Robust cross-cohort gut microbiome associations with COVID-19 severity

ABSTRACT

Although many recent studies have examined associations between the gut microbiome and COVID-19 disease severity in individual patient cohorts, questions remain on the robustness across international cohorts of the biomarkers they reported. Here, we performed a meta-analysis of eight shotgun metagenomic studies of COVID-19 patients (comprising 1,023 stool samples) and 23 > 16S rRNA gene amplicon sequencing (16S) cohorts (2,415 total stool samples). We found that disease severity (as defined by the WHO clinical progression scale) was associated with taxonomic and functional microbiome differences. This alteration in gut microbiome configuration peaks at days 7–30 post diagnosis, after which the gut microbiome returns to a configuration that becomes more similar to that of healthy controls over time. Furthermore, we identified a core set of species that were consistently associated with disease severity across shotgun metagenomic and 16S cohorts, and whose abundance can accurately predict disease severity category of SARS-CoV-2 infected subjects, with Actinomyces oris abundance predicting population-level mortality rate of COVID-19. Additionally, we used relational diet-microbiome databases constructed from cohort studies to predict microbiota-targeted diet patterns that would modulate gut microbiota composition toward that of healthy controls. Finally, we demonstrated the association of disease severity with the composition of intestinal archaeal, fungal, viral, and parasitic communities. Collectively, this study has identified robust COVID-19 microbiome biomarkers, established accurate predictive models as a basis for clinical prognostic tests for disease severity, and proposed biomarker-targeted diets for managing COVID-19 infection.

KEYWORDS:

• COVID
• gut microbiome
• meta-analysis
• disease severity
• microbiota-targeted diet
• eukaryotic microorganisms

Acknowledgments

We thank Manasi Nadkarni for technical assistance.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Contributions

J.L., T.S.G., C.H., and P.W.O.T. contributed to the conceptual development of this study. J.L. curated the data and performed data analysis. J.L. and P.W.O.T. wrote the manuscript with editorial contributions from all authors. P.W.O.T. supervised the study. C.H. and P.W.O.T. conceived the study. D.S. provided data. L.J.F., C.S., and M.H. provided clinical coordination support. R.S. helped provide clinical data. All authors approved the final manuscript.

Data availability statement

The raw sequencing data are available from public sources as identified in Table S1.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2242615

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This study was supported by Science Foundation Ireland through the COVID-19 Rapid Response Funding scheme award to CH and PWOT for the Covidbiome project [20/COV/0125] and a Centre award to APC Microbiome Ireland [12/RC/2273].