High dimensional profiling identifies specific immune types along the recovery trajectories of critically ill COVID19 patients.

The COVID-19 pandemic poses a major burden on healthcare and economic systems across the globe. Even though a majority of the population develops only minor symptoms upon SARS-CoV-2 infection, a significant number are hospitalized at intensive care units (ICU) requiring critical care. While insights into the early stages of the disease are rapidly expanding, the dynamic immunological processes occurring in critically ill patients throughout their recovery at ICU are far less understood. Here, we have analysed whole blood samples serially collected from 40 surviving COVID-19 patients throughout their recovery in ICU using high-dimensional cytometry by time-of-flight (CyTOF) and cytokine multiplexing. Based on the neutrophil-to-lymphocyte ratio (NLR), we defined four sequential immunotypes during recovery that correlated to various clinical parameters, including the level of respiratory support at concomitant sampling times. We identified classical monocytes as the first immune cell type to recover by restoration of HLA-DR-positivity and the reduction of immunosuppressive CD163 + monocytes, followed by the recovery of CD8 + and CD4 + T cell and non-classical monocyte populations. The identified immunotypes also correlated to aberrant cytokine and acute-phase reactant levels. Finally, integrative analysis of cytokines and immune cell profiles showed a shift from an initially dysregulated immune response to a more coordinated immunogenic interplay, highlighting the importance of longitudinal sampling to understand the pathophysiology underlying recovery from severe COVID-19.

Monocyte-driven atypical cytokine storm and aberrant neutrophil activation as key mediators of COVID-19 disease severity.

Epidemiological and clinical reports indicate that SARS-CoV-2 virulence hinges upon the triggering of an aberrant host immune response, more so than on direct virus-induced cellular damage. To elucidate the immunopathology underlying COVID-19 severity, we perform cytokine and multiplex immune profiling in COVID-19 patients. We show that hypercytokinemia in COVID-19 differs from the interferon-gamma-driven cytokine storm in macrophage activation syndrome, and is more pronounced in critical versus mild-moderate COVID-19. Systems modelling of cytokine levels paired with deep-immune profiling shows that classical monocytes drive this hyper-inflammatory phenotype and that a reduction in T-lymphocytes correlates with disease severity, with CD8+ cells being disproportionately affected. Antigen presenting machinery expression is also reduced in critical disease. Furthermore, we report that neutrophils contribute to disease severity and local tissue damage by amplification of hypercytokinemia and the formation of neutrophil extracellular traps. Together our findings suggest a myeloid-driven immunopathology, in which hyperactivated neutrophils and an ineffective adaptive immune system act as mediators of COVID-19 disease severity.

Delusion as psychopathological metaphor.

The equivocity of the term delusion has led to it being considered a mere artifact. In this study, its meaning is considered as a psychopathological metaphor to be able to consider the relationships of man with the distorted reality. To do so, the meaning of the concept of man must be adequately understood, and based on this, observe the relationships that man establishes with reality. This relationship is always an aspiration to truth, although not exclusively as judicative as is usually understood. From this time, a series of apparently unconnected and rare psychopathological phenomena can be joined in view of the essentially veritative relationship. This relationship has been subjected to serious and deep philosophical considerations during the XX century and has left its mark on the psychopathological concept of delusion. This equivocity of delusion, finally dependent on a psychopathology that is understood in regards to an unsatisfactory idea of man, may be explained based on a better and more purified psycholopathological practice that is up-dated in regards to concepts of subjectivity and truth.

[Review on the study of the theory of the mind in pervasive development disorders and schizophrenia]. / Revisión sobre el estudio de la "teoría de la mente" en trastornos generalizados del desarrollo y esquizofrenia.

The theory of mind (ToM) is a new concept which could be defined as the ability to make inferences on the intentions of others. This capacity has been used to explain childhood autism symptoms and recently an attempt has been made to refer it to schizophrenia. The authors aim to review the theory of mind concept, the different questions that could appear in neurocognitive sciences and the utilities that this hypothetical model has been given in the clinical practice. The authors also consider the contributions and restrictions that its use has in the field of pervasive developmental disorders and schizophrenia.

[Schizophrenia and subjectivity]. / Esquizofrenia y subjetividad.

Recently, the group of symptoms known as "subjective experiences" of schizophrenia has raised a growing interest. These phenomena have been shaped through concepts like depersonalization-derealization, mental automatism, disorders of the self and autism. The authors propose to review these syndromes, as well as their relationship with subjectivity understood as consciousness of the self (or self-awareness) and the shortcomings due to such a relationship. To finish, we will provide some hints into psychopathology understood as a technique of production of intelligibility which will hopefully help to provide a better grasp of the process described above.