Characterization of the Upper Respiratory Bacterial Microbiome in Critically Ill COVID-19 Patients

Abstract

The upper respiratory tract (URT) microbiome can contribute to the acquisition and severity of respiratory viral infections. The described associations between URT microbiota and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited at microbiota genus level and by the lack of functional interpretation. Our study, therefore, characterized the URT bacterial microbiome at species level and their encoded pathways in patients with COVID-19 and correlated these to clinical outcomes. Whole metagenome sequencing was performed on nasopharyngeal samples from hospitalized patients with critical COVID-19 (n = 37) and SARS-CoV-2-negative individuals (n = 20). Decreased bacterial diversity, a reduction in commensal bacteria, and high abundance of pathogenic bacteria were observed in patients compared to negative controls. Several bacterial species and metabolic pathways were associated with better respiratory status and lower inflammation. Strong correlations were found between species biomarkers and metabolic pathways associated with better clinical outcome, especially Moraxella lincolnii and pathways of vitamin K2 biosynthesis. Our study demonstrates correlations between the URT microbiome and COVID-19 patient outcomes; further studies are warranted to validate these findings and to explore the causal roles of the identified microbiome biomarkers in COVID-19 pathogenesis.

The nasopharyngeal microbiome in COVID-19

“…This work revealed that the nasopharyngeal microbiota of all those patients was dominated by the bacterial genera Staphylococcus and Corynebacterium , but woefully the study did not include any less severely ill, asymptomatic, or uninfected individuals as controls with whom to compare (Table S1) [ 60 ]. On the other hand, consistent with these results, the work by Bai and colleagues, which included 37 critically ill COVID-19 patients and 20 uninfected controls, showed a reduction in commensal bacteria and higher abundance of pathogenic bacteria in patients compared to healthy uninfected controls (Table S1) [ 52 ]. But even more interesting are the approaches analyzing the nasopharyngeal microbiota composition of COVID-19 patients with different levels of disease severity within the same study, since most of these works observed significant differences when comparing symptomatic subjects to asymptomatic/paucisymptomatic individuals and/or uninfected controls (Table S1) [ 46 , 50 , 54-56 , 64-66 , 68-70 ].…”

“…Besides these two publications that did not find any differences at all, including microbiota diversity and composition, there are other studies which were also unable to observe significant differences in nasopharyngeal microbiota alpha and/or beta diversity, although in these cases they showed that the nasopharyngeal microbiota composition was altered in SARS-CoV-2 positive subjects compared to uninfected controls (Table S1) [ 46-50 ]. Interestingly, while most of the studies that observed significant differences in the nasopharyngeal microbiota diversity reported a decrease in SARS-CoV-2 positive subjects compared to uninfected individuals [ 51 , 52 ], or in the most severe cases of COVID-19 disease compared with milder cases [ 53-56 ], the only work exploring the nasopharyngeal microbiota profile of pregnant women with SARS-CoV-2 infection, conducted by Crovetto and colleagues, found that alpha diversity was higher in pregnant infected women compared to uninfected (Table S1) [ 57 ]. Unfortunately, as there were no previous data on the nasopharyngeal microbiota during pregnancy, and this study did not include samples from women in a nonpregnant status, it was not possible to determine whether changes were a consequence only of the pregnancy status itself (Table S1) [ 57 ].…”

“…While an important part of the research in this field, especially at the initial moments of the COVID-19 pandemic, has focused mainly on comparing the nasopharyngeal microbiota of SARS-CoV-2 positive individuals to uninfected controls independently on the symptomatology of those patients or the severity of their disease [ 44-49 , 51 , 52 , 57-63 ], many of the most recent studies have gone further and have examined the possible association between the nasopharyngeal microbiota and the COVID-19 disease severity or outcome (Table S1) [ 50 , 53-56 , 64-70 ]. The publications which only compared the nasopharyngeal microbiota composition of asymptomatic or paucisymptomatic SARS-CoV-2 positive subjects to negative healthy controls generally found little or no differences (Table S1) [ 44 , 63 , 65 ].…”

Moraxella occupied the largest proportion in the nasal microbiome in healthy children, which potential protect them from COVID-19

“…In addition, Moraxella can affect the immune system of the respiratory tract [ 25 ]. Sönnerborg A et al demonstrated that Moraxella correlated inversely to inflammation marker CRP and D-dimer [ 26 ]. These results suggest that Moraxella may be associated with better outcomes after COVID-19 infection.…”

A Time-series Metabolomic Analysis of SARS-CoV-2 Infection in a Ferret Model

“…Due to this phenomenon, biochemicals such as 2-deoxy glucose (2DG) and benfooxythiamine (BOT) which inhibit the non-oxidative pathways of PPP, have shown to inhibit SARS-CoV-2 replication [28,29]. In addition to this, recent correlation network analysis in patients with COVID-19, has also shown that in addition to the viral infection, the upper respiratory microbiota also gets affected during SARS-CoV-2, which in turn has been shown to be correlated with the upregulation of pathways such as PPP [30]. Although we did not study the impact of SARS-CoV-2 infection on nasal microbial population and metabolism, a further study of host-microbiome-virus interactomics is expected to shed more light on this biochemical mechanism.…”