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The subset of patients who develop critical illness in Covid-19 have extensive inflammation affecting the lungs[PMID: 32526193] and are strikingly different from other patients: immunosuppressive therapy benefits critically-ill patients, but may harm some non-critical cases.[PMID: 32678530] Since susceptibility to life-threatening infections and immune-mediated diseases are both strongly heritable traits, we reasoned that host genetic variation may identify mechanistic targets for therapeutic development in Covid-19.[PMID: 24855243] GenOMICC (Genetics Of Mortality In Critical Care, <a href="https://genomicc.org">genomicc.org</a>) is a global collaborative study to understand the genetic basis of critical illness. Here we report the results of a genome-wide association study (GWAS) in 2244 critically-ill Covid-19 patients from 208 UK intensive care units (ICUs), representing >95% of all ICU beds. Ancestry-matched controls were drawn from the UK Biobank population study and results were confirmed in GWAS comparisons with two other population control groups: the 100,000 genomes project and Generation Scotland. We identify and replicate three novel genome-wide significant associations, at chr19p13.3 (rs2109069, p = 3.98 x 10-12), within the gene encoding dipeptidyl peptidase 9 (DPP9), at chr12q24.13 (rs10735079, p = 1.65 x 10-8) in a gene cluster encoding antiviral restriction enzyme activators (OAS1, OAS2, OAS3), and at chr21q22.1 (rs2236757, p = 4.99 x 10-8) in the interferon receptor gene IFNAR2. Consistent with our focus on extreme disease in younger patients with less comorbidity, we detect a stronger signal at the known 3p21.31 locus than previous studies (rs73064425, p = 4.77 x 10-30).

The capacity for imagery, enabling us to visualise absent items and events, is a ubiquitous feature of our experience. This paper describes the case of a patient, MX, who abruptly lost the ability to generate visual images. He rated himself as experiencing almost no imagery on standard questionnaires, yet performed normally on standard tests of perception, visual imagery and visual memory. These unexpected findings were explored using functional MRI scanning (fMRI). Activation patterns while viewing famous faces were not significantly different between MX and controls, including expected activity in the fusiform gyrus. However, during attempted imagery, activation in MX's brain was significantly reduced in a network of posterior regions while activity in frontal regions was increased compared to controls. These findings are interpreted as suggesting that MX adopted a different cognitive strategy from controls when performing the imagery task. Evidence from experimental tasks thought to rely on mental imagery, such as the Brooks' matrices and mental rotation, support this interpretation. Taken together, these results indicate that successful performance in visual imagery and visual memory tasks can be dissociated from the phenomenal experience of visual imagery.

BACKGROUND The amygdala plays a central role in detecting and responding to fear related stimuli. A number of recent studies have reported decreased amygdala activation in schizophrenia to emotional stimuli (such as fearful faces) compared to matched neutral stimuli (such as neutral faces). Here we have investigated whether the apparent decrease in amygdala activation in schizophrenia could actually derive from increased amygdala activation to the neutral comparator stimuli.METHODS Nineteen patients with schizophrenia and 24 matched control participants viewed pictures of faces with either fearful or neutral facial expressions, and a baseline condition, during functional magnetic resonance imaging scanning.RESULTS Patients with schizophrenia showed a relative decrease in amygdala activation to fearful faces when compared to neutral faces. However this difference resulted from an increase in amygdala activation to the neutral faces in patients with schizophrenia, not from a decreased response to the fearful faces. 2. The relevance of the findings to symptoms that characterize the disorder would strengthen the paper (i.e., relate the findings to symptoms in individuals with schizophrenia in the context of theories in the literature on amygdala function). Otherwise, the findings seem overly data driven.Response: We have sought to relate the current data to two of the main theories of the pathogenesis of schizophrenia in the discussion (2, 3). The former of these theories (2) argues for inappropriate amygdala activation in schizophrenia, a view which is directly supported by our data. The second hypothesis (3) argues that individual with schizophrenia attribute increased affective salience to otherwise neutral events, providing the setting for the formation of symptoms such as delusional beliefs. We believe that the present finding of increased amygdala activation to neutral faces in schizophrenia provides a potential biological basis for such a liability to psychosis. We have attempted to re-word part of the discussion to make these links more explicit, although fuller coverage is precluded by the word limit. Fear of faces in schizophreniaHall et al looked at the response of the amygdala, a brain region mediating fear, to faces in control subjects and participants with schizophrenia. They found that control subjects show amygdala activation to fearful faces, but not neutral faces. However patients with schizophrenia activated the amygdala fear system to both neutral and fearful faces. These results suggest that people with schizophrenia may perceive neutral faces as fearful, potentially contributing to the development of psychotic symptoms. IN THIS ISSUE StatementHall J et al AbstractBackground The amygdala plays a central role in detecting and responding to fear