Background & Aims: Coronavirus disease 2019 (COVID-19) patients with severe complications have shown comorbidities with cardiovascular-disease, hypertension and type 2 diabetes mellitus; clinical disorders that share the common metabolic alterations of insulin resistance and dyslipidaemia. A high triglyceride to high density lipoprotein cholesterol (Tg/HDL c) ratio has been associated with reduced insulin sensitivity, metabolic syndrome and adverse cardiovascular events. Our aim in this study was to determine the association between different components of the lipid profile and particularly the Tg/HDL c ratio with severe complications like the requirement of invasive mechanical ventilation in COVID-19 patients., Methods: We collected demographic, clinical and biochemical data to conduct a cohort study in 43 adult patients with confirmed COVID-19 diagnosis by quantitative polymerase chain reaction (qPCR) at baseline and in the subsequent 15 days. Patients were subjected to a very similar treatment scheme with the JAK1/2 inhibitor ruxolitinib. Descriptive statistics, variable association and logistic regression were applied to identify predictors of disease severity among elements and calculations from the lipid profile., Results: Patients were aged 57 ± 14 years; 55.8% were male from which 75% required hospitalization and 44.2% were female who 58% were hospitalized. The most common comorbidities were type 2 diabetes mellitus (58%) and hypertension (40%). Hospitalized and critical care patients showed lower HDL c blood levels and increased Tg/HDL c ratio than those with outpatient management and mild/asymptomatic COVID-19. Tg/HDL c ratio correlated with variables of disease severity such as lactate dehydrogenase (LDH) levels (r = 0.356; p < 0.05); National Early Warning Score 2 (NEWS 2) (r = 0.495; p < 0.01); quick sequential organ failure assessment (qSOFA) (r = 0.538; p < 0.001); increased need of oxygen support (r = 0.447; p < 0.01) and requirement of mechanical ventilation (r = 0.378; p < 0.05). Tg/HDL c ratio had a negative correlation with partial oxygen saturation/fraction of inspired oxygen (SaO 2/FiO2) ratio (r = -0.332;p < 0.05). Linear regression analysis showed that Tg/HDL c ratio can predict increases in inflammatory factors like LDH (p < 0.01); ferritin (p < 0.01) and D-dimer (p < 0.001). Logistic regression model indicated that ≥7.45 Tg/HDL c ratio predicts requirement of invasive mechanical ventilation (OR 11.815, CI 1.832-76.186, p < 0.01)., Conclusions: The Tg/HDLc ratio can be used as an early biochemical marker of COVID-19 severe prognosis with requirement of invasive mechanical ventilation., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2021 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)