Metatranscriptomic Analysis of Oropharyngeal Samples Reveals Common Respiratory Viruses and a Potential Interspecies Transmitted Picobirnavirus in the Wayuu Population, La Guajira, Colombia

Acute respiratory infections and other infectious diseases causing acute febrile syn-drome are major public health concerns in Colombia, particularly among vulnerable populations such as the Wayuu Indigenous community in La Guajira. To investigate their viral etiology, 55 oro/nasopharyngeal swabs and 58 serum samples were collected from febrile Wayuu individuals in Manaure. RT-qPCR screening identified Corona-virus, Enteroviruses, Adenovirus, and Influenza A/B in respiratory samples, while no arboviruses were detected in serum. Sixteen representative samples underwent meta-transcriptomic next-generation sequencing (mtNGS) using the CZ-ID platform. This analysis confirmed RT-qPCR findings and additionally revealed six viral contigs re-lated to Orthopicobirnavirus hominis. Sequencing coverage enabled the reconstruction of a consensus RdRp segment, which was phylogenetically compared with sequences from diverse hosts. The virus clustered within genogroup 1, alongside Colombian iso-lates linked to severe acute respiratory infection. The absence of strict host-specific clustering suggests possible interspecies transmission. These findings underscore the complementary roles of targeted and unbiased approaches: RT-qPCR detected com-mon respiratory viruses, whereas mtNGS uncovered a virus previously unreported in this community. Overall, mtNGS emerges as a powerful tool to support viral surveil-lance and provide baseline evidence in indigenous populations, emphasizing the need to decentralize advanced molecular diagnostics and strengthen public health capacity in Colombia.