Analysis of SARS-CoV-2 Recombinant Lineages XBC and XBC.1 in the Philippines and Evidence for Delta-Omicron Co-infection as a Potential Origin

We report the sequencing and analysis of 60 XBC and 114 XBC.1 SARS-CoV-2 lineages detected in the Philippines from August to September 2022, which are regarded as recombinant lineages of the BA.2 Omicron and B.1.617.2 Delta (21I Clade) variants. The sequences described here place the Philippines as the country with the earliest and highest number of XBC and XBC.1 cases within the included period. Majority of the detected cases were sampled from the adjacent Davao and Soccskargen regions in southern Philippines, but have also been observed at lower proportions in other regions of the country. Time-scaled phylogenetic analysis with global samples from GISAID reaffirms the supposed root of XBC-like cases from the Philippines. Furthermore, the apparent clustering of some foreign cases separate from those collected in the country suggests several occurrences of cross-border transmissions resulting in the spread of XBC-like lineages within and among those countries. The consensus mutation profile shows regions harboring mutations specific to either the Omicron BA.2 or Delta B.1.617.2 lineages, supporting the recombinant nature of XBC. Finally, alternative allele fraction pattern and intrahost mutation analysis revealed that a relatively early case of XBC collected in March 2022 is likely to be an active co-infection event. This suggests that co-infection of Omicron and Delta was already occurring in the Philippines early in 2022, facilitating the generation of recombinants that may have further evolved and gained additional mutations enabling its spread across certain local populations at a later time. Author summaryMore recently, various lineages of the SARS-CoV-2 virus, the causative agent COVID-19 pandemic, have been observed to form recombinant lineages, further expanding the ways by which the virus can evolve and adapt to human interventions. Therefore, a large part of biosurveillance efforts is dedicated to detecting and observing new lineages, including recombinants, for early and effective control. In this paper, we present an analysis of 174 XBC and XBC.1 cases detected in the Philippines between August and September of 2022 which contextualize these cases as some of the earliest reported cases of this hybrid lineage. We show that when compared to cases from other countries collected at a similar time, the earliest cases of the XBC lineage are from the Philippines. Additionally, when samples were reclassified following an update of Pangolin, a tool for assigning SARS-CoV-2 lineages to samples, we found two samples of interest reclassified as XBC pointing to a potential origin via co-infection events occurring as early as March of 2022.