Doctoral Degrees (Pulmonology)

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    The impact of comorbidities on coronavirus disease 2019 in a population with high human immunodeficiency virus, tuberculosis and obesity prevalence.
    (Stellenbosch : Stellenbosch University, 2023-12) Parker, Arifa; Koegelenberg, Coenraad FN; Meintjes, Graeme; Taljaard, Jantjie J; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medicine: Internal Medicine.
    ENGLISH ABSTRACT: Introduction The emergence of a novel coronavirus in Wuhan, China in December 2019 launched a devastating global pandemic, with over 6.9 million reported deaths. This virus, subsequently named severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) resulted in coronavirus disease 2019 (COVID-19), a clinical spectrum of respiratory illness ranging from mild upper respiratory infections to severe pneumonia with hyperinflammation. Prior to any cases in South Africa, early reports suggested a link between comorbidities such as hypertension and COVID-19 severity. The impact of the pandemic on the overburdened public healthcare system South Africa with a high prevalence of Human Immunodeficiency Virus (HIV), non-communicable diseases, and high incidence of Tuberculosis was not known. The aim of this PhD study was to describe the local epidemiology, including clinical features, the prevalence and role of comorbidities (specifically HIV, Tuberculosis, and obesity) and outcome in patients hospitalised with COVID-19. The secondary aim was to explore pathophysiology by investigating the role of adipose tissue in the pathogenesis of COVID-19 severity and outcome. Methods A single-centre descriptive study was done to describe the clinical features, comorbidities, and outcome of an early cohort of patients admitted to hospital with COVID-19. Then a robust multicentre cohort study using a COX proportional model was conducted to identify independent risk factors of mortality. To identify the true prevalence of obesity, including in people with HIV (PWH) we conducted a point prevalence study of measured body mass indices (BMI’s) in all COVID-19 admissions over a 14-day period. Lastly, an exploratory cross-sectional cohort study investigating adipose tissue (AT) for presence of SARS-CoV-2 RNA and associations between adipokine concentrations with COVID-19 severity and outcome in persons with HIV/and or obesity was performed. Results In persons hospitalised with COVID-19, one in five (20%) were PWH. By measuring heights and weights the prevalence of obesity (BMI ≥ 30) was higher than previously reported (69%), including in PWH (75%). A BMI ≥ 25 was prevalent in 85% of all admissions, and in 83% of PWH. Prevalence of active tuberculosis was low (3-4%). With active tuberculosis, PWH had higher mortality (n=11, 38%) than persons without HIV (n=3, 20%, p=0.001). On survival regression analysis, higher risk of mortality was only associated with older age, male sex and being “overweight or obese” (Adjusted Hazard Ratio 1,3 (95%confidence interval 1.03-1.61) p=0.02). HIV and active TB were not associated with increased risk of COVID-19 mortality. We detected SARS-CoV-2 RNA in adipose tissue of 3 of 8 patients who died, and one of 30 who survived (38% vs 3%, p=0.02). There was no cytokine or adipokine differences in PWH. Obesity was associated with significantly higher leptin concentrations, lower adiponectin/leptin ratios, and higher leptin/resistin ratios. Only higher leptin/resistin and lower adiponectin resistin in adipose tissue, but not serum, was associated with mortality. Conclusion The findings of this PhD study highlight the need for urgent measures to address obesity, including in PWH. Eliminating obesity may improve resilience against future pandemics, where obesity may contribute to clinical severity and mortality.