RNA editing in host lncRNAs as potential modulator in SARS-CoV-2 variants-host immune response dynamics.

Both host and viral RNA editing plays a crucial role in host's response to infection, yet our understanding of host RNA editing remains limited. In this study of in-house generated RNA sequencing (RNA-seq) data of 211 hospitalized COVID-19 patients with PreVOC, Delta, and Omicron variants, we observed a significant differential editing frequency and patterns in long non-coding RNAs (lncRNAs), with Delta group displaying lower RNA editing compared to PreVOC/Omicron patients. Notably, multiple transcripts of UGDH-AS1 and NEAT1 exhibited high editing frequencies. Expression of ADAR1/APOBEC3A/APOBEC3G and differential abundance of repeats were possible modulators of differential editing across patient groups. We observed a shift in crucial infection-related pathways wherein the pathways were downregulated in Delta compared to PreVOC and Omicron. Our genomics-based evidence suggests that lncRNA editing influences stability, miRNA binding, and expression of both lncRNA and target genes. Overall, the study highlights the role of lncRNAs and how editing within host lncRNAs modulates the disease severity.

Dry Mouth Dilemma: A Comprehensive Review of Xerostomia in Complete Denture Wearers.

Xerostomia, commonly known as dry mouth, presents a significant challenge for individuals wearing complete dentures, affecting their oral health and quality of life. This review explores the relationship between saliva and complete dentures, highlighting the varied management strategies for xerostomia. Saliva plays a critical role in denture retention, lubrication, and oral environment buffering. Complete denture wearers often experience reduced salivary flow, aggravating symptoms of xerostomia. Various management approaches are discussed, including general measures such as hydration and salivary stimulation techniques which aim to boost saliva production naturally. The use of salivary substitutes provides artificial lubrication and moisture to alleviate dry mouth discomfort. Oral lubricating devices, such as sprays, gels, and lozenges, offer relief by mimicking saliva's lubricating properties, thereby improving denture stability and comfort. This review addresses the etiology of xerostomia in complete denture wearers and explores preventive measures to reduce its impact. A comprehensive approach has been discussed for the management of xerostomia which will help to improve the oral health and well-being of complete denture wearers experiencing dry mouth.

Correction: Carcinoma Ex Ameloblastoma of the Mandible: A Rare Case Report.

[This corrects the article DOI: 10.7759/cureus.49536.].

Assessment of Pathology Domain-Specific Knowledge of ChatGPT and Comparison to Human Performance.

CONTEXT.­: Artificial intelligence algorithms hold the potential to fundamentally change many aspects of society. Application of these tools, including the publicly available ChatGPT, has demonstrated impressive domain-specific knowledge in many areas, including medicine. OBJECTIVES.­: To understand the level of pathology domain-specific knowledge for ChatGPT using different underlying large language models, GPT-3.5 and the updated GPT-4. DESIGN.­: An international group of pathologists (n = 15) was recruited to generate pathology-specific questions at a similar level to those that could be seen on licensing (board) examinations. The questions (n = 15) were answered by GPT-3.5, GPT-4, and a staff pathologist that recently passed their Canadian pathology licensing exams. Participants were instructed to score answers on a 5-point scale and to predict which answer was written by ChatGPT. RESULTS.­: GPT-3.5 performed at a similar level to the staff pathologist, while GPT-4 outperformed both. The overall score for both GPT-3.5 and GPT-4 was within the range of meeting expectations for a trainee writing licensing examinations. In all but one question, the reviewers were able to correctly identify the answers generated by GPT-3.5. CONCLUSIONS.­: By demonstrating the ability of ChatGPT to answer pathology-specific questions at a level similar to (GPT-3.5) or exceeding (GPT-4) a trained pathologist, this study highlights the potential of large language models to be transformative in this space. In the future, more advanced iterations of these algorithms with increased domain-specific knowledge may have the potential to assist pathologists and enhance pathology resident training.

Carcinoma Ex Ameloblastoma of the Mandible: A Rare Case Report.

Ameloblastoma is a benign yet locally aggressive tumor of the jaw bones and is most commonly found in the lower mandibular region. Histologically, it shows benign characteristics. However, ameloblastoma can turn malignant to show a more aggressive clinical course. Carcinoma ex ameloblastoma is an extremely rare malignancy arising from a pre-existing long-standing ameloblastoma or a recurrence of an ameloblastoma. According to the literature search, six to seven cases have so far been documented, and the majority of the lesions had a propensity to metastasize. Here, we present a case of carcinoma ex ameloblastoma implicating a 19-year-old male patient manifesting in the mandible, which arises from pre-existing ameloblastoma.

