The role of adiposity and physical activity for protection and recovery from severe COVID-19

<p dir="ltr">In December 2019, the emergence of coronavirus disease-2019 (COVID-19) in Wuhan, China marked the beginning of a global health crisis. The alarming spread and severity of COVID-19 led to an unprecedented worldwide research effort to identify risk factors to help us understand how we can protect ourselves against the disease. Impaired immune function, higher levels of inflammation and adverse cardiometabolic health were identified as key contributors to disease severity. Given that adiposity, physical activity and sedentary behaviour are known to modulate these factors, they are prime candidates for investigation as modifiable risk factors. Adding to the concerns surrounding COVID-19 is the phenomenon of long COVID, a condition wherein individuals experience lasting symptoms after the initial infection. With long COVID being characterised by compromised immunity and higher levels of systemic inflammation, there is a risk of long-term health ramifications for affected individuals. The immunomodulatory role of exercise suggests it may help to bolster immunity and provide anti-inflammatory effects in individuals with long COVID.</p><p dir="ltr">Based on the above, this thesis had two distinct, but related, overarching goals. First, this thesis sought to explore the interplay between adiposity, physical activity and TV viewing time (a proxy for sedentary time) in relation to COVID-19 severity (Chapters 2-6). Second, this thesis aimed to assess the effects of an exercise intervention on immune biomarkers in individuals with long COVID (Chapter 7). This thesis used a combination of epidemiological studies using data from the UK Biobank as well as lab-based research to achieve these aims.</p><p dir="ltr">With respect to the first major goal, the findings from the epidemiological studies (Chapters 2-5) included in this thesis offer several novel insights. Overall, they indicate that a low physical activity level and a high TV viewing time are independent risk factors for COVID-19 mortality. The higher risks associated with these factors were found to be largely, but not completely, explained by higher levels of adiposity (as assessed by body mass index and waist circumference) (Chapter 4). Furthermore, a high physical activity level and a low TV viewing time may partly attenuate adiposity-related risk of COVID-19 severity (Chapters 2 and 3). Another interesting observation was that a high TV viewing time not only exacerbated the risk of COVID-19 mortality associated with a low physical activity level, but also that it may be associated with elevated risk even in highly active individuals (Chapter 4). Using isotemporal substitution modelling, Chapter 5 found that replacing one hour of TV viewing with one hour of walking was associated with a significant reduction in COVID-19 mortality risk. In relation to the second goal of this thesis, the results of the randomised controlled trial in Chapter 7 provided novel evidence that, for individuals with long COVID, regular exercise may help counteract the compromised immunity associated with the condition. Indeed, the exercise intervention led to favourable changes in the circulating numbers of several immune cell populations known to be adversely affected by long COVID.</p><p dir="ltr">To conclude, this thesis highlights the combined roles of adiposity, physical activity and TV viewing in COVID-19 severity. Addressing these factors individually may be inadequate; an optimal approach to mitigating COVID-19 risk requires their collective consideration. Amid the rising concern of long COVID globally, this thesis also showcases the potential immunological benefits of regular exercise in affected individuals. The findings documented herein may help guide measures against the immediate and prolonged effects of COVID-19. Importantly, they may also prove instrumental in developing our understanding of how we can fortify ourselves against future respiratory disease outbreaks.</p>