One hundred twenty patients with coronavirus disease 2019 were hospitalized in our intensive care unit, Geneva, Switzerland, between March 9 and April 16, 2020. We report the clinical evolution of 5 consecutive patients intubated because of COVID-19related acute respiratory distress syndrome, presenting with a pathologic recovery of consciousness, which was responsive to high-dose glucocorticoids. These patients all presented with angio-MRI signs of inflammation of CNS arteries, consistent with an endothelialitis rather than a vasculitis. The median time between COVID-19 first symptoms and intubation was 10 days (IQR 10-11 days).After at least 2 weeks of mechanical ventilation, all 5 patients presented with delayed awakening (Glasgow Coma Scale [GCS] score 4-9). Sedation/agitation Confusion assessment method for the intensive care unit or Richmond agitation sedation scale scores were not measured due to the severity of the impaired consciousness. Other causes of impaired consciousness classically found in such patients were assessed. Metabolic disorders including renal or hepatic insufficiency, dysnatremia, persistence of sedatives effects, or hypoxemia were not present in these patients and could therefore not explain their clinical status (tables S1-S3, available from Dryad, doi.org/10.5061/dryad.dv41ns1vq). An EEG was performed in all patients, ruling out epilepsy showing only nonspecific changes.

Covid-19, initially described as a respiratory system's infection, is currently more and more recognized as a multiorganic disease, including neurological manifestations. There is growing evidence about a potential neuroinvasive role of SARS-CoV-2. The purpose of this study is to describe new findings, in the form of cerebral microbleeds affecting different brain structures, observed in MRIs of critically ill patients. METHODS: For this purpose, the MR images of 9 patients with a common pattern of abnormal findings (2 women/7 men; 55-79 years of age; mean age: 67.7 years) were depicted. All patients were tested positive for SARS-CoV-2 and presented with delayed recovery of consciousness or important agitation, requiring brain MRI. RESULTS: All patients had suffered from severe (5/9) or moderate (4/9) acute respiratory distress syndrome, requiring prolonged stay in the intensive care unit. Their common MRI finding was the presence of microbleeds in unusual distribution with a specific predilection for the corpus callosum. Other uncommon locations of microbleeds were the internal capsule (5/9), as well as middle cerebellar peduncles (5/9). Subcortical regions were also affected in the majority of patients. CONCLUSIONS: Brain MRI raised evidence that Covid-19 or its related treatment may involve the brain with an unusual pattern of microbleeds, predominantly affecting the corpus callosum. The mechanism of this finding is still unclear but the differential diagnosis should include thrombotic microangiopathy related to direct or indirect-through the cytokine cascade-damage by the SARS-CoV-2 on the endothelium of brain's vessels, as well as mechanisms similar to the hypoxemia brain-blood-barrier injury.

BackgroundPseudomonas aeruginosa (Pa) is a Gram-negative bacteria frequently involved in healthcare-associated pneumonia with poor clinical outcome. To face the announced post-antibiotic era due to increasing resistance and lack of new antibiotics, new treatment strategies have to be developed. Immunomodulation of the host response involved in outcome could be an alternative therapeutic target in Pa-induced lung infection. Kynurenines are metabolites resulting from tryptophan catabolism and are known for their immunomodulatory properties. Pa catabolizes tryptophan through the kynurenine pathway. Interestingly, many host cells also possess the kynurenine pathway, whose metabolites are known to control immune system homeostasis. Thus, bacterial metabolites may interfere with the host’s immune response. However, the kynurenine pathway in Pa, including functional enzymes, types and amounts of secreted metabolites remains poorly known. Using liquid chromatography coupled to mass spectrometry and different strains of Pa, we determined types and levels of metabolites produced by Pa ex vivo in growth medium, and the relevance of this production in vivo in a murine model of acute lung injury.ResultsEx vivo, Pa secretes clinically relevant kynurenine levels (μM to mM). Pa also secretes kynurenic acid and 3-OH-kynurenine, suggesting that the bacteria possess both a functional kynurenine aminotransferase and kynurenine monooxygenase. The bacterial kynurenine pathway is the major pathway leading to anthranilate production both ex vivo and in vivo. In the absence of the anthranilate pathway, the kynurenine pathway leads to kynurenic acid production.ConclusionPa produces and secretes several metabolites of the kynurenine pathway. Here, we demonstrate the existence of new metabolic pathways leading to synthesis of bioactive molecules, kynurenic acid and 3-OH-kynurenine in Pa. The kynurenine pathway in Pa is critical to produce anthranilate, a crucial precursor of some Pa virulence factors. Metabolites (anthranilate, kynurenine, kynurenic acid) are produced at sustained levels both ex vivo and in vivo leading to a possible immunomodulatory interplay between bacteria and host. These data may imply that pulmonary infection with bacteria highly expressing the kynurenine pathway enzymes could influence the equilibrium of the host’s tryptophan metabolic pathway, known to be involved in the immune response to infection. Further studies are needed to explore the effects of these metabolic changes on the pathophysiology of Pa infection.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-016-0756-x) contains supplementary material, which is available to authorized users.