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The ultraviolet (UV) radiation triggers a pigmentation response in human skin, wherein, melanocytes rapidly activate divergent maturation and proliferation programs. Using single-cell sequencing, we demonstrate that these 2 programs are segregated in distinct subpopulations in melanocytes of human and zebrafish skin. The coexistence of these 2 cell states in cultured melanocytes suggests possible cell autonomy. Luria-Delbrück fluctuation test reveals that the initial establishment of these states is stochastic. Tracking of pigmenting cells ascertains that the stochastically acquired state is faithfully propagated in the progeny. A systemic approach combining single-cell multi-omics (RNA+ATAC) coupled to enhancer mapping with H3K27 acetylation successfully identified state-specific transcriptional networks. This comprehensive analysis led to the construction of a gene regulatory network (GRN) that under the influence of noise, establishes a bistable system of pigmentation and proliferation at the population level. This GRN recapitulates melanocyte behaviour in response to external cues that reinforce either of the states. Our work highlights that inherent stochasticity within melanocytes establishes dedicated states, and the mature state is sustained by selective enhancers mark through histone acetylation. While the initial cue triggers a proliferation response, the continued signal activates and maintains the pigmenting subpopulation via epigenetic imprinting. Thereby our study provides the basis of coexistence of distinct populations which ensures effective pigmentation response while preserving the self-renewal capacity.
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Host-microbe interactions are complex and ever-changing, especially during infections, which can significantly impact human physiology in both health and disease by influencing metabolic and immune functions. Infections caused by pathogens such as bacteria, viruses, fungi, and parasites are the leading cause of global mortality. Microbes have evolved various immune evasion strategies to survive within their hosts, which presents a multifaceted challenge for detection. Intracellular microbes, in particular, target specific cell types for survival and replication and are influenced by factors such as functional roles, nutrient availability, immune evasion, and replication opportunities. Identifying intracellular microbes can be difficult because of the limitations of traditional culture-based methods. However, advancements in integrated host microbiome single-cell genomics and transcriptomics provide a promising basis for personalized treatment strategies. Understanding host-microbiota interactions at the cellular level may elucidate disease mechanisms and microbial pathogenesis, leading to targeted therapies. This article focuses on how intracellular microbes reside in specific cell types, modulating functions through persistence strategies to evade host immunity and prolong colonization. An improved understanding of the persistent intracellular microbe-induced differential disease outcomes can enhance diagnostics, therapeutics, and preventive measures.
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Genômica , Análise de Célula Única , Humanos , Genômica/métodos , Animais , Interações Hospedeiro-Patógeno/imunologia , Interações Hospedeiro-Patógeno/genética , Interações entre Hospedeiro e Microrganismos/imunologia , Interações entre Hospedeiro e Microrganismos/genética , Evasão da Resposta Imune , Microbiota/imunologia , Bactérias/genética , Bactérias/imunologia , Índice de Gravidade de DoençaRESUMO
Bacteria are the most prevalent form of microorganisms and are classified into two categories based on their mode of existence: intracellular and extracellular. While most bacteria are beneficial to human health, others are pathogenic and can cause mild to severe infections. These bacteria use various mechanisms to evade host immunity and cause diseases in humans. The susceptibility of a host to bacterial infection depends on the effectiveness of the immune system, overall health, and genetic factors. Malnutrition, chronic illnesses, and age-related vulnerabilities are the additional confounders to disease severity phenotypes. The impact of bacterial pathogens on public health includes the transmission of these pathogens from healthcare facilities, which contributes to increased morbidity and mortality. To identify the most significant threats to public health, it is crucial to understand the global burden of common bacterial pathogens and their pathogenicity. This knowledge is required to improve immunization rates, improve the effectiveness of vaccines, and consider the impact of antimicrobial resistance when assessing the situation. Many bacteria have developed antimicrobial resistance, which has significant implications for infectious diseases and favors the survival of resilient microorganisms. This review emphasizes the significance of understanding the bacterial pathogens that cause this health threat on a global scale.
