Metagenomic assessment of gut microbial communities and risk of severe COVID-19

Long H Nguyen; Daniel Okin; David A Drew; Vincent M Battista; Sirus J Jesudasen; Thomas M Kuntz; Amrisha Bhosle; Kelsey N Thompson; Trenton Reinicke; Chun-Han Lo; Jacqueline E Woo; Alexander Caraballo; Lorenzo Berra; Jacob Vieira; Ching-Ying Huang; Upasana Das Adhikari; Minsik Kim; Hui-Yu Sui; Marina Magicheva-Gupta; Lauren McIver; Marcia B Goldberg; Douglas S Kwon; Curtis Huttenhower; Andrew T Chan; Peggy S Lai

doi:10.1186/s13073-023-01202-6

Metagenomic assessment of gut microbial communities and risk of severe COVID-19

Genome Med. 2023 Jul 12;15(1):49. doi: 10.1186/s13073-023-01202-6.

Authors

Long H Nguyen^#^{1

2

3}, Daniel Okin^#⁴, David A Drew^#^{1

2}, Vincent M Battista^{1

2}, Sirus J Jesudasen⁵, Thomas M Kuntz³, Amrisha Bhosle^{3

6

7}, Kelsey N Thompson^{3

7}, Trenton Reinicke^{1

2}, Chun-Han Lo^{1

2}, Jacqueline E Woo^{1

2}, Alexander Caraballo^{1

2}, Lorenzo Berra⁸, Jacob Vieira⁴, Ching-Ying Huang⁴, Upasana Das Adhikari⁹, Minsik Kim⁴, Hui-Yu Sui⁴, Marina Magicheva-Gupta^{1

2}, Lauren McIver⁷, Marcia B Goldberg^{10

11

12}, Douglas S Kwon^{9

10}, Curtis Huttenhower^{3

6

7

11}, Andrew T Chan^#^{13

14

15

16}, Peggy S Lai^#^{17

18}

Affiliations

¹ Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
² Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
³ Harvard Chan Microbiome in Public Health Center, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁴ Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
⁵ Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
⁶ Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁷ Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
⁸ Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
⁹ Ragon Institute of MGH, Harvard, and MIT, Cambridge, MA, USA.
¹⁰ Division of Infectious Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
¹¹ Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹² Department of Microbiology, Harvard Medical School, Boston, MA, USA.
¹³ Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. achan@mgh.harvard.edu.
¹⁴ Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. achan@mgh.harvard.edu.
¹⁵ Harvard Chan Microbiome in Public Health Center, Harvard T.H. Chan School of Public Health, Boston, MA, USA. achan@mgh.harvard.edu.
¹⁶ Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA. achan@mgh.harvard.edu.
¹⁷ Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. plai@mgh.harvard.edu.
¹⁸ Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. plai@mgh.harvard.edu.

^# Contributed equally.

Abstract

Background: The gut microbiome is a critical modulator of host immunity and is linked to the immune response to respiratory viral infections. However, few studies have gone beyond describing broad compositional alterations in severe COVID-19, defined as acute respiratory or other organ failure.

Methods: We profiled 127 hospitalized patients with COVID-19 (n = 79 with severe COVID-19 and 48 with moderate) who collectively provided 241 stool samples from April 2020 to May 2021 to identify links between COVID-19 severity and gut microbial taxa, their biochemical pathways, and stool metabolites.

Results: Forty-eight species were associated with severe disease after accounting for antibiotic use, age, sex, and various comorbidities. These included significant in-hospital depletions of Fusicatenibacter saccharivorans and Roseburia hominis, each previously linked to post-acute COVID syndrome or "long COVID," suggesting these microbes may serve as early biomarkers for the eventual development of long COVID. A random forest classifier achieved excellent performance when tasked with classifying whether stool was obtained from patients with severe vs. moderate COVID-19, a finding that was externally validated in an independent cohort. Dedicated network analyses demonstrated fragile microbial ecology in severe disease, characterized by fracturing of clusters and reduced negative selection. We also observed shifts in predicted stool metabolite pools, implicating perturbed bile acid metabolism in severe disease.

Conclusions: Here, we show that the gut microbiome differentiates individuals with a more severe disease course after infection with COVID-19 and offer several tractable and biologically plausible mechanisms through which gut microbial communities may influence COVID-19 disease course. Further studies are needed to expand upon these observations to better leverage the gut microbiome as a potential biomarker for disease severity and as a target for therapeutic intervention.

Keywords: Machine learning; Microbiome; SARS-CoV-2.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

COVID-19*
Gastrointestinal Microbiome*
Humans
Metagenome
Microbiota*
Post-Acute COVID-19 Syndrome

Abstract

Publication types

MeSH terms

Grants and funding