Approach for Blockchain Technology Implementation in Indian Courts for Speedy Disposal of Cases

Blockchain as a technology if implemented judiciously will prove to be effective and efficient for both private as well public sector enterprises. The use cases in Blockchain provide ample demonstration of improvement in the processes. The paper intends to provide insight into the application of Blockchain in the Indian Judiciary System. Some of the benefits as envisaged by the Blockchain implementation are time-efficient, cost-effective, greater security, and transparency resulting enhancement of trust in the overall working of the legal system. India's global counterparts such as Estonia, China, the UK, Ghana, Ukraine, Canada, and Sweden have already integrated the Blockchain into their legal system. The judicial system in India is under tremendous pressure. According to the data from National Judicial Data Grid, 4.7 Crore cases are pending as on May 2022 at different levels of the judiciary, out of which 1.82 Lac cases have been pending for at least 30 years. For many years courts have been following the traditional working system, but during the Covid-19 pandemic, the courts have adopted the e-justice paradigm via online case hearings and video conferencing. Since, the system has already experienced the use of digital platforms, the experimentation if continued post-pandemic will yield a faster and better result. The technological advancements should complement the traditional working systems for the greater benefit of the entire system. The overall objective of the paper is to explore the application of Blockchain that will help improve the efficiency and transparency in operations in the Indian Judicial system. © 2023 IEEE.

COROID: A Crowdsourcing-based Companion Drones to Tackle Current and Future Pandemics

Due to the current COVID-19 virus, which has already been declared a pandemic by the World Health Or-ganization (WHO), we are witnessing the greatest pandemic of the decade. Millions of people are being infected, resulting in thousands of deaths every day across the globe. Even the world's best healthcare-providing countries could not handle the pandemic because of the strain of treating thousands of patients at a time. The count of infections and deaths is increasing at an alarming rate because of the spread of the virus. We believe that innovative technologies could help reduce pandemics to a certain extent until we find a definite solution from the medical field to handle and treat such pandemic situations. Technology innovation has the potential to introduce new technologies that could support people and society during these difficult times. Therefore, this paper proposes the idea of using drones as a companion to tackle current and future pandemics. Our COROID drone is based on the principle of crowdsourcing sensors data of the public's smart devices, which can correlate the reading of the infrared cameras equipped on COROID drones. To the best of our knowledge, this concept has yet to be investigated either as a concept or as a product. Therefore, we believe that the COROID drone is innovative and has a huge potential to tackle COVID-19 and future pandemics. © 2022 IEEE.

PERSISTENT IMMUNE CELL ABNORMALITIES IN THE INTESTINAL MUCOSA OF PATIENTS AFTER RECOVERY FROM COVID-19 INFECTION

Background: Although respiratory failure is the hallmark of severe disease, it is increasingly clear that Coronavirus Disease 2019 (COVID-19) is a multi-system disorder. The presence of gastrointestinal (GI) involvement by Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been suggested by epidemiological, clinical, non-human primate, in-vitro (enteroid) and ex-vivo (human biopsy) studies. Having recently documented persistence of SARS-CoV-2 within the intestinal epithelium 7 months after infection, here we aimed to study mucosal immune cell abnormalities in individuals with prior history of COVID-19. Methods: Individuals with previous COVID-19 diagnosis (by either RT–PCR or seroconversion) and controls (without RT-PCR or serological evidence of prior COVID-19 infection) undergoing endoscopic evaluation were recruited into the study (Table 1). Colonic and small intestinal (duodenal and ileal) biopsies were analyzed by multiparameter flow cytometry for mucosal immune cell populations including myeloid cells (classical and non-classical monocytes, dendritic cell subsets), T cells (subsets and activation state), B cells (including plasma cells) and NK cells. Persistence of viral antigens was determined by immunofluorescence microscopy (n=30) using a previously published anti-nucleocapsid (NP) antibody. Results: Thirty subjects with a previous history of COVID-19 (post-COVID), median of 4 months from diagnosis (range 1-10 months), were recruited and compared with 40 normal volunteer (NV) controls. Relative to controls, post-COVID subjects displayed higher frequencies of classical (CD14+) monocytes in both, the colon and the small bowel, while significantly higher frequencies of conventional dendritic cells (cDC)1 (lin-HLA-DRhiCD14- CD11c+CD141+) and cDC2 (lin-HLA-DRhiCD14-CD11c+CD1c+) were noted in the colon. Among NK subsets, CD56bright CD16- NK cells were significantly higher in the colon of post-COVID subjects. Among T cell subsets, CD8+ tissue resident memory T cells (CD8+CD69+CD103+) were significantly increased in colon of post-COVID subjects compared to NV. Among B cell subsets, plasma cells (CD3-CD27+CD38hi) trended higher (p= 0.06), while mucosal B cells (CD3-CD19+) were significantly lower in the terminal ileum of post-COVID subjects compared to NV. Finally, with IF, we detected SARS-CoV-2 NP in 10 out of 30 (33%) of post-COVID subjects (Figure 1). Conclusion: Innate and adaptive immune cell abnormalities persist in the intestinal mucosa of post-COVID subjects for up to 10 months and may reflect viral persistence or immune cell dysregulation in the intestines. These findings have major implications for understanding the pathogenesis of long-term sequelae of COVID-19, including long-haul COVID.(Table Presented)(Figure Presented)

