Endothelial and inflammatory pathophysiology in dengue shock: New insights from a prospective cohort study in Vietnam

• Published in: PLoS neglected tropical diseases 2024-03, Vol.18 (3), p.e0012071-e0012071
• Main Authors: McBride, Angela, Duyen, Huynh Thi Le, Vuong, Nguyen Lam, Tho, Phan Vinh, Tai, Luong Thi Hue, Phong, Nguyen Thanh, Ngoc, Nguyen Thanh, Yen, Lam Minh, Nhat, Phung Tran Huy, Vi, Tran Thuy, Llewelyn, Martin J, Thwaites, Louise, Hao, Nguyen Van, Yacoub, Sophie
• Format: Article
• Language: English
• Subjects: Analysis; Bacterial infections; Biology and Life Sciences; Biomarkers; Care and treatment; Clinical trials; Cohort analysis; Complications and side effects; Consent; Dengue; Dengue fever; Dengue hemorrhagic fever; Dosage and administration; Ethics; Ferritin; Heparan sulfate; Human diseases; Hyaluronic acid; Hypovolemia; Illnesses; Immunomodulation; Infections; Inflammation; Interleukin 6; Leakage; Medicine and Health Sciences; Modulators; Mortality; Observational studies; Pathophysiology; Patients; Physical Sciences; Physiology, Pathological; Plasma; Pleural effusion; Pleural fluid; Prevention; R&D; Research & development; Risk factors; Sepsis; Septic shock; Syndecan; Tropical diseases; Ultrasonic imaging; Vascular cell adhesion molecule 1; Vector-borne diseases
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0012071

Dengue shock (DS) is the most severe complication of dengue infection; endothelial hyperpermeability leads to profound plasma leakage, hypovolaemia and extravascular fluid accumulation. At present, the only treatment is supportive with intravenous fluid, but targeted endothelial stabilising therapies and host immune modulators are needed. With the aim of prioritising potential therapeutics, we conducted a prospective observational study of adults (≥16 years) with DS in Vietnam from 2019-2022, comparing the pathophysiology underlying circulatory failure with patients with septic shock (SS), and investigating the association of biomarkers with clinical severity (SOFA score, ICU admission, mortality) and pulmonary vascular leak (daily lung ultrasound for interstitial and pleural fluid). Plasma was collected at enrolment, 48 hours later and hospital discharge. We measured biomarkers of inflammation (IL-6, ferritin), endothelial activation (Ang-1, Ang-2, sTie-2, VCAM-1) and endothelial glycocalyx breakdown (hyaluronan, heparan sulfate, endocan, syndecan-1). We enrolled 135 patients with DS (median age 26, median SOFA score 7, 34 required ICU admission, 5 deaths), together with 37 patients with SS and 25 healthy controls. Within the DS group, IL-6 and ferritin were associated with admission SOFA score (IL-6: βeta0.70, p