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1.
J Infect Dis ; 2023 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-37996071

RESUMO

BACKGROUND: The emergence of rapidly evolving SARS-CoV-2 variants, coupled with waning vaccine-induced immunity, has contributed to the rise of vaccine breakthrough infections. It is crucial to understand how vaccine-induced protection is mediated. METHODS: We examined two prospective cohorts of mRNA-vaccinated-and-boosted individuals during the Omicron wave of infection in Singapore. RESULTS: We found that, individuals, who remain uninfected over the follow-up period, had a higher variant-specific IgA, but not IgG, antibody response at 1-month post booster vaccination, compared with individuals who became infected. CONCLUSIONS: We conclude that IgA may have a potential contributory role in protection against Omicron infection.

2.
J Med Virol ; 95(11): e29204, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37937705

RESUMO

The Omicron variant has been reported to present with milder disease compared with Delta, although this may be due to immunity from vaccination and prior exposure. Predictors of severity with recent strains have not been well characterized. We retrospectively examined consecutive cases of moderate-to-severe COVID-19 (defined as requiring supplemental oxygenation, intensive care or mortality) admitted to seven tertiary hospitals across Singapore in April 2023. Whole genome sequencing was performed on each isolate to determine the sublineage, while baseline clinical, laboratory data and outcomes were tabulated. We reviewed 182 patients with moderate-to-severe illness and 466 controls hospitalized at the same time. Advanced age and presence of chronic kidney disease predicted adverse outcome. Previously reported markers such as radiographic evidence of pneumonia, elevated C-reactive protein and serum creatinine levels at presentation also correlated with adverse outcomes. There were no observable differences in outcomes with any specific Omicron XBB sublineage. We did not find any specific Omicron XBB sublineage that was associated with worse outcomes. Larger multinational studies would be important to track the clinical evolution of the virus in its current endemic state.


Assuntos
COVID-19 , Humanos , COVID-19/diagnóstico , Gravidade do Paciente , Estudos Retrospectivos , SARS-CoV-2/genética
3.
Clin Infect Dis ; 73(9): e2932-e2942, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-32856707

RESUMO

BACKGROUND: Key knowledge gaps remain in the understanding of viral dynamics and immune response of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. METHODS: We evaluated these characteristics and established their association with clinical severity in a prospective observational cohort study of 100 patients with PCR-confirmed SARS-CoV-2 infection (mean age, 46 years; 56% male; 38% with comorbidities). Respiratory samples (n = 74) were collected for viral culture, serum samples for measurement of IgM/IgG levels (n = 30), and plasma samples for levels of inflammatory cytokines and chemokines (n = 81). Disease severity was correlated with results from viral culture, serologic testing, and immune markers. RESULTS: Fifty-seven (57%) patients developed viral pneumonia, of whom 20 (20%) required supplemental oxygen, including 12 (12%) with invasive mechanical ventilation. Viral culture from respiratory samples was positive for 19 of 74 patients (26%). No virus was isolated when the PCR cycle threshold (Ct) value was >30 or >14 days after symptom onset. Seroconversion occurred at a median (IQR) of 12.5 (9-18) days for IgM and 15.0 (12-20) days for IgG; 54/62 patients (87.1%) sampled at day 14 or later seroconverted. Severe infections were associated with earlier seroconversion and higher peak IgM and IgG levels. Levels of IP-10, HGF, IL-6, MCP-1, MIP-1α, IL-12p70, IL-18, VEGF-A, PDGF-BB, and IL-1RA significantly correlated with disease severity. CONCLUSIONS: We found virus viability was associated with lower PCR Ct value in early illness. A stronger antibody response was associated with disease severity. The overactive proinflammatory immune signatures offer targets for host-directed immunotherapy, which should be evaluated in randomized controlled trials.