Myeloid and lymphoid cell abnormalities persist in the intestinal mucosa of patients who recover from COVID-19 infection

Background: Although respiratory failure is the hallmark of severe disease, it is increasingly clear that Coronavirus Disease 2019 (COVID-19) is a multi-system disorder. The presence of gastrointestinal (Gl) involvement by Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been suggested by epidemiological, clinical, non-human primate, invitro (enteroid) and ex-vivo (human biopsy) studies. Having recently documented persistence of SAR-CoV-2 within the intestinal epithelium 7 months after infection, here we aimed to study mucosal immune cell abnormalities in individuals with prior history of COVID-19. Methods: Individuals with previous COVID-19 diagnosis (by either RT- PCR or seroconversion) and controls (without RT-PCR or serological evidence of prior COVID-19 infection) undergoing endoscopic evaluation were recruited into the study (Table 1,2). Colonic and small intestinal (duodenal and ileal) biopsies were analyzed by multiparameter flow cytometry for mucosal immune cell populations including myeloid cells (classical and non-classical monocytes, dendritic cell subsets), T cells (subsets and activation state), B cells (including plasma cells). Persistence of viral antigens was determined by immunofluorescence microscopy (n=30) using a previously published anti-nucleocapsid (NP) antibody. Results: Thirty subjects with a previous history of COVID-19 (post- COVID), median of 4 months from diagnosis (range 1-10 months), were recruited and compared with 40 normal volunteer (NV) controls. Relative to controls, post-COVID subjects displayed higher frequencies of classical (CD14+) monocytes in both, the colon and the small bowel, while significantly higher frequencies of conventional dendritic cells (cDC) 1 (lin-HLA-DRhiCD14-CD11c+CD141+) and cDC2 (lin-HLA-DRhiCD14-- CD11c+CD1c+) were noted in the colon only. Among T cell subsets, CD8+ tissue resident memory T cells (CD8+CD69+CD103+) were significantly increased in colon of post-COVID subjects compared to NV. Among B cell subsets, plasma cells (CD3-CD27+CD38hi) trended higher (p=0.06), while mucosal B cells (CD3-CD19+) were significantly lower in the terminal ileum of post-COVID subjects compared to NV. Finally, with IF, we detected SARS-CoV-2 NP in 10 out of 30 (33%) of post-COVID subjects (Figure 1). There were no significant correlations of these cell populations with either time after the infection or IF positivity. Conclusion: Innate and adaptive immune cell abnormalities persist in the intestinal mucosa of post-COVID subjects for up to 10 months and may reflect viral persistence or immune cell dysregulation in the intestines. These findings have major implications for understanding the pathogenesis of long term sequela of COVID-19, including long-haul COVID.

