Chapter 9 278 As described above, the RECoVERED cohort reported that one-third of participants with mild disease reporting ongoing symptoms 12 weeks after illness onset and 16.4% after 12 months. Meanwhile, within the Lifelines Cohort, which adjusted for pre-existing symptoms, 13% of all participants with SARS-CoV-2 infection had symptoms attributable to COVID-19 at 90-150 days after infection. Given that least three-quarters of the population of the Netherlands is estimated to have been infected with SARS-CoV-2[57], the absolute number of individuals who have had (or currently have) long COVID in the Netherlands is therefore likely to be substantial. What are the clinical features of long COVID? In Chapters 4, 5, and 6 of this thesis, we outlined the long-term clinical features of COVID-19 in our prospective cohort. Placing our analyses in the context of wider research reveals three major conclusions. First, it has become clear that long COVID is associated with a wide range of different clinical features. For instance, by 12 weeks after illness onset, two-fifths of RECoVERED participants had reported myalgia and a quarter (24%) had reported diarrhoea (significantly more among those with severe/critical COVID-19 [44%]) (this thesis, Chapter 4). In other studies, persistent cardiovascular symptoms (particularly arrhythmia and tachycardia) and endocrine disorders (such as new-onset diabetes mellitus) have also been reported following SARS-CoV-2 infection[58]. Indeed, post-orthostatic tachycardia syndrome (POTS) is estimated to be present in up to 30% of individuals with long COVID[59]. Furthermore, underlying brain pathology has even been detected among individuals who experienced mild COVID-19[60]. Although these symptoms were not explored in the RECoVERED cohort, partnerships with initiatives such as the VECoSCO Study[61], which aims to investigate long-term fatigue and concentration problems through questionnaires and imaging, have allowed our study participants to also contribute to research on the neurological consequences of COVID-19. These results from the RECoVERED cohort and wider literature illustrate that it is difficult to define the typical or characteristic clinical phenotype for long COVID. Second, it was striking to observe the poor prognosis for recovery beyond the first 6 months after illness onset (this thesis, Chapter 4), also when observing recovery from fatigue, the most-commonly reported symptom in our cohort (this thesis, Chapter 5) and other studies [52, 62]. In a systematic review and meta-analysis, the relative contribution of pre-COVID characteristics (including non-modifiable factors such as female sex) in
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