Assuntos
COVID-19 , Pneumonia Viral , Anticorpos Antivirais , Feminino , Humanos , Imunoglobulina M , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , SARS-CoV-2 , Soroconversão
4.
Lancet ; 396(10251): 603-611, 2020 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-32822564

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with a 382-nucleotide deletion (∆382) in the open reading frame 8 (ORF8) region of the genome have been detected in Singapore and other countries. We investigated the effect of this deletion on the clinical features of infection. METHODS: We retrospectively identified patients who had been screened for the ∆382 variant and recruited to the PROTECT study-a prospective observational cohort study conducted at seven public hospitals in Singapore. We collected clinical, laboratory, and radiological data from patients' electronic medical records and serial blood and respiratory samples taken during hospitalisation and after discharge. Individuals infected with the ∆382 variant were compared with those infected with wild-type SARS-CoV-2. Exact logistic regression was used to examine the association between the infection groups and the development of hypoxia requiring supplemental oxygen (an indicator of severe COVID-19, the primary endpoint). Follow-up for the study's primary endpoint is completed. FINDINGS: Between Jan 22 and March 21, 2020, 278 patients with PCR-confirmed SARS-CoV-2 infection were screened for the ∆382 deletion and 131 were enrolled onto the study, of whom 92 (70%) were infected with the wild-type virus, ten (8%) had a mix of wild-type and ∆382-variant viruses, and 29 (22%) had only the ∆382 variant. Development of hypoxia requiring supplemental oxygen was less frequent in the ∆382 variant group (0 [0%] of 29 patients) than in the wild-type only group (26 [28%] of 92; absolute difference 28% [95% CI 14-28]). After adjusting for age and presence of comorbidities, infection with the ∆382 variant only was associated with lower odds of developing hypoxia requiring supplemental oxygen (adjusted odds ratio 0·07 [95% CI 0·00-0·48]) compared with infection with wild-type virus only. INTERPRETATION: The ∆382 variant of SARS-CoV-2 seems to be associated with a milder infection. The observed clinical effects of deletions in ORF8 could have implications for the development of treatments and vaccines. FUNDING: National Medical Research Council Singapore.


Assuntos
Infecções por Coronavirus/virologia , Deleção de Genes , Genoma Viral/genética , Pneumonia Viral/virologia , Adulto , Idoso , Betacoronavirus , COVID-19 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Humanos , Hipóxia/etiologia , Hipóxia/terapia , Pessoa de Meia-Idade , Fases de Leitura Aberta , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Estudos Prospectivos , Terapia Respiratória , SARS-CoV-2 , Índice de Gravidade de Doença , Singapura/epidemiologia , Replicação Viral
5.
Artigo em Inglês | MEDLINE | ID: mdl-31383670

RESUMO

Carbapenem-resistant Enterobacteriaceae (CRE) can be mechanistically classified into carbapenemase-producing Enterobacteriaceae (CPE) and non-carbapenemase-producing carbapenem nonsusceptible Enterobacteriaceae (NCPCRE). We sought to investigate the effect of antecedent carbapenem exposure as a risk factor for NCPCRE versus CPE. Among all patients with CRE colonization and infection, we conducted a case-control study comparing patients with NCPCRE (cases) and patients with CPE (controls). The presence of carbapenemases was investigated with phenotypic tests followed by PCR for predominant carbapenemase genes. We included 843 unique patients with first-episode CRE, including 387 (45.9%) NCPCRE and 456 (54.1%) CPE. The resistance genes detected in CPEs were blaNDM (42.8%), blaKPC (38.4%), and blaOXA-48-like (12.1%). After adjusting for confounders and clustering at the institutional level, the odds of prior 30-day carbapenem exposure was three times higher among NCPCRE than CPE patients (adjusted odds ratio [aOR], 3.48; 95% confidence interval [CI], 2.39 to 5.09; P < 0.001). The odds of prior carbapenem exposure and NCPCRE detection persisted in stratified analyses by Enterobacteriaceae species (Klebsiella pneumoniae and Escherichia coli) and carbapenemase gene (blaNDM and blaKPC). CPE was associated with male gender (aOR, 1.45; 95% CI, 1.07 to 1.97; P = 0.02), intensive care unit stay (aOR, 1.84; 95% CI, 1.24 to 2.74; P = 0.003), and hospitalization in the preceding 1 year (aOR, 1.42; 95% CI, 1.01 to 2.02; P = 0.05). In a large nationwide study, antecedent carbapenem exposure was a significant risk factor for NCPCRE versus CPE, suggesting a differential effect of antibiotic selection pressure.


