Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Overweight/obesity (Ov/Ob) and diabetes mellitus (DM) are known as independent risk factors for severe COVID-19 outcomes, which disproportionately affect the South Asian population. South Asians with a body mass index (BMI) of 27 kg/m2 have the same risk of COVID-19 mortality as white ethnicities at a BMI of 40 kg/m2. This thesis investigates the effects of Ov/Ob and DM on humoral and cellular immune responses to SARS-CoV-2 in 198 individuals during the first pandemic wave prior to the global rollout of vaccines in Bangladesh. The study cohorts include healthy controls (n=63), individuals with severe acute COVID-19 (n=60), and those who have recovered from COVID-19 (n=75). A variety of immunoassays were performed, including the Meso Scale Discovery (MSD) immunoassay, B cell FluoroSpot, Focus Reduction Neutralisation assay for antibody responses, and IFN-γ ELISpot, intracellular cytokine staining, and proliferation assays for T cell responses. Acute patients with Ov/Ob (BMI ≥ 23 kg/m2) demonstrated higher levels of IgG responses to the SARS-CoV-2 spike compared to those without Ov/Ob. Following COVID-19 recovery, individuals with Ov/Ob displayed reduced neutralising antibody capacity against SARS-CoV-2 despite comparable IgG responses, alongside increased anti-SARS-CoV-2 IFN-γ responses, CD8+ T cell proliferation, and IL-2 production compared to those without Ov/Ob. DM was not associated with antibody and T cell responses in acute infection and recovery. Single-cell transcriptomic analysis of resting peripheral blood mononuclear cells from 11 COVID-19 survivors with and without DM revealed distinctive transcriptomic profiles marked by significant upregulation of immune activation pathways and metabolic reprogramming in DM across major immune cell types. T cells in DM showed upregulation in Th1 and Th17 differentiation pathways and oxidative phosphorylation. NK cell-mediated cytotoxicity as well as antigen processing and presentation by monocytes were upregulated in DM. B cells showed a metabolic shift towards glycolysis and a Th2 immune response under DM conditions. Collectively, the work presented in this thesis advances our understanding of the adaptive immune response to SARS-CoV-2 in individuals with metabolic diseases. This biological insight paves the way for future studies to improve the management of not only COVID-19 but also future pandemics, ensuring better outcomes for patients burdened with comorbidities such as Ov/Ob and DM.

Type

Thesis / Dissertation

Publication Date

16/07/2024

Keywords

SARS-CoV-2, diabetes, adaptive immunity, Bangladesh, obesity