Browsing by Author "Kumar, Sujeet"

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    COVID-19 Mechanisms in the Human Body�What We Know So Far
    (Frontiers Media S.A., 2021) Kumar, Ashutosh; Narayan, Ravi K.; Prasoon, Pranav; Kumari, Chiman; Kaur, Gurjot; Kumar, Santosh; Kulandhasamy, Maheswari; Sesham, Kishore; Pareek, Vikas; Faiq, Muneeb A.; Pandey, Sada N.; Singh, Himanshu N.; Kant, Kamla; Shekhawat, Prakash S.; Raza, Khursheed; Kumar, Sujeet
    More than one and a half years have elapsed since the commencement of the coronavirus disease 2019 (COVID-19) pandemic, and the world is struggling to contain it. Being caused by a previously unknown virus, in the initial period, there had been an extreme paucity of knowledge about the disease mechanisms, which hampered preventive and therapeutic measures against COVID-19. In an endeavor to understand the pathogenic mechanisms, extensive experimental studies have been conducted across the globe involving cell culture-based experiments, human tissue organoids, and animal models, targeted to various aspects of the disease, viz., viral properties, tissue tropism and organ-specific pathogenesis, involvement of physiological systems, and the human immune response against the infection. The vastly accumulated scientific knowledge on all aspects of COVID-19 has currently changed the scenario from great despair to hope. Even though spectacular progress has been made in all of these aspects, multiple knowledge gaps are remaining that need to be addressed in future studies. Moreover, multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have emerged across the globe since the onset of the first COVID-19 wave, with seemingly greater transmissibility/virulence and immune escape capabilities than the wild-type strain. In this review, we narrate the progress made since the commencement of the pandemic regarding the knowledge on COVID-19 mechanisms in the human body, including virus�host interactions, pulmonary and other systemic manifestations, immunological dysregulations, complications, host-specific vulnerability, and long-term health consequences in the survivors. Additionally, we provide a brief review of the current evidence explaining molecular mechanisms imparting greater transmissibility and virulence and immune escape capabilities to the emerging SARS-CoV-2 variants. Copyright � 2021 Kumar, Narayan, Prasoon, Kumari, Kaur, Kumar, Kulandhasamy, Sesham, Pareek, Faiq, Pandey, Singh, Kant, Shekhawat, Raza and Kumar.
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    COVID-19 vaccination may enhance hippocampal neurogenesis in adults
    (Academic Press Inc., 2023) Kumar, Ashutosh; Narayan, Ravi K.; Prasoon, Pranav; Jha, Rakesh K.; Kumar, Sujeet; Kumari, Chiman; Pandey, Sada N.; Faiq, Muneeb A.
    Emerging evidence suggests a detrimental impact of COVID-19 illness on the continued hippocampal neurogenesis in adults. In contrast, the existing literature supports an enhancing effect of COVID-19 vaccination on adult hippocampal neurogenesis. Vaccines against respiratory infections, including influenza, have been shown to enhance hippocampal neurogenesis in adult-age animals. We propose that a similar benefit may happen in COVID-19 vaccinated adults. The vaccine-induced enhancement of the hippocampal neurogenesis in adults thus may protect against age-related cognitive decline and mental disorders. It also hints at an added mental health benefit of the COVID-19 vaccination programs in adults. � 2022 Elsevier Inc.
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    Emerging SARS-CoV-2 variants can potentially break set epidemiological barriers in COVID-19
    (John Wiley and Sons Inc, 2022) Kumar, Ashutosh; Parashar, Rakesh; Kumar, Sujeet; Faiq, Muneeb A; Kumari, Chiman; Kulandhasamy, Maheswari; Narayan, Ravi K.; Jha, Rakesh K.; Singh, Himanshu N.; Prasoon, Pranav; Pandey, Sada N.; Kant, Kamla
    Young age, female sex, absence of comorbidities, and prior infection or vaccination are known epidemiological barriers for contracting the new infection and/or increased disease severity. Demographic trends from the recent coronavirus disease 2019 waves, which are believed to be driven by newer severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, indicate that the aforementioned epidemiological barriers are being breached and a larger number of younger and healthy individuals are developing severe disease. The new SARS-CoV-2 variants have key mutations that can induce significant changes in the virus-host interactions. Recent studies report that, some of these mutations, singly or in a group, enhance key mechanisms, such as binding of the receptor-binding domain (RBD) of the viral spike protein with the angiotensin-converting enzyme 2 (ACE2) receptor in the host-cells, increase the glycosylation of spike protein at the antigenic sites, and enhance the proteolytic cleavage of the spike protein, thus leading to improved host-cell entry and the replication of the virus. The putative changes in the virus�host interactions imparted by the mutations in the RBD sequence can potentially be the reason behind the breach of the observed epidemiological barriers. Susceptibility for contracting SARS-CoV-2 infection and the disease outcomes are known to be influenced by host-cell expressions of ACE2 and other proteases. The new variants can act more efficiently, and even with the lesser availability of the viral entry-receptor and the associated proteases, can have more efficient host-cell entry and greater replication resulting in high viral loads and prolonged viral shedding, widespread tissue-injury, and severe inflammation leading to increased transmissibility and lethality. Furthermore, the accumulating evidence shows that multiple new variants have reduced neutralization by both, natural and vaccine-acquired antibodies, indicating that repeated and vaccine breakthrough infections may arise as serious health concerns in the ongoing pandemic. � 2021 Wiley Periodicals LLC.