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Post COVID-19, there has been renewed interest in understanding the pathogens challenging the human health and evaluate our preparedness towards dealing with health challenges in future. In this endeavour, it is not only the bacteria and the viruses, but a greater community of pathogens. Such pathogenic microorganisms, include protozoa, fungi and worms, which establish a distinct variety of disease-causing agents with the capability to impact the host's well-being as well as the equity of ecosystem. This review summarises the peculiar characteristics and pathogenic mechanisms utilized by these disease-causing organisms. It features their role in causing infection in the concerned host and emphasizes the need for further research. Understanding the layers of pathogenesis encompassing the concerned infectious microbes will help expand targeted inferences with relation to the cause of the infection. This would strengthen and augment benefit to the host's health along with the maintenance of ecosystem network, exhibiting host-pathogen interaction cycle. This would be key to discover the layers underlying differential disease severities in response to similar/same pathogen infection.
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Introduction: Microbial biofertilizers or biocontrol agents are potential sustainable approaches to overcome the limitations of conventional agricultural practice. However, the limited catalog of microbial candidates for diversified crops creates hurdles in successfully implementing sustainable agriculture for increasing global/local populations. The present study aimed to explore the wheat rhizosphere microbiota for microbial strains with a biofertilizer and biocontrol potential. Methods: Using a microbial culturing-based approach, 12 unique microbial isolates were identified and screened for biofertilizer/biocontrol potential using genomics and physiological experimentations. Results and discussion: Molecular, physiological, and phylogenetic characterization identified Stenotrophomonas maltophilia BCM as a potential microbial candidate for sustainable agriculture. Stenotrophomonas maltophilia BCM was identified as a coccus-shaped gram-negative microbe having optimal growth at 37°C in a partially alkaline environment (pH 8.0) with a proliferation time of ~67 minutes. The stress response physiology of Stenotrophomonas maltophilia BCM indicates its successful survival in dynamic environmental conditions. It significantly increased (P <0.05) the wheat seed germination percentage in the presence of phytopathogens and saline conditions. Genomic characterization decoded the presence of genes involved in plant growth promotion, nutrient assimilation, and antimicrobial activity. Experimental evidence also correlates with genomic insights to explain the potential of Stenotrophomonas maltophilia BCM as a potential biofertilizer and biocontrol agent. With these properties, Stenotrophomonas maltophilia BCM could sustainably promote wheat production to ensure food security for the increasing population, especially in native wheat-consuming areas.
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A plethora of studies have demonstrated the roles of lncRNAs in modulating disease severity and outcomes during infection. However, the spatio-temporal expression of these lncRNAs is poorly understood. In this study, we used single-cell RNA-seq to understand the spatio-temporal expression dynamics of lncRNAs across healthy, SARS-CoV-2-infected, and recovered individuals and their functional role in modulating the disease and recovery. We identified 203 differentially expressed lncRNAs, including cell type-specific ones like MALAT1, NEAT1, ZFAS1, SNHG7, SNHG8, and SNHG25 modulating immune function in classical monocyte, NK T, proliferating NK, plasmablast, naive, and activated B/T cells. Interestingly, we found invariant lncRNAs (no significant change in expression across conditions) regulating essential housekeeping functions (for example, HOTAIR, NRAV, SNHG27, SNHG28, and UCA1) in infected and recovered individuals. Despite similar repeat element abundance, variant lncRNAs displayed higher Alu content, suggesting increased interactions with proximal and distal genes, crucial for immune response modulation. The comparable repeat abundance but distinct expression levels of variant and invariant lncRNAs highlight the significance of investigating the regulatory mechanisms of invariant lncRNAs. Overall, this study offers new insights into the spatio-temporal expression patterns and functional roles of lncRNAs in SARS-CoV-2-infected and recovered individuals while highlighting the importance of invariant lncRNAs in the disease context.