SIGNIFICANTLY REDUCED MORTALITY IN COVID-19 PATIENTS WITH GASTROINTESTINAL MANIFESTATIONS

Background: Gastrointestinal (GI) symptoms are the most common extrapulmonary manifestation of coronavirus disease 2019 (COVID-19). Therefore, we sought to determine the impact of GI symptoms on disease outcomes and the systemic inflammatory response in COVID-19. Methods: In two large, independent cohorts of hospitalized COVID-19 patients in the United States (n=634) and Italy (n=287) we examined GI symptoms on admission and related them to mortality and circulating proteomic biomarkers. Disease severity defined by oxygenation and end organ damage was also examined as an outcome in the US cohort. In both cohorts, a multivariate logistic regression was performed to determine the association of GI symptoms (nausea, vomiting, and diarrhea) present on admission and outcomes adjusting for age, gender and examined comorbid diseases. A prediction model was built based on the initial US cohort and validated with a distinct US cohort (n=242). In a subset of patients (n=238), circulating cytokines and chemokines were examined using a multiplexed proteomic assay (Olink) that simultaneously quantified 92 protein analytes. Results: A significant reduction in disease-associated mortality in COVID-19 patients presenting with GI symptoms was observed both in the US cohort (OR 0.54, 95% CI 0.34-0.86) and the Italian cohort (OR 0.33, 95% CI 0.13-0.67) which was independent of age, gender and comorbidities. A prediction model consisting of age and BMI with the addition of GI symptoms had a significantly improved ability to predict disease severity and mortality compared with age and BMI alone (median area under the curve (AUC) of 0.64 (age + BMI+ GI symptoms) vs 0.59 (age + BMI) for disease severity and 0.73 (age + BMI + GI symptoms) vs 0.70 (age + BMI) for mortality). The proteomic analysis revealed 6 clusters based on their co-segregation across all COVID-19 patients. Among these 6 clusters, clusters 4 and 5, which were enriched in the "Hallmark Inflammatory Response" and “KEGG JAK/STAT Signaling Pathway” respectively, and were reduced in patients with diarrhea. The observed mortality reduction in COVID-19 patients with GI symptoms was associated with lower circulating levels of key inflammatory proteins including IL-6, IL-8, IL-17A and CCL28 that are known to be associated with poor outcomes in COVID-19;while there was an increase in IL-7 and TRAIL, which both have important immunoregulatory functions. Conclusions: COVID-19 patients with GI symptoms have reduced inflammatory biomarkers and improved survival after adjusting for comorbidities, age and gender. These data highlight GI involvement as an important parameter for severity stratification in COVID-19 and point towards an immunomodulatory role of the GI tract in response to SARS-CoV-2 infection. (Figure presented)

FIRST HIGH DIMENSIONAL EXAMINATION OF INTESTINAL BIOPSIES IN PATIENTS WITH COVID-19

Introduction: SARS-CoV-2, the causative pathogen for COVID-19, engages host ACE2 receptor for cellular entry. The brush border of the small intestines express high levels of ACE2. Gastrointestinal (GI) manifestations are common among COVID-19 patients. However, to date, there is limited information regarding intestinal response to SARS-CoV-2 infection. Methods: Intestinal biopsies were obtained from 17 COVID-19 patients (17.3 ± positive nasal swab) for cellular and transcriptomic analyses using mass cytometry and RNA-sequencing, respectively. Ten uninfected individuals served as compartment (EC) and lamina propria (LP) were analyzed separately. Results: The cellular profiles from LP of COVID-19 patients showed reduced frequencies of CD206+ conventional dendritic cells (CDC2s) and plasmacytoid (CD123+) dendritic cells Effector T cell (PD1+CD38+) frequency was increased in the LP and Intraepithelial lymphocytes (IEL) were increased in the EC of COVID-19 patients, with a concomitant decrease in CD206+ CDC2s. RNA sequencing active downregulation of genes involved in inflammatory pathways including IBD-associated pathways, while an upregulation of intestinal barrier function Gene expression of Neuropilin-1 (NRP-1), a putative SARS-CoV-2 receptor as well as key inflammatory cytokines (IL-1b, IFN-g, CCL24 and CXCL8) were significantly reduced in controls. A low intensity antiviral host response signature was observed predominantly in EC as opposed to LP suggesting viral localization to epithelium. Conclusions: Epithelial, myeloid and lymphoid cell alterations characterize intestinal response to SARS-CoV-2 infection with an unanticipated downregulation of key inflammatory pathways that have been implicated in adverse outcomes associated with These data stand in contrast to the inflammatory response reported in the systemic compartments and identify a potential mitigating role of the GI

