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The structural and characteristic features of HIV-1 broadly neutralizing antibodies (bnAbs) from chronically infected pediatric donors are currently unknown. Herein, we characterized a heavy chain matured HIV-1 bnAb 44m, identified from a pediatric elite-neutralizer. Interestingly, in comparison to its wild-type AIIMS-P01 bnAb, 44m exhibited moderately higher level of somatic hypermutations (SHM) of 15.2%. 44m neutralized 79% of HIV-1 heterologous viruses tested, with a geometric mean IC50titer of 0.36 μg/ml. The cryoEM structure of 44m Fab in complex with fully-cleaved glycosylated native-like BG505.SOSIP envelope trimer at 4.4 Å resolution revealed that 44m targets the V3-glycan N332-supersite and GDIR motif to neutralize HIV-1 with improved potency and breadth, plausibly attributed by a matured heavy chain as compared to that of wild-type AIIMS-P01 bnAb. This study improves our understanding on pediatric HIV-1 bnAbs and structural basis of broad HIV-1 neutralization by 44m may be useful blueprint for vaccine design in future.

A detailed understanding of the molecular features of the neutralizing epitopes developed by viral escape mutants is important for predicting and developing vaccines or therapeutic antibodies against continuously emerging SARS-CoV-2 variants. Here, we report three human monoclonal antibodies (mAbs) generated from COVID-19 recovered individuals during first wave of pandemic in India. These mAbs had publicly shared near germline gene usage and potently neutralized Alpha and Delta, but poorly neutralized Beta and completely failed to neutralize Omicron BA.1 SARS-CoV-2 variants. Structural analysis of these three mAbs in complex with trimeric spike protein showed that all three mAbs are involved in bivalent spike binding with two mAbs targeting class-1 and one targeting class-4 Receptor Binding Domain (RBD) epitope. Comparison of immunogenetic makeup, structure, and function of these three mAbs with our recently reported class-3 RBD binding mAb that potently neutralized all SARS-CoV-2 variants revealed precise antibody footprint, specific molecular interactions associated with the most potent multi-variant binding / neutralization efficacy. This knowledge has timely significance for understanding how a combination of certain mutations affect the binding or neutralization of an antibody and thus have implications for predicting structural features of emerging SARS-CoV-2 escape variants and to develop vaccines or therapeutic antibodies against these.

In this study, by characterizing several human monoclonal antibodies (mAbs) isolated from single B cells of the COVID-19–recovered individuals in India who experienced ancestral Wuhan strain (WA.1) of SARS-CoV-2 during early stages of the pandemic, we found a receptor binding domain (RBD)–specific mAb 002-S21F2 that has rare gene usage and potently neutralized live viral isolates of SARS-CoV-2 variants including Alpha, Beta, Gamma, Delta, and Omicron sublineages (BA.1, BA.2, BA.2.12.1, BA.4, and BA.5) with IC 50 ranging from 0.02 to 0.13 μg/ml. Structural studies of 002-S21F2 in complex with spike trimers of Omicron and WA.1 showed that it targets a conformationally conserved epitope on the outer face of RBD (class 3 surface) outside the ACE2-binding motif, thereby providing a mechanistic insights for its broad neutralization activity. The discovery of 002-S21F2 and the broadly neutralizing epitope it targets have timely implications for developing a broad range of therapeutic and vaccine interventions against SARS-CoV-2 variants including Omicron sublineages.

Previous studies showed that a discrete population of the CD8 T cells with HLADR+CD38+ phenotype expand massively during the acute febrile phase of dengue natural infection. Although about a third of these massively expanding HLADR+CD38+ CD8 T cells were of CD69high phenotype, only a small fraction of them produced IFNγ upon in vitro peptide stimulation. What other cytokines/ chemokines do these peptides stimulated HLADR+CD38+ CD8 T cells express, what transcriptional profiles distinguish the CD69+IFNγ+, CD69+IFNγ-, and CD69-IFNγ- subsets, and whether the expansion of the total HLADR+CD38+ CD8 T cells or the IFNγ producing CD8 T cells differ depending on disease severity remained unclear. This study addresses these knowledge gaps. We find that the CD69+IFNγ+ subset uniquely expressed key genes involved in protein translation, cellular metabolism, proliferation and dendritic cell cross talk. Both the CD69+IFNγ+ and CD69+IFNγ- subsets had an antigen responsive gene signature with genes involved in cytotoxic effector functions, regulation of T cell receptor signaling, signaling by MAPK, chemotaxis and T cell trafficking to inflamed tissues with the expression being more robust in the IFNγ+ CD69+ subset. On the other hand, the CD69- IFNγ- subset was biased towards expression of genes that both augment and dampen T cell responses. Lastly, the expansion of total HLADR+ CD38+ CD8 T cells and also the IFNγ producing HLADR+ CD38+ CD8 T cells was similar in patients with different grades of disease. Taken together, this study provides valuable insights into the inherent diversity of the effector CD8 T cell response during dengue.

