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Context: SARS-CoV-2 virus causes COVID-19 by infecting nasal and oral cavities primarily by attaching its spike proteins to ACE 2 receptors expressed in epithelial cells. Aim: This study was done to evaluate the micronucleated cell count, metanuclear abnormalities, and genotoxic factor in exfoliated buccal mucosal cell among the COVID-19 suspected patients. Settings and Design: This cross-sectional study was conducted at AIIMS, Mangalagiri, between August and October 2022. Methods: One hundred COVID-19 suspected patients were recruited for this study after obtaining informed and written consent; buccal smear was obtained and stained for papanicolaou test (PAP). The PAP-stained slides were analyzed for micronuclei (MN), pyknotic, karyolytic, and karyorrhexic cell count, respectively. Based on their reverse transcription-polymerase chain reaction (RT-PCR) report, the patients were grouped into COVID-19 positive and negative groups. Statistical Analysis: The genotoxicity factor was calculated using the micronucleated cell count from both the groups using mean and standard deviation. Results: The MN, micronucleated cell, pyknotic, karyolitic, and karyorrhexic cell count in COVID-19 positive patients were 24.12, 15.24, 3.08, 2.88 and 4.40, respectively, than COVID-19 negative patients 5.69, 8.17, 1.08, 1.00 and 2.43, respectively. The genotoxicity factor for SARS-CoV-2 was 2.68 which is a positive genotoxic effect on buccal mucosal cells. Conclusion: SARS-CoV-2 increases the expression of micronucleated cells, pyknotic cells, karyolytic cells, and karyorhexic cells and concludes SARS-CoV-2 is having cytogenotoxic effect on the buccal mucosal cells. This can be used as a reliable marker in identifying the early carcinogenic effects of virus causing COVID-19. [ABSTRACT FROM AUTHOR]

Many drugs were recommended as antiviral agents for infection control and effective therapy to reduce the mortality rate for COVID-19 patients. Hydroxychloroquine (HCQ), an antimalarial drug, has been controversially recommended for prophylactic use in many countries, including India, to control SARS-CoV-2 infections. We have explored the effect of prophylactic HCQ from the cells of bronchoalveolar lavage fluids from COVID-19-induced acute respiratory distress syndrome patients to determine the level of infection and ultrastructural alterations in the ciliated epithelium, type II pneumocytes, alveolar macrophages, neutrophils, and enucleated granulocytes. Ultrastructural investigation of ciliated epithelium and type II pneumocytes showed lesser infections and cellular impairment in the prophylactic HCQ+ group than HCQ− group. However, macrophages and neutrophils displayed similar infection and ultrastructural alterations in both patient groups. The enucleated fragments of granulocytes showed phagocytosis of the matured virus in HCQ+ groups. The present report unveils the ultrastructural proof to complement the paradox regarding the role of prophylactic HCQ in COVID-19 patients. [ABSTRACT FROM AUTHOR]

