Defining factors that influence vaccine-induced, cross-variant neutralizing antibodies for SARS-CoV-2 in Asians

The scale and duration of neutralizing antibody responses targeting SARS-CoV-2 viral variants represents a critically important serological parameter that predicts protective immunity for COVID-19. In this study, we present longitudinal data illustrating the impact of age, sex and comorbidities on the kinetics and strength of vaccine-induced neutralizing antibody responses for key variants in an Asian volunteer cohort. We demonstrate a reduction in neutralizing antibody titres across all groups six months post-vaccination and show a marked reduction in the serological binding and neutralizing response targeting Omicron compared to other viral variants. We also highlight the increase in cross-protective neutralizing antibody responses against Omicron induced by a third dose (booster) of vaccine. These data illustrate how key virological factors such as immune escape mutation combined with host factors such as age and sex of the vaccinated individuals influence the strength and duration of cross-protective serological immunity for COVID-19.

Data-driven analysis of COVID-19 reveals specific severity patterns distinct from the temporal immune response

Key immune signatures of SARS-CoV-2 infection may associate with either adverse immune reactions (severity) or simply an ongoing anti-viral response (temporality); how immune signatures contribute to severe manifestations and/or temporal progression of disease and whether longer disease duration correlates with severity remain unknown. Patient blood was comprehensively immunophenotyped via mass cytometry and multiplex cytokine arrays, leading to the identification of 327 basic subsets that were further stratified into more than 5000 immunotypes and correlated with 28 plasma cytokines. Low-density neutrophil abundance was closely correlated with hepatocyte growth factor levels, which in turn correlated with disease severity. Deep analysis also revealed additional players, namely conventional type 2 dendritic cells, natural killer T cells, plasmablasts and CD16+ monocytes, that can influence COVID-19 severity independent of temporal progression. Herein, we provide interactive network analysis and data visualization tools to facilitate data mining and hypothesis generation for elucidating COVID-19 pathogenesis.

Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early prognostic marker for severe COVID-19

SARS-CoV-2 is the novel coronavirus responsible for the current COVID-19 pandemic. Severe complications are observed only in a small proportion of infected patients but the cellular mechanisms underlying this progression are still unknown. Comprehensive flow cytometry of whole blood samples from 54 COVID-19 patients revealed a dramatic increase in the number of immature neutrophils. This increase strongly correlated with disease severity and was associated with elevated IL-6 and IP-10 levels, two key players in the cytokine storm. The most pronounced decrease in cell counts was observed for CD8 T-cells and VD2 {gamma}{delta} T-cells, which both exhibited increased differentiation and activation. ROC analysis revealed that the count ratio of immature neutrophils to CD8 or VD2 T-cells predicts pneumonia onset (0.9071) as well as hypoxia onset (0.8908) with high sensitivity and specificity. It would thus be a useful prognostic marker for preventive patient management and improved healthcare resource management.

Potent neutralizing antibodies in the sera of convalescent COVID-19 patients are directed against conserved linear epitopes on the SARS-CoV-2 spike protein

The ongoing SARS-CoV-2 pandemic demands rapid identification of immunogenic targets for the design of efficient vaccines and serological detection tools. In this report, using pools of overlapping linear peptides and functional assays, we present two immunodominant regions on the spike glycoprotein that were highly recognized by neutralizing antibodies in the sera of COVID-19 convalescent patients. One is highly specific to SARS-CoV-2, and the other is a potential pan-coronavirus target.

Chest Radiography in Coronavirus Disease 2019 (COVID-19): Correlation with Clinical Course

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 and was declared a global pandemic by the World Health Organization on 11 March 2020. A definitive diagnosis of COVID-19 is made after a positive result is obtained on reverse transcription-polymerase chain reaction assay. In Singapore, rigorous contact tracing was practised to contain the spread of the virus. Nasal swabs and chest radiographs (CXR) were also taken from individuals who were suspected to be infected by COVID-19 upon their arrival at a centralised screening centre. From our experience, about 40% of patients who tested positive for COVID-19 had initial CXR that appeared "normal". In this case series, we described the temporal evolution of COVID-19 in patients with an initial "normal" CXR. Since CXR has limited sensitivity and specificity in COVID-19, it is not suitable as a first-line diagnostic tool. However, when CXR changes become unequivocally abnormal, close monitoring is recommended to manage potentially severe COVID-19 pneumonia.

Pregnancy Outcomes in COVID-19: A Prospective Cohort Study in Singapore

INTRODUCTION@#Pregnant women are reported to be at increased risk of severe coronavirus disease 2019 (COVID-19) due to underlying immunosuppression during pregnancy. However, the clinical course of COVID-19 in pregnancy and risk of vertical and horizontal transmission remain relatively unknown. We aim to describe and evaluate outcomes in pregnant women with COVID-19 in Singapore.@*METHODS@#Prospective observational study of 16 pregnant patients admitted for COVID-19 to 4 tertiary hospitals in Singapore. Outcomes included severe disease, pregnancy loss, and vertical and horizontal transmission.@*RESULTS@#Of the 16 patients, 37.5%, 43.8% and 18.7% were infected in the first, second and third trimesters, respectively. Two gravidas aged ≥35 years (12.5%) developed severe pneumonia; one patient (body mass index 32.9kg/m2) required transfer to intensive care. The median duration of acute infection was 19 days; one patient remained reverse transcription polymerase chain reaction (RT-PCR) positive >11 weeks from diagnosis. There were no maternal mortalities. Five pregnancies produced term live-births while 2 spontaneous miscarriages occurred at 11 and 23 weeks. RT-PCR of breast milk and maternal and neonatal samples taken at birth were negative; placenta and cord histology showed non-specific inflammation; and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulins were elevated in paired maternal and umbilical cord blood (n=5).@*CONCLUSION@#The majority of COVID-19 infected pregnant women had mild disease and only 2 women with risk factors (obesity, older age) had severe infection; this represents a slightly higher incidence than observed in age-matched non-pregnant women. Among the women who delivered, there was no definitive evidence of mother-to-child transmission via breast milk or placenta.

