG concentrations higher than 500 BAU/mL and neutralising antibody titres of 1024 or more are thresholds for immunological protection from SARS-CoV-2 delta variant infection. Potentially, updated protective thresholds against emerging variants of concern could be calculated, which could support decision makers on administration of new vaccination strategies and on the optimal period between vaccine doses. FUNDING: Israeli Ministry of Health.


Assuntos
COVID-19 , SARS-CoV-2 , Adulto , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Israel/epidemiologia , Vacina BNT162 , Estudos Prospectivos , Anticorpos Neutralizantes , Imunoglobulina G
20.
Microorganisms ; 11(2)2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36838249

RESUMO

The emergency department (ED) is the initial point of contact between hospital staff and patients potentially infected with SARS-CoV-2, thus, prevention of inadvertent exposure to other patients is a top priority. We aimed to assess whether the introduction of antigen-detecting rapid diagnostic tests (Ag-RDTs) to the ED affected the likelihood of unwanted SARS-CoV-2 exposures. In this retrospective single-center study, we compared the rate of unwarranted exposure of uninfected adult ED patients to SARS-CoV-2 during two separate research periods; one before Ag-RDTs were introduced, and one with Ag-RDT used as a decision-support tool. The introduction of Ag-RDTs to the ED significantly decreased the relative risk of SARS-CoV-2-negative patients being incorrectly assigned to the COVID-19 designated site ("red ED"), by 97%. There was no increase in the risk of SARS-CoV-2-positive patients incorrectly assigned to the COVID-19-free site ("green ED"). In addition, duration of ED admission was reduced in both the red and the green ED. Therefore, implementing the Ag-RDT-based triage protocol proved beneficial in preventing potential COVID-19 nosocomial transmission.

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