Ignite Creation Date:
2024-05-06 @ 3:39 PM
Last Modification Date:
2024-10-26 @ 1:54 PM
Study NCT ID:
NCT04709302
Status:
ENROLLING_BY_INVITATION
Last Update Posted:
2023-03-10
First Post:
2021-01-12
Brief Title:
Effects of COVID-19 on Endothelium in HIV-Positive Patients in Sub-Saharan Africa
Sponsor:
Medical University of Graz
Organization:
Medical University of Graz
Study Overview
Official Title:
COVID-19 and Its Effects on Endothelium in HIV-Positive Patients in Sub-Saharan Africa Cardiometabolic Risk Thrombosis and Vascular Function
Status:
ENROLLING_BY_INVITATION
Status Verified Date:
2023-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ENDOCOVID
Brief Summary:
Background Coronavirus disease 2019 COVID-19 has affected almost every country in the world especially in terms of health system capacity and economic burden People from sub-Saharan Africa SSA often face interaction between human immunodeficiency virus HIV infection and non-communicable diseases such as cardiovascular disease Role of HIV infection and anti-retroviral treatment ART in altered cardiovascular risk is questionable and there is still need to further carry out research in this field However thus far it is unclear what impact the COVID-19 co-infection in people living with HIV PLHIV with or without therapy will have The ENDOCOVID project aims to investigate whether and how HIV-infection in COVID-19 patients modulates the time course of the disease alters cardiovascular risk and changes vascular endothelial function and coagulation parameters thrombosis risk
Methods In this long-term study cardiovascular research on PLHIV with or without ART with COVID-19 and HIV-negative with COVID-19 will be carried out via clinical and biochemical measurements for cardiovascular risk factors and biomarkers of cardiovascular disease CVD Vascular and endothelial function will be measured by brachial artery flow-mediated dilatation FMD carotid intima-media thickness IMT assessments and retinal blood vessel analyses along with vascular endothelial biomarkers and coagualation markers The correlation between HIV-infection in COVID-19 PLHIV with or without ART and its role in enhancement of cardiovascular risk and endothelial dysfunction will be assessed Potential changes in these endpoints by COVID-19 will be followed for 4 weeks across the three groups PLHIVwith or without ART and HIV negatives
Impact of project The ENDOCOVID project aims to evaluate in the long-term the cardiovascular risk and vascular endothelial function in PLHIV thus revealing an important transitional cardiovascular phenotype in COVID-19
Methods In this long-term study cardiovascular research on PLHIV with or without ART with COVID-19 and HIV-negative with COVID-19 will be carried out via clinical and biochemical measurements for cardiovascular risk factors and biomarkers of cardiovascular disease CVD Vascular and endothelial function will be measured by brachial artery flow-mediated dilatation FMD carotid intima-media thickness IMT assessments and retinal blood vessel analyses along with vascular endothelial biomarkers and coagualation markers The correlation between HIV-infection in COVID-19 PLHIV with or without ART and its role in enhancement of cardiovascular risk and endothelial dysfunction will be assessed Potential changes in these endpoints by COVID-19 will be followed for 4 weeks across the three groups PLHIVwith or without ART and HIV negatives
Impact of project The ENDOCOVID project aims to evaluate in the long-term the cardiovascular risk and vascular endothelial function in PLHIV thus revealing an important transitional cardiovascular phenotype in COVID-19
Detailed Description:
Background
SARS-CoV-2 has affected almost every country worldwide with regard to health system capacities and economic burden so far The typical clinical presentations of COVID-19 are fever sore through cough dyspnea abdominal pain and diarrhea Approximately 15 of patients with COVID-19 must be hospitalized and 5 are critically ill and often develop acute respiratory distress syndrome and need to be admitted to intensive care units Risk of severe disease increases with age male sex and with co-morbidities such as chronic lung disease CVDs and diabetes COVID-19 can also affect the nervous systems and cause loss of smell or taste sensation
Populations in SSA are increasingly facing a double burden of disease involving the interaction between HIV-AIDS and non-communicable diseases such as CVDs In general vascular endothelial function can be regarded as a marker of the net harmful effects of cardiovascular risk factors on the vascular wall HIV- infected patients have premature atherosclerosis and increased risk of ischemic heart disease The cardiovascular risk represented by HIV-infection is moreover affected by anti-retroviral treatment ART ART may among other effects prompt dyslipidaemic and metabolic changes in patients over to systemic immune activation stimulation of endothelial inflammation and atherosclerosis However a recent meta-analysis showed that evidence for - and against - a role for ART in the development of CVDs remains unconvincing and that more research is necessary
With the current COVID-19 pandemic which has also spread across Africa another burden is added However thus far it is unclear what effect the additional COVID-19 co-infection in people with HIV PLHIV will have as there are no data yet on how HIVAIDS a prevalent diseases SSA will affect COVID-19 infection rates or outcomes Currently there is no proof for a higher COVID -19 infection rate in PLHIV compared to HIV-negatives However there is a possibility that HIV infection may have an influence on the course of infection PLHIV who are on ART with a normal CD4 T-cell count and suppressed viral load should not be at an increased risk of severe disease On the other hand this theoretically positive situation could be counterbalanced by recent evidence that ART could also have effects on COVID-19 Furthermore HIV-infected patients may additionally suffer from co-morbidities which could pose a greater risk of COVID-19 infection Currently there is no data available about COVID-19 infection in PLHIV in SSA reflecting who in particular is at high risk for infections complications and fatal outcomes As COVID-19 associated multisystem inflammation and the way organ damage caused by COVID-19 occurring in patients with COVID-19 is still incompletely understood and current treatment options are limited There is therefore an urgent need to better understand the risk of severe and fatal COVID-19 outcomes especially in PLHIV - ART