The SARS-CoV-2 BA.1 and BA.2 (Omicron) variants contain more than 30 mutations within the spike protein and evade therapeutic monoclonal antibodies (mAbs). Here, we report a receptor-binding domain (RBD) targeting human antibody (002-S21F2) that effectively neutralizes live viral isolates of SARS-CoV-2 variants of concern (VOCs) including Alpha, Beta, Gamma, Delta, and Omicron (BA.1 and BA.2) with IC50 ranging from 0.02 – 0.05 μg/ml. This near germline antibody 002-S21F2 has unique genetic features that are distinct from any reported SARS-CoV-2 mAbs. Structural studies of the full-length IgG in complex with spike trimers (Omicron and WA.1) reveal that 002-S21F2 recognizes an epitope on the outer face of RBD (class-3 surface), outside the ACE2 binding motif and its unique molecular features enable it to overcome mutations found in the Omicron variants. The discovery and comprehensive structural analysis of 002-S21F2 provide valuable insight for broad and potent neutralization of SARS-CoV-2 Omicron variants BA.1 and BA.2.

Monocytes are known to play a critical role in dengue pathophysiology. However, which monocyte subset expresses what inflammatory mediator(s) and what transcriptional features distinguish each of the monocyte subset

Angiotensin-converting enzyme 2 (ACE2) is a key host protein by which severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enters and multiplies within cells. The level of ACE2 expression in the lung is hypothesised to correlate with an increased risk of severe infection and complications in COVID-19 (COrona VIrus Disease 2019). To test this hypothesis, we compared the protein expression status of ACE2 by immunohistochemistry (IHC) in post-mortem lung samples of patients who died of severe COVID-19 and lung samples obtained from non-COVID-9 patients for other indications. IHC for CD61 and CD163 were performed for assessment of platelet-rich microthrombi and macrophages, respectively. IHC for SARS-CoV-2 viral antigen was also performed. Quantification of immunostaining, random sampling, and correlation analysis was used to substantiate the morphologic findings. Our results show that among a total of 44 COVID-19 post-mortem lung tissues and 15 lung biopsies in non-COVID-19 patients included, ACE2 protein expression was significantly higher in COVID-19 patients than in controls, regardless of sample size. Histomorphology in COVID-19 lungs showed diffuse alveolar damage (DAD), acute bronchopneumonia, and acute lung injury with SARS-CoV-2 viral protein detected in a subset of cases. ACE2 expression levels positively correlated with increased expression levels of CD61 and CD163. In conclusion, our results show significantly higher ACE2 protein expression in severe COVID-19 disease, correlating with increased macrophage infiltration and microthrombi, suggesting a pathobiological role in disease severity.

Angiotensin-converting enzyme 2 (ACE2) is a key host protein by which severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enters and multiplies within cells. The level of ACE2 expression in the lung is hypothesised to correlate with an increased risk of severe infection and complications in COrona VIrus Disease 2019 (COVID-19). To test this hypothesis, we compared the protein expression status of ACE2 by immunohistochemistry (IHC) in post-mortem lung samples of patients who died of severe COVID-19 and lung samples obtained from non-COVID-19 patients for other indications. IHC for CD61 and CD163 was performed for the assessment of platelet-rich microthrombi and macrophages, respectively. IHC for SARS-CoV-2 viral antigen was also performed. In a total of 55, 44 COVID-19 post-mortem lung samples were tested for ACE2, 36 for CD163, and 26 for CD61, compared to 15 non-covid 19 control lung sections. Quantification of immunostaining, random sampling, and correlation analysis were used to substantiate the morphologic findings. Our results show that ACE2 protein expression was significantly higher in COVID-19 post-mortem lung tissues than in controls, regardless of sample size. Histomorphology in COVID-19 lungs showed diffuse alveolar damage (DAD), acute bronchopneumonia, and acute lung injury with SARS-CoV-2 viral protein detected in a subset of cases. ACE2 expression levels were positively correlated with increased expression levels of CD61 and CD163. In conclusion, our results show significantly higher ACE2 protein expression in severe COVID-19 disease, correlating with increased macrophage infiltration and microthrombi, suggesting a pathobiological role in disease severity.