Assuntos
Antibacterianos/efeitos adversos , Proteínas de Bactérias/metabolismo , Carbapenêmicos/efeitos adversos , Enterobacteriaceae/efeitos dos fármacos , beta-Lactamases/metabolismo , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/metabolismo , Estudos de Casos e Controles , Enterobacteriaceae/metabolismo , Infecções por Enterobacteriaceae/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Feminino , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Masculino , Testes de Sensibilidade Microbiana/métodos , Fatores de Risco
6.
Clin Infect Dis ; 64(suppl_2): S61-S67, 2017 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-28475790

RESUMO

BACKGROUND: We conducted a national point prevalence survey (PPS) to determine the prevalence of healthcare-associated infections (HAIs) and antimicrobial use (AMU) in Singapore acute-care hospitals. METHODS: Trained personnel collected HAI, AMU, and baseline hospital- and patient-level data of adult inpatients from 13 private and public acute-care hospitals between July 2015 and February 2016, using the PPS methodology developed by the European Centre for Disease Prevention and Control. Factors independently associated with HAIs were determined using multivariable regression. RESULTS: Of the 5415 patients surveyed, there were 646 patients (11.9%; 95% confidence interval [CI], 11.1%-12.8%) with 727 distinct HAIs, of which 331 (45.5%) were culture positive. The most common HAIs were unspecified clinical sepsis (25.5%) and pneumonia (24.8%). Staphylococcus aureus (12.9%) and Pseudomonas aeruginosa (11.5%) were the most common pathogens implicated in HAIs. Carbapenem nonsusceptibility rates were highest in Acinetobacter species (71.9%) and P. aeruginosa (23.6%). Male sex, increasing age, surgery during current hospitalization, and presence of central venous or urinary catheters were independently associated with HAIs. A total of 2762 (51.0%; 95% CI, 49.7%-52.3%) patients were on 3611 systemic antimicrobial agents; 462 (12.8%) were prescribed for surgical prophylaxis and 2997 (83.0%) were prescribed for treatment. Amoxicillin/clavulanate was the most frequently prescribed (24.6%) antimicrobial agent. CONCLUSIONS: This survey suggested a high prevalence of HAIs and AMU in Singapore's acute-care hospitals. While further research is necessary to understand the causes and costs of HAIs and AMU in Singapore, repeated PPSs over the next decade will be useful to gauge progress at controlling HAIs and AMU.


Assuntos
Antibacterianos/uso terapêutico , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Fatores Etários , Idoso , Combinação Amoxicilina e Clavulanato de Potássio/administração & dosagem , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Carbapenêmicos/farmacologia , Infecção Hospitalar/tratamento farmacológico , Feminino , Cirurgia Geral , Inquéritos Epidemiológicos , Hospitais , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica/estatística & dados numéricos , Prevalência , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Fatores Sexuais , Singapura/epidemiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação
7.
Clin Infect Dis ; 64(suppl_2): S68-S75, 2017 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-28475792

