Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Contextual Social Cognition Impairments in Schizophrenia and Bipolar Disorder

Background: The ability to integrate contextual information with social cues to generate social meaning is a key aspect of social cognition. It is widely accepted that patients with schizophrenia and bipolar disorders have deficits in social cognition; however, previous studies on these disorders did not use tasks that replicate everyday situations.Methodology/Principal Findings: This study evaluates the performance of patients with schizophrenia and bipolar disorders on social cognition tasks (emotional processing, empathy, and social norms knowledge) that incorporate different levels of contextual dependence and involvement of real-life scenarios. Furthermore, we explored the association between social cognition measures, clinical symptoms and executive functions. Using a logistic regression analysis, we explored whether the involvement of more basic skills in emotional processing predicted performance on empathy tasks. The results showed that both patient groups exhibited deficits in social cognition tasks with greater context sensitivity and involvement of real-life scenarios. These deficits were more severe in schizophrenic than in bipolar patients. Patients did not differ from controls in tasks involving explicit knowledge. Moreover, schizophrenic patients’ depression levels were negatively correlated with performance on empathy tasks.Conclusions/Significance: Overall performance on emotion recognition predicted performance on intentionality attribution during the more ambiguous situations of the empathy task. These results suggest that social cognition deficits could be related to a general impairment in the capacity to implicitly integrate contextual cues. Important implications for the assessment and treatment of individuals with schizophrenia and bipolar disorders, as well as for neurocognitive models of these pathologies are discussed.</p

Contextual social cognition impairments in schizophrenia and bipolar disorder.

The ability to integrate contextual information with social cues to generate social meaning is a key aspect of social cognition. It is widely accepted that patients with schizophrenia and bipolar disorders have deficits in social cognition; however, previous studies on these disorders did not use tasks that replicate everyday situations.This study evaluates the performance of patients with schizophrenia and bipolar disorders on social cognition tasks (emotional processing, empathy, and social norms knowledge) that incorporate different levels of contextual dependence and involvement of real-life scenarios. Furthermore, we explored the association between social cognition measures, clinical symptoms and executive functions. Using a logistic regression analysis, we explored whether the involvement of more basic skills in emotional processing predicted performance on empathy tasks. The results showed that both patient groups exhibited deficits in social cognition tasks with greater context sensitivity and involvement of real-life scenarios. These deficits were more severe in schizophrenic than in bipolar patients. Patients did not differ from controls in tasks involving explicit knowledge. Moreover, schizophrenic patients' depression levels were negatively correlated with performance on empathy tasks.Overall performance on emotion recognition predicted performance on intentionality attribution during the more ambiguous situations of the empathy task. These results suggest that social cognition deficits could be related to a general impairment in the capacity to implicitly integrate contextual cues. Important implications for the assessment and treatment of individuals with schizophrenia and bipolar disorders, as well as for neurocognitive models of these pathologies are discussed

Performance on neutral, intentional and accidental situations during EPT depending on the performance on emotional morphing and TASIT.

<p>A) Regression on empathic neutral situations. Observe how the low p-values (5% level of significance) in the emotional morphing evidence a relationship with neutral but no with TASIT. B) Regression on empathic intentional situations. Non significant effects were observed in both (TASIT and emotional morphing) evidencing no dependence among these variables and intentional situations. C) Regression on empathic accidental situations. The performance of accidental situations was depending on both emotional scores. Observe the monotone increasing relationship between both variables and the performance on accidental intention related tasks. Asterisks (*) indicate the expected (exp) values obtained from the data, and circles (o) referred to the observed (obs) measures.</p

Significant differences between groups in social cognition tasks.

<p>(A) TASIT (accuracy per category). A = anger; D = disgust; SD = sadness; F = fear; SR = surprise. (B) Emotional morphing (accuracy per category). (C) Emotional morphing reaction times. H = happiness; D = disgust; A = anger; F = fear; SU = surprise; SD = sadness. (D) Empathy for pain task, comprehension accuracy. (E) Empathy for pain task, ratings for accidental situations. (F) Empathy for pain task, reaction times for intentional situations. (G) Empathy for pain task, reaction times for neutral situations. EC = empathic concern; DS = discomfort; IH = intention to hurt; H = happiness; C = correctness; P = punishment. Asterisk (*) indicates significant differences.</p

Emotional morphing accuracy and reaction times.

<p>RTs = Reaction Times.</p

Significant correlations between clinical symptoms and social cognition measures in SC.

<p>(A) Negative correlation between depression symptoms and intention to hurt ratings for intentional pain situations. (B) Negative correlation between depression symptoms and correctness ratings for intentional pain situations. (C) Negative correlation between depression symptoms and punishment ratings for intentional pain situations.</p

Empathy for pain task. Ratings and reaction times.

<p>NS =  neutral situations; IS =  intentional situations; AS =  accidental situations; RTs =  reaction times.</p

Demographic, clinical and executive functions assessments.

<p>MADRS: Montgomery-Asberg Depression Rating Scale; YMRS: Young Mania Rating Scale. PANSS: positive and negative syndrome scale. IFS: INECO frontal screening.</p

Regression scores of emotional variables on empathy performance.

<p>Regression scores of emotional variables on empathy performance.</p