Background: Coronavirus disease 2019 (COVID-19) has affected almost every country in theworld, especially in terms of health system capacity and economic burden. People fromsub-Saharan Africa (SSA) often face interaction between human immunodeficiency virus(HIV) infection and non-communicable diseases such as cardiovascular disease. Role of HIVinfection and anti-retroviral treatment (ART) in altered cardiovascular risk isquestionable 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 livingwith HIV (PLHIV), with or without therapy will have. The ENDOCOVID project aims toinvestigate whether and how HIV-infection in COVID-19 patients modulates the time courseof the disease, alters cardiovascular risk, and changes vascular endothelial function andcoagulation parameters/ thrombosis risk.Methods: In this long-term study, cardiovascular research on PLHIV with or without ARTwith COVID-19 and HIV-negative with COVID-19 will be carried out via clinical andbiochemical measurements for cardiovascular risk factors and biomarkers of cardiovasculardisease (CVD). Vascular and endothelial function will be measured by brachial arteryflow-mediated dilatation (FMD), carotid intima-media thickness (IMT) assessments, andretinal blood vessel analyses, along with vascular endothelial biomarkers andcoagualation markers. The correlation between HIV-infection in COVID-19 PLHIV with orwithout ART and its role in enhancement of cardiovascular risk and endothelialdysfunction will be assessed. Potential changes in these endpoints by COVID-19 will befollowed for 4 weeks across the three groups (PLHIVwith or without ART and HIVnegatives).Impact of project: The ENDOCOVID project aims to evaluate in the long-term thecardiovascular risk and vascular endothelial function in PLHIV thus revealing animportant transitional cardiovascular phenotype in COVID-19.
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
HIV/AIDS 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 endothelial/vascular function and
biomarkers.
4. Evaluation of the effects of COVID-19 on endothelial/vascular function, thrombotic
factors, and oro-naso sensory alterations over infection and after recovery.
5. Correlation of hospitalization and mortality of COVID-19 infected PLHIV(with or
without ART) and HIV negatives with co-morbidity incidence;
6. Assessment of the incidence of obesity and insulin resistance in the 3 groups.
Biological: COVID-19
Patients diagnosed with a COVID-19 infection
Other Name: SARS-CoV-2 positive
Biological: HIV
Patients diagnosed HIV-positive
Drug: ART
Patients on ART
Inclusion criteria:
- PLHIV without antiretroviral therapy but with COVID-19 infection
- PLHIV with antiretroviral therapy and COVID-19 infection
- HIV-negative patients, sex- and age matched, infected with COVID-19;
- older than 18 years
Exclusion criteria:
- Those with known co-infections such as hepatitis B and C
- with a viral load of HIV RNA >1000 copies/ml under ART or with advanced symptoms of
AIDS
- negative for SARS-CoV-2 RNA
University of Ilorin Teaching Hospital
Ilorin, Kwara State, Nigeria
Lagos Stae University Teaching Hospital Ikeja
Lagos, Nigeria
Walter Sisulu University
Mthatha, South Africa
Nandu Goswami, Dr PhD, Principal Investigator
Medical University of Graz