Severe COVID-19 Is Associated With an Altered Upper Respiratory Tract Microbiome

Abstract

BackgroundThe upper respiratory tract (URT) is the portal of entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and SARS-CoV-2 likely interacts with the URT microbiome. However, understanding of the associations between the URT microbiome and the severity of coronavirus disease 2019 (COVID-19) is still limited.ObjectiveOur primary objective was to identify URT microbiome signature/s that consistently changed over a spectrum of COVID-19 severity.MethodsUsing data from 103 adult participants from two cities in the United States, we compared the bacterial load and the URT microbiome between five groups: 20 asymptomatic SARS-CoV-2-negative participants, 27 participants with mild COVID-19, 28 participants with moderate COVID-19, 15 hospitalized patients with severe COVID-19, and 13 hospitalized patients in the ICU with very severe COVID-19.ResultsURT bacterial load, bacterial richness, and within-group microbiome composition dissimilarity consistently increased as COVID-19 severity increased, while the relative abundance of an amplicon sequence variant (ASV), Corynebacterium_unclassified.ASV0002, consistently decreased as COVID-19 severity increased.ConclusionsWe observed that the URT microbiome composition significantly changed as COVID-19 severity increased. The URT microbiome could potentially predict which patients may be more likely to progress to severe disease or be modified to decrease severity. However, further research in additional longitudinal cohorts is needed to better understand how the microbiome affects COVID-19 severity.

Role of Microbiota in Viral Infections and Pathological Progression

“…Furthermore, dysbiosis in the gut microbiota (decrease in bacteria producing short-chain fatty acids) after an infection in animal models using hamsters has also been reported [ 69 ]. Changes in the oral microbiota after infection with SARS-CoV-2 have also been reported in many studies [ 70 , 71 , 72 , 73 , 74 , 75 ]. Ma et al reported that an analysis of oropharyngeal swab specimens showed that changes in the oral microbiota after infection with SARS-CoV-2 elicited an inflammatory response and affected the severity of the disease [ 71 ].…”

Nasopharyngeal Bacterial Microbiota Composition and SARS-CoV-2 IgG Antibody Maintenance in Asymptomatic/Paucisymptomatic Subjects

“…In terms of taxa, the BNM composition was similar to the one reported for healthy (not infected) populations of adult subjects ( Man et al., 2017 ; Bomar et al., 2018 ; Mariani et al., 2018 ; Budden et al., 2019 ). Our results are supported by other previous studies reporting that patients with mild or asymptomatic COVID-19 were characterized by a bNM similar to that of negative healthy controls, suggesting that in asymptomatic/paucisymptomatic subjects who tested positive for SARS-CoV-2 RNA, the BNM composition apparently is not affected by the viral infection ( De Maio et al., 2020 ; Rosas-Salazar et al., 2021 ; Shilts et al., 2022 ). The link between BNM composition and SARS-CoV-2 RNA has been investigated by a growing number of case–control studies that specifically focused on SARS-CoV-2-positive patients, either symptomatic or paucisymptomatic, compared to not infected healthy controls.…”

Increased Abundance of Achromobacter xylosoxidans and Bacillus cereus in Upper Airway Transcriptionally Active Microbiome of COVID-19 Mortality Patients Indicates Role of Co-Infections in Disease Severity and Outcome

“…Although the present study did not reveal significant shifts in diversity and composition of the nasopharyngeal transcriptionally active isolates among the four clinical sub-phenotypes of COVID-19, this could be attributable to the Anna Karenina principle (AKP) of microbiome dysbiosis ( 46 – 48 ), which implies that a greater observed variability exists among individuals with dysbiotic microbiome. Additionally, multiple studies investigating the bacterial communities and the respiratory microbiome in COVID-19 revealed drastic reduction in diversity and composition with increasing disease severity ( 23 , 49 ).…”