FHS COVID-19 Research Summary

Study title UCT PI Name of lead organisation Status
Reagent and candidate vaccine development for SARS-CoV-2 Ed Rybicki, Anna-Lise Williamson UCT (UCT Biopharming Research Unit and IDM) In progress

Study Summary:

Profs Anna-Lise Williamson and Ed Rybicki presently have a very experienced team working on HIV-1 vaccines for South Africa, using technologies such as soluble trimeric spike protein production for HIV Env in animal cells and plants, and use of DNA and poxvirus-based vaccine vectors for HIV protein delivery. The DNA, poxvirus, cell culture, and plant production approaches are already being used for SARS-CoV-2 S protein and its gene to make candidate vaccines (Dr Mani Margolin, Biopharming Research Unit BRU). The protein is already being tested by other groups for suitability as a reagent for serology. A DNA and a poxvirus vaccine candidate could be tested in animals soon. Within this work Prof Ed Sturrock will lead the testing of the SARS-CoV-2 S protein products for binding to the receptor ACE2 protein / transfected cells using bio-layer interferometry (BLI), and comparison of binding of different products to ACE2 and inhibition of binding by mAbs. S protein binding to ACE2 and interference using mAbs could constitute a sensitive pseudo-neutralisation assay.

 
Study title UCT PI Name of lead organisation Status
Analysis of antibody responses to SARS CoV-2 antigens in Covid-19 patients Jonathan Blackburn, Wendy Burgers UCT In progress

Study Summary:

Profs Jonathan Blackburn and Wendy Burgers aim to develop and apply novel serological platforms to quantify antibody responses to specific SARS-CoV-2 antigens in patients with on-going or previous COVID-19 infections. This, in order to gain insight into the natural history of COVID-19 infections. Specifically, they will use novel protein microarrays and ELISAs that contain up to 20 different recombinant human coronaviral antigens, to determine the timing and magnitude of antibody responses to different SARS-CoV-2 antigens in different peripheral fluids. They also aim to identify antibody correlates of acquired immunity in convalescent COVID-19 patients. In addition, they aim to understand whether there is significant pre-existing immunity due to cross-reactivity against the four naturally circulating human coronaviruses. Through these studies, the goal is to inform future design and use of serological tools in immunological and epidemiological studies.

 
Study title UCT PI Name of lead organisation Status
Evaluation of a novel human coronaviral antigen microarray-based antibody test in Covid-19 patients Jonathan Blackburn UCT In progress

Study Summary:

Prof Jonathan Blackburn has developed a novel human coronaviral (hCoV) antigen microarray. He aims to evaluate its utility as an antibody-based serological test for current or previous SARS-CoV-2 infection, as part of an in-hospital COVID-19 surveillance program headed by Profs Shabir Mahdi and Keertan Dheda. The hCoV antigen array comprises the SARS-CoV-2 surface spike protein (both full length and isolated S1 domain), the SARS nucleocapsid (N) protein (which is 90% identical to SARS-CoV-2 N protein and is known to cross-react with COVID-19 patient antibodies), plus N proteins from three of the four naturally-circulating human coronaviruses (hCoV HKU1, hCoV NL63 & hCoV 229E), as well as 12 serotypes of influenza HA. Their goal is to understand the utility of this novel test for confirmatory testing and whether quantitative IgM/IgM ratios can be used for disease staging.

 
Study title UCT PI Name of lead organisation Status
Infectious co-morbidity, age and epithelial trained immunity against SARS-COV2 William Horsnell UCT and Norwegian University of Science and Technology In progress

Study Summary:

COVID-19 severity depends on comorbidity and is age-associated. Lung infectious history is very likely to influence COVID-19 severity. How different infection-induced immune responses may contribute to host responses to SARS-CoV-2 is not well understood. The team will test, in young and aged mice, how either Nb and Sp infection, or challenge with Nb and Sp infection associated cytokines (IL-13 and IL-17) respectively, alter lung epithelial expression and function of ACE2, anti-viral activity (e.g. Type1 interferon expression), innate immune response (e.g. production of Surfactant proteins A and D). These will be associated with host lung inflammatory responses. They will then identify how epithelial and expected host immune responses to a subsequent SARS-CoV-2 S1 protein challenge (e.g. raised IL-6 and TNF) are altered by either infection. 
To provide mechanistic insight for their in vivo work, they will use lung organoid cultures that will be treated with infection-specific cytokines in combination with SARS-CoV-2 S1 protein and live infections. They will combine microscopy to detect COVID-19 relevant lung cell lineages (bronchial transient secretory cells) with bulk RNA-seq analysis to define epithelial signatures and responses to the different treatments. This, to ultimately identify new cellular signalling pathways that contribute to pathology and are targets for regulating disease severity. 
Together this study will identify how two common sources of infection (helminth and pneumococcal) may have contributed to age-dependent changes to host immunity to SARS-CoV-2 infection, and how this relates to the onset of minor or severe COVID pathologies.

 
Study title  UCT PI Name of Lead organisation Status  
Determinants and characteristics of cough and expired aerosol in patients with COVID‑19 Keertan Dheda UCT Lung Institute's Centre for Lung Infection and Immunity (CLII) In progress  

Study Summary:

A significant majority of people infected with SARS-CoV-2 will not develop symptoms or remain mildly symptomatic. It is not known how many of these people go on to infect others. Evidence suggests that people with SARS-CoV-2symptoms are most infectious, but the disease can be transmitted before these symptoms develop. Proposed mechanisms of transmission include people breathing in, aerosol generated through sneezing, mild and sporadic coughs, and contact dissemination through the sharing, handling or touching of common items. So it is a priority to develop an understanding of the level of infectiousness of this silent mass which also exhibits the highest mobility and contacts in the community. This will help inform in the establishment of effective guidelines to curb community spread. The CLII has expertise in cough aerosol studies (Theron & Dheda, Nature Med, 2020) and will use the specialised cubicle at one of its research facilities to conduct this study.

 
Study title  UCT PI Name of Lead organisation Status
ChAdOx Vaccine Trial Keertan Dheda RMPRU, WITS University In progress

Study Summary:

This is an adaptive phase I/II randomized placebo-controlled trial to determine safety, immunogenicity and efficacy of non-replicating ChAdOx1 SARS-CoV-2 vaccine in South African adults living without HIV; and safety and immunogenicity in adults living with HIV. The ChAdOx1 nCoV-19, is a non-replicating simian adenoviral vector expressing the spike (S) protein of SARS-CoV-2. This study will enrol 200 participants who will be followed up for a period of one year, and will contribute to achieving 2000 enrolled participants nationally.

 
Study title  UCT PI Name of Lead organisation Status
Novavax vaccine trial Keertan Dheda Novavax Inc Planned

Study Summary:

This is a phase II a/b, randomized, observer-blinded, placebo controlled study to evaluate the efficacy, immunogenicity, and safety of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine (SARS-CoV-2 rS) with Matrix-M1™ adjuvant in South African adult subjects living without HIV; and safety and immunogenicity in adults living with HIV. A total of 330 participants will be randomised into the study at the UCT Lung Institute vaccine site. Like for the ChAdOx SARS-CoV-2 vaccine trial, participants in the Novavax trial will be followed up with for a period of a year.

 
Study title  UCT PI Name of Lead organisation Status
Sentinel, hospital-based surveillance for investigation of SARS-Coronavirus–2 and other respiratory pathogens in adults hospitalized for Severe Acute Respiratory Infection (SS-COVID) Keertan Dheda  Wits SAMRC Respiratory and Meningeal Pathogens Research Unit (PIs: Prof Shabir Mahdi and A/Prof Marta Nunes) Planned

Study Summary:

Prof Keertan Dheda and colleagues are collaborating to undertake a hospital-based sentinel surveillance study led by Prof Shabir Madhi from the University of Witwatersrand. This study seeks to evaluate COVID disease burden in those presenting with lower respiratory tract infections. The utility of different diagnostic approaches will also be studied.