RESUMO

BACKGROUND: Since 2010, the incidence of carbapenem-resistant Enterobacteriaceae (CRE) has been increasing in Singapore. We analyzed the clinical and molecular epidemiology of CRE among adult inpatients in Singapore. METHODS: Quarterly incidence of unique subjects (per 100000 patient-days) with positive clinical and surveillance cultures for CRE were estimated based on mandatory data submitted to the National Public Health Laboratory by public hospitals between 2010 and 2015. CRE-positive adult inpatients were prospectively recruited from 6 public sector hospitals between December 2013 and April 2015. Subjects answered a standardized epidemiologic questionnaire and provided samples for this study. Further clinical information was extracted from subjects' electronic medical records. Whole-genome sequencing was performed on study isolates to determine transmission clusters. RESULTS: Incidence of CRE clinical cultures among adult inpatients plateaued from 2013 (range: 7.73 to 10.32 per 100000 patient-days) following an initial increase between 2010 and end-2012. We prospectively recruited 249 subjects. Their median age was 65 years, 108 (43%) were female, and 161 (64.7%) had carbapenemase-producing Enterobacteriaceae (CPE). On multivariate analysis, prior carbapenem exposure (OR: 3.23; 95% CI: 1.67-6.25) and hematological malignancies (OR: 2.85; 95% CI: 1.10-7.41) were associated with non-carbapenemase-producing CRE (NCPE) (n = 88) compared with CPE (n = 161) subjects. Among 430 CRE isolates from the 249 subjects, 307(71.3%) were CPE, of which 154(50.2%) were blaKPC-positive, 97(31.6%) blaNDM-positive, and 42 (13.7%) blaOXA-positive. Klebsiella pneumoniae (n = 180, 41.9%), Escherichia coli (n = 129, 30.0%) and Enterobacter cloacae (n = 62, 14.4%) were the main Enterobacteriaceae species. WGS (n = 206) revealed diverse bacterial strain type (STs). The predominant blaKPC-positive plasmid was pHS102707 (n = 62, 55.4%) and the predominant blaNDM-positive plasmid was pNDM-ECS01 (n = 46, 48.9%). Five transmission clusters involving 13 subjects were detected. CONCLUSIONS: Clinical CRE trend among adult inpatients showed stabilization following a rapid rise since introduction in 2010 potentially due to infection prevention measures and antimicrobial stewardship. More work is needed on understanding CPE transmission dynamics.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Infecção Hospitalar/epidemiologia , Infecções por Enterobacteriaceae/epidemiologia , Pacientes Internados , Adulto , Idoso , Antibacterianos/uso terapêutico , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , DNA Bacteriano/genética , Registros Eletrônicos de Saúde , Enterobacter cloacae/genética , Enterobacter cloacae/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/transmissão , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/epidemiologia , Feminino , Genoma Bacteriano , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Incidência , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/isolamento & purificação , Masculino , Inquéritos e Questionários , Adulto Jovem , Resistência beta-Lactâmica , beta-Lactamases/biossíntese , beta-Lactamases/genética
8.
J Antimicrob Chemother ; 71(11): 3081-3089, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27494913

RESUMO

OBJECTIVES: Owing to gene transposition and plasmid conjugation, New Delhi metallo-ß-lactamase (NDM) is typically identified among varied Enterobacteriaceae species and STs. We used WGS to characterize the chromosomal and plasmid molecular epidemiology of NDM transmission involving four institutions in Singapore. METHODS: Thirty-three Enterobacteriaceae isolates (collection years 2010-14) were sequenced using short-read sequencing-by-synthesis and analysed. Long-read single molecule, real-time sequencing (SMRTS) was used to characterize genetically a novel plasmid pSg1-NDM carried on Klebsiella pneumoniae ST147. RESULTS: In 20 (61%) isolates, blaNDM was located on the pNDM-ECS01 plasmid in the background of multiple bacterial STs, including eight K. pneumoniae STs and five Escherichia coli STs. In six (18%) isolates, a novel blaNDM-positive plasmid, pSg1-NDM, was found only in K. pneumoniae ST147. The pSg1-NDM-K. pneumoniae ST147 clone (Sg1-NDM) was fully sequenced using SMRTS. pSg1-NDM, a 90 103 bp IncR plasmid, carried genes responsible for resistance to six classes of antimicrobials. A large portion of pSg1-NDM had no significant homology to any known plasmids in GenBank. pSg1-NDM had no conjugative transfer region. Combined chromosomal-plasmid phylogenetic analysis revealed five clusters of clonal bacterial NDM-positive plasmid transmission, of which two were inter-institution clusters. The largest inter-institution cluster involved six K. pneumoniae ST147-pSg1-NDM isolates. Fifteen patients were involved in transmission clusters, of which four had ward contact, six had hospital contact and five had an unknown transmission link. CONCLUSIONS: A combined sequencing-by-synthesis and SMRTS approach can determine effectively the transmission clusters of blaNDM and genetically characterize novel plasmids. Plasmid molecular epidemiology is important to understanding NDM spread as blaNDM-positive plasmids can conjugate extensively across species and STs.


