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

Water masses in Kangerlussuaq, a large fjord in West Greenland: the processes of formation and the associated foraminiferal fauna

The water masses in Kangerlussuaq (Søndre Strømfjord) in West Greenland were studied during both a summer and a winter field survey. In order to obtain an improved understanding of the relationship between the physical oceanography and modern foraminiferal assemblage distributions, conductivity–temperature–density measurements were carried out in connection with sediment surface sampling along a transect through the 180 km long fjord. The exchange between the inner part of Kangerlussuaq (275 m deep) and the ocean is restricted by an almost 100 km long outer, shallow part. Our study shows that the water mass in this inner part is almost decoupled from the open ocean, and that in winter the inner part of the fjord is ice covered and convection occurs as a result of brine release. These processes are reflected in the foraminiferal assemblage, which consists of a sparse agglutinated fauna, indicative of carbonate dissolution. A monospecific, calcareous assemblage (Elphidium excavatum forma clavata) occurs in the innermost, shallow part, which is strongly influenced by sediment-loaded meltwater during the summer. The outer, shallow part of the fjord is dominated by strong tidal mixing, and in summer the density of the incoming water does not exceed the bottom water density in the inner fjord. The foraminiferal assemblage here reflects high bottom water current velocity and an influence of water with relatively high salinity. Kangerlussuaq can be regarded as a modern analogue for ice-proximal environments in the Quaternary, with a strong seasonal forcing caused by freshwater run-off and sea-ice formation

Local controls on sediment accumulation and distribution in a fjord in the West Antarctic Peninsula: implications for palaeoenvironmental interpretations

We analyse surface sediment and its distribution in Flandres Bay, West Antarctic Peninsula, in order to understand modern day sediment dispersal patterns in a fjord with retreating, tidewater glaciers. The surface sediment descriptions of 41 cores are included in this study. The sediment facies described include muddy diatomaceous ooze, diatomaceous mud, pebbly mud, sandy mud and mud, with scattered pebbles present in most samples. In contrast to a traditional conceptual model of glacial sediment distribution in fjords, grain size in Flandres Bay generally coarsens from the inner to outer bay. The smallest grain size sediments were found in the bay head and are interpreted as fine-grained deposits resulting from meltwater plumes and sediment gravity flows occurring close to the glacier front. The middle of the bay is characterized by a high silt percentage, which correlates to diatom-rich sediments. Sediments in the outer bay have a high component of coarse material, which is interpreted as being the result of winnowing from currents moving from the Bellingshausen Sea into the Gerlache Strait. Palaeoenvironmental reconstructions of glacial environments often use grain size as an indicator of proximity to the ice margin. After a detailed analysis of a large number of cores collected in the study area, our findings highlight the variability in sedimentation patterns within a fjord and provide a valuable evidence of the complexity that may occur in the sedimentary record

CELLDEX2018

Data and code associated with the manuscript: SD Tiegs, DM Costello, MW Isken, G Woodward, PB McIntyre, MO Gessner, E Chauvet, NA Griffiths, AS Flecker, et al. Global patterns and drivers of ecosystem functioning in rivers and riparian zones