Genetic variations in the Orf7a protein of SARS-CoV-2 and its possible role in vaccine development

coronavirus disease (COVID-19) that has been creating an unprecedented situation globally. The recurrent mutations in SARS-CoV-2 genomes impact on the vaccine designing strategies. The Orf7a is a 121-amino acid-long type I transmembrane accessory protein encoded by the genome of SARSCoV- 2 and plays a crucial role in the virus-host interaction. The present study aimed to analyze the variations occurring in Orf7a due to multiple mutations and its immunological role in developing a promising therapeutic target to curb SARS-CoV-2 infections. Methods: 16,161 sequences of Orf7a reported from the onset of this disease until 13 June 2021 from five continents were compared to identify genetic variations in the protein. Results: A total of 470 point mutations were detected in the sequences submitted. Subsequently, the nature of mutations (deleterious or neutral) was determined. Furthermore, the physicochemical properties, antigenicity, allergenicity, toxicity, and stability of Orf7a protein were estimated to demonstrate the stability of the protein. Additionally, we identified three B-cell immune e pitopes, and their MHC cluster analysis was also performed. Conclusion: The recurrent mutations in Orf7a of SARS-CoV-2 provide a deep understanding of its role in the virus-host interactions. Findings of our study revealed that the predicted epitopes could be promising candidates for a vaccine against COVID-19 infections.

Pharmacological intervention of various Indian medicinal plants in combating COVID-19 infection

Coronavirus pandemic is progressing rapidly causing an eruption of successive waves around the globe due to its ability to cause recurrent mutations, making the prevention and control measures extremely essential. The success of therapeutic benefits of natural plants and herbs are well-known to humans since ancient times. Medicinal plants play an important role in curing human diseases due to the presence of phytochemicals and bioactive compounds. India is known for its heritage of medicinal plants, and Traditional Indian Medicines (TIM) have shown the potential to treat several diseases. The review highlights the detailed information of various Indian medicinal plants and their potential therapeutic role as an antiviral and immunomodulatory therapeutics. Ministry of AYUSH (Ayurveda, Yoga and Naturopathy, Unani, Siddha and Homeopathy) has already issued several health advisory and routinely use of medicinal plants to strengthen the immune system to fight against COVID-19. Various medicinal plants, such as Ocimum sanctum, Withania somnifera, Tinospora cordifolia, Curcuma longa, Zingiber officinalis, Azadirachta indica, Piper nigrum, Nigella sativa, Allium sativum, Glycyrrhiza glabra with their antiviral properties against several viruses including SARS-CoV-2 virus have been discussed in the review, which might be an effective prophylaxis against COVID-19. Special emphasis has been given on the antiviral activities of these plants against SARS-CoV-2, highlighting their efficacy as potential drug candidates.

Immunological and mutational analysis of SARS-CoV-2 structural proteins from Asian countries