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The elucidation of the role of microorganisms in human infections has been hindered by difficulties using conventional culture-based techniques. Here, we present a protocol for the investigation of transcriptionally active microbes (TAMs) using an RNA sequencing (RNA-seq)-based approach. We describe the steps for RNA isolation, viral genome sequencing, RNA-seq library preparation, and metatranscriptomic and transcriptomic analysis. This protocol permits a comprehensive evaluation of TAMs' contributions to the differential severity of infectious diseases, with a particular focus on diseases such as COVID-19. For complete details on the use and execution of this protocol, please refer to Devi et al.1.
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COVID-19 , RNA Viral , RNA-Seq , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/virologia , COVID-19/genética , RNA-Seq/métodos , RNA Viral/genética , Genoma Viral/genética , Análise de Sequência de RNA/métodos , Transcrição Gênica/genética , Perfilação da Expressão Gênica/métodos , Transcriptoma/genéticaRESUMO
Introduction: Single-cell multi-omics studies, such as multidimensional transcriptomics (whole transcriptomic analysis, WTA), and surface marker analysis (antibody sequencing, AbSeq), have turned out to be valuable techniques that offer inaccessible possibilities for single-cell profiling of mRNA, lncRNA, and proteins. Methods: We used this technique to understand the dynamics of mRNA and protein-level differences in healthy, COVID-19-infected and recovered individuals using peripheral blood mononuclear cells (PBMCs). Our results demonstrate that compared to mRNA expression, protein abundance is a better indicator of the disease state. Results: We demonstrate that compared to mRNA expression, protein abundance is a better indicator of the disease state. We observed high levels of cell identity and regulatory markers, CD3E, CD4, CD8A, CD5, CD7, GITR, and KLRB1 in healthy individuals, whereas markers related to cell activation, CD38, CD28, CD69, CD62L, CD14, and CD16 elevated in the SARS-CoV-2 infected patients at both WTA and AbSeq levels. Curiously, in recovered individuals, there was a high expression of cytokine and chemokine receptors (CCR5, CCR7, CCR4, CXCR3, and PTGRD2). We also observed variations in the expression of markers within cell populations under different states. Discussion: Furthermore, our study emphasizes the significance of employing an oligo-based method (AbSeq) that can help in diagnosis, prognosis, and protection from disease/s by identifying cell surface markers that are unique to different cell types or states. It also allows simultaneous study of a vast array of markers, surpassing the constraints of techniques like FACS to query the vast repertoire of proteins.
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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.
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India saw a spike in COVID-19 cases in early 2023, and this wave of infection was attributed to XBB sublineages of SARS-CoV-2 Omicron variant. The impact of XBB wave was significantly shorter with low burden of severe cases or hospitalization as compared with previous SARS-CoV-2 variants of concern. Although a combination of old and new mutations in the spike region of XBB.1.16 variant led to a drastic reduction in the ability of antibodies from prior immunity to neutralize this virus, additional nonspike mutations suggested a possible change in its ability to suppress innate immune responses. In this study, we tested the sensitivity of Delta, BA.2.75, and XBB.1.16 variants to interferon-ß (IFN-ß) treatment and found that XBB.1.16 variant was most sensitive to IFN-ß. We next tested the ability of serum antibodies from healthy individuals to neutralize XBB.1.16. We showed that most of the individuals with hybrid immunity maintained a low but significant level of neutralizing antibodies to XBB.1.16 variant. Therefore, our observations indicated that both hybrid immunity because of natural infection and enhanced sensitivity to IFNs may have contributed to the low impact of XBB.1.16 infections in India.
