The gut microbiota contributes to maintaining human health and regulating immune responses. Severe COVID-19 illness is associated with a dysregulated pro-inflammatory immune response. The effect of SARS-CoV-2 on altering the gut microbiome and the relevance of the gut microbiome on COVID-19 severity needs to be clarified. In this prospective study, we analyzed the gut microbiome of 212 patients of a tertiary care hospital (117 patients infected with SARS-CoV-2 and 95 SARS-CoV-2 negative patients) using 16S rRNA gene sequencing of the V3-V4 region. Inflammatory markers and immune cells were quantified from blood. The gut microbiome in SARS-CoV-2 infected patients was characterized by a lower bacterial richness and distinct differences in the gut microbiome composition, including an enrichment of the phyla Proteobacteria and Bacteroidetes and a decrease of Actinobacteria compared to SARS-CoV-2 negative patients. The relative abundance of several genera including Bifidobacterium, Streptococcus and Collinsella was lower in SARS-CoV-2 positive patients while the abundance of Bacteroides and Enterobacteriaceae was increased. Higher pro-inflammatory blood markers and a lower CD8+ T cell number characterized patients with severe COVID-19 illness. The gut microbiome of patients with severe/critical COVID-19 exhibited a lower abundance of butyrate-producing genera Faecalibacterium and Roseburia and a reduction in the connectivity of a distinct network of anti-inflammatory genera that was observed in patients with mild COVID-19 illness and in SARS-CoV-2 negative patients. Dysbiosis of the gut microbiome associated with a pro-inflammatory signature may contribute to the hyperinflammatory immune response characterizing severe COVID-19 illness.

Studies of cerebellar patients employing modern lesion-symptom mapping techniques have provided valuable insights into the contribution of the cerebellum to motor adaptation. In patients with chronic focal lesions of the cerebellum, the process of adapting reaching movements to force field (FF) and visuomotor rotation (VM) perturbations relies on different anatomical structures located primarily within the territory of the superior hand area. By contrast, results within the territory of the inferior hand area are less consistent. Compensatory mechanisms may have masked the contribution of the inferior hand area. To test this hypothesis, reaching adaptation to FF and VM perturbations was investigated in 24 patients with acute and subacute lesions of the cerebellum. High-resolution magnetic resonance images were acquired to perform voxel-based lesion-symptom mapping (VLSM). VLSM confirmed that distinct and only partially overlapping areas located primarily within the territory of the superior hand area were crucial for adaptation to FF and VM. More specifically, current results add to previous findings that lobule V is of particular importance in FF adaptation, whereas lobule VI plays a more important role in VM adaptation. No clear evidence for a contribution of the inferior hand area to either task was found. Reach adaptation appears to depend primarily on the superior hand area within the cerebellum.

Clinical and experimental studies indicate that the bacterial and fungal gut microbiota modulates immune responses in distant organs including the lungs. Immune dysregulation is associated with severe SARS-CoV-2 infection, and several groups have observed gut bacterial dysbiosis in SARS-CoV-2 infected patients, while the fungal gut microbiota remains poorly defined in these patients. We analyzed the fungal gut microbiome from rectal swabs taken prior to anti-infective treatment in 30 SARS-CoV-2 positive (21 non-severe COVID-19 and 9 developing severe/critical COVID-19 patients) and 23 SARS-CoV-2 negative patients by ITS2-sequencing. Pronounced but distinct interconnected fungal communities distinguished SARS-CoV-2 positive and negative patients. Fungal gut microbiota in severe/critical COVID-19 illness was characterized by a reduced diversity, richness and evenness and by an increase of the relative abundance of the Ascomycota phylum compared with non-severe COVID-19 illness. A dominance of a single fungal species with a relative abundance of >75% was a frequent feature in severe/critical COVID-19. The dominating fungal species were highly variable between patients even within the groups. Several fungal taxa were depleted in patients with severe/critical COVID-19.The distinct compositional changes of the fungal gut microbiome in SARS-CoV-2 infection, especially in severe COVID-19 illness, illuminate the necessity of a broader approach to investigate whether the differences in the fungal gut microbiome are consequences of SARS-CoV-2 infection or a predisposing factor for critical illness.

Zusammenfassung Hintergrund Systemische Entzündungsprozesse gehen mit unspezifischen körperlichen und psychischen Krankheitssymptomen einher, darunter Schmerz und affektbezogene Symptome. Diese immunvermittelten Symptome („Sickness Behavior“) beruhen auf der zentralnervösen Wirkung von Immunbotenstoffen wie proinflammatorischen Zytokinen und vermitteln bei akuten Entzündungsreaktionen, etwa nach einer Impfung oder Verletzung, ein adaptives Schonverhalten. Bei chronischen Entzündungsprozessen können die Symptome des Sickness Behavior jedoch zu Einschränkungen der Lebensqualität führen und zur Komorbidität bei chronischen Schmerzerkrankungen beitragen. Trotz der hohen klinischen Relevanz des Sickness Behavior wurden bisher psychologische Ansätze zur Modulation der immunvermittelten Sickness-Symptome kaum untersucht. Einen Ansatz könnte die Nutzung von Erwartungseffekten bieten, da positive und negative Erwartungen (Placebo- bzw. Nocebo-Effekte) nachweislich einen Einfluss auf Schmerz und affektbezogene Symptome haben. Ziel der Arbeit In dieser Übersichtsarbeit werden die immunologischen und psychobiologischen Faktoren, die zu Schmerz im Kontext des Sickness Behavior beitragen, zusammengefasst. Aufbauend wird diskutiert, wie durch positive und negative Erwartungen Sickness-Symptome beeinflusst werden können und welche biologischen und psychologischen Mechanismen dabei involviert sind. Ziel ist es, potenzielle Ansatzpunkte zur Optimierung von Erwartungen im Kontext immunvermittelter Sickness-Symptome zu identifizieren. Perspektivisch lassen sich darauf aufbauend Interventionen entwickeln, um diese Symptome zu reduzieren sowie die Wirkungen und Nebenwirkungen von immunassoziierten Therapien durch gezielte Erwartungsinduktionen im Rahmen der Kommunikation mit Patient:innen positiv zu beeinflussen.