Associations of viral ribonucleic acid (RNA) shedding patterns with clinical illness and immune responses in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection.

OBJECTIVES: A wide range of duration of viral RNA shedding in patients infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been observed. We aimed to investigate factors associated with prolonged and intermittent viral RNA shedding in a retrospective cohort of symptomatic COVID-19 patients. METHODS: Demographic, clinical and laboratory data from hospitalised COVID-19 patients from a single centre with two consecutive negative respiratory reverse transcription-polymerase chain reaction (RT-PCR) results were extracted from electronic medical records. Kaplan-Meier survival curve analysis was used to assess the effect of clinical characteristics on the duration and pattern of shedding. Plasma levels of immune mediators were measured using Luminex multiplex microbead-based immunoassay. RESULTS: There were 201 symptomatic patients included. Median age was 49 years (interquartile range 16-61), and 52.2% were male. Median RNA shedding was 14 days (IQR 9-18). Intermittent shedding was observed in 77 (38.3%). We did not identify any factor associated with prolonged or intermittent viral RNA shedding. Duration of shedding was inversely correlated with plasma levels of T-cell cytokines IL-1ß and IL-17A at the initial phase of infection, and patients had lower levels of pro-inflammatory cytokines during intermittent shedding. CONCLUSIONS: Less active T-cell responses at the initial phase of infection were associated with prolonged viral RNA shedding, suggesting that early immune responses are beneficial to control viral load and prevent viral RNA shedding. Intermittent shedding is common and may explain re-detection of viral RNA in recovered patients.

Temporal Trends and Patient Characteristics Associated With Drug Utilisation After First-Ever Stroke: Insights From Chronic Disease Registry Data in Singapore.

INTRODUCTION: Data on drug utilisation among stroke patients of Asian ethnicities are lacking. The objectives of the study were to examine the temporal trends and patient characteristics associated with prescription of thrombolytic, antithrombotic and statin medications among patients with first-ever stroke. MATERIALS AND METHODS: First-ever ischaemic and haemorrhagic stroke patients admitted to 2 Singapore tertiary hospitals between 2010‒2014 were included. Data were extracted from the National Healthcare Group Chronic Disease Management System. Association between drug utilisation and admission year, as well as characteristics associated with drug use, were explored using multivariable logistic regression. RESULTS: There was an increasing trend in the combined use of all 3 guideline medications in ischaemic stroke patients (P <0.001)-specifically thrombolytic agents (P <0.001), oral antithrombotics (P = 0.002) and statins (P = 0.003) at discharge. Among antithrombotics, the use of clopidogrel (P <0.001) and aspirin-clopidogrel (P <0.001) had increased, whereas prescription of dipyridamole (P <0.001) and aspirin-dipyridamole (P <0.001) had declined. For statins, the increase in atorvastatin prescription (P <0.001) was accompanied by decreasing use of simvastatin (P <0.001). Age, ethnicity and certain comorbidities (hyperlipidaemia, atrial fibrillation and chronic kidney disease) were associated with the combined use of all 3 guideline medications (P <0.05). In haemorrhagic stroke, prescription of statins at discharge were comparatively lower. CONCLUSION: This study reveals changes in prescription behaviour over time in a multiethnic Asian population with first-ever stroke. Patient characteristics including younger age, Malay ethnicity and certain comorbidities (i.e. hyperlipidaemia, atrial fibrillation) were associated with the combined use of all 3 guideline medications among ischaemic stroke patients.

Incipient Albuminuria in Persons with Newly Diagnosed Type 2 Diabetes Mellitus: A 5-Year Retrospective Cohort Study.

INTRODUCTION: This study aimed to determine the 5-year incidence of albuminuria among Asian persons with newly diagnosed type 2 diabetes mellitus (DM), and to identify the risk factors at diagnosis for progression to albuminuria. MATERIALS AND METHODS: A retrospective 5-year closed cohort study was conducted among 1016 persons aged ≥18 years old who were diagnosed with type 2 DM between 1 January 2007 and 31 December 2009 at primary care facilities in Singapore. The cumulative incidence of progression from normoalbuminuria to albuminuria-termed "progression"-was determined. The risk factors associated with progression were evaluated using multiple logistic regression analysis. RESULTS: A total of 541 (53.2%) participants were men. The mean (SD) onset age of type 2 DM was 54 (11) years. From diagnosis of type 2 DM, the 5-year cumulative incidence of progression was 17.3% and mean (SD) duration to progression was 2.88 (1.23) years. Higher onset age (OR 1.02; 95% CI, 1.00-1.04), history of hypertension (OR, 1.88; 95% CI, 1.32-2.70) and higher glycated haemoglobin (HbA1c) (OR, 1.17; 95% CI, 1.09-1.26) at diagnosis were associated with progression. In addition, being on angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) treatment at baseline modified the effect of hypertension on progression. CONCLUSION: This study highlighted the importance of early screening and treatment of diabetes as well as prevention of hypertension, which could potentially delay the onset of microalbuminuria in persons with type 2 DM. Persons on ACEI or ARB treatment should continue to be monitored regularly for progression to albuminuria.