Dynamic Changes in Circulatory Cytokines and Chemokines Levels in Mild to Severe COVID-19 Patients

Immune dysregulation is a key feature of the coronavirus disease-2019 (COVID-19). However, disparities in responses across ethnic groups are underappreciated. This study aimed to determine the relationship between chemokines and cytokines and the severity of COVID-19. Multiplex magnetic bead-based Luminex-100 was used to assess chemokine and cytokine levels in COVID-19 patients at admission (day-1) and after 4 days. The mean age of the patients recruited was 54.3 years, with 19 (63.3%) males. COVID-19 patients had significantly lower lymphocyte, monocyte, hemoglobin and eosinophil levels than controls (p < 0.05). COVID-19 patients showed significantly higher neutrophil levels than controls (p < 0.05). The baseline levels of IL-2, IL-6, IL-8, IL-10, and IFN-α/γ significantly increased in COVID-19 patients (p < 0.05). Chemokine levels (IP-10, MCP-1, MIG, and CCL-5) were significantly in COVID-19 patients. IL-8, IP-10, and MIG levels were significantly higher in the patients with severe COVID-19 (p < 0.05). Individuals with mild COVID-19 showed significantly higher levels of INF-α, IL-2, IL-6, and IL-8, whereas IL-10 levels were significantly lower (p < 0.05). TNF-levels decreased significantly in individuals with severe COVID-19, whereas IL-6, IL-8, and MIG levels increased (p < 0.05). After 4 days, INFα-, IL-2, IL-6, IL-8, IP-10, and MIG levels were significantly higher in patients with mild disease, whereas IL-6, MIG, and TNF-αlevels were significantly higher in patients with severe disease (p < 0.05). Thus, we conclude that COVID-19 is characterized by INF-α/γ, IL-6, IL-10, IP-10, MCP-1, MIG, and CCL5 dysregulation. IL-8, MIG, and IP-10 levels distinguish between moderate and severe COVID-19. Changes in INF-α, IL-2, IL-6, IL-8, IP-10, and MIG levels can be used to monitor disease progression.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12291-022-01108-x.     

Circulating Cell-Free DNA Level in Prediction of COVID-19 Severity and Mortality: Correlation of with Haematology and Serum Biochemical Parameters

Lymphocyte dysregulation in coronavirus disease-19 (COVID-19) is a major contributing factor linked to disease severity and mortality. Apoptosis results in the accumulation of cell-free DNA (cfDNA) in circulation. COVID-19 has a heterogeneous clinical course. The role of cfDNA levels was studied to assess the severity and outcome of COVID-19 patients and correlated with other laboratory parameters. The current case series included 100 patients with mild COVID-19 (MCOV-19) and 106 patients with severe COVID-19 (SCOV-19). Plasma cfDNA levels were quantified using SYBR green quantitative real-time PCR through amplification of the β-actin gene. CfDNA level was significantly higher in SCOV-19 at 706.7 ng/ml (522.6–1258) as compared to MCOV-19 at 219.8 ng/ml (167.7–299.6). The cfDNA levels were significantly higher in non-survivor than in survivors (p = 0.0001). CfDNA showed a significant correlation with NLR, ferritin, LDH, procalcitonin, and IL-6. The diagnostic sensitivity and specificity of cfDNA in the discrimination of SCOV-19 from MCOV-19 were 90.57% & 80%, respectively. CfDNA showed a sensitivity of 94.74% in the differentiation of non-survivors from survivors. CfDNA levels showed a significant positive correlation with other laboratory and inflammatory markers of COVID-19. CfDNA levels, NLR, and other parameters may be used to stratify and monitor COVID-19 patients and predict mortality. CfDNA may be used to predict COVID-19 severity with higher diagnostic sensitivity.     

