Hypoechogenicity of brainstem raphe in long-COVID syndrome–less common but independently associated with depressive symptoms: a cross-sectional study

Abstract

Objective Long coronavirus disease (Long-COVID) syndrome is a hitherto poorly understood phenomenon with a broad spectrum of symptoms, including depression and anxiety. Depressive symptoms have been associated with brainstem raphe (BR) alterations in transcranial sonography (TCS) that might reflect dysfunction of the serotonergic system. The primary aim was to investigate the connection of BR alterations with depressive and anxiety symptoms in patients with Long-COVID syndrome. Methods In a cross-sectional study design, we included outpatients fulfilling the criteria of Long-COVID syndrome. All patients were examined by TCS in the axial plane with focus on BR signal alterations. The Hospital Anxiety and Depression Scale (HADS) was used to test for symptoms of anxiety and depression. Results We included n = 70 patients with Long-COVID syndrome, of which 28.6% (n = 20) exhibited a reduced echogenicity of BR in the TCS examination. Patients with hypoechogenic BR had higher subscores for anxiety and depression compared to normoechogenic patients (HADS depression: median 8 versus 5.5, p = 0.006; HADS anxiety: median 9 versus 6.5, p = 0.006). After adjustment for reasonable confounders, only the odds ratio (OR) for relevant depressive symptoms was higher among Long-COVID patients with hypoechogenic raphe (adjusted OR 3.884, 95% CI 1.244–12.123). Discussion Hypoechogenic BR alterations are independently associated with depressive symptoms in Long-COVID patients but are not highly frequent. Future studies should investigate whether the hypoechogenicity of the BR is a direct consequence or whether it reflects a priori a higher susceptibility to depressive symptoms after COVID-19, thus enabling to identify COVID-19 patients at higher risk of developing Long-COVID depressive symptoms.

Cross-sectional analysis of clinical aspects in patients with long-COVID and post-COVID syndrome

“…These data support the notion that patients with persistent long-COVID symptoms should receive diagnostic and therapeutic help to reduce the risk of developing an affective disorder. Using transcranial sonography, we found that patients with a hypoechogenic brainstem raphe structure have a 3.9-fold (95% CI 1.2-12.1) increased risk of depressive symptoms, presumably arguing for increased susceptibility to developing depressive symptoms following a stressful event such as COVID (28). Transcranial sonography could, therefore, be used to identify patients at risk of developing depressive symptoms following COVID.…”

Brainstem raphe hypoechogenicity is an independent predictor of post-stroke depression

“…Hence, TCS investigation of the BR could also be helpful in the case of other critical life-events to predict a depressive reaction. This concept has also been suggested by recent data on patients with post-COVID syndrome [11].…”

“…A reduced echogenic signal of the BR on TCS is thought to indicate a dysfunction in the serotonergic system, although the detailed pathophysiological concept is unknown [9]. Previous studies on BR have only used a cross-sectional study design, but it has been suggested that BR hypoechogenicity could be a marker of vulnerability for depressive symptoms that can occur after critical life events [10,11]. Therefore, the primary aim of this study was to investigate the association of BR hypoechogenicity and PSD in a prospective observational study design.…”

Are the Comorbidities Constitute an Intrinsic Factor for Long COVID?

“…Furthermore, the associations of long COVID symptoms, clinical characteristics, and affective psychological constructs in a non-hospitalized cohort were studied. That was emphasizing the need for understanding the correlations of long COVID symptoms and affective psychological constructs on non-hospitalized patients [105,106].…”