Profiling of oral microbiota and cytokines in COVID-19 patients

Abstract

SARS-CoV-2 presence has been recently demonstrated in the sputum or saliva, suggesting how the shedding of viral RNA outlasts the end of symptoms. Recent data from transcriptome analysis show that oral cavity mucosa harbors high levels of ACE2 and TMPRSS2, highlighting its role as a double-edged sword for SARS-CoV-2 body entrance or interpersonal transmission. In the present study, for the first time, we demonstrate the oral microbiota structure and inflammatory profile of COVID-19 patients. Hospitalized COVID-19 patients and matched healthy controls underwent naso/oral-pharyngeal and oral swabs. Microbiota structure was analyzed by 16S rRNA V2 automated targeted sequencing, while oral and sera concentrations of 27 cytokines were assessed using magnetic bead-based multiplex immunoassays. A significant diminution in species richness was observed in COVID-19 patients, along with a marked difference in beta-diversity. Species such as Prevotella salivae and Veillonella infantium were distinctive for COVID-19 patients, while Neisseria perflava and Granulicatella elegans were predominant in controls. Interestingly, these two groups of oral species oppositely clustered within the bacterial network, defining two distinct Species Interacting Group (SIGs). Pro-inflammatory cytokines were distinctive for COVID-19 in both oral and serum samples, and we found a specific bacterial consortium able to counteract them, following a novel index called C4 firstly proposed here. We even introduced a new parameter, named CytoCOV, able to predict COVID-19 susceptibility for an unknown subject at 71% of power with an AUC equal to 0.995. This pilot study evidenced a distinctive oral microbiota composition in COVID-19 subjects, with a definite structural network in relation to secreted cytokines. Our results would pave the way for a theranostic approach in fighting COVID-19, trying to enlighten the intimate relationship among microbiota and SARS-CoV-2 infection.