Immediate and delayed immune and inflammatory responses to COVID-19
File(s)
Author(s)
Liew, Felicity
Type
Thesis
Abstract
The COVID-19 pandemic has had widespread effects. New SARS-CoV-2 variants continue to cause disease outbreaks and many infections result in debilitating sequelae termed ’long COVID’. A better understanding of local, mucosal IgA responses to SARS-CoV-2 infection may support development of new vaccines that can prevent infection and transmission. Furthermore, understanding why sequelae develop may expedite treatment discovery for long COVID.
Local and systemic immune and inflammatory responses were measured sequentially over 1 year in a cohort of patients, previously hospitalised with COVID-19. Within the multicentre UK studies, PHOSP-COVID and ISARIC4C, a total of 446 individuals had longitudinal nasal and plasma antibody responses measured. Strong nasal anti-N and anti-S IgA responses were demonstrated after COVID-19, which persisted for nine months, but were independent of plasma IgG responses. Unlike plasma IgG anti-S responses, nasal IgA anti-S responses did not rise after vaccination.
In a subgroup of PHOSP-COVID participants, clinical data collected from 719 individuals 6 months after hospitalisation was used to group patients according to their long COVID status. Inflammatory proteins were measured via Olink to determine immunobiological signatures associated with each long COVID subgroup, when compared to recovered individuals. Elevated markers of myeloid inflammation and complement activation were associated with each long COVID subgroup. However, subtle differences were observed between groups. Distinct signatures suggestive of tissue-specific responses were observed in association with cardio-respiratory, GI and cognitive symptoms. SARSCoV-2-specific IgG was persistently elevated in plasma from all individuals with long COVID, but virus was not detected in sputum. Taken together, this work highlights the need for mucosal vaccines that can induce and boost mucosal immunity, limiting SARS-CoV-2 transmission, COVID-19 sequelae and evolution of new variants. Furthermore, it highlights potential inflammatory processes underlying different long COVID symptoms, highlighting the possibility of different endotypes that need to be accounted for in clinical trials.
Local and systemic immune and inflammatory responses were measured sequentially over 1 year in a cohort of patients, previously hospitalised with COVID-19. Within the multicentre UK studies, PHOSP-COVID and ISARIC4C, a total of 446 individuals had longitudinal nasal and plasma antibody responses measured. Strong nasal anti-N and anti-S IgA responses were demonstrated after COVID-19, which persisted for nine months, but were independent of plasma IgG responses. Unlike plasma IgG anti-S responses, nasal IgA anti-S responses did not rise after vaccination.
In a subgroup of PHOSP-COVID participants, clinical data collected from 719 individuals 6 months after hospitalisation was used to group patients according to their long COVID status. Inflammatory proteins were measured via Olink to determine immunobiological signatures associated with each long COVID subgroup, when compared to recovered individuals. Elevated markers of myeloid inflammation and complement activation were associated with each long COVID subgroup. However, subtle differences were observed between groups. Distinct signatures suggestive of tissue-specific responses were observed in association with cardio-respiratory, GI and cognitive symptoms. SARSCoV-2-specific IgG was persistently elevated in plasma from all individuals with long COVID, but virus was not detected in sputum. Taken together, this work highlights the need for mucosal vaccines that can induce and boost mucosal immunity, limiting SARS-CoV-2 transmission, COVID-19 sequelae and evolution of new variants. Furthermore, it highlights potential inflammatory processes underlying different long COVID symptoms, highlighting the possibility of different endotypes that need to be accounted for in clinical trials.
Version
Open Access
Date Issued
2024-08-16
Date Awarded
01/01/2025
License URL
Advisor
Openshaw, Peter
Thwaites, Ryan
Fontanella, Sara
Sponsor
Medical Research Council
Grant Number
MR/W000970/1
Publisher Department
National Heart & Lung Institute
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)