Background: The COVID-19 pandemic led lockdown-an unprecedented event wherein people globally have been hit hard. This lockdown has caused a deep impact on lifestyle-related parameters like sleep pattern, diet pattern, stress level, physical activity level and circadian rhythms. Objective: This study was designed to study effect of COVID-19 pandemic on lifestyle of young adults and adolescents. Method: Online survey was conducted in 1065 respondents in the age group of 13 to 25 years. Result: Questionnaire-based survey showed mean sleep duration changing from 6.85 hours to 8.17 hours, average screen time increased to 5.12 hours from 3.5 hours, 51.9% subjects experienced higher stress levels, 76.4% subjects experienced more food intake and 38.6% subjects had decreased levels of physical activity as per self-monitoring. Conclusion: These changes might have long lasting effects on their physical, mental and social health and need counteractive measures to help young people lead a healthy lifestyle during the epidemic and beyond. How to cite this article: Roy S, Tiwari S, Kanchan S, Bajpai P. Impact of COVID-19 Pandemic Led Lockdown on the Lifestyle of Adolescents and Young Adults. Ind J Youth Adol Health 2020; 7(2): 12-15. DOI: https://doi.org/10.24321/2349.2880.202008

BACKGROUND The corona virus disease 2019(COVID-19) is caused by the virus SARS-CoV-2 and is declared as a global pandemic by World Health Organization (WHO). Various hematological parameters alteration has been documented in the Chinese literature in SARS-Cov-2 infection. However, there is a need for research to evaluate the pattern of the hematological parameters of COVID-19 patients in the Indian population. OBJECTIVE The objective of the study is to see the Neutrophil-Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), and other hematological parameters alteration of COVID-19 patients along with their clinical course in the Indian scenario. METHODS A single-center prospective study of 32 patients with laboratory-confirmed COVID-19 admitted to Super Speciality Pediatric Hospital & Post Graduate Teaching Institute NOIDA, from March to April, were enrolled for the study. The demographic date, the clinical status of the patients during admission and follow up, baseline, and follow up hematological findings were recorded. Statistical analysis of the data was carried out, and relevant findings were presented. RESULTS Demographic characterization shows a mean age of 37.7 years, male (41.9%),female (58.1%)with majority patients are mildly symptomatic to asymptomatic(93%). The CBC values and NLR, PLR at baseline between the male and the female patients, are not showing any statistically significant difference as the 95% C.I. A statistically significant increment in the lab parameters is observed in follow-up visits. CONCLUSIONS Majority of the patients are younger and have mild clinical presentation with female predominance. Pediatric cases have mild symptomology. Baseline CBC findings show mild neutrophilia, lymphopenia, eosinopenia and normal to mild thrombocytopenia. An increase in CBC parameters, NLR was noted in follow up cases. Anemia was not noted in baseline CBC andin follow up group. A onetime PLR is not indicative of disease progression. CLINICALTRIAL NA

Human mitochondria are descendants of microbes and altered mitochondrial function has been implicated in processes ranging from ageing to diabetes. Recent work has highlighted the importance of gut microbial communities in human health and disease. While the spotlight has been on the influence of such communities on the human immune system and the extraction of calories from otherwise indigestible food, an important but less investigated link between the microbes and mitochondria remains unexplored. Microbial metabolites including short chain fatty acids as well as other molecules such as pyrroloquinoline quinone, fermentation gases, and modified fatty acids influence mitochondrial function. This review focuses on the known direct and indirect effects of microbes upon mitochondria and speculates regarding additional links for which there is circumstantial evidence. Overall, while there is compelling evidence that a microbiota-mitochondria link exists, explicit and holistic mechanistic studies are warranted to advance this nascent field.

RNA editing ofmiRNAs, especially in the seed region,\ud adds another layer to miRNA mediated gene regulation\ud which can modify its targets, altering cellular signaling\ud involved in important processes such as differentiation.\ud In this study, we have explored the role\ud of miRNA editing in CD4+ T cell differentiation. CD4+\ud T cells are an integral component of the adaptive immune\ud system. Na¨ıve CD4+ T cells, on encountering\ud an antigen, get differentiated either into inflammatory\ud subtypes like Th1, Th2 or Th17, or into immunosuppressive\ud subtype Treg, depending on the cytokine\ud milieu. We found C-to-U editing at fifth position of\ud mature miR-100, specifically in Treg. The C-to-U editing\ud of miR-100 is functionally associated with at least\ud one biologically relevant target change, from MTOR\ud to SMAD2. Treg cell polarization by TGFβ1 was reduced\ud by both edited and unedited miR-100 mimics,\ud but percentage of Treg in PBMCs was only reduced\ud by edited miR-100 mimics, suggesting a model in\ud which de-repression of MTOR due to loss of unedited\ud mir-100, promotes tolerogenic signaling, while gain\ud of edited miR-100 represses SMAD2, thereby limiting\ud the Treg. Such delicately counterbalanced systems\ud are a hallmark of immune plasticity and we propose\ud that miR-100 editing is a novel mechanism toward\ud this end.