Oral microbiome and local immune/inflammatory response in Covid-19 patients: a cross-sectional study

Background: The new human coronavirus SARS-CoV-2, responsible for the development of COVID-19 disease, has become a global pandemic emergency. Like other respiratory viruses, the primary site of the entrance is represented by the oropharynx, and the local microbiome environment may influence its capability to infect and induce the disease. The aim of the present study was therefore to characterize the oral microbiome in a cohort of COVID-19 patients with different symptom levels, to evidence the eventual association between virus-induced disease and the microbial environment of the oral cavity. Moreover, the inflammation and local immune response were also assessed in parallel. Methods: Overall, 75 oral rinse samples were collected from 39 COVID-19 subjects and 36 controls recruited in the study. Each specimen was reassessed by digital droplet PCR to measure the load of SARS-CoV-2 at the time of withdrawal. The profile of the oral microbiome was analyzed by Whole Genome Sequencing (WGS), allowing to evidence also the non-bacterial components (mycome and virome) of the oral microbiome. In parallel, the local immune response (secretory IgA) and inflammatory cytokine release (IL-6, IL-17, TNFα, and GM-CSF) were assessed by specific ELISA assays. Results: WGS results showed significant alterations in the oral microbiome of COVID-19 patients compared with matched controls. In particular, alpha-diversity was significantly different in COVID-19 patients and controls, and lower richness was associated with symptom severity. Notably, several genera associated with poor oral hygiene and periodontitis were more abundant in COVID-19 subjects (Prevotella, Capnocytophaga, Porphyromonas, Abiotrophia, Aggregatibacter). Enterococcus and Enterobacter spp. were exclusively detectable in COVID-19 patients. Increased amounts of Candida and Saccharomyces, and Aspergillus, Nakaseomyces, and Malassezia were detected, as well as increased herpesviruses (EBV, HSV-1). Notably, oral dysbiosis was associated with the increased local concentration of inflammatory cytokines and decreased mucosal secretory IgA response. Conclusions: The oral microbiome may be important in defining the individual susceptibility to SARS-CoV-2 infection and the subsequent development of symptomatic COVID-19. In particular, poor oral hygiene might facilitate inflammation and a worse course of COVID-19 disease. Instead, sIgA presence associated with mild symptoms should be considered as an important marker in monitoring therapy and vaccine development.