Microbiome of Lung Predicts COVID-19 Severity

A new study published on a pre-print server found that changes to the lung microbiome during SARS-CoV-2 infection influence COVID-19 disease severity. Researchers from the University of Pennsylvania Perelman School of Medicine have suggested a wide diversity in the microbiome is associated with less severe illness and the need for hospitalization.

The researchers collected oropharyngeal or nasopharyngeal swabs from 83 patients hospitalized due to COVID-19 infection. Except for five, all had comorbidities. A total of 582 specimens for microbiome analysis was collected from COVID-positive patients and 75 from non-COVID. Study controls consisted of 30 healthy individuals who provided swab samples and 12 samples that underwent bronchoscopy and bronchoalveolar lavage. RNA extracted from patient samples was variable, and the viral load declined to undetectable in most patients during disease progression. However, some patients continued to exhibit SARS-CoV-2 RNA 3 weeks after symptom onset. RNA levels did not correlate with clinical outcomes. Genome sequencing from 26 patient samples showed SARS-CoV-2 fell under the B.1 lineage. This lineage contains the D614G mutation on the spike protein along with the P314L variant.

The respiratory microbiomes across intubated patients included common respiratory pathogens, including Staphylococcus, Klebsiella, and Stenotrophomonas. However, less diverse microbiomes were observed in patients with COVID-19. Of the 24 intubated patients, 6 microbiomes showed a high prevalence for Staphylococcus. About 5 patients showed Staphylococcus dominance in the microbiome one week after culture testing, and only 3 had S. aureus. Three patients had Enterococcus. Other pathogens present but in smaller quantities included Stenotrophomonas, Enterobacteriaceae, and Enterobacterales. Researchers found stability in the microbiome for some patients while others showed changes over time.

The team also looked at 193 individual cellular immune features from peripheral blood mononuclear cell phenotyping samples from 34 patients. Results showed the oropharyngeal microbiome is associated with systemic immune cell composition. Early sampling showed Anelloviridae and Redondoviridae were one of the most excellent microbial indicators for requiring intubation in the hospital. The DNA viruses were also linked to a higher WHO score, which indicated greater disease severity.

Researchers used machine learning algorithms in two patients to find elevated levels of small circular DNA viruses predicted if a person would be intubated — although they were not as strong as bacteria in predicting COVID-19 disease severity. Prevotella and Mycoplasma in oropharyngeal samples were also associated with a greater risk of hospitalized intubation. This suggests bacterial lineages rather than DNA viruses correlated with higher disease severity.

Ref Link: https://doi.org/10.1101/2021.04.02.21254514