Association of triglyceride-glucose index with vascular risk factors and clinical outcomes among COVID-19 patients: a retrospective cross-sectional study in Mengo Hospital, Kampala, Uganda.

Introduction: triglyceride-glucose (TyG) index is a reliable surrogate marker of insulin resistance. We assessed the association between triglyceride-glucose (TyG) index and vascular risk factors and clinical outcomes of critically ill adult COVID-19 patients. Methods: data from the charts of all patients with a confirmed diagnosis of COVID-19 who were hospitalized at Mengo Hospital Uganda from December 2020 to August 2021 was used for this study. Data on demographics, past medical history, clinical presentation, laboratory findings and clinical outcomes within the first 10 days of admission was extracted. TyG index was calculated as Inverse (triglyceride (mg/dl) x fasting glucose level (mg/dl)/2 and defined vascular risk factors using standard methods. Bivariate and multivariate logistic regression was conducted to establish a significant association. Statistical significance was set at p< 0.05. Results: out of 314 patients, 176 (56%) were females. The mean age ± SD was 58.2 years ± 16.82. The median TyG index was 9.76 (9.29-10.33). A high TyG index was found among 85.4% (n= 268, 95% CI: 0.809-0.889) of patients. Elevated total cholesterol was in 55.4% (n=174), triglycerides 70.7% (n=222), LDL 64.7% (n=203), blood glucose 80.6% (n=253), systolic blood pressure 43% (n=135) and 24.8% (n=78) diastolic blood pressure. The majority 49.7% ( n=156) were discharged, 22.0% (n=69) needed admission to the intensive care unit (ICU), 15.3% (n=48) died in the unit and 13.0% (n=41) had a composite outcome. The TyG index was significantly associated with glycated hemoglobin (AOR=1.029, 95%CI 0.561-1.496, p<0.001), low-density lipoprotein cholesterol (AOR=0.121,95%CI 0.023-0.219, p=0.016), high-density cholesterol (AOR=1.956, 95%CI 1.299-2.945, p=0.001), total cholesterol (AOR=2.177, 95%CI 1.5222-3.144, p<0.001, hospital death (AOR=0.778, 95%CI 0.623-0.972, p=0.028) and composite outcome (AOR=1.823, 95% CI 1.221-2.559, p=0.023). There was no association between hypertension and TyG index. Conclusion: a high TyG index was associated with vascular risk factors and clinical outcomes.

Association of triglyceride-glucose index with vascular risk factors and clinical outcomes among COVID -19 patients: a retrospective cross-sectional study in Mengo Hospital, Kampala, Uganda

Introduction: triglyceride-glucose (TyG) index is a reliable surrogate marker of insulin resistance. We assessed the association between triglyceride-glucose (TyG) index and vascular risk factors and clinical outcomes of critically ill adult COVID-19 patients. Methods: data from the charts of all patients with a confirmed diagnosis of COVID-19 who were hospitalized at Mengo Hospital Uganda from December 2020 to August 2021 was used for this study. Data on demographics, past medical history, clinical presentation, laboratory findings and clinical outcomes within the first 10 days of admission was extracted. TyG index was calculated as Inverse (triglyceride (mg/dl) x fasting glucose level (mg/dl)/2 and defined vascular risk factors using standard methods. Bivariate and multivariate logistic regression was conducted to establish a significant association. Statistical significance was set at p< 0.05. Results: out of 314 patients, 176 (56%) were females. The mean age ± SD was 58.2 years ± 16.82. The median TyG index was 9.76 (9.29-10.33). A high TyG index was found among 85.4% ( n= 268, 95% CI: 0.809-0.889) of patients. Elevated total cholesterol was in 55.4% (n=174), triglycerides 70.7% (n=222), LDL 64.7% (n=203), blood glucose 80.6% (n=253), systolic blood pressure 43% (n=135) and 24.8% (n=78) diastolic blood pressure. The majority 49.7% ( n=156) were discharged, 22.0% (n=69) needed admission to the intensive care unit (ICU), 15.3% (n=48) died in the unit and 13.0% (n=41) had a composite outcome. The TyG index was significantly associated with glycated hemoglobin (AOR=1.029, 95%CI 0.561-1.496, p<0.001), low-density lipoprotein cholesterol (AOR=0.121,95%CI 0.023-0.219,p=0.016), high-density cholesterol (AOR=1.956, 95%CI 1.299-2.945, p=0.001), total cholesterol (AOR=2.177, 95%CI 1.5222-3.144, p<0.001, hospital death (AOR=0.778, 95%CI 0.623-0.972, p=0.028) and composite outcome (AOR=1.823, 95% CI 1.221-2.559, p=0.023). There was no association between hypertension and TyG index Conclusion: a high TyG index was associated with vascular risk factors and clinical outcomes.