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Anticorpos Neutralizantes , COVID-19 , Interferon beta , SARS-CoV-2 , Replicação Viral , Humanos , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Interferon beta/imunologia , Interferon beta/genética , COVID-19/imunologia , COVID-19/virologia , Anticorpos Neutralizantes/imunologia , Mutação , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Índia , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Antivirais/farmacologia , Chlorocebus aethiops , Células VeroRESUMO
Wastewater-based epidemiology (WBE) has been used for monitoring infectious diseases like polio, hepatitis, etc. since the 1940s. It is also being used for tracking the SARS-CoV-2 at the population level. This article aims to compile and assess the information for the qualitative and quantitative detection of the SARS-CoV-2 in wastewater. Based on the globally published studies, we highlight the importance of monitoring SARS-CoV-2 presence/detection in the wastewater and concurrently emphasize the development of early surveillance techniques. SARS-CoV-2 RNA sheds in the human feces, saliva, sputum and mucus that ultimately reaches to the wastewater and brings viral RNA into it. For the detection of the virus in the wastewater, different detection techniques have been optimized and are in use. These are based on serological, biosensor, targeted PCR, and next generation sequencing for whole genome sequencing or targeted amplicon sequencing. The presence of the SARS-CoV-2 RNA in wastewater could be used as a potential tool for early detection and devising the strategies for eradication of the virus before it is spread in the community. Additionally, with the right and timely understanding of viral behavior in the environment, an accurate and instructive model that leverages WBE-derived data may be created. This might help with the creation of technological tools and doable plans of action to lessen the negative effects of current viral epidemics or future potential outbreaks on public health and the economy. Further work toward whether presence of viral load correlates with its ability to induce infection, still needs evidence. The current increasing incidences of JN.1 variant is a case in point for continued early detection and surveillance, including wastewater.
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Understanding the dynamic changes in gene expression during Acute Respiratory Distress Syndrome (ARDS) progression in post-acute infection patients is crucial for unraveling the underlying mechanisms. Study investigates the longitudinal changes in gene/transcript expression patterns in hospital-admitted severe COVID-19 patients with ARDS post-acute SARS-CoV-2 infection. Blood samples were collected at three time points and patients were stratified into severe and mild ARDS, based on their oxygenation saturation (SpO2/FiO2) kinetics over 7 d. Decline in transcript diversity was observed over time, particularly in patients with higher severity, indicating dysregulated transcriptional landscape. Comparing gene/transcript-level analyses highlighted a rather limited overlap. With disease progression, a transition towards an inflammatory state was evident. Strong association was found between antibody response and disease severity, characterized by decreased antibody response and activated B cell population in severe cases. Bayesian network analysis identified various factors associated with disease progression and severity, viz. humoral response, TLR signaling, inflammatory response, interferon response, and effector T cell abundance. The findings highlight dynamic gene/transcript expression changes during ARDS progression, impact on tissue oxygenation and elucidate disease pathogenesis.
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COVID-19 , Síndrome do Desconforto Respiratório , Humanos , COVID-19/genética , Estudos Longitudinais , Teorema de Bayes , SARS-CoV-2 , Síndrome do Desconforto Respiratório/genética , Imunidade , Unidades de Terapia Intensiva , Progressão da DoençaRESUMO
Dengue fever, a neglected tropical arboviral disease, has emerged as a global health concern in the past decade. Necessitating a nuanced comprehension of the intricate dynamics of host-virus interactions influencing disease severity, we analysed transcriptomic patterns using bulk RNA-seq from 112 age- and gender-matched NS1 antigen-confirmed hospital-admitted dengue patients with varying severity. Severe cases exhibited reduced platelet count, increased lymphocytosis, and neutropenia, indicating a dysregulated immune response. Using bulk RNA-seq, our analysis revealed a minimal overlap between the differentially expressed gene and transcript isoform, with a distinct expression pattern across the disease severity. Severe patients showed enrichment in retained intron and nonsense-mediated decay transcript biotypes, suggesting altered splicing efficiency. Furthermore, an up-regulated programmed cell death, a haemolytic response, and an impaired interferon and antiviral response at the transcript level were observed. We also identified the potential involvement of the RBM39 gene among others in the innate immune response during dengue viral pathogenesis, warranting further investigation. These findings provide valuable insights into potential therapeutic targets, underscoring the importance of exploring transcriptomic landscapes between different disease sub-phenotypes in infectious diseases.
