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METAGENOMIC INTERROGATION OF RESPIRATORY AND GUT MICROBIAL COMMUNITIES, HOST IMMUNE RESPONSE, AND RISK OF SEVERE COVID-19
Gastroenterology ; 162(7):S-278-S-279, 2022.
Article in English | EMBASE | ID: covidwho-1967265
ABSTRACT

Background:

Human-associated microbial communities have been linked to host immune response to respiratory viral infections. Prior investigations have observed shifts in the composition of the gut or respiratory microbiome in severe COVID-19. However, there has been no comprehensive metagenomic evaluation of the interaction between lower respiratory and gut microbiomes and host immune factors in COVID-19.

Methods:

From April 2020 to May 2021, we prospectively enrolled 153 hospitalized patients with mild (n=12), moderate (n=65), and severe (n=76) COVID-19 infection categorized using established clinical criteria. We longitudinally collected stool (n=270) for metagenomic profiling, and in a subset, we generated comprehensive host-microbiome-molecular profiles by collecting sputum metagenomes (n=87 participants with 212 samples) and blood cytokine levels (n=109 with 181 samples) weekly until hospital discharge. We performed omnibus testing of overall gut and respiratory community structure, species-level differential abundance testing using mixed effects modeling accounting for repeated sampling, hierarchical clustering of paired gut and respiratory metagenomic profiles, and multi-omic machine learning classification of disease severity.

Results:

Patients with severe COVID-19 tended to be older, were more frequently male, had higher rates of overweight/obesity, and a greater mean Charlson Comorbidity Index. Patients with severe COVID-19 infection had significantly decreased stool and respiratory microbiome a-diversity irrespective of antibiotic administration. COVID severity accounted for a small proportion of variance in stool (R2=2.4%, p=0.002) and sputum (R2=4.4%, p= 0.03) profiles. Hierarchical clustering of paired gut and respiratory samples from patients with severe COVID revealed the joint expansion of oral-typical taxa typically present during systemic inflammation (i.e., increases in Streptococcus and Peptostreptococus spp. in both gut and sputum). A pro-inflammatory milieu defined by a composite elevation of circulating plasma cytokines (e.g., IL-6, TNF-a, and IL-29 among others) were linked to broad microbial excursions in community structure for both stool and sputum as measured by Bray-Curtis distances. A random forest classifier incorporating either stool or sputum taxonomic features and accounting for age, sex, body mass index, and recent antibiotic use achieved excellent classification of biospecimens from patients with severe vs. non-severe COVID patients (AUROC > 0.80).

Conclusions:

Alterations of the gut and respiratory microbiome were associated with differences in host immune response and COVID-19 disease severity. Further studies are needed to identify the potential role of human-associated microbial communities as a biomarker for poor patient outcomes in COVID-19 who may warrant escalated levels of care.(Figure Presented) Fig. 1. (A) Using unsupervised feature selection (species abundance > 0.001) inclusive of taxa differentially abundant by non-parametric Wilcoxon rank-sum testing (nominal p-value < 0.05), (B) we performed random forest classification using a twice-repeated 5-fold crossvalidation scheme to predict COVID-19 disease severity from shotgun metagenomic stool profiles (C) yielding an AUROC of 0.91.
Keywords

Full text: Available Collection: Databases of international organizations Database: EMBASE Type of study: Prognostic study Language: English Journal: Gastroenterology Year: 2022 Document Type: Article

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Full text: Available Collection: Databases of international organizations Database: EMBASE Type of study: Prognostic study Language: English Journal: Gastroenterology Year: 2022 Document Type: Article