Severe Dysbiosis and Specific Haemophilus and Neisseria Signatures as Hallmarks of the Oropharyngeal Microbiome in Critically Ill Coronavirus Disease 2019 (COVID-19) Patients

Abstract

Background At the entry site of respiratory virus infections, the oropharyngeal microbiome has been proposed as a major hub integrating viral and host immune signals. Early studies suggested that infections with Coronavirus 2 (SARS-CoV-2) are associated with changes of the upper and lower airway microbiome, and that specific microbial signatures may predict COVID-19 illness. However, the results are not conclusive, as critical illness can drastically alter a patient’s microbiome through multiple confounders. Methods To study oropharyngeal microbiome profiles in SARS-CoV-2 infection, clinical confounders, and prediction models in COVID-19, we performed a multi-center, cross-sectional clinical study analyzing oropharyngeal microbial metagenomes in healthy adults, patients with non-SARS-CoV-2 infections, or with mild, moderate and severe COVID-19 (n=322 participants). Results In contrast to mild infections, patients admitted to a hospital with moderate or severe COVID-19 showed dysbiotic microbial configurations, which were significantly pronounced in patients treated with broad-spectrum antibiotics, receiving invasive mechanical ventilation, or when sampling was performed during prolonged hospitalization. In contrast, specimens collected early after admission allowed us to segregate microbiome features predictive of hospital COVID-19 mortality utilizing machine learning models. Taxonomic signatures were found to perform better than models utilizing clinical variables with Neisseria and Haemophilus species abundances as most important features. Conclusion In addition to the infection per se, several factors shape the oropharyngeal microbiome of severely affected COVID-19 patients and deserve consideration in the interpretation of the role of the microbiome in severe COVID-19. Nevertheless, we were able to extract microbial features that can help to predict clinical outcomes.

Gut microbiota and COVID-19: A systematic review

“…A notable association between URT and in ammatory Cytokines levels (like IL-6, TNF-α, and IL-1b) was observed and it can explain the signi cant link between URT microbiota and COVID-19 severity and mortality rate [70,72]. These statements are consistent with the ndings of some studies about the higher reduction of anti-in ammatory metabolic factors in long COVID-19 patients treated with antibiotics, invasive mechanical ventilation, and ICU admission compared to mild patients [22,45,54,62]. In addition, a quick return of dysbiosis level to normal values during recovery in mild COVID-19 cases was reported [47,53].…”

“…The impact of URT microbiota on the preservation of the lung immune system is one of the important aspects as it correlates with respiratory infections [45,74,162]. Unusual changes in URT microbiota in COVID-19 patients, especially moderate and severe patients, were reported in comparison to healthy individuals [21,45]. The richness of microbiota was higher in COVID-19 patients [57,72] and most of them were opportunistic bacteria [56].…”

“…In the current review, 24 studies discussed the role of URT microbiota in the pathogenesis of COVID-19 infection. The impact of URT microbiota on the preservation of the lung immune system is one of the important aspects as it correlates with respiratory infections [45,74,162]. Unusual changes in URT microbiota in COVID-19 patients, especially moderate and severe patients, were reported in comparison to healthy individuals [21,45].…”

“…The richness of microbiota was higher in COVID-19 patients [57,72] and most of them were opportunistic bacteria [56]. COVID-19 infection may induce URT microbiota to multiply the in ammatory bacteria like Haemophilusin uenzeae and parain uenzae which are associated with acute respiratory diseases like pneumonia [45]. Also, it may increase Neisseria sub ava; which is less abundant of it in COVID-19 patients are signi cantly related to a high rate of mortality [21,45].…”

“…COVID-19 infection may induce URT microbiota to multiply the in ammatory bacteria like Haemophilusin uenzeae and parain uenzae which are associated with acute respiratory diseases like pneumonia [45]. Also, it may increase Neisseria sub ava; which is less abundant of it in COVID-19 patients are signi cantly related to a high rate of mortality [21,45]. The high level of Klebsiella and Serratia were also associated with more severe diseases [25].…”