Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

The ocean is not deep enough: pressure tolerances during early ontogeny of the blue mussel Mytilus edulis

Early ontogenetic adaptations reflect the evolutionary history of a species. To understand the evolution of the deep-sea fauna and its adaptation to high-pressure, it is important to know the effects of pressure on their shallow-water relatives. In this study we analyse the temperature and pressure tolerances of early life history stages of the shallow-water species Mytilus edulis. This species expresses a close phylogenetic relationship with hydrothermal-vent mussels of the subfamily Bathymodiolinae. Tolerances to pressure and temperature are defined in terms of fertilisation success and embryo developmental rates in laboratory-based experiments. In Mytilus edulis, successful fertilisation under pressure is possible up to 500atm (50.66MPa), at 10 ºC, 15 ºC and 20 ºC. A slower embryonic development is observed with decreasing temperature and with increasing pressure; principally, pressure narrows the physiological tolerance window in different ontogenetic stages of M. edulis, and slows down metabolism. This study provides important clues on possible evolutionary pathways of hydrothermal vent and cold-seep bivalve species and their shallow-water relatives. Evolution and speciation patterns of species derive mostly from their ability to adapt to variable environmental conditions, within environmental constraints, which promote morphological and genetic variability, often differently for each life history stage. The present results support the view that a direct colonisation of deep-water hydrothermal vent environments by a cold-eurythermal shallow-water ancestor is indeed a possible scenario for the Mytilinae, challenging previous hypothesis of a wood/bone to seep/vent colonization pathway

1923 Fall catalog /

192

Seed catalog : 1924 /

192

Seed catalog : 1923 /

192

1925 annual seed catalog /

192

Fall catalog : 1922 /

192