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    Low expression of TMPRSS2�a SARS-CoV-2 internalization protease�associates with basal subtype of head and neck squamous cell carcinoma
    (Neoplasia Press, Inc., 2022) Tiwari, Jayesh; Tripathi, Nancy; Srivastava, Ravi Shanker; Kumar, Sujeet; Singh, Sanjay; Jain, Shreyans; Khattri, Arun
    SARS-CoV-2 is a single-stranded RNA virus that has caused the ongoing COVID-19 pandemic. ACE2 and other genes utilized by SARS-CoV-2 to enter human cells have been shown to express in Head and Neck Squamous Cell Carcinoma (HNSCC) patients. However, their expression pattern in different subtypes has not been investigated. Hence, in the current study, we have analyzed the expression of ACE2, TMPRSS2 and FURIN in 649 HNSCC patients from two independent cohorts. Our analysis showed significantly lower expression of TMPRSS2 while significantly increased expression of ACE2 and FURIN in HPV-negative HNSCC. Comparison of expression of these genes in the three subtypes of HNSCC patients (basal, classical and inflamed/mesenchymal) showed no significant difference in the expression of ACE2 among the three subtypes; however, the basal subtype showed significantly reduced expression of TMPRSS2 but significantly increased expression of FURIN. Comparison of expression of these genes between the HPV-negative patients of basal subtype vs all others confirmed significantly lower expression of TMPRSS2 in HPV-negative patients of basal subtype as compared to all others. Our study shows that the different subtypes of HNSCC patients have different expression patterns of genes utilized by the SARS-CoV-2 to enter human cells, and hence, their susceptibility to SARS-CoV-2 may also be different. As the expression of TMPRSS2 is significantly lower in the HNSCC patients of the basal subtype, we predict that these patients would be less susceptible to SARS-CoV-2 infection than the patients of other subtypes. However, these findings need to be further validated. � 2022
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    SARS-CoV-2 Omicron Variant Genomic Sequences and Their Epidemiological Correlates Regarding the End of the Pandemic: In Silico Analysis
    (JMIR Publications Inc., 2023) Kumar, Ashutosh; Asghar, Adil; Singh, Himanshu N.; Faiq, Muneeb A.; Kumar, Sujeet; Narayan, Ravi K.; Kumar, Gopichand; Dwivedi, Prakhar; Sahni, Chetan; Jha, Rakesh K.; Kulandhasamy, Maheswari; Prasoon, Pranav; Sesham, Kishore; Kant, Kamla; Pandey, Sada N.
    Background: Emergence of the new SARS-CoV-2 variant B.1.1.529 worried health policy makers worldwide due to a large number of mutations in its genomic sequence, especially in the spike protein region. The World Health Organization (WHO) designated this variant as a global variant of concern (VOC), which was named �Omicron.� Following Omicron�s emergence, a surge of new COVID-19 cases was reported globally, primarily in South Africa. Objective: The aim of this study was to understand whether Omicron had an epidemiological advantage over existing variants. Methods: We performed an in silico analysis of the complete genomic sequences of Omicron available on the Global Initiative on Sharing Avian Influenza Data (GISAID) database to analyze the functional impact of the mutations present in this variant on virus-host interactions in terms of viral transmissibility, virulence/lethality, and immune escape. In addition, we performed a correlation analysis of the relative proportion of the genomic sequences of specific SARS-CoV-2 variants (in the period from October 1 to November 29, 2021) with matched epidemiological data (new COVID-19 cases and deaths) from South Africa. Results: Compared with the current list of global VOCs/variants of interest (VOIs), as per the WHO, Omicron bears more sequence variation, specifically in the spike protein and host receptor-binding motif (RBM). Omicron showed the closest nucleotide and protein sequence homology with the Alpha variant for the complete sequence and the RBM. The mutations were found to be primarily condensed in the spike region (n=28-48) of the virus. Further mutational analysis showed enrichment for the mutations decreasing binding affinity to angiotensin-converting enzyme 2 receptor and receptor-binding domain protein expression, and for increasing the propensity of immune escape. An inverse correlation of Omicron with the Delta variant was noted (r=�0.99, P<.001; 95% CI �0.99 to �0.97) in the sequences reported from South Africa postemergence of the new variant, subsequently showing a decrease. There was a steep rise in new COVID-19 cases in parallel with the increase in the proportion of Omicron isolates since the report of the first case (74%-100%). By contrast, the incidence of new deaths did not increase (r=�0.04, P>.05; 95% CI �0.52 to 0.58). Conclusions: In silico analysis of viral genomic sequences suggests that the Omicron variant has more remarkable immune-escape ability than existing VOCs/VOIs, including Delta, but reduced virulence/lethality than other reported variants. The higher power for immune escape for Omicron was a likely reason for the resurgence in COVID-19 cases and its rapid rise as the globally dominant strain. Being more infectious but less lethal than the existing variants, Omicron could have plausibly led to widespread unnoticed new, repeated, and vaccine breakthrough infections, raising the population-level immunity barrier against the emergence of new lethal variants. The Omicron variant could have thus paved the way for the end of the pandemic. � 2023, JMIR Publications Inc.. All rights reserved.