Safety and effectiveness of improving carbapenem use via prospective review and feedback in a multidisciplinary antimicrobial stewardship programme

<p><b>INTRODUCTION</b>Antimicrobial stewardship programmes (ASP) can reduce antibiotic use but patient safety concerns exist. We evaluated the safety of prospective carbapenem review and feedback and its impact on carbapenem use and patient outcomes.</p><p><b>MATERIALS AND METHODS</b>After 3 months implementation of our ASP, we compared patients with and without acceptance of ASP recommendations on the use of carbapenems. Primary outcome was 30-day mortality. Secondary outcomes included duration of carbapenem use, length of hospitalisation, clinical response, microbiological clearance, 30-day readmission and mortality at discharge.</p><p><b>RESULTS</b>Of 226 recommendations for 183 patients, 59.3% was accepted. De-escalation, switching to oral antibiotics and antibiotic cessation comprised 72% of recommendations. Patients with acceptance of ASP recommendations had lower 30-day mortality and higher end-of-therapy clinical response despite shorter carbapenem duration (P <0.05). Predictors of 30-day mortality were Pitt bacteraemia score (adjusted odds ratio [aOR] 1.39, 95% confidence interval [CI], 1.11 to 1.74; P = 0.004) and non-acceptance of ASP recommendations (aOR 2.84, 95% CI, 1.21 to 6.64; P = 0.016).</p><p><b>CONCLUSION</b>Our prospective carbapenem review and feedback mainly comprising of reducing carbapenem use is safe.</p>

The excess financial burden of multidrug resistance in severe gram-negative infections in Singaporean hospitals

<p><b>INTRODUCTION</b>Multidrug-resistant (MDR) Gram-negative healthcare-associated infections are prevalent in Singaporean hospitals. An accurate assessment of the socioeconomic impact of these infections is necessary in order to facilitate appropriate resource allocation, and to judge the costeffectiveness of targeted interventions.</p><p><b>MATERIALS AND METHODS</b>A retrospective cohort study involving inpatients with healthcare-associated Gram-negative bacteraemia at 2 large Singaporean hospitals was conducted to determine the hospitalisation costs attributed to multidrug resistance, and to elucidate factors affecting the financial impact of these infections. Data were obtained from hospital administrative, clinical and financial records, and analysed using a multivariate linear regression model.</p><p><b>RESULTS</b>There were 525 survivors of healthcare-associated Gram-negative bacteraemia in the study cohort, with 224 MDR cases. MDR bacteraemia, concomitant skin and soft tissue infection, higher APACHE II score, ICU stay, and appropriate definitive antibiotic therapy were independently associated with higher total hospitalisation costs, whereas higher Charlson comorbidity index and concomitant urinary tract infection were associated with lower costs. The excess hospitalisation costs attributed to MDR infection was $8638.58. In the study cohort, on average, 62.3% of the excess cost attributed to MDR infection was paid for by government subvention.</p><p><b>CONCLUSION</b>Multidrug resistance in healthcare-associated Gram-negative bacteraemia is associated with higher financial costs--a significant proportion of which are subsidised by public funding in the form of governmental subvention. More active interventions aimed at controlling antimicrobial resistance are warranted, and the results of our study also provide possible benchmarks against which the cost-effectiveness of such interventions can be assessed.</p>

When less is more: can we abandon prophylactic platelet transfusion in Dengue fever?

Dengue fever (DF) has several hematological manifestations including thrombocytopenia and increased bleeding risk. Prophylactic platelet transfusion-in the absence of major bleeding-is utilized in DF with thrombocytopenia with the intention of preventing hemorrhagic complications. However, prophylactic platelet transfusion in DF is neither standardized nor supported by clinical evidence. We conclude that risks, costs and poor resource utilization associated with prophylactic platelet transfusion in DF far outweigh any potential hematological benefit, and as such, should not constitute routine clinical practice.

Dengue knowledge, attitudes, and practices among primary care physicians in Singapore

<p><b>INTRODUCTION</b>Dengue fever remains a significant public health concern in Singapore. Appropriate, timely diagnosis and risk stratification for severe disease are crucial in the optimal management of this illness. In the outpatient setting, the primary care physician plays a key role in dengue diagnosis, management, and triage. We present a descriptive analysis of the variations in dengue knowledge, attitudes, and practices among primary care physicians (PCPs) in Singapore.</p><p><b>MATERIALS AND METHODS</b>A survey of 25 multiple-choice questions was mailed to 2000 PCPs in Singapore. Responses were analysed by physician age group (21-40, 41-60, and >61) and practice setting (government subsidised polyclinic or private practice).</p><p><b>RESULTS</b>Of the 3 questions assessing dengue knowledge, 89.9% chose 2 or 3 of the preferred responses. Half of the respondents utilised dengue diagnostic tests at least 50% of the time, and 75% used serology when doing so. Older respondents and those from private practices used diagnostic tests more often than their counterparts, and both groups favoured non-serology tests. About 85% of surveyed PCPs monitored confirmed or suspected cases daily, and one-third referred patients to a hospital always or often.</p><p><b>CONCLUSIONS</b>While no major gaps in knowledge about dengue were identified in PCPs in Singapore, there were significant variations in clinical practice by physician age group and practice setting. The results of this survey provide a useful opportunity to identify strengths and areas in need of improved awareness in primary care management of dengue.</p>