Inflammation, Immunity and Immunogenetics in COVID-19: A Narrative Review.

The novel Coronavirus Disease 2019 (COVID-19), that began in Wuhan Province, China was labelled as an International Public Health Emergency on January 30, 2020 and later was declared a pandemic by the World Health Organisation (WHO) on March 11, 2020. The causative agent, SARS-CoV-2 was the third coronavirus responsible for causing major disease outbreaks in human population after Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) caused by SARS-CoV and MERS-CoV respectively. The patients of COVID-19 present with a clinical feature resembling mild form of viral pneumonia which in certain cases progress to a severe form characterised by adult respiratory distress syndrome (ARDS) and/or multiorgan failure leading to death. The transition from mild to severe form of COVID-19 is affected by a lot of factors like age, co-morbidities etc. In the absence of an absolute cure, it is essential to explore the molecular pathogenesis of the disease to identify people at risk of developing severity so that alternative treatment modalities may be planned. The aim of this review is to provide an update on the general characteristics of SARS-CoV-2 and highlight the inflammatory changes and immune dysregulation that may help in identification of molecular predictors of disease severity.

Single Cell Omics of Breast Cancer: An Update on Characterization and Diagnosis.

Breast cancer is recognized for its different clinical behaviors and patient outcomes, regardless of common histopathological features at diagnosis. The heterogeneity and dynamics of breast cancer undergoing clonal evolution produces cells with distinct degrees of drug resistance and metastatic potential. Presently, single cell analysis have made outstanding advancements, overshadowing the hurdles of heterogeneity linked with vast populations. The speedy progression in sequencing analysis now allow unbiased, high-output and high-resolution elucidation of the heterogeneity from individual cell within a population. Classical therapeutics strategies for individual patients are governed by the presence and absence of expression pattern of the estrogen and progesterone receptors and human epidermal growth factor receptor 2. However, such tactics for clinical classification have fruitfulness in selection of targeted therapies, short-term patient responses but unable to predict the long-term survival. In any phenotypic alterations, like breast cancer disease, molecular signature have proven its implication, as we aware that individual cell's state is regulated at diverse levels, such as DNA, RNA and protein, by multifaceted interplay of intrinsic biomolecules pathways existing in the organism and extrinsic stimuli such as ambient environment. Thus for complete understanding, complete profiling of single cell requires a synchronous investigations from different levels (multi-omics) to avoid incomplete information produced from single cell. In this article, initially we briefed on novel updates of various methods available to explore omics and then we finally pinpointed on various omics (i.e. genomics, transcriptomics, epigenomics, proteomics and metabolomics) data and few special aspects of circulating tumor cells, disseminated tumor cells and cancer stem cells, so far available from various studies that can be used for better management of breast cancer patients.

Urinary Screening in Asymptomatic Indian Children: A Cross Sectional Epidemiological Study.

Background and aims: Early detection and management of renal abnormalities in children can reduce the progression of paediatric chronic kidney disease. Currently, data on the prevalence of routine abnormal urinary parameters are scarce in Indian population. This study aims to identify the prevalence of asymptomatic kidney diseases in Indian school children and the population who may benefit from routine urinary screening tests for timely identification and intervention of asymptomatic renal diseases. Materials and methods: A total of 1675 children from a North Indian, multiethnic population aged 5-19 years were screened for hematuria and proteinuria by dipstick test from a midstream, clean urine specimen. The children who tested positive had their urine tested further for microscopy. The incidences of proteinuria and hematuria were also separately checked in hypertensive children. Results: 76 children had urinary abnormalities with the prevalence of isolated haematuria in 1.9%, isolated proteinuria in 0.35% and glycosuria in 0.06%. When these children were followed with urine microscopy, 44 were observed to have abnormal findings. Of these, 4.5% children had proteinuria, 34% had isolated hematuria, and 47.7% had isolated WBCs. The prevalence for proteinuria was 0.60% and the prevalence for hematuria was 2.99% (in upper decile of SBP) in hypertensive children, both of which were more than the prevalence in otherwise healthy children. Conclusion: Urine screening is a non-invasive, inexpensive test for early detection of occult renal diseases. A large-scale study with follow-up of children with urinary abnormalities will further establish the benefit, if any, of a national paediatric urine screening programme.

Alterations in Th17 and Treg Lymphocyte Subset in Workers Occupationally Exposed to Lead.

Occupational exposure to lead (Pb) may have a deleterious effect on health of the workers. Among the various physiological systems, the immune system is one of the most susceptible targets of lead. Previous studies have been inconclusive in establishing the effect of Pb on the immune system. With this background, the aim of our study was to determine the effect of occupational Pb exposure on workers' immune parameters. A total of 110 individuals who were occupationally exposed to Pb and 97 apparently healthy non-exposed individuals were recruited in this study. Blood lead levels (BLL) were determined by atomic absorption spectrophotometry (AAS). Lymphocyte subsets (Th1, Th17, and Tregs) were analyzed using flow cytometry, and the cytokine levels (IL-2, IL-4, IL-6, IL-10, IL-17, and TNF-α) were determined by ELISA. BLL were found to be significantly higher in the exposed group than non-exposed. A significant increase of CD8 cells (%) was observed in the lead-exposed group, while CD4 cells (%), although higher in the exposed group did not differ significantly. Among the T lymphocyte subsets, proportion of Th1 and Tregs was found to be lower in the exposed group with a significant increase in Th17 (%). Additionally, the levels of estimated cytokines suggested a predominant pro-inflammatory response in Pb-exposed workers with significant increase in IL-4, IL-6, and TNF-α, and a significant decrease in IL-2 and IL-10. IL-17 levels did not show any significant difference between the two groups. Increased Th17/Tregs ratio in the exposed group is also suggestive of an increased pro-inflammatory immune response in the exposed group. In conclusion, Pb exposure may induce functional alteration in the immune cells, which may predispose to other abnormalities.

Estimation of lymphocyte subsets and cytokine levels in workers occupationally exposed to cadmium.

INTRODUCTION: Occupational exposure to Cadmium (Cd) may have serious health effect on workers. However, little is known about its effect on immune system. Moreover, previous studies have been inconclusive in stating the effect of Cd on immune system. The aim of our study was to estimate immune parameters in workers occupationally exposed to Cd. MATERIAL AND METHODS: 110 individuals occupationally exposed to Cd and 97 apparently healthy non-exposed individuals were recruited for this study. Blood Cadmium levels were determined by AAS. Lymphocyte subset were analyzed using flow cytometry and the cytokine levels were determined by ELISA. RESULTS: Exposed group have significantly higher levels of B-Cd. % of CD8 cells were higher in exposed while % of CD4 cells showed a decreasing trend in the exposed group. Among the CD3CD4 T cell subsets Th1 (%) and Tregs (%) cells were lower while Th17 (%) were higher in exposed group. Increased levels of IL-4 (Th2), IL-6 (Th2) and TNF- α (Th1) and decreased levels of IL-2 (Th1) and IL-10 (Tregs) were observed in Cd exposed workers which is indicative of a predominant pro-inflammatory response in Cd exposed workers. IL-17 (Th17) levels did not show any significant difference between the two groups. Increased Th17/Tregs ratio in the exposed group is also suggestive of an increased pro-inflammatory immune response in exposed group. CONCLUSION: To conclude, even low level of exposure to Cd in occupational settings is associated with alterations in Th17 cells, which may further predispose an individual to other systemic abnormalities.