Background SARS-CoV-2 has evolved rapidly, resulting in the emergence of lineages with a competitive advantage over one another. Co- infections with different SARS-CoV-2 lineages can give rise to recombinant lineages. To date, the XBB lineage is the most widespread recombinant lineage worldwide, with the recently named XBB.1.16 lineage causing a surge in the number of COVID-19 cases in India. Methodology The present study involved retrieval of SARS-CoV-2 genome sequences from India (between December 1, 2022 and April 8, 2023) through GISAID; sequences were curated, followed by lineage and phylogenetic analysis. Demographic and clinical data from Maharashtra, India were collected telephonically, recorded in Microsoft (R) Excel, and analyzed using IBM (R) SPSS statistics, version 29.0.0.0 (241). Results A total of 2,944 sequences were downloaded from the GISAID database, of which 2,856 were included in the study following data curation. The sequences from India were dominated by the XBB.1.16* lineage ( 36.17%) followed by XBB.2.3* (12.11%) and XBB.1.5* (10.36%). Of the 2,856 cases, 693 were from Maharashtra; 386 of these were included in the clinical study. The clinical features of COVID-19 cases with XBB.1.16* infection ( XBB.1.16* cases, 276 in number) showed that 92% of those had a symptomatic disease, with fever (67%), cough (42%), rhinorrhea ( 33.7%), body ache (14.5%) and fatigue (14.1%) being the most common symptoms. The presence of comorbidity was found in 17.7% of the XBB.1.16* cases. Among the XBB.1.16* cases, 91.7% were vaccinated with at least one dose of vaccine against COVID-19. While 74.3% of XBB.1.16* cases were home-isolated; 25.7% needed hospitalization/institutional quarantine, of these, 33.8% needed oxygen therapy. Out of 276 XBB.1.16* cases, seven (2.5%) cases succumbed to the disease. The majority of XBB.1.16* cases who died belonged to an elderly age group (60 years and above), had underlying comorbid condition/s, and needed supplemental oxygen therapy. The clinical features of COVID-19 cases infected with other co-circulating Omicron variants were similar to XBB.1.16* cases. Conclusion The study reveals that XBB.1.16* lineage has become the most predominant SARS-CoV-2 lineage in India. The study also shows that the clinical features and outcome of XBB.1.16* cases were similar to those of other co-circulating Omicron lineage infected cases in Maharashtra, India.
