Upper respiratory tract microbiota dynamics following COVID-19 in adults

Abstract

To date, little is known about the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, on the upper respiratory tract (URT) microbiota over time. To fill this knowledge gap, we used 16S ribosomal RNA gene sequencing to characterize the URT microbiota in 48 adults, including (1) 24 participants with mild-to-moderate COVID-19 who had serial mid-turbinate swabs collected up to 21 days after enrolment and (2) 24 asymptomatic, uninfected controls who had mid-turbinate swabs collected at enrolment only. To compare the URT microbiota between groups in a comprehensive manner, different types of statistical analyses that are frequently employed in microbial ecology were used, including ⍺-diversity, β-diversity and differential abundance analyses. Final statistical models included age, sex and the presence of at least one comorbidity as covariates. The median age of all participants was 34.00 (interquartile range=28.75–46.50) years. In comparison to samples from controls, those from participants with COVID-19 had a lower observed species index at day 21 (linear regression coefficient=−13.30; 95 % CI=−21.72 to −4.88; q=0.02). In addition, the Jaccard index was significantly different between samples from participants with COVID-19 and those from controls at all study time points (PERMANOVA q<0.05 for all comparisons). The abundance of three amplicon sequence variants (ASVs) (one Corynebacterium ASV, Frederiksenia canicola , and one Lactobacillus ASV) were decreased in samples from participants with COVID-19 at all seven study time points, whereas the abundance of one ASV (from the family Neisseriaceae ) was increased in samples from participants with COVID-19 at five (71.43 %) of the seven study time points. Our results suggest that mild-to-moderate COVID-19 can lead to alterations of the URT microbiota that persist for several weeks after the initial infection.

Lactobacilli in COVID-19: A Systematic Review Based on Next-Generation Sequencing Studies

“…Nevertheless, we chose to include only works published in the English language. Four studies assessed the upper respiratory tract [ 21 , 22 , 23 , 24 ], including samples such as saliva, throat, tongue, oral, and nasopharyngeal. Four studies examined stool samples [ 25 , 26 , 27 , 28 ], and only one study evaluated the microbiome in both the gut and URT [ 29 ].…”

“…One study focused on the microbiota of children [ 27 ]. The V3–V4 region was the most commonly used amplicon sequencing approach [ 21 , 25 , 28 , 29 ], while the V1–V2 region was used in two studies [ 21 , 25 ], and the V4 region was applied in one study [ 23 ] ( Figure 2 ). Whole genome sequencing methodology was applied in two studies [ 20 , 24 ].…”

“…Whole genome sequencing methodology was applied in two studies [ 20 , 24 ]. There was a notable variation in the selection of databases used for taxonomy classification among studies, with four studies using the Greengenes database [ 21 , 22 , 23 , 25 ]; the RDP [ 22 ], SILVA v132 [ 23 ], SILVA v138 [ 21 ], and MetaPhlAn2 (V.20) [ 28 ] databases were used in only one study each ( Figure 2 ). One study did not specify the database [ 24 ].…”

“…In terms of the statistical analysis employed to detect differences in the amount of the lactobacilli between groups, LEfSe (Linear Discriminant Analysis Effect Size) was the most commonly used approach [ 21 , 25 , 26 , 27 , 28 , 29 ], while two studies used DESeq2 [ 22 , 23 ], and one study used the Kruskal–Wallis method [ 24 ] ( Figure 2 ).…”

“…The enrichment of the genus in the gut microbiota of patients was also demonstrated by Gaibani et al [ 25 ]. At the species level, the differential abundance of a lactobacilli ASV (identified as Lactobacillus jensenii by the BLAST database) was decreased at all seven time points assessed in a longitudinal study of upper respiratory tract samples (days 1, 3, 5, 7, 10, 14, and 21) [ 23 ]. In children, the LEfSe assessment of the intestinal microbiota showed that Lactobacillus ruminis was one of the dominant species in the control group compared to COVID-19 patients and those with both COVID-19 and multisystem inflammatory syndrome (MIS-C) [ 27 ].…”