 
Study title UCT PI Name of lead organisation Status
A community-based active case finding strategy for COVID-19 using a mobile clinic (COVID XACT) Keertan Dheda  UCT Planned

Study Summary:

Prof Keertan Dheda will lead this community-based sentinel surveillance study where mobile teams will screen patients in informal settlements in the Mitchell’s Plain and Klipfontein districts. Different diagnostic approaches will be evaluated.

 
Study title UCT PI Name of lead organisation Status
Nitazoxanide for mild to moderate COVID-19 disease: a randomised control trial (COVID-19 containment using chloroquine; C3 RCT) Keertan Dheda  UCT In progress

Study Summary:

Nitazoxanide is an anti-parasitic agent with potent anti-viral properties that has resulted in beneficial clinical outcomes in various viral diseases including influenza. As there is no antiviral agent that has consistently shown to improve outcomes in hospitalised patients with COVID-19, intervening early during a disease (as is the case with influenza) makes sense. In this study several hundred patients across five trial sites in the country will received either Nitazoxanide or placebo. The primary outcome measure is the comparative rates of clinical progression to hospitalisation. Only COVID-19 at risk individuals are being recruited to this trial.

 
Study title UCT PI Name of lead organisation Status
The clinical and epidemiological outcomes associated with COVID-19/HIV co-infection (HI-COVID) Keertan Dheda  UCT In progress

Study Summary:

Prof Keertan Dheda will lead this study which will interrogate the clinical presentation, epidemiology, transmission dynamics, and prognosis in HIV-infected versus uninfected persons.

 
Study title UCT PI Name of lead organisation Status
Health facility-based observational studies to investigate interaction and overlap between SARS-CoV2, HIV-1 and M. tuberculosis infections
Study Acronym: The HIATUS Study
Robert Wilkinson UCT In progress

Study Summary:

Prof Robert J Wilkinson's team, from the Centre for Infectious Diseases Research in Africa (CIDRI-Africa) in the IDM/Medicine, will seek to further understand the pathogenesis of SARS-CoV-2; the interaction and overlap between SARS-CoV2, HIV-1 and Mtb infections; and the potential of SARS-CoV-2 as a neuroinvasive organism. They will undertake pragmatic observational cohort and case-control studies consisting of four components in patients presenting with COVID-19 during the outbreak in South Africa. These include studying: 
1: a. SARS-CoV-2-specific T cell immune response and its relationship with disease outcome in HIV-infected and uninfected persons.
    b. Development of a simplified assay of T cell sensitisation for community-based assessment of immune status.
2: SARS-CoV-2-specific B cell immune response and its relationship with disease outcome in HIV-infected and uninfected persons, including cloning of human monoclonal antibodies and development of an in-house ELISA assay.
3: Secondary haemophagocytic lymphohistiocytosis, coagulopathy and hypercytokinaemia and its role in the pathogenesis of severe COVID-19 in HIV-infected and uninfected people.
4: Neurological manifestations of COVID-19 in HIV-infected and uninfected people.
5: Clinical presentation and immune interaction of SARS-CoV-2 and subclinical Mtb infection via an existing cohort of HIV-infected and uninfected persons with PET/CT lung radiology.

 
Study title UCT PI Name of lead organisation Status
Medical devices for handling the COVID-19 pandemic Sudesh Sivarasu, Salome Maswime, Stephen Roche, Saberi Marais UCT In progress

Study Summary:

Dr Sudesh Sivarasu, working with a team in Biomedical Engineering, Global Surgery and Orthopaedic Surgery, is developing various medical devices with applications including the protection of health workers, testing and the care of COVID-19 positive patients: 
1. With respect to the protection of healthcare workers, two designs of face visors as personal protective equipment (PPE) for clinicians and health workers are complete: a 3D-printed face visor and a fully disposable face visor combining features recommended by RAENG. The latter is easily and rapidly manufactured from available materials at the low cost of <R10 per mask. Dr Sivarasu is in discussion with the various stakeholders for provision of PPE about rolling the latter out in the public healthcare setting.
2. The shortage of appropriate respirator masks, critical to minimise the infection of health care professionals, has been recognised through the COVID-19 pandemic. Availability of well-fitting respirator masks which require the minimum amount of N95 or N99 filter material is critical. This team has developed a biodegradable 3D-printed respirator mask. This respirator is fitted with a small but effective N95 filter. It is estimated that one standard N95 mask will provide filter material for up to five of these printed respirator masks i.e. much more efficient use of N95 materials which are under high demand and cannot be produced fast enough. The modular design allows for device disinfection and disposal of only the contaminated parts i.e. the filter cartridge.
3. An intubation shield to protect healthcare workers while applying tracheal intubation to patients, which is known to generate SARS-CoV-2 aerosols, has been designed. This Perspex shield encloses the patient’s head in a clear case with access holes for the clinicians’ arms and a channel for the patient’s neck. The shield is fitted with a fan and filter to reduce condensation inside the shield and vent air without virus or pathogen. Materials for the prototype device are estimated to cost less than R1500 per unit.
4. The rollout of extensive testing is limited by both test reagents, viral transport medium and nasopharyngeal swabs, all of which are imported currently. Testing from the upper respiratory tract is preferential, requiring nasopharyngeal swabs. Dr Sivarasu’s team has developed a prototype to 3D print swabs from surgical grade dental resins.
5. UCT adaption of PeRSo - A Personal Respirator for Healthcare Professionals on frontline COVID-19. UCT is collaborating with Prof Elkington and team from University of Southampton (the original inventor) to recreate the PeRSo in South Africa. The team is working on the first prototype with assistance from Prof Alkinington’s team.
6. The final contribution of this team is a mechanical ventilator (OpenAir) to support the body’s breathing process when the patient cannot support this un-aided. Working in consultation with clinicians at Groote Schuur Hospital, they have designed a low cost non-invasive mechanical ventilator using a standard bag valve mask (or a bellows) to ventilate the patient. This can be made in South Africa from available materials. UCT’s OpenAir has been presented to the National Ventilator Project (NVP) which has been screened by the Technical team. UCT’s team is also collaborating with CSIR to create a platform for ventilators which have been presented to NVP and screened by the technical team. The team is awaiting the outcome from the NVP.

 
Study title UCT PI Name of lead organisation Status
Global study WHF COVID CVD Survey Karen Sliwa World Heart Federation and UCT Hatter Institute for Cardiovascular Research in Africa In progress

Study Summary:

Prof Karen Sliwa is leading a team in her capacity as the World Heart Federation president, with the World Heart Federation and the UCT Hatter Institute (Sliwa is Director) as lead institutions in a global registry on Cardiovascular Disease in the COVID-pandemic with a focus on low-to-middle income countries. They will conduct a pragmatic prospective web-based research study on hospitalised patients with confirmed COVID-19, who either have cardiovascular disease (e.g. heart failure, rheumatic heart disease, Chagas disease) or who develop cardiovascular disease (as acute myocarditis). They have specific cardiovascular disease profiles in low-to-middle income countries with a rather young population. It is unknown if those patients have an increased risk and poor outcome compared to e.g. an older population with a different CVD profile. Having this information is important for the strategic planning of clinical service in the COVID-19 but also future viral epidemics. The study aims to recruit approximately 5000 patients from across 40 countries. This survey commenced in May 2020.

 
Study title UCT PI Name of lead organisation Status
Paediatric COVID-19 Repository Liesl Zühlke UCT (Department of Paediatrics) Planned

Study Summary:

This study aims to gain an understanding of key clinical and epidemiological characteristics of paediatric COVID-19 by developing a database to compile a comprehensive medical profile of paediatric patients undergoing investigation for, and testing positive for, COVID-19 infection. As well as develop a repository for specimens which will provide an ongoing resource for further studies of paediatric patients presenting for COVID-19 testing.