Assuntos
Infecções por Enterobacteriaceae/microbiologia , Enterobacteriaceae/enzimologia , Enterobacteriaceae/isolamento & purificação , Sequenciamento de Nucleotídeos em Larga Escala , Plasmídeos/isolamento & purificação , Análise de Sequência de DNA , beta-Lactamases/genética , Enterobacteriaceae/classificação , Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/transmissão , Transferência Genética Horizontal , Instalações de Saúde , Humanos , Epidemiologia Molecular , Plasmídeos/classificação , Singapura/epidemiologia
9.
Curr Opin Infect Dis ; 28(4): 369-74, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26098501

RESUMO

PURPOSE OF REVIEW: In order to ensure patient safety and prevent surgical site infections (SSIs), operating theaters/rooms have evolved into complex, highly technical environments. Prevention of healthcare-associated infections, and strategies to limit patient harm, have gained momentum over the last decade. This article aims to examine and dispute some commonly held beliefs with specific reference to: laminar airflow, noise and operating theater door openings and how these impact SSI. RECENT FINDINGS: Laminar airflow may not be necessary for prosthetic implant surgery. Some recent data suggest that there may be patient harm. With the development of better surgical techniques and perioperative care, such costly systems may not be needed. Operating rooms with a high number of door openings have also been shown to experience higher SSI rates, as have operating rooms with high noise levels. These may serve as surrogate markers for operating room discipline. Initiatives which target these areas may be worth considering when devising strategies to reduce SSIs. SUMMARY: Improved surveillance systems for SSIs are needed and should include operating theater airflow type. This will allow further analysis of the effect of laminar air flow on SSIs and provide evidence for a decisive recommendation. Cultivating a culture of good operating theater discipline may also reduce SSIs.


Assuntos
Controle de Infecções/métodos , Salas Cirúrgicas , Segurança do Paciente , Infecção da Ferida Cirúrgica/prevenção & controle , Microbiologia do Ar , Humanos , Ruído
11.
Artigo em Inglês | MEDLINE | ID: mdl-38156208

RESUMO

The COVID-19 pandemic led to an initial increase in the incidence of carbapenem-resistant Enterobacterales (CRE) from clinical cultures in South-East Asia hospitals, which was unsustained as the pandemic progressed. Conversely, there was a decrease in CRE incidence from surveillance cultures and overall combined incidence. Further studies are needed for future pandemic preparedness.

12.
Singapore Med J ; 63(2): 61-67, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-32729311

RESUMO

The complete picture regarding transmission modes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. This review summarises the available evidence on its transmission modes, our preliminary research findings and implications for infection control policy, and outlines future research directions. Environmental contamination has been reported in hospital settings occupied by infected patients, and is higher in the first week of illness. Transmission via environmental surfaces or fomites is likely, but decontamination protocols are effective in minimising this risk. The extent of airborne transmission is also unclear. While several studies have detected SARS-CoV-2 ribonucleic acid in air samples, none has isolated viable virus in culture. Transmission likely lies on a spectrum between droplet and airborne transmission, depending on the patient, disease and environmental factors. Singapore's current personal protective equipment and isolation protocols are sufficient to manage this risk.