Co-evolution of SARS-CoV-2 variants and host immune response trajectories underlie COVID-19 pandemic to epidemic transition.

COVID-19 pandemic saw emergence of multiple SAR-CoV-2 variants. Exacerbated risk of severe outcome and hospital admissions led us to comprehend differential host-immune kinetics associated with SARS-CoV-2 variants. Longitudinal investigation was conducted through different time periods of Pre-VOC and VOCs (Delta & Omicron) mapping host transcriptome features. Robust antiviral type-1 interferon response marked Omicron infection, which was largely missing during Pre-VOC and Delta waves. SARS-CoV-2-host protein-protein interactions and docking complexes highlighted N protein to interact with HNRNPA1 in Pre-VOC, demonstrating its functional role for enhanced viral replication. Omicron revealed enhanced binding efficiency of LARP1 to N protein, probably potentiating antiviral effects of LARP1. Differential expression of zinc finger protein genes, especially in Omicron, mechanistically support induction of strong IFN (Interferon) response, thereby strengthening early viral clearance. Study highlights eventual adaptation of host to immune activation patterns that interrupt virus evolution with enhanced immune-evasion mutations and counteraction mechanisms, delimiting the next phase of COVID-19 pandemic.

Comparative immunohistochemical analysis of WT-1, Syndecan and Snail in Ameloblastoma and odontogenic keratocyst: A retrospective study.

Background: The purpose of this experimental study was to evaluate and compare the degree of expression of Wilm's Tumor Gene-1 (WT-1), Syndecan (CD 138) and Snail in Ameloblastoma and odontogenic keratocyst (OKC) and to analyse their potential role in pathogenesis. Methods and Material: Immunohistochemical analysis was performed to evaluate WT-1, Syndecan and Snail expression in Ameloblastoma (n = 20) and OKC (n = 20). Topographical immunoexpression pattern of Ameloblast-like cells, Stellate Reticulum-like cells in Ameloblastoma and basal layer as well as suprabasal layer of cells of OKC were also compared. The results obtained were subjected to ANOVA test and Tukey HSD test through SPSS software 20.0 for Microsoft Windows. Results: WT-1 and Snail overexpression was seen in both Ameloblastoma and OKCs. Syndecan, responsible for maintaining normal cellular morphology, cell-cell adhesion and differentiation was significantly downregulated in both the lesions. The Ameloblasts-like cells and the basal cells showed significantly higher immunopositivity for WT-1 and Syndecan as compared to that of basal cells. An inverse relation was noted for Snail protein. The ANOVA test predicted a statistically significant difference of expression across the lesions with a P value <0.0001 for Syndecan and Snail. Conclusions: The under-expression of epithelial membrane protein Syndecan-1 and upregulation of EMT transcription factor Snail can promote local invasion and is indicative of poor prognosis of these lesions. The overexpression of WT-1 results in tumorigenesis, proliferation and localized aggressiveness of Ameloblastoma and intrabony growth of OKC. Further investigation on the biologic behaviour of OKC is still recommended to arrive at more specific conclusions regarding its nature.

The Study of Expression of Hypoxia-Inducible Factor-1 Alpha (HIF-1 Alpha) and Hypoxia-Inducible Factor-2 Alpha (HIF-2 Alpha) in Oral Squamous Cell Carcinoma: An Immunohistochemical Study.

CONTEXT: Oral cancer is the major cause of mortality and morbidity worldwide. There are many factors that influence the tumor microenvironment that promotes tumorigenesis. Hypoxia is one of the factors that affects the process of angiogenesis by inducing proangiogenic factors to maintain the blood supply which in turn enhances the aggressiveness of the tumor and prognosis of solid tumors such as oral squamous cell carcinoma. AIM AND OBJECTIVE: The aim of the study was to compare the expression of hypoxia-inducible factor 1α (HIF-1α) and hypoxia-inducible factor 2α (HIF-2α) in various histological grades of oral squamous cell carcinoma immunohistochemically. METHODOLOGY: Immunohistochemical evaluation of HIF-1α and HIF-2α was done in 90 samples of oral squamous cell carcinoma which were graded histologically into 30 samples each of well, moderately and poorly differentiated squamous cell carcinoma. Statistical evaluation: Statistical analysis was done to study the prognostic significance of the biomarkers. RESULTS: All the cases showed positivity for expression of HIF-1α and HIF-2α. The number of positive staining in both markers reduced as the tumor severity increased from well to poorly differentiated. The expression of MIL of HIF-2α was higher than HIF 1α and HIF 2α expression was mostly seen in cytoplasmic in well-differentiated and nuclear in both moderately and poorly differentiated OSCC suggestive that HIF-2α is a more specific marker to hypoxia. CONCLUSION: Hypoxia is an essential factor that triggers other angiogenic switch and inflammatory factors which facilitates the process of tumorigenesis. This is also important for predicting the treatment outcome and prognosis of the patients. HIF-2α is a more sensitive marker that appears to be correlated and could perhaps serve as a good surrogate marker of hypoxia.

Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma.

Cancer stem cells (CSCs) are a small sub-population of cells within a tumor mass proficient of tumor initiation and progression. Distinguishing features possessed by CSCs encompass self-renewal, regeneration and capacity to differentiate. These cells are attributed to the phenomenon of aggression, recurrence and metastasis in neoplasms. Due to their cancer initiating and contributing features, a proper understanding of these CSCs and its microenvironment would aid in better understanding of cancer and designing better targeted therapeutic strategies for improved clinical outcome, thus improving the prognosis. This article dispenses a narrative review of CSCs in the context of head and neck carcinoma under the sub headings of overview of cancer stem cells, methods of isolation of these cells, putative CSC markers of head and neck cancer, signaling pathways used by these cells and their therapeutic implications.

Recognition of Oral Pathology as a Subject among Dental Undergraduates: Addressing their Concerns.

Oral and Maxillofacial Pathology is a speciality department of dentistry which deals with identification of diseases affecting oral and maxillofacial regions and investigates the cause, processes and effect of these diseases. Books, internet, lectures have made great progress but there is still a gap between students' understanding and interest in the subject. The aim of this study was to evaluate and analyse the challenges faced by undergraduate students in understanding oral pathology theory & practical and modify the teaching process accordingly. A descriptive cross-sectional study of 300 BDS third year students was conducted in our college. The results stated that 83% of the participants attended classes, 90% found the topics covered to be useful, 97% reported that the classes were taken to provide an in depth view of the subject, 71% faced difficulties in understanding the topics in theory classes. 46% attended seminars, 68% viewed more than 4 slides on an average in one practical class, and 80% faced difficulties in identifying the slide. Our data concluded, that if certain measures will be taken so as to engage the students' interests, then this subject would prove to be a much better scope of learning for the budding dentists.

Awareness and Attitude of Dental Practitioners on Impact of Music Therapy on Patients Anxiety Level during Various Types of Dental Treatments.

Music therapy plays an important role in reducing the anxiety of patients during various procedures of dental treatments. Dental practitioners should also be aware of the employment of music therapy on patients before various dental treatments to reduce dental anxiety and the feasibility of its implementation in regular dental practice. A questionnaire study was conducted regarding the awareness and attitude of dental practitioners on the impact of music therapy on dental patients, to which 305 participants responded. A comparison was made between the Undergraduates, Postgraduates, Faculties, Interns, and Private practitioners. They were also asked about the drawbacks associated with music therapy. There was a level of agreement amongst participants regarding the awareness of music therapy. But there was a statistically significant difference (p = 0.011) noted across groups. The majority of the participants agreed that it could be incorporated into a regular dental practice as a stress management procedure.

Yoga Programme for Type 2 Diabetes Prevention (YOGA-DP): A Qualitative Study Exploring the Trial Team's Facilitators and Challenges in Conducting a Feasibility Trial in India.