Population differences in vaccine responses (POPVAC): scientific rationale and cross-cutting analyses for three linked, randomised controlled trials assessing the role, reversibility and mediators of immunomodulation by chronic infections in the tropics.

INTRODUCTION: Vaccine-specific immune responses vary between populations and are often impaired in low income, rural settings. Drivers of these differences are not fully elucidated, hampering identification of strategies for optimising vaccine effectiveness. We hypothesise that urban-rural (and regional and international) differences in vaccine responses are mediated to an important extent by differential exposure to chronic infections, particularly parasitic infections. METHODS AND ANALYSIS: Three related trials sharing core elements of study design and procedures (allowing comparison of outcomes across the trials) will test the effects of (1) individually randomised intervention against schistosomiasis (trial A) and malaria (trial B), and (2) Bacillus Calmette-Guérin (BCG) revaccination (trial C), on a common set of vaccine responses. We will enrol adolescents from Ugandan schools in rural high-schistosomiasis (trial A) and rural high-malaria (trial B) settings and from an established urban birth cohort (trial C). All participants will receive BCG on day '0'; yellow fever, oral typhoid and human papilloma virus (HPV) vaccines at week 4; and HPV and tetanus/diphtheria booster vaccine at week 28. Primary outcomes are BCG-specific IFN-γ responses (8 weeks after BCG) and for other vaccines, antibody responses to key vaccine antigens at 4 weeks after immunisation. Secondary analyses will determine effects of interventions on correlates of protective immunity, vaccine response waning, priming versus boosting immunisations, and parasite infection status and intensity. Overarching analyses will compare outcomes between the three trial settings. Sample archives will offer opportunities for exploratory evaluation of the role of immunological and 'trans-kingdom' mediators in parasite modulation of vaccine-specific responses. ETHICS AND DISSEMINATION: Ethics approval has been obtained from relevant Ugandan and UK ethics committees. Results will be shared with Uganda Ministry of Health, relevant district councils, community leaders and study participants. Further dissemination will be done through conference proceedings and publications. TRIAL REGISTRATION NUMBERS: ISRCTN60517191, ISRCTN62041885, ISRCTN10482904.

Effect of intensive treatment for schistosomiasis on immune responses to vaccines among rural Ugandan island adolescents: randomised controlled trial protocol A for the 'POPulation differences in VACcine responses' (POPVAC) programme.

INTRODUCTION: Several licensed and investigational vaccines have lower efficacy, and induce impaired immune responses, in low-income versus high-income countries and in rural, versus urban, settings. Understanding these population differences is essential to optimising vaccine effectiveness in the tropics. We suggest that repeated exposure to and immunomodulation by chronic helminth infections partly explains population differences in vaccine response. METHODS AND ANALYSIS: We have designed an individually randomised, parallel group trial of intensive versus standard praziquantel (PZQ) intervention against schistosomiasis, to determine effects on vaccine response outcomes among school-going adolescents (9-17 years) from rural Schistosoma mansoni-endemic Ugandan islands. Vaccines to be studied comprise BCG on day 'zero'; yellow fever, oral typhoid and human papilloma virus (HPV) vaccines at week 4; and HPV and tetanus/diphtheria booster vaccine at week 28. The intensive arm will receive PZQ doses three times, each 2 weeks apart, before BCG immunisation, followed by a dose at week 8 and quarterly thereafter. The standard arm will receive PZQ at week 8 and 52. We expect to enrol 480 participants, with 80% infected with S. mansoni at the outset.Primary outcomes are BCG-specific interferon-γ ELISpot responses 8 weeks after BCG immunisation and for other vaccines, antibody responses to key vaccine antigens at 4 weeks after immunisation. Secondary analyses will determine the effects of intensive anthelminthic treatment on correlates of protective immunity, on waning of vaccine response, on priming versus boosting immunisations and on S. mansoni infection status and intensity. Exploratory immunology assays using archived samples will enable assessment of mechanistic links between helminths and vaccine responses. ETHICS AND DISSEMINATION: Ethics approval has been obtained from relevant ethics committes of Uganda and UK. Results will be shared with Uganda Ministry of Health, relevant district councils, community leaders and study participants. Further dissemination will be done through conference proceedings and publications. TRIAL REGISTRATION NUMBER: ISRCTN60517191.