Chapter 10 302 symptoms (fatigue, cough, dyspnoea and loss of smell and/or taste), it was observed that some individuals develop new symptoms as other complaints resolve. These findings show that the clinical presentation of long COVID may vary over time: an important takehome message for clinicians monitoring patient progression. In addition, belonging to a trajectory reporting a 6 or more persistent symptoms was associated with a more negative illness perception score, suggesting that symptom quantity is an indicator of a more debilitating lived experience of the condition. The underlying pathogenesis of long COVID has yet to be fully elucidated. Chapter 7 of this thesis explores whether specific cytokines were associated with long COVID in our cohort. In a multivariable model in which other possible determinants of cytokine concentration were included, individuals with long COVID at 6 months after illness onset had higher concentrations of CRP. When restricting the definition of long COVID to those with abnormal diffusion capacity at 6 months (i.e., long-term pulmonary sequelae), an association with numerous pro-inflammatory cytokines (interleukin [IL]-6, tumour necrosis factor [TNF]-α, interferon gamma inducible protein [IP]-10, IL10, an IL17) was identified. This suggests that persistent hyperinflammation may underpin long COVID symptomatology, at least among individuals with objectifiable pulmonary sequelae. In addition, given that early identification of those at high risk of developing long COVID is of great clinical consequence, we aimed to identify possible acute-phase biomarkers of long COVID. Interleukin (IL-)1β measured at 0-4 weeks after illness onset was a stronger predictor than body mass index (BMI) of ongoing symptoms 6 months after illness onset. Given the urgent need for objective predictive markers for long COVID, further exploration of this finding is warranted. In addition to predictive biomarkers, there is a pressing need to develop treatment options for long COVID. To this end, Chapter 8, evaluates the possible effect of COVID-19 vaccination on existing long COVID symptoms. After matching unvaccinated with vaccinated study participants on age, sex, obesity status and months since illness onset, there was no difference in the number of long COVID symptoms reported over a 3-month period between the two groups. To further evaluate the role of immunity in long COVID pathogenesis, differences in antibody titers and their waning between participants with and without long COVID were explored. Early samples (30-60 days after illness onset) of IgG antibodies binding to spike (S) or receptor binding domain (RBD) were no different between participants who did and did not develop long COVID. Rates of anti-S and anti-RBG IgG antibody waning up to 9 months after illness onset was also comparable between individuals with and without long COVID. Taken together, these findings suggest that vaccination has no significant effect on long COVID
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