Mosaic Recombination Inflicted Various SARS-CoV-2 Lineages to Emerge into Novel Virus Variants: a Review Update

Human Coronaviruses (hCoVs) belongs to the enormous and dissimilar family of positive-sense, non-segmented, single-stranded RNA viruses. The RNA viruses are prone to high rates of mutational recombination resulting in emergence of evolutionary variant to alter various features including transmissibility and severity. The evolutionary changes affect the immune escape and reduce effectiveness of diagnostic and therapeutic measures by becoming undetectable by the currently available diagnostics and refractory to therapeutics and vaccines. Whole genome sequencing studies from various countries have adequately reported mosaic recombination between different lineage strain of SARS-CoV-2 whereby RNA dependent RNA polymerase (RdRp) gene reconnects with a homologous RNA strand at diverse position. This all lead to evolutionary emergence of new variant/ lineage as evident with the emergence of XBB in India at the time of writing this review. The continuous periodical genomic surveillance is utmost required for understanding the various lineages involved in recombination to emerge into hybrid variant. This may further help in assessing virus transmission dynamics, virulence and severity factor to help health authorities take appropriate timely action for prevention and control of any future COVID-19 outbreak.     

Assessment of oxidative stress and effect of antioxidant supplementation during radiotherapy in carcinoma of upper digestive tract

Oxidative stress was studied by estimating plasma levels of malondialdehyde (MDA), beta carotene, vitamin E and erythrocytic superoxide dismutase(E-SOD) activity in 50 cases of carcinoma of upper digestive tract which included carcinoma of oral cavity, pharynx and oesophagus. While plasma MDA level was found to be increased (3.5±1.0 nmole/ml), a significant decrease in beta carotene (81.2±14.5mg%), vitamin E (8.5±1.1 mg/L) level and E-SOD activity (657.0±80.6 U/G Hb) were observed in carcinoma of upper digestive tract. Patients were treated with radiotherapy which itself was toxic enough and produced its deleterious effects by generation of reactive oxygen species (ROS). As antioxdiants can detoxify ROS, beneficial effect if any, of antioxidant administration during radiotherapy was studied in two groups of patients, group A (n=5, supplemented with antioxidants) and group B (n=5, without antioxidant supplementation). Plasma MDA level was found to be elevated in both the groups but the increase in group B was significant, compared to pretreatment level. Further, body weight was found to be significantly decreased in group B patients, which was maintained in group A patients. Moreover, group A patients showed significant elevation in beta carotene concentration, thus showing beneficial effect of administration of antioxidants during radiotherapy without disturbing the desirable therapeutic effect of radiotherapy.     

Social justice and curriculum renewal for Samoan students: an Australian case study

This paper examines the construction of ‘socially just’ curriculum renewal initiatives for Samoan students in a low socio-economic secondary school. Basil Bernstein's concept of recontextualization is used to investigate the implementation of Queensland's Social Justice Strategy at the school level. Interview data provided by the school's first two ‘social justice coordinators’ is analysed, focussing on the categorizations of students and discourses operative within the reform initiatives. Shifts in what counted as socially just curriculum for Samoan students are documented. The focus is on the varying strength of the boundaries of cultural categories (i.e. ‘Samoan’) and on tensions over the emphasis on the cultural knowledge of community representatives and the professional knowledge of school educators. The findings make explicit implications for the distribution of discursive resources to the Samoan students and, hence, life chances in a world in which English is a tool needed by young Australians irrespective of their cultural background.     

A Narrative Review of Potential Future Antidiabetic Drugs: Should We Expect More?

Prevalence of diabetes mellitus, a chronic metabolic disease characterized by hyperglycemia, is growing worldwide. The majority of the cases belong to type 2 diabetes mellitus (T2DM). Globally, India ranks second in terms of diabetes prevalence among adults. Currently available classes of therapeutic agents are used alone or in combinations but seldom achieve treatment targets. Diverse pathophysiology and the need of therapeutic agents with more favourable pharmacokinetic-pharmacodynamics profile make newer drug discoveries in the field of T2DM essential. A large number of molecules, some with novel mechanisms, are in pipeline. The essence of this review is to track and discuss these potential agents, based on their developmental stages, especially those in phase 3 or phase 2. Unique molecules are being developed for existing drug classes like insulins, DPP-4 inhibitors, GLP-1 analogues; and under newer classes like dual/pan PPAR agonists, dual SGLT1/SGLT2 inhibitors, glimins, anti-inflammatory agents, glucokinase activators, G-protein coupled receptor agonists, hybrid peptide agonists, apical sodium-dependent bile acid transporter (ASBT) inhibitors, glucagon receptor antagonists etc. The heterogeneous clinical presentation and therapeutic outcomes in phenotypically similar patients is a clue to think beyond the standard treatment strategy.