Nasopharyngeal microbiota influences SARS-CoV-2 infection status and severity

In a recent study published on medRxiv*preprint server, Canadian researchers studied how infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) alters the composition of the microbiota of the host’s nasopharyngeal region.

Study: Alterations in the nasopharyngeal microbiome associated with SARS-CoV-2 infection status and disease severity. Image Credit: Christoph Burgstedt/Shutterstock

Background

The risk and clinical outcomes of SARS-CoV-2 infection vary widely from person to person. However, the mechanisms underlying these differences in the progression and pathogenesis of coronavirus disease 2019 (COVID-19) remain unclear. Studies have shown that the mucosal microbiome influences the expression of the host toll-like receptor (TLR), which is involved in virus detection. Studies have also shown the prevalence of bacterial co-infections in COVID-19 patients at 6.9%.

Similarly, elevated nasal cytokines have been implicated in adverse clinical outcomes in influenza patients. Therefore, exploring compositional changes in the upper respiratory tract microbiota after SARS-CoV-2 infection could help assess its impact on infection severity.

About the study

In the present study, researchers performed 16S Nanopore ribosomal ribonucleic acid (rRNA) sequencing on 194 nasopharyngeal swab specimens collected between March 2020 and January 2022 from the general population in British Columbia, Canada. They formed four study groups consisting of hospitalized COVID-19 patients (HOSPOS), community-dwelling COVID-19 patients (COMPOS), hospitalized patients not infected with SARS-CoV-2 (HOSNEG), and uninfected inhabitants of the community (COMNEG).

Side-by-side boxplots of relative abundance at the species level among our four study groups.

Additionally, the team performed sequence data analysis using the BugSeq 16S analysis pipeline. They performed routine diagnostic tests and a laboratory-developed real-time reverse transcription-polymerase chain reaction (RT-PCR) test (LDT) on the study samples to detect the envelope (E) of the SARS-CoV-2 and RNA-dependent RNA polymerase (RdRp) gene targets. They also used an in-house developed PCR-based test to screen for SARS-CoV-2 (COV), Alpha, Beta, Gamma, Delta and Omicron variants of concern in the study samples. Finally, they used ALDEx2 to examine the differential abundance of microbial taxa across the four study groups.

Study results

The longer duration of the study provided access to clinical specimens positive for a range of SARS-CoV-2 variants. While all study participants had a similar age distribution, there were 60.3% males and only 39.7% females. The authors observed a trend towards lower mean Shannon/Simpson diversity and regularity in samples from COMPOS groups compared to COMNEG groups. However, there was no significant alpha diversity among all study groups, as indicated by Kruskal-Wallis test results with p values ​​less than 0.05. Additionally, the authors observed a degree of overlap in the 95% confidence ellipses among four study groups; however, they differed in their microbial community composition with significant clustering at the three taxonomic ranks, species, genus, and family. Accordingly, the p-values ​​for taxonomic ranks at the species, genus, and family level were 0.009, 0.028, and 0.027, respectively.

In hospitalized groups and SARS-CoV-2 infected groups living in the community, Acinetobacter and Moraxella were respectively the most abundant genera. In the two groups not infected with SARS-CoV-2, Staphylococcus was the most abundant genus on average. At the species level, SARS-CoV-2 infected groups had common nasal and opportunistic pathogens, including Haemophilus influenzae, Staphylococcus haemolyticusand Staphylococcus aureus. Notably, the hospitalized group infected with SARS-CoV-2 had Klebsiella aerogenes as the most abundant species and a higher average relative abundance of Enterobacteriaceae than any other study group.

Individuals infected with SARS-CoV-2 living in the community exhibited all differentially abundant taxa, such as families Propionibacteriaceae, Neisseriaceae, Peptostreptococcales-Tissierellalesthe species Cutibacterium acnesand genders Cutibacteria and Peptinophilus.

ALDEx2 revealed significant differences in Streptococcus. and Corynebacterium species among samples from SARS-CoV-2 infected individuals collected during the first three waves of the COVID-19 pandemic between March 2020 and May 2021. However, the authors observed no significant alpha or beta diversity related at viral load or by SARS-CoV-2 VOC type.

conclusion

Overall, the study results presented a granular picture of microbiota differences in SARS-CoV-2 infected and uninfected individuals. Despite significant overlap in confidence ellipses, differences in nasopharyngeal microbiota composition between study groups were relatively small.

A non-influenza respiratory viral infection increases the host’s susceptibility to S. aureus superinfection by reducing the ability of the immune system to regulate its clearance from the nasal passage. Therefore, medical interventions such as intubation or exposure to antibiotics most likely increased the abundance of Enterobacteriaceae among the hospitalized study group infected with SARS-CoV-2. However, the presence of Neisseriaceae taxa in the community-dwelling SARS-CoV-2 infected group remains unexplained.

Further work is needed to determine the functional characteristics of the nasopharyngeal microbiome. This knowledge could help develop new COVID-19 prognostic markers and open new avenues for novel approaches to COVID-19 treatments.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be considered conclusive, guide clinical practice/health-related behaviors, or treated as established information.