COVID-19 and Its Effects on Endothelium in HIV-Positive Patients in Sub-Saharan Africa: Cardiometabolic Risk, Thrombosis and Vascular Function

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).