BACKGROUND: In India, around 77 million people are at high risk of developing type 2 diabetes mellitus (T2DM). Yoga interventions can be effective in preventing T2DM. We conducted a feasibility randomized controlled trial (RCT) in India, and the intervention was the Yoga Programme for T2DM Prevention (YOGA-DP). This study aimed to identify and explore the facilitators and challenges in conducting the feasibility trial in India, and more specifically, to explore the perceptions and experiences of trial staff in relation to running the feasibility trial and Yoga instructors in relation to delivering the intervention. METHODS: An exploratory qualitative study was conducted at two trial sites in India (Yoga centers in New Delhi and Bengaluru). Semi-structured interviews were conducted with ten participants (six trial staff and four Yoga instructors) to explore their perceptions and experiences related to the study's aim. Data were analyzed using deductive as well as inductive logic and an interpretative phenomenological approach. RESULTS: Feasibility-trial-related facilitators were useful participant recruitment strategies and help and support received from the trial coordination center. Intervention-related facilitators were strengths of the intervention content, structure, and delivery (including materials) and competencies of Yoga instructors. Feasibility-trial-related challenges were lack of awareness about T2DM among potential participants, stigma and fear associated with T2DM among potential participants, difficulties in explaining the research and obtaining written informed consent from potential participants, expectations and demands of potential participants and control-group participants, gender and language issues in participant recruitment, other participant recruitment-related challenges, issues in participant follow-up, and issues in data collection and trial documentation. Intervention-related challenges were the limited interest of participants in Yoga, participants' time constraints on practicing Yoga, participants' health issues hindered Yoga practice, beginners' difficulties with practicing Yoga, participants' demotivation to practice Yoga at home, issues with the Yoga practice venue, confusion regarding the intervention structure, issues with intervention materials, and the incompetence of Yoga instructors. CONCLUSIONS: The perceptions and experiences of trial staff and Yoga instructors helped us to understand the facilitators and challenges in running a feasibility trial and delivering the intervention for T2DM prevention, respectively. These findings and their suggestions will be used when designing the definitive RCT for evaluating YOGA-DP's effectiveness, and may be helpful to researchers planning similar trials. TRIAL REGISTRATION NUMBER: India (CTRI) CTRI/2019/05/018893.

Time-resolved transcriptomic profile of oleaginous yeast Rhodotorula mucilaginosa during lipid and carotenoids accumulation on glycerol.

The study reports the exploration of the transcriptome landscape of the red oleaginous yeast Rhodotorula mucilaginosa IIPL32 coinciding with the fermentation kinetics of the yeast cultivated in a two-stage fermentation process to exploit the time-series approach to get the complete transcripts picture and reveal the persuasive genes for fatty acid and terpenoid synthesis. The finding displayed the molecular drivers with more than 2-fold upregulation in the nitrogen-limited stage than in the nitrogen-excess stage. The rate-limiting diphosphomevalonate decarboxylase, acetylCoA-citrate lyase, and acetyl-CoA C-acetyltransferase were significant in controlling the metabolic flux in the synthesis of reduced compounds, and acetoacetyl-CoA synthase, 3-ketoacyl-acyl carrier-protein reductase, and ß-subunit enoyl reductase catalyze the key starting steps of lipids or terpenoid synthesis. The last two catalyze essential reduction steps in fatty acid synthesis. These enzymes would be the prime targets for the metabolic engineering of the oleaginous yeast for enhanced fatty acids and terpenoid production.

Intertwined Dysregulation of Ribosomal Proteins and Immune Response Delineates SARS-CoV-2 Vaccination Breakthroughs.

Globally, COVID-19 vaccines have emerged as a boon, especially during the severe pandemic phases to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, saving millions of lives. However, mixed responses to vaccination with breakthrough challenges provided a rationale to explore the immune responses generated postvaccination, which plausibly alter the subsequent course of infection. In this regard, we comprehensively profiled the nasopharyngeal transcriptomic signature of double-dose-vaccinated individuals with breakthrough infections in comparison to unvaccinated infected persons. The vaccinated individuals demonstrated a gross downregulation of ribosomal proteins along with immune response genes and transcription/translational machinery that methodically modulated the entire innate immune landscape toward immune tolerance, a feature of innate immune memory. This coordinated response was orchestrated through 17 transcription factors captured as differentially expressed in the vaccination breakthroughs, including epigenetic modulators of CHD1 and LMNB1 and several immune response effectors, with ELF1 emerging as one of the important transcriptional regulators of the antiviral innate immune response. Deconvolution algorithm using bulk gene expression data revealed decreased T-cell populations with higher expression of memory B cells in the vaccination breakthroughs. Thus, vaccination might synergize the innate immune response with humoral and T-cell correlates of protection to more rapidly clear SARS-CoV-2 infections and reduce symptoms within a shorter span of time. An important feature invariably noted after secondary vaccination is downregulation of ribosomal proteins, which might plausibly be an important factor arising from epigenetic reprogramming leading to innate immune tolerance. IMPORTANCE The development of multiple vaccines against SARS-CoV-2 infection is an unprecedented milestone achieved globally. Immunization of the mass population is a rigorous process for getting the pandemic under control, yet continuous challenges are being faced, one of them being breakthrough infections. This is the first study wherein the vaccination breakthrough cases of COVD-19 relative to unvaccinated infected individuals have been explored. In the context of vaccination, how do innate and adaptive immune responses correspond to SARS-CoV-2 infection? How do these responses culminate in a milder observable phenotype with shorter hospital stay in vaccination breakthrough cases compared with the unvaccinated? We identified a subdued transcriptional landscape in vaccination breakthroughs with decreased expression of a large set of immune and ribosomal proteins genes. We propose a module of innate immune memory, i.e., immune tolerance, which plausibly helps to explain the observed mild phenotype and fast recovery in vaccination breakthroughs.

