Coronavirus Disease 2019 and Endothelialitis

In the era of the global COVID-19 pandemic, questions remain about the pathophysiology, and the severity markers and potential treatment targets. In high HIV prevalence settings, the burden of COVID-19 is yet to be documented, and how these two pandemics will collide and interact remains to be seen. Health care teams would like to understand and pre-empt the cytokine storm that is associated with SARS-CO-V-2 infection, and would like to target those at highest risk of disease severity. We raise some questions in this study in an aid to better understand the interaction between SARS-Co-V-2 infection and endothelialitis. First, there is no data comparing the difference between lung lesions and right heart strain between patients with COVID-19 pneumonia and non-COVID-19 pneumonia. Second, there have been few studies to our knowledge documenting markers of endothelial damage, and none specifically looking at ADAMTS13 deficiency and von Willebrand factor activity in COVID-19. There is also no data comparing these levels to the traditional HIV-associated TTP. Third, there is preliminary evidence from small cohorts that, although COVID-19 patients have diffuse alveolar damage on post mortem lung biopsies, there is evidence of viral inclusion in the endothelium and increased incidence of intussusceptive angiogenesis. COVID-19 causing endothelialitis may be a useful concept when planning potential treatment targets for future disease. We plan to contribute to the evidence.

In Sub-study 1, we will measure the number of lung lesions using ultrasound, and add this to information we get on echocardiogram of the right heart, looking for right heart strain. We will compare this relationship in COVID-19 pneumonia participants, to non-COVID-19 pneumonia participants, to establish if right hear strain is out of keeping with the number of lung lesions in COVID-19 pneumonia, setting the stage for the following question: if it is not the lung lesions causing the hypoxia and right heart strain, what is it?

In Sub-study 2, we will prospectively measure the ADAMTS13 activity and von Willebrand activity profile in severe and critically ill COVID-19 participants, and compare our findings with a historical cohort of HIV-associated TTP participants collected by collaborators. In this prospective observational analysis, we will look at disease parameters traditionally associated with HIV-associated TTP, such as lactate dehydrogenase, presence of fragments on blood smear, and anaemia (micorangiopathic haemolytic anaemia), thrombocytopenia, urea and creatinine (renal dysfunction), liver function tests and INR, PT, aPTT, GCS and AVPU score for neurologic function, and compare this to the historical cohort in order to draw any parallels that COVID-19 endothelialitis may have with HIV-associated TTP.

In Sub-study 3, we will perform post mortem minimally invasive lung tissue sampling of COVID-19 participants, and look specifically for viral inclusion and inflammation of the endothelium, as well as compare the histologic findings to non-COVID-19 pneumonia participants. We will co-collect samples with our collaborators, and our collaborators will sample both COVID-19 and non-COVID-19 pneumonia participants, whereas we will only be sampling COVID-19 pneumonia particiapnts.