Predicting COVID-19 severity and clinical outcome using routine and novel diagnostic biomarkers

The number of incident cases of COVID-19 is increasing at a rapid rate in Sub-Saharan Africa. The spread of SARS-CoV-2 in certain regional disease epicentres such as Western Cape Province in South Africa, is associated with high death rate despite young age structure of the population which is demographically different from the Chinese, European and North American populations. Our population is much younger but with a high burden of TB, HIV, malaria among others. Hence, the biochemical, haematological and immunological profile may be considerably different. This may therefore result in the development of a completely different prognostic model of COVID-19 that may be unique to Africa. We will furthermore examine biomarkers not routinely tested but possibly associated with increased risk of severe illness, e.g. NTproBNP, TnT, PCT, lymphocyte subsets, iron studies and ferritin, albumin, inflammatory cytokines and markers of endothelial damage. Correlation of markers of inflammation, coagulopathy, thrombocytopenia and FBC parameters are more likely to yield a predictive or management algorithm tool for COVID-19, which may influence treatment/management alternatives. Previous studies have shown that individuals aged ≥65 years as well as individuals of any age with underlying cardio-metabolic comorbidities such as hypertension; diabetes mellitus and obesity are at significant higher risk of hospitalization and critical care admission due to severe COVID-19. However, a proportion of individuals with non-communicable diseases such as diabetes, hypertension etc., remain undiagnosed as such pose a challenge when infected with SARS-CoV-2. In such conditions, microRNAs would be of potentially diagnostic and prognostic value. Identification of such biomarkers will potentiate personalized and targeted COVID-19 therapeutic approach including assessing presence of vireamia in these patients as viral load or intracellular RNA levels in blood might help to evaluate the efficacy of treatment interventions. Furthermore, whole blood and serum will also be stored for possible future research. Expected Outputs The main aim of the study is to determine clinically relevant routine and novel predictive biomarkers for COVID-19 severity among patients admitted in critical care units. The severity outcome measures will be need for ventilator support, non-invasive and invasive mechanical ventilation, discharge and mortality. The specific objectives include: determining routine biochemical, immunological and haematological abnormalities of COVID-19 patients admitted in critical care unit at Tygerberg Hospital, Pietersburg Hospital and Kenyatta National Hospital; performing immunophenotyping with exhaustion profiling of cells from fresh whole blood samples; measuring NT-proBNP, PCT, iron studies, ferritin, inflammatory cytokines and endothelial markers; investigating whether the 10 miRNAs may potentially have prognostic value in patients with COVID19; identifying prognostic biomarkers present at baseline and develop a risk predictive score of clinical disease severity requiring critical care; to assess the relationship between baseline levels of biomarkers and clinical outcomes among severe COVID-19 patients admitted in critical care unit at Tygerberg hospital, Pietersburg hospital and Kenyatta National hospital; and to assess predictive biomarkers of severe illness and poor outcomes among patients with HIV/AIDS (CD4, HIV viral load) and or Tuberculosis (IFN-γ).