Background
Long COVID is defined as the persistence of symptoms beyond 3 months after SARS-CoV-2 infection. To better understand the long-term course and etiology of symptoms we analyzed a cohort of COVID-19 patients prospectively.
Methods
Patients were included at 5 months after acute COVID-19 in this prospective, non-interventional follow-up study. Patients followed until 12 months after COVID-19 symptom onset (n=96, 32.3% hospitalised, 55.2% females) were included in this analysis of symptoms, quality of life (based on a SF-12 survey), laboratory parameters including antinuclear antibodies (ANA), and SARS-CoV-2 antibody levels.
Results
At month 12, only 22.9% of patients were completely free of symptoms and the most frequent symptoms were reduced exercise capacity (56.3%), fatigue (53.1%), dyspnoea (37.5%), concentration problems (39.6%), problems finding words (32.3%), and sleeping problems (26.0%). Females showed significantly more neurocognitive symptoms than males.
ANA titres were ≥1:160 in 43.6% of patients at 12 months post COVID-19 symptom onset, and neurocognitive symptom frequency was significantly higher in the group with an ANA titre ≥1:160 compared to <1:160. Compared to patients without symptoms, patients with at least one long COVID symptom at 12 months did not differ significantly with respect to their SARS-CoV-2-antibody levels, but had a significantly reduced physical and mental life quality compared to patients without symptoms.
Conclusions
Neurocognitive long COVID symptoms can persist at least for one year after COVID-19 symptom onset, and reduce life quality significantly. Several neurocognitive symptoms were associated with ANA titre elevations. This may indicate autoimmunity as cofactor in aetiology of long COVID.
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Nonstationarity of the event rate is a persistent problem in modeling time series of events, such as neuronal spike trains. Motivated by a variety of patterns in neurophysiological spike train recordings, we define a general class of renewal processes. This class is used to test the null hypothesis of stationary rate versus a wide alternative of renewal processes with finitely many rate changes (change points). Our test extends ideas from the filtered derivative approach by using multiple moving windows simultaneously. To adjust the rejection threshold of the test, we use a Gaussian process, which emerges as the limit of the filtered derivative process. We also develop a multiple filter algorithm, which can be used when the null hypothesis is rejected in order to estimate the number and location of change points. We analyze the benefits of multiple filtering and its increased detection probability as compared to a single window approach. Application to spike trains recorded from dopamine midbrain neurons in anesthetized mice illustrates the relevance of the proposed techniques as preprocessing steps for methods that assume rate stationarity. In over 70% of all analyzed spike trains classified as rate nonstationary, different change points were detected by different window sizes.
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