Assuntos
COVID-19 , SARS-CoV-2 , Hospitais , Humanos , Controle de Infecções/métodos , Equipamento de Proteção Individual
13.
Res Sq ; 2022 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-35233568

RESUMO

The SARS-CoV-2 B.1.1.529 lineage, Omicron variant, was first detected in November 2021 and carries 32 amino acid mutations in the spike protein (15 in RBD) and exhibits significant escape of neutralizing antibodies targeting the parental SARS-CoV-2 virus. Here, we performed a high-resolution multiplex (16-plex) surrogate virus neutralization assay covering all major SARS-CoV-2 variants and pre-emergent ACE2-binding sarbecoviruses against 20 different human serum panels from infected, vaccinated and hybrid immune individuals which had vaccine-breakthrough infections or infection followed by vaccination. Among all sarbecoviruses tested, we observed 1.1 to 4.7-, 2.3 to 10.3- and 0.7 to 33.3-fold reduction in neutralization activities to SARS-CoV-2 Beta, Omicron and SARS-CoV-1, respectively. Among the SARS-CoV-2 related sarbecoviruses, it is found that the genetically more distant bat RaTG13 and pangolin GX-P5L sarbecoviruses had less neutralization escape than Omicron. Our data suggest that the SARS-CoV-2 variants emerged from the changed immune landscape of human populations are more potent in escaping neutralizing antibodies, from infection or vaccination, than pre-emergent sarbecoviruses naturally evolved in animal populations with no or less immune selection pressure.

14.
Front Microbiol ; 13: 1043049, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36483199

RESUMO

Introduction: COVID-19 has a wide disease spectrum ranging from asymptomatic to severe. While humoral immune responses are critical in preventing infection, the immune mechanisms leading to severe disease, and the identification of biomarkers of disease progression and/or resolution of the infection remains to be determined. Methods: Plasma samples were obtained from infections during the initial wave of ancestral wildtype SARS-CoV-2 and from vaccine breakthrough infections during the wave of Delta variant, up to six months post infection. The spike-specific antibody profiles were compared across different severity groups and timepoints. Results: We found an association between spike-specific IgM, IgA and IgG and disease severity in unvaccinated infected individuals. In addition to strong IgG1 and IgG3 response, patients with severe disease develop a robust IgG2 and IgG4 response. A comparison of the ratio of IgG1 and IgG3 to IgG2 and IgG4 showed that disease progression is associated with a smaller ratio in both the initial wave of WT and the vaccine breakthrough Delta infections. Time-course analysis revealed that smaller (IgG1 and IgG3)/(IgG2 and IgG4) ratio is associated with disease progression, while the reverse associates with clinical recovery. Discussion: While each IgG subclass is associated with disease severity, the balance within the four IgG subclasses may affect disease outcome. Acute disease progression or infection resolution is associated with a specific immunological phenotype that is conserved in both the initial wave of WT and the vaccine breakthrough Delta infections.

15.
Nat Microbiol ; 7(11): 1756-1761, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36195753

RESUMO

The SARS-CoV-2 Omicron variant (B.1.1.529 lineage) escapes antibodies that neutralize the ancestral virus. We tested human serum panels from participants with differing infection and vaccination status using a multiplex surrogate virus neutralization assay targeting 20 sarbecoviruses. We found that bat and pangolin sarbecoviruses showed significantly less neutralization escape than the Omicron variant. We propose that SARS-CoV-2 variants have emerged under immune selection pressure and are evolving differently from animal sarbecoviruses.


