Evaluating recovery post COVID-19: from the clinical to the epithelial
File(s)
Author(s)
Vijayakumar, Bavithra
Type
Thesis
Abstract
COVID-19 has resulted in significant morbidity and mortality across the globe. The aim of this thesis is to better understand recovery post COVID-19.
COVID-19 resulted in persistent clinical, psychological and quality of life impairment even 3 months post hospital discharge, necessitating a variety of patient-driven coping strategies to mitigate impact. In particular, a positive mindset, external support from family and friends, and religious faith were important factors positively impacting individuals’ quality of life.
Radiological and physiological sequelae were common, but usually regressed with time, with only the minority having radiologically-evident fibrosis. Abnormal fractional exhaled nitric oxide levels were not associated with airway or peripheral eosinophilia or markers of epithelial damage and although small airways disease was detectable in some individuals, expiratory flow limitation was not seen.
Upregulation of immune cell subsets and epithelial damage markers was seen in the airways 3-6 months post COVID-19 and differential cell count analysis showed marked lymphocytosis and neutrophilia in some, even in the absence of a culture-positive micro-organism. A trend towards increased airway lymphocytes and faster radiological recovery was seen.
A defect in epithelial wound closure was seen post COVID-19, but in contrast, immunological responses to Influenza A virus were preserved compared to healthy controls. Dipeptidyl peptidase 4 and amphiregulin were both differentially upregulated in the post COVID-19 airway in vivo and show a possible counter-regulatory relationship in vitro. Additionally, inhibition of DPP4 may have immunomodulatory effects.
In summary, despite significant abnormalities post COVID-19, improvement with time is seen in the majority. Further mechanistic evaluation of some of the clinical and in vitro findings is required, to determine the clinical and translational impact of these results.
COVID-19 resulted in persistent clinical, psychological and quality of life impairment even 3 months post hospital discharge, necessitating a variety of patient-driven coping strategies to mitigate impact. In particular, a positive mindset, external support from family and friends, and religious faith were important factors positively impacting individuals’ quality of life.
Radiological and physiological sequelae were common, but usually regressed with time, with only the minority having radiologically-evident fibrosis. Abnormal fractional exhaled nitric oxide levels were not associated with airway or peripheral eosinophilia or markers of epithelial damage and although small airways disease was detectable in some individuals, expiratory flow limitation was not seen.
Upregulation of immune cell subsets and epithelial damage markers was seen in the airways 3-6 months post COVID-19 and differential cell count analysis showed marked lymphocytosis and neutrophilia in some, even in the absence of a culture-positive micro-organism. A trend towards increased airway lymphocytes and faster radiological recovery was seen.
A defect in epithelial wound closure was seen post COVID-19, but in contrast, immunological responses to Influenza A virus were preserved compared to healthy controls. Dipeptidyl peptidase 4 and amphiregulin were both differentially upregulated in the post COVID-19 airway in vivo and show a possible counter-regulatory relationship in vitro. Additionally, inhibition of DPP4 may have immunomodulatory effects.
In summary, despite significant abnormalities post COVID-19, improvement with time is seen in the majority. Further mechanistic evaluation of some of the clinical and in vitro findings is required, to determine the clinical and translational impact of these results.
Version
Open Access
Date Issued
2023-04-30
Date Awarded
01/10/2023
License URL
Advisor
Shah, Pallav L
Lloyd, Clare M
Harker, James A
Sponsor
Westminster Medical School Research Trust
CW+ Trust
Publisher Department
National Heart & Lung Institute
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)