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Processamento Alternativo , Vírus da Dengue , Dengue Grave , Humanos , Processamento Alternativo/genética , Feminino , Masculino , Vírus da Dengue/genética , Adulto , Dengue Grave/genética , Dengue Grave/imunologia , Dengue Grave/virologia , Pessoa de Meia-Idade , Transcriptoma/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Perfilação da Expressão Gênica/métodos , Imunidade Inata/genética , Dengue/genética , Dengue/imunologia , Dengue/virologia , Adulto Jovem , Índice de Gravidade de Doença , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologiaRESUMO
Two of the deadliest infectious diseases, COVID-19 and tuberculosis (TB), have combined to establish a worldwide pandemic, wreaking havoc on economies and claiming countless lives. The optimised, multitargeted medications may diminish resistance and counter them together. Based on computational expression studies, 183 genes were co-expressed in COVID-19 and TB blood samples. We used the multisampling screening algorithms on the top ten co-expressed genes (CD40, SHP2, Lysozyme, GATA3, cCBL, SIVmac239 Nef, CD69, S-adenosylhomocysteinase, Chemokine Receptor-7, and Membrane Protein). Imidurea is a multitargeted inhibitor for COVID-19 and TB, as confirmed by extensive screening and post-filtering utilising MM\GBSA algorithms. Imidurea has shown docking and MM\GBSA scores of -8.21 to -4.75 Kcal/mol and -64.16 to -29.38 Kcal/mol, respectively. The DFT, pharmacokinetics, and interaction patterns suggest that Imidurea may be a drug candidate, and all ten complexes were tested for stability and bond strength using 100 ns for all MD atoms. The modelling findings showed the complex's repurposing potential, with a cumulative deviation and fluctuation of <2 Å and significant intermolecular interaction, which validated the possibilities. Finally, an inhibition test was performed to confirm our in-silico findings on SARS-CoV-2 Delta variant infection, which was suppressed by adding imidurea to Vero E6 cells after infection.
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Tratamento Farmacológico da COVID-19 , COVID-19 , Simulação de Acoplamento Molecular , Mycobacterium tuberculosis , SARS-CoV-2 , SARS-CoV-2/efeitos dos fármacos , Humanos , COVID-19/virologia , Mycobacterium tuberculosis/enzimologia , Mycobacterium tuberculosis/efeitos dos fármacos , Simulação de Dinâmica Molecular , Muramidase/química , Muramidase/metabolismo , Antivirais/farmacologia , Antivirais/química , Ureia/farmacologia , Ureia/química , Antígenos de Diferenciação de Linfócitos T/metabolismoRESUMO
Rubinstein Taybi Syndrome (RSTS) is a rare genetic disorder which is caused by mutations in either CREBBP or EP300. RSTS with mutations in CREBBP is known as RSTS-1. We have generated an induced pluripotent stem cell (iPSC) line, IGIBi018-A from an Indian RSTS-patient using the episomal reprogramming method. The CREBBP gene in the patient harbours a nonsense mutation at position NM_004380.3(c.6876 del C). IGIBi018-A iPSC showed expression of pluripotent stem cell markers, has a normal karyotype and could be differentiated into three germ layers. This iPSC line will help to explore the role of CREBBP in RSTS associated developmental defects.
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Células-Tronco Pluripotentes Induzidas , Síndrome de Rubinstein-Taybi , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Síndrome de Rubinstein-Taybi/genética , Síndrome de Rubinstein-Taybi/metabolismo , Síndrome de Rubinstein-Taybi/patologia , Linhagem Celular , Diferenciação Celular , Índia , Masculino , Proteína de Ligação a CREB/genética , Proteína de Ligação a CREB/metabolismoRESUMO
The "Investigating and translating genomic evidence for public health response to SARS-CoV-2 (INSIDE SARS-CoV-2)" project is part of the initiative "Joint science and technology cooperation call for joint project proposals for the years 2021-2023" promoted by the Italian Ministry of Foreign Affairs and International Cooperation (MAECI) and the Republic of India. To start the project activities, the pandemic response and the epidemiological situation in Italy and in India, together with the genomic surveillance strategies for SARS-CoV-2 virus in the two countries, are here described.
