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

Transcriptional Regulation in Yeast during Diauxic Shift and Stationary Phase

The preferred source of carbon and energy for yeast cells is glucose. When yeast cells are grown in liquid cultures, they metabolize glucose predominantly by glycolysis, releasing ethanol in the medium. When glucose becomes limiting, the cells enter diauxic shift characterized by decreased growth rate and by switching metabolism from glycolysis to aerobic utilization of ethanol. When ethanol is depleted from the medium, cells enter quiescent or stationary phase G0. Cells in diauxic shift and stationary phase are stressed by the lack of nutrients and by accumulation of toxic metabolites, primarily from the oxidative metabolism, and are differentiated in ways that allow them to maintain viability for extended periods of time. The transition of yeast cells from exponential phase to quiescence is regulated by protein kinase A, TOR, Snf1p, and Rim15p pathways that signal changes in availability of nutrients, converge on transcriptional factors Msn2p, Msn4p, and Gis1p, and elicit extensive reprogramming of the transcription machinery. However, the events in transcriptional regulation during diauxic shift and quiescence are incompletely understood. Because cells from multicellular eukaryotic organisms spend most of their life in G0 phase, understanding transcriptional regulation in quiescence will inform other fields, such as cancer, development, and aging