Signatures of COVID-19 severity and immune response in the respiratory tract microbiome

Abstract

Rationale: Viral infection of the respiratory tract can be associated with propagating effects on the airway microbiome, and microbiome dysbiosis may influence viral disease. Objective: To define the respiratory tract microbiome in COVID-19 and relationship disease severity, systemic immunologic features, and outcomes. Methods and Measurements: We examined 507 oropharyngeal, nasopharyngeal and endotracheal samples from 83 hospitalized COVID-19 patients, along with non-COVID patients and healthy controls. Bacterial communities were interrogated using 16S rRNA gene sequencing, commensal DNA viruses Anelloviridae and Redondoviridae were quantified by qPCR, and immune features were characterized by lymphocyte/neutrophil (L/N) ratios and deep immune profiling of peripheral blood mononuclear cells (PBMC). Main Results: COVID-19 patients had upper respiratory microbiome dysbiosis, and greater change over time than critically ill patients without COVID-19. Diversity at the first time point correlated inversely with disease severity during hospitalization, and microbiome composition was associated with L/N ratios and PBMC profiles in blood. Intubated patients showed patient-specific and dynamic lung microbiome communities, with prominence of Staphylococcus. Anelloviridae and Redondoviridae showed more frequent colonization and higher titers in severe disease. Machine learning analysis demonstrated that integrated features of the microbiome at early sampling points had high power to discriminate ultimate level of COVID-19 severity. Conclusions: The respiratory tract microbiome and commensal virome are disturbed in COVID-19, correlate with systemic immune parameters, and early microbiome features discriminate disease severity. Future studies should address clinical consequences of airway dysbiosis in COVID-19, possible use as biomarkers, and role of bacterial and viral taxa identified here in COVID-19 pathogenesis.

Gut and airway microbiota and their role in COVID-19 infection and pathogenesis: a scoping review

“…The main characteristics of the studies are shown in Tables 2 , 3 , 4 . Ten studies investigated the association between gut microbiota and COVID-19 [ 26 – 35 ], 11 studies investigated the association between airway microbiota and COVID-19 [ 36 – 46 ] and one study investigated the association between both gut and airway microbiota and COVID-19 [ 47 ]. All studies collected their samples after onset of infection with SARS-CoV-2.…”

“…The search identified 10 cohort studies [ 36 – 43 , 45 , 46 ] and one case–control study [ 44 ] investigating the association between airway microbiota and COVID-19 (Table 3 ).…”

“…Eleven studies investigated the composition of the airway microbiota during COVID-19 infection [ 36 – 46 ], 2 studies examined the association between the composition of airway microbiota and COVID-19 severity [ 40 , 46 ] and 2 studies assessed the prevalence of co-infection during COVID-19 [ 41 , 45 ]. Ten studies examined the DNA of the microbiota collected from nasopharyngeal swabs [ 36 – 42 , 44 – 46 ], 2 studies collected DNA samples from endotracheal aspiration [ 41 , 46 ] and 2 studies collected samples using bronchoalveolar lavage [ 41 , 43 ].…”

The Complexity of Co-Infections in the Era of COVID-19

“…The occurrence of secondary infections is generally anticipated, albeit the frequency of the same could be variable. Such perturbation is also evident during COVID-19 as shown through molecular epidemiological studies of the upper respiratory microbiome [115][116][117]. Admission to healthcare centers carries with it the opportunity for nosocomial infections.…”

Manipulation of the Upper Respiratory Microbiota to Reduce Incidence and Severity of Upper Respiratory Viral Infections: A Literature Review

“…There have been several studies examining correlations between the URT microbiota and SARS-CoV2 infection since the beginning of the COVID-19 global pandemic. These studies indicate that the microbiota is shifted with an enrichment of pathobionts and opportunistic pathogens in COVID-19 patients compared to non-infected individuals (Engen et al, 2021;Merenstein et al, 2021;Rhoades et al, 2021). We note that at the time of writing, some of these studies have not yet been peer reviewed.…”