Multiomics data analysis workflow to assess severity in longitudinal plasma samples of COVID-19 patients.

Elucidation of molecular markers related to the mounted immune response is crucial for understanding the disease pathogenesis. In this article, we present the mass-spectrometry-based metabolomic and proteomic data of blood plasma of COVID-19 patients collected at two-time points, which showed a transition from non-severe to severe conditions during these time points. Metabolites were extracted and subjected to mass spectrometric analysis using the Q-Exactive mass spectrometer. For proteomic analysis, depleted plasma samples were tryptic digested and subjected to mass spectrometry analysis. The expression of a few significant proteins was also validated by employing the targeted proteomic approach of multiple reaction monitoring (MRM). Integrative pathway analysis was performed with the significant proteins to obtain biological insights into disease severity. For discussion and more information on the dataset creation, please refer to the related full-length article (Suvarna et al., 2021).

Study of Demographic Profile, Etiology, and Clinical Outcome in Patients Admitted With Acute Encephalitis Syndrome From the Western Part of India.

Background Determining the etiology of encephalitis always remains a challenge to clinicians, and also, variables that predict outcome in acute phase settings are not known precisely. The autoimmune causes of acute encephalitis are increasing due to the availability of newer diagnostic markers, whereas earlier studies were primarily focused on infectious causes. We conducted a prospective study to determine the demographic profile, etiological aspect, and in-hospital outcome of patients admitted with acute encephalitis syndrome (AES) in our tertiary care center. Materials and method This observational prospective study was carried out at a tertiary care hospital between November 2016 and October 2018. With a sample size of 72, appropriate statistical analysis was done. Results The incidence of AES usually escalates during the rainy season, with arboviral etiologies being predominant. The majority of the patients with AES with a likely infectious etiology could not be diagnosed with presently available viral marker studies. Among various clinical variables, a low Glasgow Coma Scale (GCS) score on admission, a high CSF protein value, and diffusion restriction on brain MRI was associated with poor outcome. Conclusion Acute encephalitis and encephalitis-related mortality impose a considerable burden on current medical practice. The reported demographics of hospitalized patients with encephalitis may be changing, which are important factors to consider for etiological workup.

A Multi-omics Longitudinal Study Reveals Alteration of the Leukocyte Activation Pathway in COVID-19 Patients.

Severe coronavirus disease 2019 (COVID-19) infection may lead to lung injury, multi-organ failure, and eventually death. Cytokine storm due to excess cytokine production has been associated with fatality in severe infections. However, the specific molecular signatures associated with the elevated immune response are yet to be elucidated. We performed a mass-spectrometry-based proteomic and metabolomic analysis of COVID-19 plasma samples collected at two time points. Using Orbitrap Fusion LC-MS/MS-based label-free proteomic analysis, we identified around 10 significant proteins, 32 significant peptides, and 5 metabolites that were dysregulated at the severe time points. Few of these proteins identified by quantitative proteomics were validated using the multiple reaction monitoring (MRM) assay. Integrated pathway analysis using distinct proteomic and metabolomic signatures revealed alterations in complement and coagulation cascade, platelet aggregation, myeloid leukocyte activation pathway, and arginine metabolism. Further, we highlight the role of leukocyte activation and arginine metabolism in COVID-19 pathogenesis and targeting these pathways for COVID-19 therapeutics.

A Case Report on Chikungunya Virus-Associated Encephalomyelitis.

Chikungunya is a rerising alphavirus infection that has resulted from enhanced vector competence. Alphaviruses are divided into arthritogenic viruses (old world) and encephalitogenic viruses (new world) including equine encephalitis viruses. Chikungunya is a dengue-like illness characterized by acute febrile polyarthralgia, arthritis, malaise, body ache, rash, headache, and nausea. The illness is self-limiting. The neurological manifestations are uncommon and incorporate meningoencephalitis, myelitis, Guillain-Barre syndrome, cranial nerve palsies, myelopathy, and neuropathy; MRI abnormalities in patients with encephalopathy from India have been reported in the form of multiple punctuate white matter lesions that are more prominent on diffusion-weighted MRI than on T2 or T1. Here, we present an intriguing case of chikungunya encephalomyelitis who presented to our tertiary care hospital with quadriparesis and urinary retention. He was treated with 5 doses of intravenous immunoglobulin along with supportive care with which he showed partial recovery.

The asparaginyl endopeptidase legumain is essential for functional recovery after spinal cord injury in adult zebrafish.

Unlike mammals, adult zebrafish are capable of regenerating severed axons and regaining locomotor function after spinal cord injury. A key factor for this regenerative capacity is the innate ability of neurons to re-express growth-associated genes and regrow their axons after injury in a permissive environment. By microarray analysis, we have previously shown that the expression of legumain (also known as asparaginyl endopeptidase) is upregulated after complete transection of the spinal cord. In situ hybridization showed upregulation of legumain expression in neurons of regenerative nuclei during the phase of axon regrowth/sprouting after spinal cord injury. Upregulation of Legumain protein expression was confirmed by immunohistochemistry. Interestingly, upregulation of legumain expression was also observed in macrophages/microglia and neurons in the spinal cord caudal to the lesion site after injury. The role of legumain in locomotor function after spinal cord injury was tested by reducing Legumain expression by application of anti-sense morpholino oligonucleotides. Using two independent anti-sense morpholinos, locomotor recovery and axonal regrowth were impaired when compared with a standard control morpholino. We conclude that upregulation of legumain expression after spinal cord injury in the adult zebrafish is an essential component of the capacity of injured neurons to regrow their axons. Another feature contributing to functional recovery implicates upregulation of legumain expression in the spinal cord caudal to the injury site. In conclusion, we established for the first time a function for an unusual protease, the asparaginyl endopeptidase, in the nervous system. This study is also the first to demonstrate the importance of legumain for repair of an injured adult central nervous system of a spontaneously regenerating vertebrate and is expected to yield insights into its potential in nervous system regeneration in mammals.