Assuntos
COVID-19 , SARS-CoV-2 , Animais , Humanos , SARS-CoV-2/genética , Testes de Neutralização , Glicoproteína da Espícula de Coronavírus/genética , Proteínas do Envelope Viral , Anticorpos Antivirais , Glicoproteínas de Membrana
16.
Front Immunol ; 13: 1031852, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36451833

RESUMO

The emergence of new SARS-CoV-2 variants, such as the more transmissible Delta and Omicron variants, has raised concerns on efficacy of the COVID-19 vaccines. Here, we examined the waning of antibody responses against different variants following primary and booster vaccination. We found that antibody responses against variants were low following primary vaccination. The antibody response against Omicron was almost non-existent. Efficient boosting of antibody response against all variants, including Omicron, was observed following a third dose. The antibody response against the variants tested was significantly higher at one month following booster vaccination, compared with two months following primary vaccination, for all individuals, including the low antibody responders identified at two months following primary vaccination. The antibody response, for all variants tested, was significantly higher at four months post booster than at five months post primary vaccination, and the proportion of low responders remained low (6-11%). However, there was significant waning of antibody response in more than 95% of individuals at four months, compared to one month following booster. We also observed a robust memory B cell response following booster, which remained higher at four months post booster than prior to booster. However, the memory B cell responses were on the decline for 50% of individuals at four months following booster. Similarly, while the T cell response is sustained, at cohort level, at four months post booster, a substantial proportion of individuals (18.8 - 53.8%) exhibited T cell response at four months post booster that has waned to levels below their corresponding levels before booster. The findings show an efficient induction of immune response against SARS-CoV-2 variants following booster vaccination. However, the induced immunity by the third BNT162b2 vaccine dose was transient. The findings suggest that elderly individuals may require a fourth dose to provide protection against SARS-CoV-2.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Idoso , Humanos , Vacina BNT162 , SARS-CoV-2 , COVID-19/prevenção & controle , Anticorpos
17.
Nat Commun ; 13(1): 3052, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35650193

RESUMO

Carbapenemase-producing Enterobacterales (CPE) infection control practices are based on the paradigm that detected carriers in the hospital transmit to other patients who stay in the same ward. The role of plasmid-mediated transmission at population level remains largely unknown. In this retrospective cohort study over 4.7 years involving all multi-disciplinary public hospitals in Singapore, we analysed 779 patients who acquired CPE (1215 CPE isolates) detected by clinical or surveillance cultures. 42.0% met putative clonal transmission criteria, 44.8% met putative plasmid-mediated transmission criteria and 13.2% were unlinked. Only putative clonal transmissions associated with direct ward contact decreased in the second half of the study. Both putative clonal and plasmid-mediated transmission associated with indirect (no temporal overlap in patients' admission period) ward and hospital contact did not decrease during the study period. Indirect ward and hospital contact were identified as independent risk factors associated with clonal transmission. In conclusion, undetected CPE reservoirs continue to evade hospital infection prevention measures. New measures are needed to address plasmid-mediated transmission, which accounted for 50% of CPE dissemination.


Assuntos
Infecções por Enterobacteriaceae , Gammaproteobacteria , Proteínas de Bactérias , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/transmissão , Gammaproteobacteria/genética , Humanos , Estudos Retrospectivos , Sequenciamento Completo do Genoma , beta-Lactamases/genética
18.
Nat Commun ; 13(1): 4615, 2022 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-35941158

RESUMO

Understanding the impact of age on vaccinations is essential for the design and delivery of vaccines against SARS-CoV-2. Here, we present findings from a comprehensive analysis of multiple compartments of the memory immune response in 312 individuals vaccinated with the BNT162b2 SARS-CoV-2 mRNA vaccine. Two vaccine doses induce high antibody and T cell responses in most individuals. However, antibody recognition of the Spike protein of the Delta and Omicron variants is less efficient than that of the ancestral Wuhan strain. Age-stratified analyses identify a group of low antibody responders where individuals ≥60 years are overrepresented. Waning of the antibody and cellular responses is observed in 30% of the vaccinees after 6 months. However, age does not influence the waning of these responses. Taken together, while individuals ≥60 years old take longer to acquire vaccine-induced immunity, they develop more sustained acquired immunity at 6 months post-vaccination. A third dose strongly boosts the low antibody responses in the older individuals against the ancestral Wuhan strain, Delta and Omicron variants.


