Chapter 9 282 predictive for the presence of long COVID 6 months after illness onset. This is perhaps not surprising given that excessive production of IL-1β is also indicative of COVID-19 severity (IL-1β blockade has even been named as possible therapeutic target to improve acute outcomes[85]). However, our model accounted for the effect of initial COVID-19 severity, suggesting that the association between early IL-1β and later to long-term symptoms is in fact independent. In summary, current evidence suggests that immune dysregulation may play an important part in long COVID pathogenesis in a proportion of individuals with long COVID, but probably not for all phenotypes that fall under the current definition. Moving forward, incorporating existing findings into studies exploring inflammation in specific organ systems (e.g. neurological, musculoskeletal, vascular)[86] may help delineate distinct pathological processes associated with the diverse symptom profiles currently grouped under the umbrella term of long COVID. Understanding the pathogenesis of long COVID is critical to developing treatments. In response to a survey that suggested more than half of individuals with existing long COVID may experience improvement in their symptoms following COVID-19 vaccination[87], there was a need to explore this possibility further in a more generalisable study population and with a comparator group. In addition, investigating an association of long COVID with vaccine-induced immunity was important to further clarify any observed effect. In Chapter 8 we therefore selected a sub-group of RECoVERED study participants with long COVID and divided their follow-up into periods prior to and after receiving their first COVID-19 vaccine. We used these follow-up data to match participants with long COVID on age, sex, obesity status and months since illness onset, to create pairs of vaccinated and unvaccinated participants. We then compared the monthly total mean number of reported long COVID symptoms over a period of 3 months since vaccination (or the matched follow-up point, for unvaccinated participants). Among 36 matched pairs, we observed no statistical difference in the mean number of symptoms over time, suggesting that vaccination had no impact on long COVID in our cohort. To complement these results, we compared the rate of antibody waning between study participants with and without long COVID. We hypothesized that individuals with long COVID may demonstrate slower antibody decay perhaps due to ongoing viral replication[88]. As such, any possible effect of vaccination on long COVID symptomatology may be due to a new boost of humeral immunity to clear any replicating virus. Although antibody decay was slower among those who had long COVID at 3 months after illness onset compared to those who did not, this difference was not statistically significant. Alongside these analyses, we conducted PCRtesting for SARS-CoV-2 in faecal samples in our cohort but found no indication of persistent
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