 
Study title UCT PI Name of lead organisation Status
An exploration of the anxiety and stress levels experienced by third year occupational therapy students from the University of Cape Town during the COVID-19 crisis Zarina Syed UCT Planned

Study Summary:

The aim of this anticipated descriptive study is to determine the anxiety levels and perceived stress among occupational therapy students at UCT during the COVID-19 crisis. The psychological impact of a pandemic has the potential to cause and exacerbate already present symptoms of depression and anxiety experienced by the general population. In this study, the author aims to highlight the potential influence COVID-19 has on the mental health of a student population in higher education. Previous studies highlighted the impact of similar epidemics on the mental health of populations including students. With the advent of COVID in 2019-2020, educators within higher education are aware of student populations within a South African context who are dealing with varying psychosocial as well as economic limitations that have the potential to lead to unmanageable stress. It's important to research how restrictions like social distancing, food insecurity, isolation and loneliness contribute to the mental health of students, some of whom already have diagnosis like depression and anxiety. Therefore being informed about the experiences of students during the COVID-19 crisis and the various factors that impact on the mental health as they navigate the crisis will be essential. A self-administered questionnaire will be created for students to fill out online. Once completed it will be returned and checked. The questionnaire is in the process of being developed. 

 
Study title UCT PI Name of lead organisation Status
University of Cape Town Faculty of Health Sciences COVID-19 Biorepository Ntobeko Ntusi UCT Planned

Study Summary:

Patients infected with SARS-CoV-2 are a vulnerable population, and, as such, need to be protected through a coordinated approach to sampling and obtaining clinical and biological data from the many proposed investigations. While there may be a single umbrella biorepository with a steering committee, there would in effect be multiple sites of sample storage and different clinical data of interest collected. The goal is to try and have a coordinated approach to sampling, not interfere with care too much, reduce research staff in the high-risk area, get people with similar approaches to collaborate and therefore not duplicate, and share specimens to increase efficiency of usage.

 
Study title UCT PI Name of lead organisation Status
A randomized, prospective, open label, phase II clinical trial of the therapeutic use of convalescent plasma in the treatment of patients with COVID-19  - The PROTECT-Patient Trial                          Short title: PROTECT-Patient study Sean Wasserman South African National Blood Service/UCT joint project Planned

Study Summary:

The study aims to assess the efficacy and safety of convalescent plasma as a therapeutic treatment for patients with COVID-19. This will be an open label, randomised controlled phase II clinical trial of patients with COVID-19 who will be randomised in a 2:1 ratio to either a treatment arm, which will receive anti-SARS-CoV-2 CP with standard of care (SOC) or to the control arm who will receive SOC only. The focus will be on patients with COVID-19 disease who are admitted to a participating public or private sector hospital who are not enrolled in any other COVID-19 treatment study, and who consent to participate. This randomised open label, phase 2 clinical trial to assess the efficacy and safety of Anti- SARS-CoV-2 convalescent plasma as treatment in patients with COVID-19. A single unit of approximately 200-250 mL of SARS-CoV-2 CP will be collected by apheresis (or recovered plasma from whole blood donations) from a volunteer who recovered from COVID-19 disease. SOC will be determined by local practice and guidelines.

 
Study title UCT PI Name of lead organisation Status
African COVID-19 Critical Care Outcomes Study (ACCCOS) Bruce Biccard and Dean Gopalan Department of Anaesthesia and Perioperative Medicine, Groote Schuur Hospital and University of Cape Town Planned

Study Summary:

ACCCOS is an African multi-centre prospective observational cohort study of adult (≥18 years) patients referred to critical care or high-care units with suspected or known COVID-19 infection. Patient follow-up will be for a maximum of 30 days in-hospital. The primary outcome is in-hospital mortality in adult patients admitted to critical care or high-care units following suspected or known COVID-19 infection in Africa. The intention is to provide a representative sample of the mortality and the risk factors associated with mortality in adult patients with suspected or known COVID-19 referred for critical care in Africa. This study is running between April to December 2020.