A severe course of COVID-19 can cause the development of COVID-19-associated coagulopathy with features of both disseminated intravascular coagulation and thrombotic microangiopathy resulting in widespread microvascular thrombosis that may involve consumption of coagulation factors and the liver There seems to be a causal relationship with the inflammatory and reparative processes involving diffuse alveolar damage DAD because thrombi are frequently detected in small pulmonary arteries most presumed secondary to endothelial damage The damage of endothelium could be due to the direct viral infection of the endothelial cells which express ACE-2 receptors or to a host response Besides the alveolar fibrin deposition in DAD may affect the local homeostasis between fibrinolysis and coagulation Alveolar and endothelial damage of smaller vessels may be followed by microvascular pulmonary thrombosis which could then extend to larger vessels Additionally elevated D-dimer has been observed in patients with COVID-19 It is known that inceased D-dimer is associated with acute pulmonary emboli APE deep venous thrombosis DVT cancer peripheral vascular disease inflammatory diseases and pregnancy It has been found that patients with COVID-19 including those not on respirators but bedconfined develop DVT and APE much earlier than expected Even with usage of prophylactic anticoagulation autopsy has shown that deaths in COVID-19 may be caused by the thrombosis in segmental and subsegmental pulmonary arterial vessels ENDOCOVID project aims to evaluate the degree to which COVID-19 induced inflammation contributes to endothelial function and coagulation changes and cardiometabolic risk in PLHIV -ART Endothelial function will be evaluated non-invasively via FMD and blood asymmetric dimethyl arginine ADMA
Problem statement HIV infection is a burden for the cardiovascular system but coinfection of HIV and SARS-CoV-2 in SSA population could be a very big load and could lead to higher menace of cardiovascular health However the potential of risk in this population including early vascular and endothelial changes is yet unclear Given the ongoing global pandemic epidemiological studies to address this knowledge gap is necessary The aim of this study is to evaluate cardiovascular risk in HIV and COVID-19 populations which also would allow assessment of current - and future - cardiovascular risk via vascular endothelial function measurements The ENDOCOVID project has been designed to give an evaluation of cardiovascular risk in PLHIV and COVID-19 living in SAA ENDOCOVID builds up on the EndoAfrica study which is currently being carried out in SSA
Aim and objectives The general aim of the ENDOCOVID project is to identify whether and how HIV-infection with or without ART in COVID-19 patients relates to the time course of the disease alters cardiovascular risk and changes vascular endothelial structure and function in adults living in the SSA
Three groups of participants will take part in this project
1 PLHIV without ART but with COVID-19
2 PLHIV with ART and COVID-19
3 HIV-negative patients with COVID-19 sex- age matched
The following objectives will be investigated
1 Evaluation of the prevalence of COVID-19 in PLHIV with or without ART admitted to clinics in South Africa and Nigeria because of COVID-19
2 Assessment of the incidence of acute respiratory distress syndrome admission to ICU fatal course of disease 30-days mortality and thromboembolic events in hospitalized patients included in the study
3 Evaluation of the influence of ART on severity of COVID-19 in PLHIV with or without ART as well as clinical presentation changes of endothelialvascular function and biomarkers
4 Evaluation of the effects of COVID-19 on endothelialvascular function thrombotic factors and oro-naso sensory alterations over infection and after recovery
5 Correlation of hospitalization and mortality of COVID-19 infected PLHIVwith or without ART and HIV negatives with co-morbidity incidence
6 Assessment of the incidence of obesity and insulin resistance in the 3 groups
SARS-CoV-2 has affected almost every country worldwide with regard to health system capacities and economic burden so far The typical clinical presentations of COVID-19 are fever sore through cough dyspnea abdominal pain and diarrhea Approximately 15 of patients with COVID-19 must be hospitalized and 5 are critically ill and often develop acute respiratory distress syndrome and need to be admitted to intensive care units Risk of severe disease increases with age male sex and with co-morbidities such as chronic lung disease CVDs and diabetes COVID-19 can also affect the nervous systems and cause loss of smell or taste sensation
Populations in SSA are increasingly facing a double burden of disease involving the interaction between HIV-AIDS and non-communicable diseases such as CVDs In general vascular endothelial function can be regarded as a marker of the net harmful effects of cardiovascular risk factors on the vascular wall HIV- infected patients have premature atherosclerosis and increased risk of ischemic heart disease The cardiovascular risk represented by HIV-infection is moreover affected by anti-retroviral treatment ART ART may among other effects prompt dyslipidaemic and metabolic changes in patients over to systemic immune activation stimulation of endothelial inflammation and atherosclerosis However a recent meta-analysis showed that evidence for - and against - a role for ART in the development of CVDs remains unconvincing and that more research is necessary