Introduction: The emergence of a novel coronavirus, SARS-CoV-2, an etiologic agent of coronavirus disease (COVID-19), has led to a pandemic of global concern. Considering the huge number of morbidity and mortality worldwide, the World Health Organization declared, on 11th March 2020, the pandemic as an unprecedented public health crisis. The virus is a member of plus sense RNA viruses that can show a high rate of mutations. The ongoing multiple mutations in the structural proteins of coronavirus drive viral evolution, enabling them to evade the host immunity and rapidly acquire drug resistance. In the present study, we focused mainly on the prevalence of mutations in the four types of structural proteins- S (spike), E (envelope), M (membrane), and N (nucleocapsid)that are required for the assembly of a complete virion particle. Further, we estimated the antigenicity and allergenicity of these structural proteins to design and develop a potentially good candidate vaccine against SARS-CoV-2. Methods: In the present in silico study, envelope protein was found to be highly antigenic, followed by the nucleocapsid, membrane, and spike proteins of SARS-CoV-2. Results: In this study, we detected 987 mutations from 729 sequences from Asia in October 2020, and compared them with China's first Wuhan isolate sequence as a reference. Spike protein showed the highest mutations with 807 point mutations among the four structural proteins, followed by nucleocapsid with 151 mutations, while envelope showed 19 mutations and membrane only 10 point mutations. Conclusion: Taken together, our study revealed that variations occurring in the structural protein of SARS-CoV-2 might be altering the viral structure and function, and that the envelope protein appears to be a promising vaccine candidate to curb coronavirus infections.

SARS-CoV-2 persists in intestinal enterocytes up to 7 months after symptom resolution

Background: Host proteins ACE-2 and TMPRSS2 facilitate SARS-CoV-2 infection and are expressed in the lungs as well as the intestinal tract, particularly in the small bowel. Gastrointestinal symptoms represent the most common extrapulmonary manifestation of COVID-19. Viral RNA has been isolated from fecal samples from COVID-19 patients, where it can persist longer than detection in nasopharyngeal swabs. While SARS-CoV-2 infection of enterocytes has been demonstrated in vitro, in vivo studies are lacking. Methods: Small intestinal biopsies from patients who underwent clinically indicated endoscopic procedures after a positive SARS-CoV-2 nasopharyngeal swab (n=27) or were found to have positive serology (n=2) were analyzed by immunofluorescence (IF) (n=25) and electron microscopy (EM) (n=14) for the presence of virus. Clinical details were also collected. Results: Sixteen of 29 patients had detectable SARS-CoV-2 antigen by either IF or EM (Figure 1). Virus was restricted to the epithelium and patchy in distribution. Virus was detected as soon as 15 days after symptom onset and persisted up to 6 months after symptom resolution. Five patients were nasopharyngeal swab positive at the time of procedure and, of these, 4 had detectable antigen on biopsy. Despite the presence of virus, only 9/16 patients had any signs of inflammation on histology, and when present, this was mild. In two patients where virus was present at 3 months and 4 months, additional biopsies were obtained at 7 months and 6 months, respectively. Viral antigen was persistently detected in both patients and both patients were nasopharyngeal swab negative for all procedures. Interestingly, only 37.5% (6 of 16) of patients with virus detected in the small bowel had GI symptoms (diarrhea, nausea or vomiting) during their acute COVID-19 illness as compared to 46.1% (6/13) of patients where no virus could be detected in the intestines. Conclusion: SARS-CoV-2 infects enterocytes in humans in vivo and can persist in the intestines up to 7 months following symptoms resolution. This persistence is not associated with an overt inflammatory infiltrate and does not appear to correlate with presence of GI symptoms in the acute COVID-19 setting.

First high-dimensional examination of intestinal biopsies in patients with COVID-19

Background: SARS-CoV-2, the etiopathological agent for COVID-19, engages host ACE2 receptor for cellular entry. The brush border of the small intestines express high levels of ACE2 in physiological conditions. Gastrointestinal (GI) manifestations are common among COVID-19 patients. However, to date, there is limited information regarding intestinal response to SARS-CoV-2 infection. Methods: Intestinal biopsies were obtained from 17 COVID-19 patients (17.3-17.5 days from the last positive nasal swab) for cellular and transcriptomic analyses using mass cytometry and RNA-sequencing. Ten COVID-uninfected individuals served as controls. The epithelial compartment (EC) and lamina propria (LP) were analyzed separately. Results: The cellular profiles of intestinal tissues from COVID-19 patients showed reduced frequencies of CD206+ CDC2s and plasmacytoid dendritic cells in the LP of COVID-19 patients by mass cytometry. Effector T cell (PD1+CD38+) frequency was increased in the LP and blood of COVID-19 patients. Intraepithelial lymphocytes (IEL) were increased in the EC of COVID-19 patients, with a concomitant decrease in CD206+ CDC2s. RNA sequencing revealed an active downregulation of genes involved in inflammatory pathways including Th17 and IBD-associated pathways, while an upregulation of intestinal barrier function (mucin biosynthesis), amino acid metabolism and mineral absorption pathways was noted. Gene expression of Neuropilin-1 (NRP-1), a putative SARSCoV-2 receptor as well as key inflammatory cytokines (IL-1β, IFNγ, CCL24 and CXCL8) were significantly reduced in COVID-19 patients compared to controls. A low intensity antiviral host response signature was observed predominantly in EC reflecting the cellular localization of the virus. Conclusion: Epithelial, myeloid and lymphoid cell alterations characterize intestinal response to SARS-CoV-2 infection with an unanticipated downregulation of key inflammatory pathways that have been implicated in adverse outcomes associated with COVID-19. These data stand in contrast to reports from the pulmonary and systemic compartments and identify a potential mitigating role of the GI tract in COVID-19-associated immunopathology.

