Exploring the connection between SARS-CoV-2 infection and the human gut microbiome

By Bhavana KunkalikarReviewed by Danielle Ellis, B.Sc.Mar 17 2022

A recent study posted to the bioRxiv* preprint server assessed the relationship between the human microbiome and coronavirus disease 2019 (COVID-19).

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

Various studies have reported that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can cause gastrointestinal (GI) manifestations in COVID-19 patients. These studies indicate that the GI tract might be an important target for SARS-CoV-2 infection. 

About the study

The present study reconstructed the microbial genome using microbiome samples obtained from COVID-19 patients to determine novel taxa and differences in the microbiome and assess their correlation to SARS-CoV-2 symptoms.

The team obtained metagenomic sequencing studies and metadata highlighting patients with COVID-19 or non-COVID-19 control status. The genomic reconstruction of the human microbiome using the metagenomic sequencing data was performed by employing the function modules of metaWRAP. It was first used to trim the raw sequence reads and remove the human contamination in each sequenced sample. The clean reads were then assembled, and the sequenced assemblies were binned according to the minimum length of contigs. The metagenome-assembled genomes (MAGs) were then refined and used to evaluate the contamination and completeness of the bins.

The MAGs were then grouped into species-level genome bins (SGBs). SGBs having a minimum of one reference genome were called known SGBs, while those with no reference genomes were called unknown genomes (uSGBs). The MAGs were then dereplicated, and the non-redundant MAGs (nrMAGs) were classified into medium-quality MAGs having completeness ranging between 50% and 90% and contamination of 5% or lesser and high-quality MAGs having completeness of 90% and more and contamination of 5% or lesser.

Results

The study results showed that a total of 514 microbiome samples were obtained from 359 individuals, including 96 nasopharyngeal and 418 fecal microbiome samples. Among these, 78.60% of the samples were from COVID-19 patients, while 21.40% were from non-COVID-19 controls.

In the 11,584 MAGs obtained, the mean completeness was 87.5%, the mean contamination was 0.99%, with a mean genome size of 2.6 megabases (Mb). The organization of the MAGs resulted in 872 SGBs, including 18.35% of uSGBs while the dereplication of the MAGs produced 5,403 nrMAGs with strain-level resolution. These nrMAGs had a mean completeness of 86.87%, mean contamination of 0.99%, and a mean genomic size of 2.4 Mb. Notably, 21.4% of the non-COVID-19 samples resulted in 38.94% of nrMAGs and 31.2% of MAGs, indicating a higher contribution of non-COVID-19 samples than of COVID-19 samples to total nrMAGS and MAGs.

Among the total number of nrMAGs, 40.53% were of medium quality, and 59.74% were of high quality. The team assigned 99.89% of the nrMAGs to the bacterial domain and 0.11% to the archaeal domain. Also, the nrMAGs predominantly belonged to five phyla with 60.61% of nrMAGs from the Firmicutes A, 14.03% from Actinobacteriota, 9.77% from Bacteroidota, 6.92% from Firmicutes, and 3.07% from Proteobacteria.        

The alpha diversity measures of the gut microbiome were markedly lower in COVID-19 patients than in non-COVID-19 persons. However, no significant differences were found between the gut microbiomes of COVID-19 patients and non-COVID-19 controls suffering from pneumonia. Moreover, no notable results were found in the nasopharyngeal microbiome samples for the patient and the control groups. 

At the nrMAG-level, principal coordinates analysis (PCoA) and permutational multivariate analysis of variance (PERMANOVA) showed a remarkable distinction in the microbial community structures of the COVID-19 patients and the non-COVID-19 controls. Also, a higher variation was observed within the patient group than within the control group.

Among the COVID-19 patients, higher alpha diversity in the gut microbiome was observed in patients with milder disease severity. The nrMAGs composition in COVID-19-recovered patients was more diverse than the non-COVID-19 controls than the pre-recovery COVID-19 patients. This indicated that the gut microbiome of COVID-19 patients did not recover to a relatively healthy state soon after recovering from COVID-19. Also, COVID-19 disease severity had a substantial positive association with the differences in gut microbiomes between COVID-19 patients and controls.

A mean AUPRC (area under the precision-recall curve) value of 0.971 and a mean AUROC (area under the receiver operating characteristic curve) value of 0.981 showed that nrMAGs accurately indicated COVID-19 infections. The study also identified key discriminatory nrMAGs and three specific nrMAGs that were common between the two cohorts.

Conclusion

The study findings showed a significant association between the human gut microbiome and COVID-19 infection. The usage of assembled genomic catalogs could prove crucial in employing the metagenomic strain-level aspects of SARS-CoV-2–human microbiome correlation for further research.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources