Summary The coronavirus disease 2019 (COVID‐19) pandemic is a rapidly evolving global emergency that continues to strain healthcare systems. Emerging research describes a plethora of patient factors—including demographic, clinical, immunologic, hematological, biochemical, and radiographic findings—that may be of utility to clinicians to predict COVID‐19 severity and mortality. We present a synthesis of the current literature pertaining to factors predictive of COVID‐19 clinical course and outcomes. Findings associated with increased disease severity and/or mortality include age > 55 years, multiple pre‐existing comorbidities, hypoxia, specific computed tomography findings indicative of extensive lung involvement, diverse laboratory test abnormalities, and biomarkers of end‐organ dysfunction. Hypothesis‐driven research is critical to identify the key evidence‐based prognostic factors that will inform the design of intervention studies to improve the outcomes of patients with COVID‐19 and to appropriately allocate scarce resources.

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Glaucoma is the most prevalent neurodegenerative disease and a leading cause of blindness worldwide. The mechanisms causing glaucomatous neurodegeneration are not fully understood. Here we show, using mice deficient in T and/or B cells and adoptive cell transfer, that transient elevation of intraocular pressure (IOP) is sufficient to induce T-cell infiltration into the retina. This T-cell infiltration leads to a prolonged phase of retinal ganglion cell degeneration that persists after IOP returns to a normal level. Heat shock proteins (HSP) are identified as target antigens of T-cell responses in glaucomatous mice and human glaucoma patients. Furthermore, retina-infiltrating T cells cross-react with human and bacterial HSPs; mice raised in the absence of commensal microflora do not develop glaucomatous T-cell responses or the associated neurodegeneration. These results provide compelling evidence that glaucomatous neurodegeneration is mediated in part by T cells that are pre-sensitized by exposure to commensal microflora.

24Primary somatosensory neurons are specialized to transmit specific types of sensory 25 information through differences in cell size, myelination, and the expression of distinct 26 receptors and ion channels, which together define their transcriptional and functional 27 identity. By transcriptionally profiling sensory ganglia at single-cell resolution, we find that 28 different somatosensory neuronal subtypes undergo a remarkably consistent and 29 dramatic transcriptional response to peripheral nerve injury that both promotes axonal 30 regeneration and suppresses cell identity. Successful axonal regeneration leads to a 31 restoration of neuronal cell identity and the deactivation of the growth program. This 32 injury-induced transcriptional reprogramming requires Atf3, a transcription factor which is 33 induced rapidly after injury and is necessary for axonal regeneration and functional 34 recovery. While Atf3 and other injury-induced transcription factors are known for their role 35 in reprogramming cell fate, their function in mature neurons is likely to facilitate major 36 adaptive changes in cell function in response to damaging environmental stimuli. 37 38

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Peripheral sensory neurons located in dorsal root ganglia relay sensory information from the peripheral tissue to the brain. Satellite glial cells (SGC) are unique glial cells that form an envelope completely surrounding each sensory neuron soma. This organization allows for close bidirectional communication between the neuron and it surrounding glial coat. Morphological and molecular changes in SGC have been observed in multiple pathological conditions such as inflammation, chemotherapy-induced neuropathy, viral infection and nerve injuries. There is evidence that changes in SGC contribute to chronic pain by augmenting neuronal activity in various rodent pain models. SGC also play a critical role in axon regeneration. Whether findings made in rodent model systems are relevant to human physiology have not been investigated.Here we present a detailed characterization of the transcriptional profile of SGC in mouse, rat and human at the single cell level. Our findings suggest that key features of SGC in rodent models are conserved in human. Our study provides the potential to leverage on rodent SGC properties and identify potential targets for the treatment of nerve repair and alleviation of painful conditions.

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Much is known about the biophysical mechanisms involved in cell crawling, but how these processes are coordinated to produce directed motion is not well understood. Here, we propose a new hypothesis whereby local cytoskeletal contraction generates fluid flow through the lamellipodium, with the pressure at the front of the cell facilitating actin polymerization which pushes the leading edge forward. The contraction, in turn, is regulated by stress in the cytoskeleton. To test this hypothesis, finite element models for a crawling cell are presented. These models are based on nonlinear poroelasticity theory, modified to include the effects of active contraction and growth, which are regulated by mechanical feedback laws. Results from the models agree reasonably well with published experimental data for cell speed, actin flow, and cytoskeletal deformation in migrating fish epidermal keratocytes. The models also suggest that oscillations can occur for certain ranges of parameter values.