SARS-CoV-2 Variant Spike and accessory gene mutations alter pathogenesis

The ongoing COVID-19 pandemic is a major public health crisis. Despite the development and deployment of vaccines against SARS-CoV-2, the pandemic persists. The continued spread of the virus is largely driven by the emergence of viral variants, which can evade the current vaccines through mutations in the Spike protein. Although these differences in Spike are important in terms of transmission and vaccine responses, these variants possess mutations in the other parts of their genome which may affect pathogenesis. Of particular interest to us are the mutations present in the accessory genes, which have been shown to contribute to pathogenesis in the host through innate immune signaling, among other effects on host machinery. To examine the effects of accessory protein mutations and other non-spike mutations on SARS-CoV-2 pathogenesis, we synthesized viruses where the WA1 Spike is replaced by each variant spike genes in a SARS-CoV-2/WA-1 infectious clone. We then characterized the in vitro and in vivo replication of these viruses and compared them to the full variant viruses. Our work has revealed that non-spike mutations in variants can contribute to replication of SARS-CoV-2 and pathogenesis in the host and can lead to attenuating phenotypes in circulating variants of concern. This work suggests that while Spike mutations may enhance receptor binding and entry into cells, mutations in accessory proteins may lead to less clinical disease, extended time toward knowing an infection exists in a person and thus increased time for transmission to occur. SignificanceA hallmark of the COVID19 pandemic has been the emergence of SARS-CoV-2 variants that have increased transmission and immune evasion. Each variant has a set of mutations that can be tracked by sequencing but little is known about their affect on pathogenesis. In this work we first identify accessory genes that are responsible for pathogenesis in vivo as well as identify the role of variant spike genes on replication and disease in mice. Isolating the role of Spike mutations in variants identifies the non-Spike mutations as key drivers of disease for each variant leading to the hypothesis that viral fitness depends on balancing increased Spike binding and immuno-evasion with attenuating phenotypes in other genes in the SARS-CoV-2 genome.

Imaging & neuropsychological changes in brain with spiritual practice: A pilot study.

BACKGROUND & OBJECTIVES: Some studies have systematically assessed the effects of spiritual practice (SP) on the brain using combined neuropsychological testing and functional imaging. The objective of the present study was to compare imaging and neuropsychological changes in healthy individuals after SP and those with only physical exercise. METHODS: Healthy adult male volunteers, aged 25-45 yr were randomized into two groups. Group 1 (SP group) underwent the SP and group 2 (controls) did brisk walk for 30 min daily. Detailed neuropsychological evaluation, resting-state functional magnetic resonance imaging (fMRI) and brain 99mTc ethyl cysteinate dimer single-photon emission computed tomography (SPECT) were carried out for both groups before and three months after intervention. RESULTS: Post-intervention, resting state fMRI showed increased connections of left precuneus (in the posterior cingulate cortex area of default mode network) in group 1 and increased left frontal connections in group 2. The neuropsychological tests showed significant improvement in 'Speed of Processing' (Digit Symbol Test) in group 1 and in Focused Attention (Trail Making A) in group 2. The SPECT data in group 1 showed significant improvement in perfusion of the frontal areas, with relatively lesser improvement in parietal areas. Group 2 showed significant improvement in perfusion predominantly in parietal areas, as compared to frontal areas. In addition, significantly improved mood was reported by group 1 and not by group 2. INTERPRETATION & CONCLUSIONS: This pilot study shows important functional imaging and neuropsychological changes in the brain with SP.

Potassium Chloride Infusion as the Cause of Altered Bio Distribution of 18F-Fluorodeoxyglucose on Whole-Body Positron Emission Tomography-Computed Tomography Scan.

18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography is a standard diagnostic imaging tool in many types of cancer. Its physiological in vivo distribution includes the brain, liver, heart, kidneys, and urinary tract at 1 h after tracer injection. Skeletal muscle is known to show variable amounts of 18F-FDG uptake because it has a relatively high-glucose metabolism. We report a case of a 20-year-old patient with gross 18F-FDG uptake involving multiple muscle groups and its likely correlation to potassium chloride infusion before 18F-FDG injection.

Ventilators in ICU: A boon or burden.

BACKGROUND AND AIMS: Ventilator-associated pneumonia (VAP) is a major challenge in intensive care units (ICUs). This challenge is even more discernible in a neurological setting owing to the predispositions of patients. Data on VAP in the neurology and neurosurgery ICUs (NNICUs) are scanty in developing countries. This study was conducted to find out the occurrence of VAP, its risk factors, microbiological profile, and antibiotic resistance in patients admitted to the NNICU of a tertiary care institute in India. MATERIALS AND METHODS: Endotracheal aspirate and blood samples were collected from 100 patients admitted to the NNICU. Complete blood count, microscopic examination, culture and sensitivity testing of aspirate were done. Chest x-ray was also performed to aid in the diagnosis of VAP. RESULTS: Incidence rate of VAP was found to be 24%. Acinetobacter baumannii was the most common pathogen (24.3%) isolated from patients with VAP, and all of these isolates were sensitive to meropenem. Duration of mechanical ventilation (P < 0.0001) and associated comorbid illness (P = 0.005) were found to be significantly associated with VAP, and the duration of mechanical ventilation was found to be the only independent risk factor (P < 0.0001). CONCLUSIONS: This study highlights the risks and microbiological perspective of ventilator use among neurology patients so that adequate preventive strategies can be adopted on time.

Central and peripheral demyelination.

Several conditions cause damage to the inherently normal myelin of central nervous system, perepheral nervous system or both central and perepheral nervous system and hence termed as central demyelinating diseases, perepheral demyelinating diseases and combined central and perepheral demyelinating diseases respectively. Here we analysed and foccused on the etiology, prevalance, incidence and age of these demyelinating disorders. Clinical attention and various diagnostic tests are needed to adequately assess all these possibilities.