Gut microbiota diversity and C-Reactive Protein are predictors of disease severity in COVID-19 patients

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 multicentre 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 hospitalised 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.

Metagenomic analysis reveals the abundance and diversity of opportunistic fungal pathogens in the nasopharyngeal tract of COVID-19 patients

“…One of the most striking findings of the current study was the significant differences in microbiome diversity between COVID-19 patients and Healthy controls nasal cavity keeping the closest relationship of fungal population in COVID-19 patients with Recovered humans. The COVID-19 patients NT fungal microbiomes exhibited a statistically significant higher diversity (both within and between sample diversities) than those of Recovered humans and Healthy controls (Fig 1 and 2), which supports our hypothesis of dysbiosis and also agree with several recent reports [8, 36]. In contrast, most of the previous studies reported that SARS-CoV-2 infection reduces the bacterial diversity in COVID-19 patients respiratory tract and gut compared to their healthy counterpart [7, 37].…”

Gut Microbiome Dynamics and Predictive Value in Hospitalized COVID-19 Patients: A Comparative Analysis of Shallow and Deep Shotgun Sequencing

“…Since the beginning of the pandemic researchers have carried out sequencing experiments of fecal samples of patients with COVID-19 to uncover a bilateral relationship between COVID-19 and the gut microbiome. According to both alpha and beta diversity indices, SARS-CoV-2 infection was linked to changes in the microbiome community in patients as demonstrated in multiple studies (Kim et al, 2021;Moreira-Rosário et al, 2021;Newsome et al, 2021;Wu et al, 2021;Zhang et al, 2022). Moreover, the Shannon diversity was identified as a risk variable for severe COVID-19 being higher in mild COVID-19 individuals compared to moderate and severe cases.…”

“…(Moreira-Rosário et al, 2021). Patients hospitalized for COVID-19 have significant changes in stool microbiota composition characterized by an increase in opportunistic pathogens and a decrease in beneficial commensal bacteria compared to controls (Zuo et al, 2020, Moreira-Rosário et al, 2021, Yeoh et al, 2021Zhang et al, 2022).…”

“…Gut microbiome investigations among patients with COVID-19 to date characterized the makeup and diversity of the microbiota through one of two sequencing strategies. Either by targeted amplicon sequencing of a 16S rRNA marker gene (Gu et al, 2020;Tao et al, 2020;Kim et al, 2021;Moreira-Rosário et al, 2021;Newsome et al, 2021;Ward et al, 2021;Wu et al, 2021) or by using deep whole metagenomic (shotgun) strategy (Zuo et al, 2020;Yeoh et al, 2021;Sun et al, 2022). While both strategies are widely used in research, they have limitations in clinical applications of the microbiome as a diagnostic, prognostic, and therapeutic factor in patients with COVID-19.…”

“…Moreover, the Shannon diversity was identified as a risk variable for severe COVID-19 being higher in mild COVID-19 individuals compared to moderate and severe cases. (Moreira-Rosário et al, 2021). Patients hospitalized for COVID-19 have significant changes in stool microbiota composition characterized by an increase in opportunistic pathogens and a decrease in beneficial commensal bacteria compared to controls (Zuo et al, 2020, Moreira-Rosário et al, 2021, Yeoh et al, 2021Zhang et al, 2022).…”