Assuntos
COVID-19 , Vacinas Virais , Idoso , Anticorpos Antivirais , Formação de Anticorpos , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Pessoa de Meia-Idade , SARS-CoV-2 , Vacinação , Vacinas Sintéticas , Vacinas de mRNA
19.
Clin Transl Immunology ; 11(8): e1403, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36016852

RESUMO

Objective: Despite the high vaccine efficacy of mRNA COVID-19 vaccines, there are individuals who developed excessive reactogenic and/or allergic responses after the first mRNA dose and were considered ineligible for further mRNA doses. CoronaVac, an inactivated SARS-CoV-2 vaccine, is recommended in Singapore as an alternative. Methods: Individuals, ineligible for further mRNA vaccines (BNT162b2 or mRNA-1273) because of excessive reactive responses to prime mRNA vaccination, were recruited and offered two doses of CoronaVac as booster vaccination 38-224 days post their mRNA vaccine dose. Individuals who did not develop any excessive reactive responses after the prime mRNA vaccination were also recruited and given another mRNA vaccine as booster vaccination. Blood samples were collected at days 0, 21 and 90 post first CoronaVac dose and mRNA dose, respectively, for analysis. Results: We showed that two CoronaVac booster doses induced specific immunity in these mRNA vaccine-primed individuals. Although the spike-specific antibody response was lower, their memory B cell response against the receptor-binding domain (RBD) of the spike protein was similar, compared with individuals who received two BNT162b2 injections. The spike-specific memory T cell response also increased following CoronaVac booster doses. However, specific immunity against the Omicron variant was low, similar to individuals with two BNT162b2 doses. Conclusion: Our findings showed that while mRNA vaccine-primed individuals can opt for two subsequent doses of CoronaVac, an additional dose may be necessary to achieve protection, especially against newly emerging immune escape variants such as Omicron.

20.
Antimicrob Resist Infect Control ; 10(1): 81, 2021 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-34022947

RESUMO

BACKGROUND: Computerisation of various processes in hospitals and reliance on electronic devices raises the concern of contamination of these devices from the patient environment. We undertook this study to determine if an attached hand hygiene device that unlocks the screen of a computer on wheels (COW) on usage can be effective in decreasing the microbiological burden on computer keyboards. METHODS: An electronic hand sanitizer was integrated onto the COW. A prospective cohort study with a crossover design involving 2 control and 2 intervention wards was used. The study end point was the number of colony forming units found on the keyboards. Bacteria were classified into 4 main groups; pathogenic, skin flora, from the environment or those thought to be commensals in healthy individuals. We then used a mixed effects model for the statistical analysis to determine if there were any differences before and after the intervention. RESULTS: Thirty-nine keyboards were swabbed at baseline, day 7 and 14, with 234 keyboards cultured, colony forming units (CFUs) counted and organisms isolated. By mixed model analysis, the difference of mean bacteria count between intervention and control for week 1 was 32.74 (- 32.74, CI - 94.29 to 28.75, p = 0.29), for week 2 by 155.86 (- 155.86, CI - 227.45 to - 83.53, p < 0.0001), and after the 2-week period by 157.04 (- 157.04, CI - 231.53 to - 82.67, p < 0.0001). In the sub-analysis, there were significant differences of pathogenic bacteria counts for the Intervention as compared to the Control in contrast with commensal counts. CONCLUSION: A hand hygiene device attached to a COW may be effective in decreasing the microbiological burden on computer keyboards.


Assuntos
Computadores , Contaminação de Equipamentos/prevenção & controle , Higiene das Mãos , Carga Bacteriana , Contagem de Colônia Microbiana , Infecção Hospitalar/prevenção & controle , Estudos Cross-Over , Higiene das Mãos/instrumentação , Hospitais , Humanos , Estudos Prospectivos , Singapura , Software
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