Alghounaim, M. | bioRxiv Science

bioRxiv2024

Sputum production and salivary microbiome in COVID-19 patients reveals oral-lung axis

ObjectiveSARS-CoV-2 is a severe respiratory disease that primarily targets the lungs and was the leading cause of death worldwide during the pandemic. Investigating the intricate interplay between the oral microbiome and inflammatory cytokines during the acute phase of infection is crucial for understanding host immune responses. This study aimed to explore the relationship between the oral microbiome and cytokines in COVID-19 patients, specifically examining those with and without sputum production. MethodsSaliva and blood samples from 50 COVID-19 patients were subjected to 16S ribosomal RNA gene sequencing to analyze the oral microbiome. Additionally, 65 saliva and serum cytokines were assessed using Luminex multiplex analysis. The Mann-Whitney test compared cytokine levels between individuals with and without sputum production. ResultsOur study revealed significant differences in the membership (Jaccard dissimilarity: p=0.016) and abundance (PhILR dissimilarity: p=0.048; metagenomeSeq) of salivary microbial communities between COVID-19 patients with and without sputum production. Seven bacterial genera, including Prevotella, Streptococcus, Actinomyces, Atopobium, Filifactor, Leptotrichia, and Selenomonas, were present in statistically higher proportions of patients with sputum production (p<0.05, Fishers exact test). Eight bacterial genera, including Prevotella, Megasphaera, Stomatobaculum, Leptotrichia, Veillonella, Actinomyces, Atopobium, and Corynebacteria were significantly more abundant in the sputum-producing group, while Lachnoacaerobaculum was notably more prevalent in the non-sputum-producing group (p<0.05, ANCOM-BC).We observed a significant positive correlation between salivary IFN-gamma (Interferon-gamma) and Eotaxin2/CCL24 (chemokine ligand 24) with sputum production. Conversely, negative correlations were noted in serum MCP3/CCL7 (monocyte-chemotactic protein 3/Chemokine ligand 7), MIG/CXCL9 (Monokine induced by gamma/Chemokine ligand 9), IL1 beta (interleukin 1 beta), and SCF (stem cell factor) with sputum production (p<0.05, Mann-Whitney test). ConclusionSubstantial distinctions in salivary microbial communities were evident between COVID-19 patients with and without sputum production, emphasizing the notable impact of sputum production on the oral microbiome and cytokine levels during the acute phase of infection.

microbiology↗

bioRxiv2023

Host-Microbiome Associations in Saliva Predict COVID-19 Severity

Established evidence indicates that oral microbiota plays a crucial role in modulating host immune responses to viral infection. Following Severe Acute Respiratory Syndrome Coronavirus 2 - SARS-CoV-2 - there are coordinated microbiome and inflammatory responses within the mucosal and systemic compartments that are unknown. The specific roles that the oral microbiota and inflammatory cytokines play in the pathogenesis of COVID-19 are yet to be explored. We evaluated the relationships between the salivary microbiome and host parameters in different groups of COVID-19 severity based on their Oxygen requirement. Saliva and blood samples (n = 80) were collected from COVID-19 and from non-infected individuals. We characterized the oral microbiomes using 16S ribosomal RNA gene sequencing and evaluated saliva and serum cytokines using Luminex multiplex analysis. Alpha diversity of the salivary microbial community was negatively associated with COVID-19 severity. Integrated cytokine evaluations of saliva and serum showed that the oral host response was distinct from the systemic response. The hierarchical classification of COVID-19 status and respiratory severity using multiple modalities separately (i.e., microbiome, salivary cytokines, and systemic cytokines) and simultaneously (i.e., multi-modal perturbation analyses) revealed that the microbiome perturbation analysis was the most informative for predicting COVID-19 status and severity, followed by the multi-modal. Our findings suggest that oral microbiome and salivary cytokines may be predictive of COVID-19 status and severity, whereas atypical local mucosal immune suppression and systemic hyperinflammation provide new cues to understand the pathogenesis in immunologically naive populations. Significance StatementThe oral mucosa is one of the first sites encountered by bacterial and viral infections, including SARS-CoV-2. It consists of a primary barrier occupied by a commensal oral microbiome. The primary function of this barrier is to modulate immunity and provide protection against invading infection. The occupying commensal microbiome is an essential component that influences the immune systems function and homeostasis. The present study showed that the host oral immune response performs unique functions in response to SARS-CoV-2 when compared to systemic responses during the acute phase. We also demonstrated that there is a link between oral microbiome diversity and COVID-19 severity. Additionally, the salivary microbiome was predictive of not only disease status but also severity.

immunology↗