GENDER-BIAS SUSCEPTIBILITY OF CORONA VIRUS DISEASE : PEEPING INTO THE FACTORS RESPONSIBLE AND EMERGING TRENDS FROM INDIAN PERSPECTIVE

Recent pandemic of corona virus disease caused by a novel coronavirus SARS-CoV-2 in humans is the third outbreak by this family of viruses, which is reminiscent of the SARS-COV outbreak happened in the year 2003. General characteristics of the novel coronavirus (SARS-CoV-2) especially in regards to the disease susceptibility amongst males and females have been focused providing a better understanding of the coronavirus disease (COVID-19) in males, females and children. A thorough literature search for articles in major databases such as PubMed and Google Scholar etc. has been carried out. COVID-19 has been known to have varied symptoms ranging from mild flu-like symptoms to acute respiratory distress syndrome, multiple organ failure and death. Ageing, genetics, comorbidities and many other associated factors may play a crucial role in predisposing an individual towards COVID-19 disease as there exists chronic inflammation, thrombosis and immune response impairment due to SARS-CoV-2 providing a therapeutic window. Current study emphasizes upon the role of gender in morbidity and mortality in patients with COVID-19 with men higher at risk to COVID-19 than women in terms of mortality despite having the similar prevalence of the disease. The study has been well supported by the data available from the hot-spots affected states from Indian subcontinent. However, current evidence is not sufficient to conclude on the gender-bias susceptibility but certainly men have an edge over women in terms of susceptibility towards COVID-19.

Upsurge in COVID-19 testing versus latest trends of active patients in Indian scenario: Emerging trends and future predictions

World Health Organization (WHO) has already declared the COVID-19 caused by SARS-CoV-2 as the pandemic of the year 2020, after its first outbreak reported in Wuhan, China. There have been numerous efforts laid upon by respective Governments in order to contain and mitigate the spread of the virus. One of the primary initiatives in this direction was to ascertain the number of cases through testing. Testing for the diagnosis of the COVID-19 is a crucial factor to know the prevalence, spread and transmissible nature of the disease. Moreover, how effective the testing strategy is prerequisite for knowing the exact number of infected cases by COVID-19. In India, 1,58,49,068 samples have been tested, out of which 13,36,861 samples have been found to be positive up to 24th July 2020. The testing strategy adopted by India has yielded fruitful and effective results so far when compared to nations like United States, United Kingdom, Spain and Italy. Current article focuses upon the dire need to upsurge testing in accordance to daily cases identified testing based on the macro and micro analysis of Covid-19 data in Indian scenario including all the Indian States and Union Territories. This article might give some due insights into enhancing the testing capabilities as well as testing strategies so as to contain the spread of the Covid-19 Pandemic. Considering that India has started to unlock with Unlock 1.0 and Unlock 2.0, the Covid-19 pandemic has started to disseminate to rural population and smaller cities have shown significant rise in Covid-19 infections. Therefore, testing across the whole nation and especially testing of travellers from hotspot zones has become a necessity else, community transmission looks inevitable and India would be at the edge of a pandemic within a pandemic within a couple of months.