Yoga Programme for Type 2 Diabetes Prevention (YOGA-DP) Among High-Risk People in India: A Multicenter Feasibility Randomized Controlled Trial.

INTRODUCTION: Many Indians are at high risk of type 2 diabetes mellitus (T2DM). The blood glucose level can be improved through a healthy lifestyle (such as physical activity and a healthy diet). Yoga can help in T2DM prevention, being a culturally appropriate approach to improving lifestyle. We developed the Yoga Programme for T2DM Prevention (YOGA-DP), a 24-week structured lifestyle education and exercise (Yoga) program that included 27 group Yoga sessions and self-practice of Yoga at home. In this study, the feasibility of undertaking a definitive randomized controlled trial (RCT) was explored that will evaluate the intervention's effectiveness among high-risk individuals in India. METHODS: A multicenter, two-arm, parallel-group, feasibility RCT was conducted in India. The outcome assessors and data analysts were blinded. Adults with a fasting blood glucose level of 100-125 mg/dL (i.e., at high risk of T2DM) were eligible. Participants were randomized centrally using a computer-generated randomization schedule. In the intervention group, participants received YOGA-DP. In the control group, participants received enhanced standard care. RESULTS: In this feasibility trial, the recruitment of participants took 4 months (from May to September 2019). We screened 711 people and assessed 160 for eligibility. Sixty-five participants (33 in the intervention group and 32 in the control group) were randomized, and 57 (88%) participants were followed up for 6 months (32 in the intervention group and 25 in the control group). In the intervention group, the group Yoga sessions were continuously attended by 32 (97%) participants (median (interquartile range, IQR) number of sessions attended = 27 (3)). In the intervention group, Yoga was self-practiced at home by 30 (91%) participants (median (IQR) number of days per week and minutes per day self-practiced = 2 (2) and 35 (15), respectively). In the control group, one (3%) participant attended external Yoga sessions (on Pranayama) for 1 week during the feasibility trial period. There was no serious adverse event. CONCLUSIONS: The participant recruitment and follow-up and adherence to the intervention were promising in this feasibility study. In the control group, the potential contamination was low. Therefore, it should be feasible to undertake a definitive RCT in the future that will evaluate YOGA-DP's effectiveness among high-risk people in India. FEASIBILITY TRIAL REGISTRATION: Clinical Trials Registry-India (CTRI) CTRI/2019/05/018893; registered on May 1, 2019.

BA.1, BA.2 and BA.2.75 variants show comparable replication kinetics, reduced impact on epithelial barrier and elicit cross-neutralizing antibodies.

The Omicron variant of SARS-CoV-2 is capable of infecting unvaccinated, vaccinated and previously-infected individuals due to its ability to evade neutralization by antibodies. With multiple sub-lineages of Omicron emerging in the last 12 months, there is inadequate information on the quantitative antibody response generated upon natural infection with Omicron variant and whether these antibodies offer cross-protection against other sub-lineages of Omicron variant. In this study, we characterized the growth kinetics of Kappa, Delta and Omicron variants of SARS-CoV-2 in Calu-3 cells. Relatively higher amounts infectious virus titers, cytopathic effect and disruption of epithelial barrier functions was observed with Delta variant whereas infection with Omicron sub-lineages led to a more robust induction of interferon pathway, lower level of virus replication and mild effect on epithelial barrier. The replication kinetics of BA.1, BA.2 and BA.2.75 sub-lineages of the Omicron variant were comparable in cell culture and natural infection in a subset of individuals led to a significant increase in binding and neutralizing antibodies to the Delta variant and all the three sub-lineages of Omicron but the level of neutralizing antibodies were lowest against the BA.2.75 variant. Finally, we show that Cu2+, Zn2+ and Fe2+ salts inhibited in vitro RdRp activity but only Cu2+ and Fe2+ inhibited both the Delta and Omicron variants in cell culture. Thus, our results suggest that high levels of interferons induced upon infection with Omicron variant may counter virus replication and spread. Waning neutralizing antibody titers rendered subjects susceptible to infection by Omicron variants and natural Omicron infection elicits neutralizing antibodies that can cross-react with other sub-lineages of Omicron and other variants of concern.

