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Introduction: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a positive-sense enveloped single-stranded Ribonucleic Acid (RNA) virus. Structural proteins help the virus package its RNA, while other proteins enable viral replication by facilitating host entry. Through constant mutation, the virus changes its emergence profile, and combinations of mutations can lead to increased transmissibility and receptor binding capacity, altering its surface structure. Whole genome sequencing is an important tool for studying these changes. In this study, the authors report on the genome sequencing of patients who tested positive for SARS-CoV-2 using real-time Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) tests. Aim: To identify the different lineages circulating in specific districts of West Bengal, India, and perform an epidemiological analysis of the patients to control disease severity during the second wave of Coronavirus Disease-2019 (COVID-19). Materials and Methods: This retrospective hospital-based study was conducted at the Virus Research and Diagnostic Laboratory (VRDL) at RG Kar Medical College and Hospital, West Bengal, India from January 2021 to October 2021. Data collection started in January 2021 and was analysed in October 2021. Nasopharyngeal and oropharyngeal swabs were taken from patients with SARS-CoV-2, and the samples were tested using RT-PCR. Positive samples were sent to the Regional Virus Research and Diagnostic Laboratory-National Institute of Cholera and Enteric Diseases (NICED) for sequencing. Samples were collected from patients in different districts of West Bengal who were reported to the VRDL of RG Kar Medical College and Hospital. A total of 172,550 samples were tested for SARSCoV-2, and out of 13,764 positive samples, 230 were sent for genome sequencing. The primary inclusion criteria were SARSCoV-2 positive patients with CT values between 25 and 30 who were vaccinated. Patient information, address, gene variant, and gene mutation of the samples were analysed. Statistical analysis was performed using t-test with Statistical Package for Social Sciences (SPSS) software. Results: Whole-genome sequencing helped identify new trends and their prevalence in specific areas, aiding in prevention efforts. The most common type of mutation observed after double vaccination was the delta variant (B.1.617.2), followed by the kappa variant (B.1.617.1) and the alpha variant (B.1.1.7). Conclusion: Epidemiological genome sequencing studies help to identify emerging and changing viral trends, contributing to the mitigation of the spread of new variants. The delta, kappa, and alpha variants were the three primary sequences discovered in this study. The identification of these lineages facilitates the design of novel vaccines and diagnostic medications. Continuous monitoring and analysis of sequences from new cases in India and other affected countries are crucial for understanding the genetic evolution and substitution rates of SARS-CoV-2. [ABSTRACT FROM AUTHOR]