The organization of eukaryotic genome in the nucleus, a double-membraned organelle separated from the cytoplasm, is highly complex and dynamic. The functional architecture of the nucleus is confined by the layers of internal and cytoplasmic elements, including chromatin organization, nuclear envelope associated proteome and transport, nuclear–cytoskeletal contacts, and the mechano-regulatory signaling cascades. The size and morphology of the nucleus could impose a significant impact on nuclear mechanics, chromatin organization, gene expression, cell functionality and disease development. The maintenance of nuclear organization during genetic or physical perturbation is crucial for the viability and lifespan of the cell. Abnormal nuclear envelope morphologies, such as invagination and blebbing, have functional implications in several human disorders, including cancer, accelerated aging, thyroid disorders, and different types of neuro-muscular diseases. Despite the evident interplay between nuclear structure and nuclear function, our knowledge about the underlying molecular mechanisms for regulation of nuclear morphology and cell functionality during health and illness is rather poor. This review highlights the essential nuclear, cellular, and extracellular components that govern the organization of nuclei and functional consequences associated with nuclear morphometric aberrations. Finally, we discuss the recent developments with diagnostic and therapeutic implications targeting nuclear morphology in health and disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The aberrant expression of lncRNAs has been linked to the development and progression of different cancers. One such lncRNA is ABHD11 antisense RNA 1 (ABHD11-AS1), which has recently gained attention for its significant role in human malignancies. ABHD11-AS1 is highly expressed in gastric, lung, breast, colorectal, thyroid, pancreas, ovary, endometrium, cervix, and bladder cancers. Several reports highlighted the clinical significance of ABHD11-AS1 in prognosis, diagnosis, prediction of cancer progression stage, and treatment response. Significantly, the levels of ABHD11-AS1 in gastric juice had been exhibited as a clinical biomarker for the assessment of gastric cancer, while its serum levels have prognostic potential in thyroid cancers. The ABHD11-AS1 has been reported to exert oncogenic effects by sponging different microRNAs (miRNAs), altering signaling pathways such as PI3K/Akt, epigenetic mechanisms, and N6-methyladenosine (m6A) RNA modification. In contrast, the mouse homolog of AHD11-AS1 (Abhd11os) overexpression had exhibited neuroprotective effects against mutant huntingtin-induced toxicity. Considering the emerging research reports, the authors attempted in this first review on ABHD11-AS1 to summarize and highlight its oncogenic potential and clinical significance in different human cancers. Lastly, we underlined the necessity for future mechanistic studies to unravel the role of ABHD11-AS1 in tumor development, prognosis, progression, and targeted therapeutic approaches. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

COVID-19 pandemic has been a global health emergency due to its association with severe pneumonia and high rate of mortality. In the current study, we reported the direct evidence for the variable level of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infection on several types of oral epithelial cells isolated from the aspirated oropharyngeal and bronchoalveolar secretions of severely infected and intubated patients using cytology, confocal based immunofluorescence imaging (IF), scanning electron microscope (SEM) and transmission electron microscopic (TEM) studies. Cytological analysis showed the presence of keratinised and non-keratinised oral epithelial cells with viral inclusion bodies in stratum granulosum and intermedium cells. IF imaging using SARS-CoV-2 spike protein specific antibody confirmed the presence of virus inside the stratum spinosum/granulosum (keratinised) and stratum intermedium/superficial cells (non-keratinised). No SARS-CoV-2 viruses were seen in stratum corneum cells. SEM analysis also confirms the absence of virus like structure on stratum corneum surface while viruses like structure were seen on the stratum spinosum/granulosum/stratum/intermedium and stratum superficial cells. This advanced microscopic study confirms directly that the virus tends to infect and multiply in the metabolically active or sub-basal cells of oral epithelium and absent in the inactive keratinised stratum corneum from shedding zones of oral mucosa. [ABSTRACT FROM AUTHOR]

Recent epidemiological studies analysing sex-disaggregated patient data of coronavirus disease 2019 (COVID-19) across the world revealed a distinct sex bias in the disease morbidity as well as the mortality – both being higher for the men. Similar antecedents have been known for the previous viral infections, including from coronaviruses, such as severe acute respiratory syndrome (SARS) and middle-east respiratory syndrome (MERS). A sound understanding of molecular mechanisms leading to the biological sex bias in the survival outcomes of the patients in relation to COVID-19 will act as an essential requisite for developing a sex-differentiated approach for therapeutic management of this disease. Recent studies which have explored molecular mechanism(s) behind sex-based differences in COVID-19 pathogenesis are scarce; however, existing evidence, for other respiratory viral infections, viz. SARS, MERS and influenza, provides important clues in this regard. In attempt to consolidate the available knowledge on this issue, we conducted a systematic review of the existing empirical knowledge and recent experimental studies following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The qualitative analysis of the collected data unravelled multiple molecular mechanisms, such as evolutionary and genetic/epigenetic factors, sex-linkage of viral host cell entry receptor and immune response genes, sex hormone and gut microbiome-mediated immune-modulation, as the possible key reasons for the sex-based differences in patient outcomes in COVID-19. [ABSTRACT FROM AUTHOR]