The spectrum of neurological manifestations and genotype-phenotype correlation in Indian children with Gaucher disease.

Gaucher disease (GD), one of the most frequent autosomal recessive lysosomal storage disorders, occurs due to bi-allelic pathogenic variants in the GBA1. Worldwide, the c.1448T>C (L483P) homozygous pathogenic variant is reported to be associated with neurological GD phenotype. Clinical distinction between GD1 and GD3 may be challenging due to subtle neurological features. Objective methods to evaluate neurological signs and saccades may help in early diagnosis. This study was conducted to assess the neurological phenotype, and its severity using a modified severity scoring tool (mSST), and the genotype-phenotype correlation. A total of 45 children aged 2 years 6 months to 15 years with a confirmed enzymatic and molecular diagnosis of GD with or without therapy were recruited. mSST tool was used to assess the severity of the neurological phenotype. A digital eye movement tracker (View Point Tracker) was used to assess eye movements. Clinical and genetic findings were analyzed. Out of 45 patients, 39 (86.7%) had at least one neurological phenotype detected using the mSST tool, with impairment of cognitive function (68.8%, 31/45) being the commonest feature. Thirty-two of 45 (71%) were assessed for saccadic eye movements using the eye tracker. Of these, 62.5% (20/32) had absent saccades. Four children (8.9%, 4/32) without clinical oculomotor apraxia had absent saccades on the viewpoint eye tracker. Overall, 77.7% (35/45), had homozygosity for c.1448T>C in GBA1 of which 91.4% (32/35) had neurological manifestations. Other alleles associated with neurological phenotype included c.1603C>T(p.R535C), c.1184C>T (p.S395F), c.115+1G>A (g.4234G>A), c.260G>A (p.R87Q) and c.1352A>G (p.Y451C). To conclude, in India, the c.1448T>C pathogenic variant in GBA1 is the commonest  and is associated with neurological phenotype of GD. Therefore, every patient of GD should be assessed using the mSST scoring tool for an early pick up of neurological features. The routine use of a viewpoint eye tracker in children with GD would be useful for early recognition of saccadic abnormalities.

Unraveling the genetic evolution of SARS-CoV-2 Recombinants using mutational dynamics across the different lineages.

Introduction: Recombination serves as a common strategy employed by RNA viruses for their genetic evolution. Extensive genomic surveillance during the COVID-19 pandemic has reported SARS-CoV-2 Recombinant strains indicating recombination events during the viral evolution. This study introspects the phenomenon of genome recombination by tracing the footprint of prominent lineages of SARS-CoV-2 at different time points in the context of on-going evolution and emergence of Recombinants. Method: Whole genome sequencing was carried out for 2,516 SARS-CoV-2 (discovery cohort) and 1,126 (validation cohort) using nasopharyngeal samples collected between the time period of March 2020 to August 2022, as part of the genomic surveillance program. The sequences were classified according to the different lineages of SARS-CoV-2 prevailing in India at respective time points. Results: Mutational diversity and abundance evaluation across the 12 lineages identified 58 Recombinant sequences as harboring the least number of mutations (n = 111), with 14 low-frequency unique mutations with major chunk of mutations coming from the BA.2. The spontaneously/dynamically increasing and decreasing trends of mutations highlight the loss of mutations in the Recombinants that were associated with the SARS-CoV-2 replication efficiency, infectivity, and disease severity, rendering them functionally with low infectivity and pathogenicity. Linkage disequilibrium (LD) analysis revealed that mutations comprising the LD blocks of BA.1, BA.2, and Recombinants were found as minor alleles or as low-frequency alleles in the LD blocks from the previous SARS-CoV-2 variant samples, especially Pre-VOC. Moreover, a dissipation in the size of LD blocks as well as LD decay along with a high negative regression coefficient (R squared) value was demonstrated in the Omicron and BA.1 and BA.2 lineages, which corroborated with the breakpoint analysis. Conclusion: Together, the findings help to understand the evolution and emergence of Recombinants after the Omicron lineages, for sustenance and adaptability, to maintain the epidemic spread of SARS-CoV-2 in the host population already high in immunity levels.