With the current COVID-19 pandemic which has also spread across Africa another burden is added However thus far it is unclear what effect the additional COVID-19 co-infection in people with HIV PLHIV will have as there are no data yet on how HIVAIDS a prevalent diseases SSA will affect COVID-19 infection rates or outcomes Currently there is no proof for a higher COVID -19 infection rate in PLHIV compared to HIV-negatives However there is a possibility that HIV infection may have an influence on the course of infection PLHIV who are on ART with a normal CD4 T-cell count and suppressed viral load should not be at an increased risk of severe disease On the other hand this theoretically positive situation could be counterbalanced by recent evidence that ART could also have effects on COVID-19 Furthermore HIV-infected patients may additionally suffer from co-morbidities which could pose a greater risk of COVID-19 infection Currently there is no data available about COVID-19 infection in PLHIV in SSA reflecting who in particular is at high risk for infections complications and fatal outcomes As COVID-19 associated multisystem inflammation and the way organ damage caused by COVID-19 occurring in patients with COVID-19 is still incompletely understood and current treatment options are limited There is therefore an urgent need to better understand the risk of severe and fatal COVID-19 outcomes especially in PLHIV - ART
A severe course of COVID-19 can cause the development of COVID-19-associated coagulopathy with features of both disseminated intravascular coagulation and thrombotic microangiopathy resulting in widespread microvascular thrombosis that may involve consumption of coagulation factors and the liver There seems to be a causal relationship with the inflammatory and reparative processes involving diffuse alveolar damage DAD because thrombi are frequently detected in small pulmonary arteries most presumed secondary to endothelial damage The damage of endothelium could be due to the direct viral infection of the endothelial cells which express ACE-2 receptors or to a host response Besides the alveolar fibrin deposition in DAD may affect the local homeostasis between fibrinolysis and coagulation Alveolar and endothelial damage of smaller vessels may be followed by microvascular pulmonary thrombosis which could then extend to larger vessels Additionally elevated D-dimer has been observed in patients with COVID-19 It is known that inceased D-dimer is associated with acute pulmonary emboli APE deep venous thrombosis DVT cancer peripheral vascular disease inflammatory diseases and pregnancy It has been found that patients with COVID-19 including those not on respirators but bedconfined develop DVT and APE much earlier than expected Even with usage of prophylactic anticoagulation autopsy has shown that deaths in COVID-19 may be caused by the thrombosis in segmental and subsegmental pulmonary arterial vessels ENDOCOVID project aims to evaluate the degree to which COVID-19 induced inflammation contributes to endothelial function and coagulation changes and cardiometabolic risk in PLHIV -ART Endothelial function will be evaluated non-invasively via FMD and blood asymmetric dimethyl arginine ADMA
Problem statement HIV infection is a burden for the cardiovascular system but coinfection of HIV and SARS-CoV-2 in SSA population could be a very big load and could lead to higher menace of cardiovascular health However the potential of risk in this population including early vascular and endothelial changes is yet unclear Given the ongoing global pandemic epidemiological studies to address this knowledge gap is necessary The aim of this study is to evaluate cardiovascular risk in HIV and COVID-19 populations which also would allow assessment of current - and future - cardiovascular risk via vascular endothelial function measurements The ENDOCOVID project has been designed to give an evaluation of cardiovascular risk in PLHIV and COVID-19 living in SAA ENDOCOVID builds up on the EndoAfrica study which is currently being carried out in SSA
Aim and objectives The general aim of the ENDOCOVID project is to identify whether and how HIV-infection with or without ART in COVID-19 patients relates to the time course of the disease alters cardiovascular risk and changes vascular endothelial structure and function in adults living in the SSA
Three groups of participants will take part in this project
1 PLHIV without ART but with COVID-19
2 PLHIV with ART and COVID-19
3 HIV-negative patients with COVID-19 sex- age matched
The following objectives will be investigated
1 Evaluation of the prevalence of COVID-19 in PLHIV with or without ART admitted to clinics in South Africa and Nigeria because of COVID-19
2 Assessment of the incidence of acute respiratory distress syndrome admission to ICU fatal course of disease 30-days mortality and thromboembolic events in hospitalized patients included in the study
3 Evaluation of the influence of ART on severity of COVID-19 in PLHIV with or without ART as well as clinical presentation changes of endothelialvascular function and biomarkers
4 Evaluation of the effects of COVID-19 on endothelialvascular function thrombotic factors and oro-naso sensory alterations over infection and after recovery
5 Correlation of hospitalization and mortality of COVID-19 infected PLHIVwith or without ART and HIV negatives with co-morbidity incidence
6 Assessment of the incidence of obesity and insulin resistance in the 3 groups
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None