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

First investigations of the consumption of seal carcasses by terrestrial and marine scavengers

Marine mammal carrion contains a large amount of nutrients and energy of potential value to terrestrial and marine scavengers, but its impact on coastal habitats has not been studied. This study aimed to provide a detailed documentation of the fate of two grey seal (Halichoerus grypus) pup carcasses, one placed on the shore of Little Cumbrae and one at a depth of 6 m off Great Cumbrae, Firth of Clyde, and a record of the changes in the carcasses and the succession of scavengers using these resources. The carcasses were monitored using time lapse and/or motion-activated cameras. On the shore, great black-backed gulls, juvenile gulls and ravens fed on the carcass and there was a distinct shift in the relative proportions of the bird groups feeding over the period observed. Herring gulls spent significantly less of their time at the carcass feeding than other birds, while lesser black-backed gulls were not observed scavenging despite being common on the island. Over the six week period of observation, more than 90% of the carcass was consumed. However, the deployment of the carcass did not influence the spatial and temporal distribution of the scavenging birds. The underwater carcass was monitored for two periods of two weeks and one week respectively. In the first period Echinodermata (dominated by Asterias rubens) had the highest maximum number of individuals at the carcass, followed by Actinopterygii (fish) and Malacostraca (crabs). Numbers of fish and starfish dropped in the second period, while crustaceans were present in similar numbers as previously. The daily mass loss of the carcasses was 0.56 and 0.07 kg day-1 in the terrestrial and marine ecosystems respectively. Both the terrestrial and marine experiments displayed evidence of bacterial activity. In the absence of any previous detailed study, the present work provides important insights into the roles of seal carcasses in coastal systems, especially in an era when carrion from fisheries discards will become increasingly unavailable

Does seabird carrion contribute to the diet of the shore crab Carcinus maenas on the Isle of May, Scotland? An isotopic perspective

Scavengers are common in marine environments and provide an essential ecosystem service, helping to return nutrients and energy contained in carrion to the system. Knowledge of the prevalence of scavenging is required to fully understand marine food webs. As most scavengers are also predators it is usually unclear what proportion of their diet is derived from carrion, and if this proportion varies in time. In this study we set out to determine whether the input of seabird or other carrion could be detected in the stable isotope composition of the shore crab (Carcinus maenas). Shore crabs were captured in the intertidal zone of the Isle of May (Scotland) before and after the peak fledging of Atlantic puffins (Fratercula arctica). The stable isotope (delta(15)N and delta(13)C) compositions of crabs and the proposed carrion source were determined. Fifty crabs were selected (25 from before (IOM(1)) and 25 after the fledging period (IOM(2))). IOM(1) had a mean delta(15)N value of +13.85 parts per thousand and IOM(2) a mean of +13.53 parts per thousand. The mean delta(13)C values were -15.46 parts per thousand for IOM(1) and -15.87 parts per thousand for IOM(2). In contrast to our expectations, there was no evidence that shore crabs were feeding on seabird carrion following the post-fledging period of Atlantic puffins. Future sampling in autumn months following the grey seal (Halichoerus grypus) breeding season may be useful in establishing if there is another route for nutrient and energy cycling between higher predators and marine scavengers at this locatio