Englische Zusammenfassung (Abstract)

 Objectives To assess risk factors forpersistence vs improvement and to describe clinical characteristics anddiagnostic evaluation of subjects with post-acute sequelae ofCOVID-19/post-COVID-19 syndrome (PCS) persisting for more than one year.

 Methods This nested population-based case-control studyincluded PCS cases aged 18 to 65 years with (n=982) and age and sex-matchedcontrols without PCS (n=576) according to an earlier population-basedquestionnaire study (six to 12 months after acute infection, phase 1) consentingto provide follow-up information and to undergo comprehensive outpatientassessment, including neurocognitive, cardiopulmonary exercise, and laboratorytesting in four university health centres in southwestern Germany (phase 2,another 8.5 months [median] after phase 1). .

 Results At the time of clinical examination (phase 2), 67.6%of the initial cases (phase 1) remained cases, whereas 78.5% of the controlscontinued to report no health problems related to PCS. In adjusted analyses,predictors of improvement among cases were mild acute index infection, previousfull-time employment, educational status, and no specialist consultation andnot attending a rehabilitation programme. Among controls, predictors of newsymptoms or worsening with PCS development were an intercurrent secondarySARS-CoV-2 infection and educational status. At phase 2, persistent cases wereless frequently never smokers, had higher values for BMI and body fat, and hadlower educational status than controls. Fatigue/exhaustion, neurocognitivedisturbance, chest symptoms/breathlessness and anxiety/depression/ sleepproblems remained the predominant symptom clusters. Exercise intolerance withpost-exertional malaise for >14 h (PEM) and symptoms compatible with ME/CFSwere reported by 35.6% and 11.6% of persistent cases, respectively. In adjustedanalyses, significant differences between persistent cases and stable controls(at phase 2) were observed for neurocognitive test performances, scores forperceived stress and subjective cognitive disturbances, symptoms indicatingdysautonomia, depression and anxiety, sleep quality, fatigue, and quality oflife. In persistent cases, handgrip strength, maximal oxygen consumption, andventilator efficiency were significantly reduced. There were no differences inmeasures of systolic and diastolic cardiac function, in the level of pro-BNPblood levels or other laboratory measurements (including complement activity,serological markers of EBV reactivation, inflammatory and coagulation markers,cortisol, ACTH and DHEA-S serum levels). Screening for viral persistence (basedon PCR in stool samples and SARS-CoV-2 spike antigen levels in plasma in asubgroup of the cases) was negative. Sensitivity analyses (pre-existingillness/comorbidity, obesity, medical care of the index acute infection)revealed similar findings and showed that persistent cases with PEM reportedmore pain symptoms and had worse results in almost all tests.

 Conclusions The majority of PCS cases did notrecover in the second year of their illness, with patterns of reported symptomsremaining essentially similar, nonspecific and dominated by fatigue, exerciseintolerance and cognitive complaints. We found objective signs of cognitivedeficits and reduced exercise capacity likely to be unrelated to primarycardiac or pulmonary dysfunction in some of the cases, but there was no majorpathology in laboratory investigations. A history of PEM was associated withmore severe symptoms and more objective signs of disease and might help stratifycases for disease severity.

https://www.medrxiv.org/content/10.1101/2024.05.22.24307659v1

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