DENGUE PROGNOSTIC BIOMARKERS PREDICT DENGUE HAEMORRHAGIC FEVER WITH HIGH SENSITIVITY AND SPECIFICITY

Ninety-six million people are symptomatically infected with Dengue globally every year. Under the current standard-of-care, up to 20% of Dengue patients may be hospitalized, while only 500,000 develop Dengue Haemorrhagic Fever (DHF) and require hospitalization. This leads to unnecessary overwhelming of hospitals in tropical countries during large Dengue epidemics, especially when healthcare systems are grappling with large numbers of COVID-19 patients. Our research team set out to discover biomarkers to prognosticate Dengue patients, and augment the infectious disease clinician's decision-making process to hospitalize Dengue patients. Host biomarkers with concentrations significantly different between pooled serum samples of Dengue Fever (DF) patients and DHF patients were identified using protein array. The prognostication capabilities of selected biomarkers were then validated over 283 adult Dengue patients recruited from three Singapore tertiary hospitals, prior to the diagnosis of DHF. Three biomarkers (A2M, CMA1 and VEGFA) were identified that provide independent prognostication value from one another, and from clinical parameters commonly monitored in Dengue patients. The combination of all three biomarkers was able to identify from as early as Day 1 after the onset of fever, DF patients whose conditions will deteriorate into DHF. The biomarkers are robust and able to predict DHF well when trained on different AI/ML algorithms (logistic regression, support vector machine, decision tree, random forest, AdaBoost and gradient boosting). When stacked, prediction models based on the biomarkers were able to predict DHF with 97.3% sensitivity, 92.7% specificity, 66.7% PPV, 99.6% NPV and an AUC of 0.978. To the best of our knowledge, our panel of three biomarkers offers the highest accuracy in prognosticating Dengue to date. Further studies are required to validate the biomarkers in different geographical settings and pilot their implementation as part of the standard-of-care workflow for Dengue patients. [ FROM AUTHOR] Copyright of International Journal of Infectious Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

A living WHO guideline on drugs for covid-19

Clinical question What is the role of drug interventions in the treatment and prevention of covid-19? Recommendations The first version on this living guidance focuses on corticosteroids. It contains a strong recommendation for systemic corticosteroids in patients with severe and critical covid-19, and a weak or conditional recommendation against systemic corticosteroids in patients with non-severe covid-19. Corticosteroids are inexpensive and are on the World Health Organisation list of essential medicines. How this guideline was created This guideline reflects an innovative collaboration between the WHO and the MAGIC Evidence Ecosystem Foundation, driven by an urgent need for global collaboration to provide trustworthy and living covid-19 guidance. A standing international panel of content experts, patients, clinicians, and methodologists, free from relevant conflicts of interest, produce recommendations for clinical practice. The panel follows standards, methods, processes, and platforms for trustworthy guideline development using the GRADE approach. We apply an individual patient perspective while considering contextual factors (that is, resources, feasibility, acceptability, equity) for countries and healthcare systems. The evidence A living systematic review and network meta-analysis, supported by a prospective meta-analysis, with data from eight randomised trials (7184 participants) found that systemic corticosteroids probably reduce 28 day mortality in patients with critical covid-19 (moderate certainty evidence;87 fewer deaths per 1000 patients (95% confidence interval 124 fewer to 41 fewer)), and also in those with severe disease (moderate certainty evidence;67 fewer deaths per 1000 patients (100 fewer to 27 fewer)). In contrast, systemic corticosteroids may increase the risk of death in patients without severe covid-19 (low certainty evidence;absolute effect estimate 39 more per 1000 patients, (12 fewer to 107 more)). Systemic corticosteroids probably reduce the need for invasive mechanical ventilation, and harms are likely to be minor (indirect evidence). Understanding the recommendations The panel made a strong recommendation for use of corticosteroids in severe and critical covid-19 because there is a lower risk of death among people treated with systemic corticosteroids (moderate certainty evidence), and they believe that all or almost all fully informed patients with severe and critical covid-19 would choose this treatment. In contrast, the panel concluded that patients with non-severe covid-19 would decline this treatment because they would be unlikely to benefit and may be harmed. Moreover, taking both a public health and a patient perspective, the panel warned that indiscriminate use of any therapy for covid-19 would potentially rapidly deplete global resources and deprive patients who may benefit from it most as potentially lifesaving therapy. Updates This is a living guideline. Work is under way to evaluate other interventions. New recommendations will be published as updates to this guideline. Readers note This is version 1 of the living guideline, published on 4 September (BMJ 2020;370:m3379) version 1. Updates will be labelled as version 2, 3 etc. When citing this article, please cite the version number. Submitted August 28 Accepted August 31Copyright © Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to.