 
Study title UCT PI Name of lead organisation Status
Maternal and perinatal outcomes of novel coronavirus in pregnancy Salome Maswime, Mushi Matjila, Sue Fawcus University of Pretoria, South African Obstetric Surveillance System Network Planned

Study Summary:

Research from the last influenza pandemic (2009/H1N1) showed that pregnant women were particularly vulnerable to severe infection, resulting in increased maternal and perinatal mortality. Evidence from the UK Obstetric Surveillance System (UKOSS), the system on which the International Network of Obstetric Surveillance System (INOSS) has been built, highlighted specific groups of pregnant women who were at higher risk of morbidity after 2009/H1N1 infection in pregnancy. In South Africa, such outcomes were not documented or studied systematically. There is a lack of literature from Africa generally, regarding the disease course and pregnancy outcomes during the last influenza pandemic. Our population in South Africa differs significantly from European countries, not only genetically but as a consequence of the high rate of infectious and non-infectious co-morbidities, including but not limited to HIV, TB, Malaria and hypertension. The situation is compounded by the extreme socioeconomic differences in our population. This has prompted us to do a study describing the course of COVID-19 in pregnancy and maternal and perinatal outcomes.

 
Study title UCT PI Name of lead organisation Status
COVID-19 co-Morbidity and imMunity in Pregnancy Study – COMMPS Clive Gray, Mushi Matjila and Heather Jaspan University of Cape Town Planned

Study Summary:

COVID-19 disease is generally more severe in older patients with underlying co-morbidities, including pulmonary and cardiac disease, obesity, hypertension and diabetes. It is unknown whether the incidence of pregnancy-induced hypertension and gestational diabetes in pregnant women would be in the same high-risk category for severe COVID-19 symptoms. We hypothesize that SARS-CoV-2 infection causes maternal hyperinflammation leading to placental dysfunction, and that hypertension and diabetes exacerbate maternal and placental inflammatory pathways leading to adverse birth outcomes. We will enrol a pilot cohort of pregnant, SARS-CoV-2 infected women and uninfected controls and collect specimens from the women/infant during pregnancy and at delivery. We aim to:

1. Estimate the proportion of asymptomatic, mild/moderate versus severe SARS-CoV-2-associated disease amongst pregnant women with medical co-morbidities
2. Assess whether SARS-CoV-2 nucleic acid is detectable in vaginal secretions, placenta, amniotic fluid, neonatal nasopharynx, breastmilk/colostrum and meconium.
3. Compare plasma and amniotic fluid cytokine profiles during pregnancy between SARS-CoV-2 infected and uninfected pregnant women with medical co-morbidities
4. Compare transcriptomic profiles of placental tissue at delivery between SARS-CoV-2 infected and uninfected pregnant women
5. Compare the balance of inflammatory to regulatory cells in decidua, villous tissue and cord blood between SARS-CoV-2 infected and uninfected pregnant women with medical co-morbidities.

 
Study title UCT PI Name of lead organisation Status
BCG revaccination for frontline workers Jonny Peter University of Stellenbosch In progress

Study Summary:

The Allergy and Immunology unit, UCT Lung institute is part of a BCG revaccination protocol for frontline workers (HCW)s, to assess if revaccination with the BCG vaccine can decrease hospitalisation from COVID19 disease. We plan to enrol 1000-2000 frontline workers who will be randomised to BCG revaccination or placebo. The primary outcome is hospitalisations due to Covid-19.

 
Study title UCT PI Name of lead organisation Status
The effects of the COVID-19 lockdown on sleep, physical activity, mental health and daily routines Dale Rae, Gosia Lipinska Rhodes University In progress

Study Summary:

The COVID-19 pandemic and associated restrictions have created a unique situation where social or physical distancing, restrictions on movement, interaction with others, and the lockdown have resulted in a significant change in the way that we live and work. These changes may also have influenced certain aspects of daily living (lifestyle behaviours) and wellbeing, including work, sleep, physical activity and overall routines. To better understand this impact, researchers from around South Africa developed an online survey to determine the extent to which the national lockdown (level 5) in response to the COVID-19 pandemic influenced these lifestyle behaviours, and to examine the interplay between changes in these lifestyle factors with symptoms of anxiety and depression in the general population of South African adults.

 
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