The upper respiratory tract (URT) virome is crucial in respiratory health and response to pathogens. While common respiratory viruses are well-studied, the presence and potential impact of giant DNA viruses, such as Mimiviridae, in the human URT remain underexplored. This study employed a whole genome metagenomics approach to profile the URT virome of 48 SARS-CoV-2-positive patients from central India. Mimiviridae reads were detected in two elderly male patients with severe acute respiratory infection (SARI) or influenza-like illness (ILI), contributing to 24% and 44% of the total virome in their samples. The dominant species were Acanthamoeba polyphaga mimivirus and Moumouvirus. Although Mimiviridae are not traditionally associated with human respiratory infections, their presence in SARS-CoV-2 patients raises questions about their potential role in co-infections and disease severity, particularly in individuals with ongoing respiratory infections. These findings underscore the need to investigate further giant viruses' clinical significance, transmission, and pathogenicity in humans. Future research should focus on their epidemiology and the development of improved diagnostic tools to assess their contribution to human health.

The authors have declared no competing interest.

The authors are thankful to CSIR-NEERI for providing funds under project OLP-57 (March 2023 - April 2024 ) for conducting this study

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Institutional Ethics Committee for Research on Human Subjects (IEC) of CSIR-NEERI, Nagpur-20, India

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All data produced in the present study are available upon reasonable request to the authors