Dynamic changes of Bacterial Microbiomes in Oropharynx during Infection and Recovery of COVID-19 Omicron Variant

Oropharyngeal microbiomes play a significant role in the susceptibility and severity of COVID-19, yet the role of these microbiomes play for the development of COVID-19 Omicron variant have not been reported. A total of 791 pharyngeal swab samples were prospectively included in this study, including 297 confirmed cases of Omicron variant (CCO), 222 confirmed case of Omicron who recovered (CCOR), 73 confirmed cases of original strain (CCOS) and 199 healthy controls (HC). All samples completed MiSeq sequencing. The results showed that compared with HC, conditional pathogens increased in CCO, while acid-producing bacteria decreased. Based on six optimal oropharyngeal operational taxonomy units (OTUs), we constructed a marker microbial classifier to distinguish between patients with Omicron variant and healthy people, and achieved high diagnostic efficiency in both the discovery queue and the verification queue. At same time, we introduced a group of cross-age infection verification cohort and Omicron variant subtype XBB.1.5 branch, which can be accurately distinguished by this diagnostic model. We also analyzed the characteristics of oropharyngeal microbiomes in two subgroups of Omicron disease group—severity of infection and vaccination times, and found that the change of oropharyngeal microbiomes may affect the severity of the disease and the efficacy of the vaccine. In addition, we found that some genera with significant differences gradually increased or decreased with the recovery of Omicron variant infection. The results of Spearman analysis showed that 27 oropharyngeal OTUs were closely related to 6 clinical indexes in CCO and HC. Finally, we found that the Omicron variant had different characterization of oropharyngeal microbiomes from the original strain. Our research characterizes oropharyngeal microbiomes of Omicron variant cases and rehabilitation cases, successfully constructed and verified the non-invasive diagnostic model of Omicron variant, described the correlation between microbial OTUs and clinical indexes. It was found that the infection of Omicron variant and the infection of original strain have different characteristics of oropharyngeal microbiomes.Author summary: COVID-19, caused by the SARS-CoV-2 virus, was first discovered in Wuhan, Hubei Province, China in December 2019, causing a huge impact around the world. In the past three years, novel coronavirus has successively appeared many varieties through gene mutation, among which Omicron strain is the most popular variety. Studies have shown that the imbalance of microflora is closely related to the progress of novel coronavirus infection and the severity of clinical symptoms. In the previous study, we build database of oral-intestinal microbial metagenomics, immunome and metabolome of novel coronavirus Original Strain with mild, medium and severe clinical symptoms and healthy subjects, reveal the role and mechanism of the oral and intestinal microbiome in Original Strain infection and exacerbation, and build the model of susceptibility, severe warning and prognosis of Original Strain pneumonia which based on the microbiome-immunity-metabolism. Our research characterizes oropharyngeal microbiomes of Omicron variant cases and rehabilitation cases, successfully constructed and verified the non-invasive diagnostic model of Omicron variant. We also analyzed the characteristics of oropharyngeal microbiomes in two subgroups of Omicron disease group—severity of infection and vaccination times, and found that the change of oropharyngeal microbiomes may affect the severity of the disease and the efficacy of the vaccine. And we described the correlation between microbial OTUs and clinical indexes. At last, it was found that the infection of Omicron variant and the infection of original strain have different characteristics of oropharyngeal microbiomes.