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COVID-19 , Genômica , Saúde Pública , SARS-CoV-2 , COVID-19/epidemiologia , Humanos , Itália/epidemiologia , SARS-CoV-2/genética , Índia/epidemiologia , Pandemias , Cooperação Internacional , Genoma ViralRESUMO
BACKGROUND: It is important to identify the severity of acute pancreatitis in the early course of the disease. METHODS: This prospective observational study included 83 patients with acute pancreatitis. The Acute Physiology and Chronic Health Evaluation II and the Bedside Index for Severity in Acute Pancreatitis scores were assessed within 24 hours of admission, and the modified computed tomography severity index score was calculated in those patients who underwent contrast enhanced computed tomography. The sensitivity, specificity, positive predictive value, and negative predictive value of scoring systems were calculated. The area under the curve was calculated for assessing the prognostic value of scoring systems. RESULTS: The modified computed tomography severity index was the most accurate score in predicting severity and local complications with an area under the curve of 0.92 and 0.91, respectively. The Bedside Index for Severity in Acute Pancreatitis score was the most accurate in predicting organ failure and the need for intensive care unit admission with an area under the curve of 0.70 and 0.78 respectively. CONCLUSIONS: The results of this study demonstrate that modified computed tomography severity index and Bedside Index for Severity in Acute Pancreatitis scores had overall better predictive value than the Acute Physiology and Chronic Health Evaluation II score in predicting severity, organ failure, local complication, and need for intensive care unit admission.
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Pancreatite , Humanos , APACHE , Nepal , Centros de Atenção Terciária , Doença Aguda , Pancreatite/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
Introduction: Dengue virus (DENV) is a flavivirus that has emerged as a global health threat, characterized by either asymptomatic or mild self-limiting febrile illness, but a subset of DENV outbreaks have been associated with severe disease. Studies have looked into the host immune response and dengue viral load during infection. However, it remains unknown how the active microbial isolates modulate the dengue viral infection. In this study, we demonstrate the significance of in-depth analysis of microbiota composition in the serum samples of dengue-infected patients. Materials and methods: RNA was extracted from the serum samples collected from 24 dengue positive patients. The human mapped reads generated through RNA-Sequencing (RNA-Seq) were removed, while the unmapped (non-human) reads were employed for microbial taxonomic classification using Kraken2 and Bracken2. Further, we assessed the initial blood parameters analyzing the complete blood count (CBC) profile of the patients. Results: Findings revealed differential abundance of commensals and pathogenic microbes in the early febrile period of hospitalized dengue patients, segregated into, High Viral Reads (HVR) and Low Viral Reads (LVR). The Campylobacter genus was abundant in the HVR whereas Lactobacillus dominated the LVR patients. At species level, the microbiota of HVR exhibited higher abundance of unique potential opportunistic microbes, compared to the commensal microbes' enrichment in the LVR patients'. We hypothesize that the DENV might alter the microbiota composition as observed by the increase in preponderance of opportunistic pathogens and an absence of commensals in the HVR. The presence of commensals in the LVR might explain, i) overall lower dengue viral reads compared to the HVR, and ii) shift in lymphocytes (high) and neutrophils (low) counts; resulting in a comparatively milder clinical manifestation in this group. Our findings may help in understanding the co-infection aspect that will be important to develop dengue therapeutics and vaccines. Discussion: This study highlights the potential of the unexplored roles of the TAMs in modulating the dengue disease severity using the metatranscriptomic sequencing. This study serves to enhance our understanding of the distinctive microbial and hematologic signatures in the early infection stage that differentiate patients with high viral reads patients from those with low dengue viral reads.
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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.