The Intestinal and Oral Microbiomes Are Robust Predictors of Covid-19 Severity the Main Predictor of Covid-19-Related Fatality

Abstract

The reason for the striking differences in clinical outcomes of SARS-CoV-2 infected patients is still poorly understood. While most recover, a subset of people become critically ill and succumb to the disease. Thus, identification of biomarkers that can predict the clinical outcomes of COVID-19 disease is key to help prioritize patients needing urgent treatment. Given that an unbalanced gut microbiome is a reflection of poor health, we aim to identify indicator species that could predict COVID-19 disease clinical outcomes. Here, for the first time and with the largest COVID-19 patient cohort reported for microbiome studies, we demonstrated that the intestinal and oral microbiome make-up predicts respectively with 92% and 84% accuracy (Area Under the Curve or AUC) severe COVID-19 respiratory symptoms that lead to death. The accuracy of the microbiome prediction of COVID-19 severity was found to be far superior to that from training similar models using information from comorbidities often adopted to triage patients in the clinic (77% AUC). Additionally, by combining symptoms, comorbidities, and the intestinal microbiota the model reached the highest AUC at 96%. Remarkably the model training on the stool microbiome found enrichment of Enterococcus faecalis, a known pathobiont, as the top predictor of COVID-19 disease severity. Enterococcus faecalis is already easily cultivable in clinical laboratories, as such we urge the medical community to include this bacterium as a robust predictor of COVID-19 severity when assessing risk stratification of patients in the clinic.

Oral Microbiome Dysbiosis Is Associated With Symptoms Severity and Local Immune/Inflammatory Response in COVID-19 Patients: A Cross-Sectional Study

“…Despite such suggestions, the profile of the HOM is currently still not clarified, especially in the non-bacterial components, rendering it difficult to understand whether the HOM dysbiosis may be considered a risk factor for COVID-19 development ( Patel and Sampson, 2020 ). Two recent preprints reported on the bacterial profile of HOM in COVID-19 patients, suggesting relationships between some bacteria and SARS-CoV-2 infection ( Iebba et al, 2020 ; Ward et al, 2021 ). However, to date, no studies have completely addressed HOM profiling, including fungal and viral components.…”

“…Although there is potential interest in understanding these networks in SARS-CoV-2 infection, no information is yet available about the microbiome profile in COVID-19 patients, except for a two as yet unpublished reports describing the bacterial component of the oral microbiome by NGS ( Iebba et al, 2020 ; Ward et al, 2021 ). However, several reports have evidenced that the non-bacterial components of the microbiome can be very important in defining individual susceptibility to diseases besides bacteria (the mycome and virome), thus the use of Whole Genome Sequencing (WGS) technology may be more useful in elucidating the microbial environment potentially impacting on SARS-CoV-2 infecting ability.…”

Engineering Multigenerational Host-Modulated Microbiota against Soilborne Pathogens in Response to Global Climate Change

“…Finally, although the selection of “microbial hubs” or a “microbial keystone” through a natural selection of successive plant generations is a promising alternative, the application of advanced modeling techniques to detect key bacteria in humans, which are important for a particular trait such as disease resistance or disease detection, must be taken into consideration to be applied in the plant microbiome. In this sense, a mathematical model such as random forest classification (RFC) coupled with the local interpretable model–agnostic explanation (LIME) toolbox has been effectively applied to detect specific taxa from the intestinal and oral microbiome, which served as a predictor for human diseases [ 167 ]. In this same way, for more detailed information about mechanistic mathematical models of the gut microbiota, see the review of Bucci and Xavier [ 168 ].…”

The gut microbiome: a missing link in understanding the gastrointestinal manifestations of COVID-19?

“…Then immediately following infection, based on studies of RSV and influenza in mouse models, key gut microbes, such as B. fragilis, are capable of activating host antiviral immunity and determining the strength of the initial immune response. In later stages of disease, the loss of commensals such as F. prausnitzii and B. bifidum and enrichment for pathobionts such as E. faecalis may play a role in amplifying destructive inflammatory responses, as suggested by the recent findings fromWard et al 2021;Yeoh et al 2021. Finally, on a community level, the studies byZuo et al 2020b andGu et al 2020 indicate that gut dysbiosis is a common outcome following SARS-CoV-2 respiratory infection and possibly a risk factor for more severe disease.…”