Coronavirus Disease 2019 (COVID-19): The Singapore Experience. A Review of the First Eight Months

As of 27 October 2020, there have been 57,980 confirmed cases of COVID-19 in Singapore, with 28 fatalities. To summarise the Singapore experience in managing and containing COVID-19 based on available published data and from relevant sources, a review of literature using research databases such as PubMed and OVID Medline, along with non-peer-reviewed articles and other sources, was conducted with the search terms 'COVID-19' and 'Singapore'. Research conducted in Singapore has provided insight into the clinical manifestations and period of infectivity of COVID-19, demonstrated evidence of pre-symptomatic transmission, linked infection clusters using serological tools, and highlighted aspects of hospital-based environmental contamination. It has also provided guidance for diagnostic testing and has described immune and virologic correlates with disease severity. Evidence of effectiveness of containment measures such as early border control, rigorous contact training, and calibrated social distancing measures have also been demonstrated. Singapore's multipronged strategy has been largely successful at containing COVID-19 and minimising fatalities, but the risk of re-emergence is high.

Olfactory taste disorder as a presenting symptom of COVID-19: a large single-center Singapore study.

PURPOSE: To investigate the prevalence and epidemiological risk factors of olfactory and/or taste disorder (OTD), in particular isolated OTD, in patients with laboratory-confirmed COVID-19 infection. METHODS: We conducted a retrospective and cross-sectional study. Patients with laboratory-confirmed COVID-19 infection were recruited from the National Centre for Infectious Diseases (NCID) Singapore between 24 March 2020 and 16 April 2020. The electronic health records of these patients were accessed, and demographic data and symptoms reported (respiratory, self-reported OTD and other symptoms such as headache, myalgia and lethargy) were collected. RESULTS: A total of 1065 patients with laboratory-confirmed COVID-19 were recruited. Overall, the prevalence of OTD was 12.6%. Twelve patients (1.1%) had isolated OTD. The top three symptoms associated with OTD were cough, fever and sore throat. The symptoms of runny nose and blocked nose were experienced by only 29.8 and 19.3% of patients, respectively. Multivariate analysis demonstrated that the female gender, presence of blocked nose and absence of fever were significantly associated with OTD (adjusted relative risks 1.77, 3.31, 0.42, respectively). All these factors were statistically significant. CONCLUSION: Patients with COVID-19 infection can present with OTD, either in isolation or in combination with other general symptoms. Certain demographic profile, such as being female, and symptomatology such as the presence of blocked nose and absence of fever, were more likely to have OTD when infected by COVID-19. Further studies to elucidate the pathophysiology of OTD in these patients will be beneficial.

Does incubation period of COVID-19 vary with age? A study of epidemiologically linked cases in Singapore.

This study estimates the incubation period of COVID-19 among locally transmitted cases, and its association with age to better inform public health measures in containing COVID-19. Epidemiological data of all PCR-confirmed COVID-19 cases from all restructured hospitals in Singapore were collected between 23 January 2020 and 2 April 2020. Activity mapping and detailed epidemiological investigation were conducted by trained personnel. Positive cases without clear exposure to another positive case were excluded from the analysis. One hundred and sixty-four cases (15.6% of patients) met the inclusion criteria during the defined period. The crude median incubation period was 5 days (range 1-12 days) and median age was 42 years (range 5-79 years). The median incubation period among those 70 years and older was significantly longer than those younger than 70 years (8 vis-à-vis 5 days, P = 0.040). Incubation period was negatively correlated with day of illness in both groups. These findings support current policies of 14-day quarantine periods for close contacts of confirmed cases and 28 days for monitoring infections in known clusters. An elderly person who may have a longer incubation period than a younger counterpart may benefit from earlier and proactive testing, especially after exposure to a positive case.