AUTHOR=Moreira-Rosário André , Marques Cláudia , Pinheiro Hélder , Araújo João Ricardo , Ribeiro Pedro , Rocha Rita , Mota Inês , Pestana Diogo , Ribeiro Rita , Pereira Ana , de Sousa Maria José , Pereira-Leal José , de Sousa José , Morais Juliana , Teixeira Diana , Rocha Júlio César , Silvestre Marta , Príncipe Nuno , Gatta Nuno , Amado José , Santos Lurdes , Maltez Fernando , Boquinhas Ana , de Sousa Germano , Germano Nuno , Sarmento Gonçalo , Granja Cristina , Póvoa Pedro , Faria Ana , Calhau Conceição 

TITLE=Gut Microbiota Diversity and C-Reactive Protein Are Predictors of Disease Severity in COVID-19 Patients

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.705020

DOI=10.3389/fmicb.2021.705020

ISSN=1664-302X

ABSTRACT=Risk factors for COVID-19 disease severity are still poorly understood. Considering the pivotal role of gut microbiota on host immune and inflammatory functions, we investigated the association between changes in gut microbiota composition and the clinical severity of COVID-19. We conducted a multicenter cross-sectional study prospectively enrolling 115 COVID-19 patients categorized according to: 1) WHO Clinical Progression Scale - mild 19 (16.5%), moderate 37 (32.2%) or severe 59 (51.3%); and 2) location of recovery from COVID-19 - ambulatory 14 (household isolation; 12.2%), hospitalized in ward 40 (34.8%) or intensive care unit 61 (53.0%). Gut microbiota analysis was performed through 16S rRNA gene sequencing and data obtained was further related with clinical parameters of COVID-19 patients. Risk factors for COVID-19 severity were identified by univariate and multivariable logistic regression models.
In comparison with mild COVID-19 patients, the gut microbiota of moderate and severe patients has: a) lower Firmicutes/Bacteroidetes ratio, b) higher abundance of Proteobacteria; and c) lower abundance of beneficial butyrate-producing bacteria such as Roseburia and Lachnospira genera. Multivariable regression analysis showed that Shannon index diversity (odds ratio [OR] 2.85 [95% CI 1.09-7.41]; p=0.032) and C-Reactive Protein (OR 3.45 [95% CI 1.33-8.91]; p=0.011) were risk factors for COVID-19 severe disease (a score of 6 or higher in WHO clinical progression scale).
In conclusion, our results demonstrated that hospitalized moderate and severe COVID-19 patients have microbial signatures of gut dysbiosis and for the first time, the gut microbiota diversity is pointed out as a prognostic biomarker for COVID-19 disease severity.