South Africa
Overview of research project
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.
Name of researcher/developer
Sarah Alexandra van Blydenstein
Primary organisation
University of Witwatersrand
Opportunity type
Funding
Opportunity detail
Sub-study 2
Quantity Article description Total (Vat incl)
20 ADAMTS13 antibody R22 000
40 ADAMTS13 activity profile R50 000
2 Syringe 20ml NN LS 50's R 167.33
1 Needle Disp 18G x 40mm R 31.26

Sub-study 3
ARTICLE NR QUANTITY ARTICLE DESCRIPTION UNIT PRICE (EXCL VAT) UNIT PRICE (INCL VAT) TOTAL (VAT INCL)
97387 1 Linen Sav 51 x 65 x 6ply 200's R 393.60 R 452.64 R 452.64
289479 10 Gown 5's Reinforced Surgical ISO XL R 187.62 R 215.76 R 2,157.63
203486 4 Gloves 100's Exam Latex P/F Med SACLIN R 70.39 R 80.95 R 323.79
289873 1 Face 50's Masks Full Pet 350 microns R 1,437.50 R 1,653.13 R 1,653.13
106898 1 Overshoes N/W 100's R 49.20 R 56.58 R 56.58
179129 1 Mop Caps Non-woven R 38.13 R 43.85 R 43.85
218101 10 Hibitane 0.5% in water 500ml R 27.68 R 31.83 R 318.32
24888 10 Gauze Swabs 8ply 100x100mm 100's R 28.15 R 32.37 R 323.73
143068 2 Formalin Sol 500ml R 71.91 R 82.70 R 165.39
226458 50 Biopsy Device (Multicore) Disp FG14x11cm R 575.64 R 661.99 R 33,099.30
165552 1 Surgical 100's Blade no 10 R 278.72 R 320.53 R 320.53
179959 3 Suture Nylon 12's 3/0 Rc 3/8 19mm R 424.17 R 487.80 R 1463.40

50 Histology per block: R513.39 R25 669.50
50 H&E staining (per block): R165.62 R8 281.00
50 Electron Microscopy per block: R1000 R50 000
100 IHC stains (depeds on stain, so estimate) R60 000
100 Special stain (depends on stain, so estimate) R60 000


Funding
Self-funded (e.g. from own or institutional resources)
Stage of development
Protocol submission (project is a PhD in Clinical Medicine), data collection and sample collection will commence once approved, before funding
Collaboration partner
Sub-study 2:
Dr Susan Louw, based at NHLS Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) will share data on HIV-associated TTP, from her thesis entitled “The changing face of thrombotic thrombocytopenic purpura (TTP): The pathological role of endotheliitis and complement activation in the development of human immunodeficiency virus (HIV) associated TTP” M160134.

Sub-study 3:
Perinatal HIV Research Unit (PHRU) is conducting a pneumonia study based at three hospitals in three provinces of South Africa, namely, Chris Hani Baragwanath Hospital in Soweto (Gauteng), Klerksdorp/Tshepong hospital in Klerksdorp (North West) and Polokwane/Mankweng Hospitals in Polokwane (Limpopo). The study is “The Potentially Preventable Burden of Community-acquired Pneumonia in South African adults, in the era of widespread Paediatric PCV13 Immunisation and Antiretroviral Therapy Rollout”, Version 3.0 Date: 02 March 2020 South Africa WI230621. Biopsy data from this study will be used to compare findings between COVID-19 pneumonia and non-COVID-19 pneumonia biopsy findings.

Additional non COVID biopsy samples will be added by Prof Tanvier Omar from NHLS, CMJAH.
Research Category
Epidemiology
Treatment
Other
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