Gut Microbial Disruption in Critically Ill Patients with COVID-19-Associated Pulmonary Aspergillosis.

OBJECTIVES: COVID-19 disease can be exacerbated by Aspergillus superinfection (CAPA). However, the causes of CAPA are not yet fully understood. Recently, alterations in the gut microbiome have been associated with a more complicated and severe disease course in COVID-19 patients, most likely due to immunological mechanisms. The aim of this study was to investigate a potential association between severe CAPA and alterations in the gut and bronchial microbial composition. METHODS: We performed 16S rRNA gene amplicon sequencing of stool and bronchial samples from a total of 16 COVID-19 patients with CAPA and 26 patients without CAPA. All patients were admitted to the intensive care unit. Results were carefully tested for potentially confounding influences on the microbiome during hospitalization. RESULTS: We found that late in COVID-19 disease, CAPA patients exhibited a trend towards reduced gut microbial diversity. Furthermore, late-stage patients with CAPA superinfection exhibited an increased abundance of Staphylococcus epidermidis in the gut which was not found in late non-CAPA cases or early in the disease. The analysis of bronchial samples did not yield significant results. CONCLUSIONS: This is the first study showing that alterations in the gut microbiome accompany severe CAPA and possibly influence the host's immunological response. In particular, an increase in Staphylococcus epidermidis in the intestine could be of importance.

Gut bacterial dysbiosis and instability is associated with the onset of complications and mortality in COVID-19.

There is a growing debate about the involvement of the gut microbiome in COVID-19, although it is not conclusively understood whether the microbiome has an impact on COVID-19, or vice versa, especially as analysis of amplicon data in hospitalized patients requires sophisticated cohort recruitment and integration of clinical parameters. Here, we analyzed fecal and saliva samples from SARS-CoV-2 infected and post COVID-19 patients and controls considering multiple influencing factors during hospitalization. 16S rRNA gene sequencing was performed on fecal and saliva samples from 108 COVID-19 and 22 post COVID-19 patients, 20 pneumonia controls and 26 asymptomatic controls. Patients were recruited over the first and second corona wave in Germany and detailed clinical parameters were considered. Serial samples per individual allowed intra-individual analysis. We found the gut and oral microbiota to be altered depending on number and type of COVID-19-associated complications and disease severity. The occurrence of individual complications was correlated with low-risk (e.g., Faecalibacterium prausznitzii) and high-risk bacteria (e.g., Parabacteroides ssp.). We demonstrated that a stable gut bacterial composition was associated with a favorable disease progression. Based on gut microbial profiles, we identified a model to estimate mortality in COVID-19. Gut microbiota are associated with the occurrence of complications in COVID-19 and may thereby influencing disease severity. A stable gut microbial composition may contribute to a favorable disease progression and using bacterial signatures to estimate mortality could contribute to diagnostic approaches. Importantly, we highlight challenges in the analysis of microbial data in the context of hospitalization.