Oral and blood microbiota compositional changes relate to interferon and endothelial genes expression in COVID-19 patients

The role of oral and blood microbiota in COVID-19 and their relationship with interferon (IFN) pathways and endothelial cell genes remain unclear. We studied both oral and blood microbiota and the interplay among them with the transcript expression of multiple IFNs and endothelial genes in hospitalized COVID-19 patients. 16SrRNA gene sequencing was applied to the SARS-CoV-2-infected individuals' oral and blood microbiota and compared with healthy volunteers (HV). Transcript levels of IFNs and endothelial genes were evaluated in RT Real Time PCR assays. An increased alfa-diversity was observed in peripheral blood (p=2.63 10-14) and oral swabs (p=2.03 10-2) of SARS-CoV-2 infected patients as compared to HV. The same trend was observed for Shannon biodiversity index both in blood and oral samples (p=1.14 10-14 and p= 9.761 10-3, respectively). A separation of COVID-19 microbial community from those of HV was assessed with two different measures of beta-diversity both in blood (p=9.0 10-4) and oral (p=9.0 10-4) samples. Three clusters of bacterial species in the oral district were negatively correlated with mRNAs levels of almost all genes analyzed, mainly with IFNlambda1 and positively correlated with IFN-alfa, IFN-beta, IFNlambda-2, IFNlambda-3, MxA, ISG15, ISG56, and IFI27 transcript levels. By contrast, five different clusters of bacterial species at blood level were negatively correlated with IFN-alfa, IFN-beta, ISG56, IFN lambda-1 and IFNlambda-3 transcripts levels and positively correlated with IFI27, ISG15, MxA, IFNgamma, CDH5, ITGA2B, ITGAL, ITGB3, TMBS3, IFNAR1, IFNAR2, VCAN and ICA. This study evidenced a distinctive oral and blood microbiota in hospitalized COVID-19 patients, with a definite structural network in relation to IFNs and endothelial cells pathways which might help to identify specific bacterial consortia as disease biomarkers and or new therapeutic targets to improve management and treatment of COVID-19 and in order to diminish virus-induced inflammation.