Diversity, composition, and networking of saliva microbiota distinguish the severity of COVID-19 episodes as revealed by an analysis of 16S rRNA variable V1-V3 region sequences

SARS-CoV-2 infection is the most severe pandemic of humankind in the last hundred years. The outcome of the infection ranges from asymptomatic or mild to severe and even fatal cases, but reasons for this remain unknown. Microbes normally colonizing the respiratory tract form communities that may mitigate the transmission, symptoms, and severity of viral infections, but very little is known on the role of these microbial communities in the severity of COVID-19. We aimed to characterize the bacterial communities in saliva of patients with different severity of COVID-19 disease, from mild to fatal cases. Our results revealed clear differences in the composition and in the nature of interactions (networking) of the bacterial species present in the different clinical groups and show community-patterns associated with disease severity. Characterization of the microbial communities in saliva may offer important clues to learn ways COVID-19 patients may suffer from different disease severities. Studies on the role of the oral microbiome in SARS-CoV-2 infection and severity of the disease are limited. We aimed to characterize the bacterial communities present in the saliva of patients with varied COVID-19 severity to learn if there are differences in the characteristics of the microbiome among the clinical groups. We included 31 asymptomatic subjects with no previous COVID-19 infection or vaccination; 176 patients with mild respiratory symptoms, positive or negative for SARS-CoV-2 infection; 57 patients that required hospitalization because of severe COVID-19 with oxygen saturation below 92%, and 18 fatal cases of COVID-19. Saliva samples collected before any treatment were tested for SARS-CoV-2 by PCR. Oral microbiota in saliva was studied by amplification and sequencing of the V1-V3 variable regions of 16S gene using an Illumina MiSeq platform. We found significant changes in diversity, composition, and networking in saliva microbiota of patients with COVID-19, as well as patterns associated with severity of disease. The presence or abundance of several commensal species and opportunistic pathogens were associated with each clinical stage. Patterns of networking were also found associated with severity of disease: a highly regulated bacterial community (normonetting) was found in healthy people whereas poorly regulated populations (disnetting) were characteristic of severe cases. Characterization of microbiota in saliva may offer important clues in the pathogenesis of COVID-19 and may also identify potential markers for prognosis in the severity of the disease. IMPORTANCESARS-CoV-2 infection is the most severe pandemic of humankind in the last hundred years. The outcome of the infection ranges from asymptomatic or mild to severe and even fatal cases, but reasons for this remain unknown. Microbes normally colonizing the respiratory tract form communities that may mitigate the transmission, symptoms, and severity of viral infections, but very little is known on the role of these microbial communities in the severity of COVID-19. We aimed to characterize the bacterial communities in saliva of patients with different severity of COVID-19 disease, from mild to fatal cases. Our results revealed clear differences in the composition and in the nature of interactions (networking) of the bacterial species present in the different clinical groups and show community-patterns associated with disease severity. Characterization of the microbial communities in saliva may offer important clues to learn ways COVID-19 patients may suffer from different disease severities.