ORCID Profile
0000-0002-4635-3333
Current Organisations
Tan Tock Seng Hospital
,
National University of Singapore
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Publications
Sequence dynamics of three influenza A virus strains grown in different MDCK cell lines, including those expressing different sialic acid receptors
Publisher: Wiley
Date: 27-06-2021
DOI: 10.1111/JEB.13890
Abstract: Viruses are often cultured in cell lines for research and vaccine development, and those often differ from the natural hosts or tissues. Cell lines can also differ in the presence of virus receptors, such as the sialic acid (Sia) receptors used by influenza A viruses (IAV), which can vary in linkage (α2,3‐ or α2,6‐linkage) and form ( N ‐glycolylneuraminic acid [Neu5Gc] or N ‐acetylneuraminic acid [Neu5Ac]). The selective pressures resulting from passaging viruses in cell types with host‐specific variations in viral receptors are still only partially understood. IAV are commonly cultured in MDCK cells which are both derived from canine kidney tubule epithelium and inherently heterogeneous. MDCK cells naturally present Neu5Ac and α2,3‐linked Sia forms. Here, we examine natural MDCK variant lineages, as well as engineered variants that synthesize Neu5Gc and/or α2,6‐linkages. We determined how viral genetic variation occurred within human H3N2, H1N1 pandemic and canine H3N2 IAV populations when serially passaged in MDCK cell lines that vary in cell type (MDCK‐Type I or MDCK‐Type II clones) and in Sia display. Deep sequencing of viral genomes showed small numbers of consensus‐level mutations, mostly within the hemagglutinin (HA) gene. Both human IAV showed variants in the HA stem and the HA receptor‐binding site of populations passaged in cells displaying Neu5Gc. Canine H3N2 showed variants near the receptor‐binding site when passaged in cells displaying Neu5Gc or α2,6‐linkages. Viruses replicated to low titres in MDCK‐Type II cells, suggesting that not all cell types in heterogeneous MDCK cell populations are equally permissive to infection.
Hypercoagulability, endotheliopathy, and inflammation approximating 1 year after recovery: Assessing the long‐term outcomes in COVID ‐19 patients
Publisher: Wiley
Date: 28-04-2022
DOI: 10.1002/AJH.26575
Abstract: Sustained hypercoagulability and endotheliopathy are present in convalescent COVID‐19 patients for up to 4 months from recovery. The hemostatic, endothelial, and inflammatory profiles of 39 recovered COVID‐19 patients were evaluated up to 16 months after recovery from COVID‐19. These values were compared with a control group of healthy volunteers ( n = 124). 39 patients (71.8% males, median age 43 years) were reviewed at a mean of 12.7 ± 3.6 months following recovery. One patient without cardiovascular risk factors had post COVID‐19 acute ischaemic limb. Elevated D‐dimer and Factor VIII levels above normal ranges were noted in 17.9% (7/39) and 48.7% (19/39) of patients respectively, with a higher median D‐dimer 0.34 FEU μg/mL (IQR 0.28, 0.46) ( p .001) and Factor VIII 150% (IQR 171, 203) ( p = .004), versus controls. Thrombin generation (Thromboscreen) showed a higher median endogenous thrombin potential (ETP) of 1352 nM*min (IQR 1152, 1490) ( p = .002) and a higher median peak height of 221.4 nM (IQR 170.2, 280.4) ( p = 0.01) and delayed lag time 2.4 min (1.42–2.97) ( p = 0.0002) versus controls. Raised vWF:Ag and ICAM‐1 levels were observed in 17.9% (7/39) and 7.7% (3/39) of patients respectively, with a higher median VWF:Ag 117% (IQR 86, 154) ( p = 0.02) and ICAM‐1 54.1 ng/mL (IQR 43.8, 64.1) ( p = .004) than controls. IL‐6 was noted to be raised in 35.9% (14/39) of patients, with a higher median IL‐6 of 1.5 pg/mL (IQR 0.6, 3.0) ( p = 0.004) versus controls. Subgroup analysis stratifying patients by COVID‐19 severity and COVID‐19 vaccination preceding SARS‐CoV‐2 infection did not show statistically significant differences. Hypercoagulability, endothelial dysfunction, and inflammation are still detectable in some patients approximately 1 year after recovery from COVID‐19.
Mild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest
Publisher: Massachusetts Medical Society
Date: 06-07-2023
Global haemostatic tests in rapid diagnosis and management of COVID-19 associated coagulopathy in acute limb ischaemia
Publisher: Springer Science and Business Media LLC
Date: 30-05-2020
Hemorrhage, Disseminated Intravascular Coagulopathy, and Thrombosis Complications Among Critically Ill Patients with COVID-19: An International COVID-19 Critical Care Consortium Study*
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 28-02-2023
DOI: 10.1097/CCM.0000000000005798
Abstract: To determine the prevalence and outcomes associated with hemorrhage, disseminated intravascular coagulopathy, and thrombosis (HECTOR) complications in ICU patients with COVID-19. Prospective, observational study. Two hundred twenty-nine ICUs across 32 countries. Adult patients (≥ 16 yr) admitted to participating ICUs for severe COVID-19 from January 1, 2020, to December 31, 2021. None. HECTOR complications occurred in 1,732 of 11,969 study eligible patients (14%). Acute thrombosis occurred in 1,249 patients (10%), including 712 (57%) with pulmonary embolism, 413 (33%) with myocardial ischemia, 93 (7.4%) with deep vein thrombosis, and 49 (3.9%) with ischemic strokes. Hemorrhagic complications were reported in 579 patients (4.8%), including 276 (48%) with gastrointestinal hemorrhage, 83 (14%) with hemorrhagic stroke, 77 (13%) with pulmonary hemorrhage, and 68 (12%) with hemorrhage associated with extracorporeal membrane oxygenation (ECMO) cannula site. Disseminated intravascular coagulation occurred in 11 patients (0.09%). Univariate analysis showed that diabetes, cardiac and kidney diseases, and ECMO use were risk factors for HECTOR. Among survivors, ICU stay was longer (median days 19 vs 12 p 0.001) for patients with versus without HECTOR, but the hazard of ICU mortality was similar (hazard ratio [HR] 1.01 95% CI 0.92–1.12 p = 0.784) overall, although this hazard was identified when non-ECMO patients were considered (HR 1.13 95% CI 1.02–1.25 p = 0.015). Hemorrhagic complications were associated with an increased hazard of ICU mortality compared to patients without HECTOR complications (HR 1.26 95% CI 1.09–1.45 p = 0.002), whereas thrombosis complications were associated with reduced hazard (HR 0.88 95% CI 0.79–0.99, p = 0.03). HECTOR events are frequent complications of severe COVID-19 in ICU patients. Patients receiving ECMO are at particular risk of hemorrhagic complications. Hemorrhagic, but not thrombotic complications, are associated with increased ICU mortality.
Global haemostatic tests demonstrate the absence of parameters of hypercoagulability in non-hypoxic mild COVID-19 patients: a prospective matched study
Publisher: Springer Science and Business Media LLC
Date: 28-09-2021
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Related Funding Activities
No related grants have been discovered for Yew Woon Chia.