ABSTRACT
The upper respiratory tract (URT) microbiome can contribute to the acquisition and severity of respiratory viral infections. The described associations between URT microbiota and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited at microbiota genus level and by the lack of functional interpretation. Our study, therefore, characterized the URT bacterial microbiome at species level and their encoded pathways in patients with COVID-19 and correlated these to clinical outcomes. Whole metagenome sequencing was performed on nasopharyngeal samples from hospitalized patients with critical COVID-19 (n = 37) and SARS-CoV-2-negative individuals (n = 20). Decreased bacterial diversity, a reduction in commensal bacteria, and high abundance of pathogenic bacteria were observed in patients compared to negative controls. Several bacterial species and metabolic pathways were associated with better respiratory status and lower inflammation. Strong correlations were found between species biomarkers and metabolic pathways associated with better clinical outcome, especially Moraxella lincolnii and pathways of vitamin K2 biosynthesis. Our study demonstrates correlations between the URT microbiome and COVID-19 patient outcomes; further studies are warranted to validate these findings and to explore the causal roles of the identified microbiome biomarkers in COVID-19 pathogenesis.
ABSTRACT
OBJECTIVES: Humoral and cellular immunity to SARS-CoV-2 following COVID-19 will likely contribute to protection from reinfection or severe disease. It is therefore important to characterise the initiation and persistence of adaptive immunity to SARS-CoV-2 amidst the ongoing pandemic. METHODS: Here, we conducted a longitudinal study on hospitalised moderate and severe COVID-19 patients from the acute phase of disease into convalescence at 5 and 9 months post-symptom onset. Utilising flow cytometry, serological assays as well as B cell and T cell FluoroSpot assays, we assessed the magnitude and specificity of humoral and cellular immune responses during and after human SARS-CoV-2 infection. RESULTS: During acute COVID-19, we observed an increase in germinal centre activity, a substantial expansion of antibody-secreting cells and the generation of SARS-CoV-2-neutralising antibodies. Despite gradually decreasing antibody levels, we show persistent, neutralising antibody titres as well as robust specific memory B cell responses and polyfunctional T cell responses at 5 and 9 months after symptom onset in both moderate and severe COVID-19 patients. CONCLUSION: Our findings describe the initiation and, importantly, persistence of cellular and humoral SARS-CoV-2-specific immunological memory in hospitalised COVID-19 patients long after recovery, likely contributing towards protection against reinfection.