Co-infection of pathogens and microbiome from SARS-CoV-2 positive and negative samples

In a recent study published in pro swan, investigators evaluated co-infection in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients. In addition, they investigated differences in the microbial profiles of SARS-CoV-2-positive and SARS-CoV-2-negative samples.

Background

The 2019 coronavirus disease (COVID-19) has ruined the health and lives of people around the world over the past two years. Within months of its emergence, studies also reported co-infections with other microbial pathogens such as bacteria, viruses and fungi.

A meta-analysis reviewed 118 published studies between 2019 and 2021 and found that 19% of COVID-19 patients suffered from co-infection. Bacterial superinfection was associated with the most severe outcomes, including death.

These studies primarily used real-time reverse transcriptase polymerase chain reaction (RT-PCR) assays to detect co-infecting pathogens. Given the limited sensitivity of PCR assays, detection of co-infection remained limited to known or suspected targets.

About research

In this study, researchers investigated the presence of co-infective pathogens of viruses, bacteria, fungi, and non-pathogens.

The sample set consisted of 203 nasopharyngeal (NP) and oropharyngeal (OP) swab samples, of which 101 and 102 were SARS-CoV-2 positive and SARS-CoV-2 negative, respectively. The researchers also collected most of these samples after statewide “Shelter-in-Place” directives reduced the circulation of respiratory viral pathogens since March 2020.

The team used version 7 (v7) of the Lawrence Livermore Microbial Detection Array (LLMDA), a broad spectrum microbial detection platform, to analyze the collected samples. This platform rapidly processed up to 96 clinical samples simultaneously. Over 12,000 microbial species can be detected via deoxyribonucleic acid (DNA) probes, including 4219 viral, 5367 bacterial, and 265 fungal species. Additionally, 117 protozoans and 293 archaea were detected.

The team performed complementary 16S ribosomal ribonucleic acid (rRNA) sequencing analysis to assess the microbiome of study samples. Finally, they performed bioinformatics and statistical analyzes to assess the microbial profiles of these samples.

Survey results

LLMDA detected SARS-CoV-2 in all samples with a cycle threshold of 34 or greater. 92/101 (91%) of the SARS-CoV-2 RT-PCR positive samples. The five most abundant bacteria detected by LLDMA in SARS-CoV-2 positive and negative samples were Streptococcus pyogenes, streptococcus agalactiae, Prevotella Intermedia, Streptococcus pneumoniaeWhen mycoplasma turtle.

Also detected Haemophilus influenzae 8 out of 101 SARS-CoV-2 positive samples. Meta-analysis by Lansbury et al. The most common bacterial co-infections are Pseudomonas aeruginosa, mycoplasma pneumoniaWhen Haemophilus influenzaeFurthermore, we have identified that respiratory syncytial virus (RSV) and influenza A are the most frequently co-infected viruses. They reviewed 30 studies of his 3,834 patients published between January and April 2020.

LLMDA did not detect RSV or influenza A in SARS-CoV-2 positive samples. This is likely due to a drop in circulation after the government enacted a mandatory masking policy. However, they found human metapneumovirus in six SARS-CoV-2-negative samples collected in March/April 2020.

Overall, LLMDA detected viruses and bacteria in 125 of the 203 samples. The remaining 78 samples either had insufficient microbial or viral DNA or had viral and bacterial concentrations below the LLMDA detection limit in these samples. Previous evaluations of other versions of LLMDA have shown that nasal/throat swab samples are more efficient than downstream NP samples. nucleic acid extract.

Firmicutes, Proteobacteria, Actinobacteria, Bacteroidetes, and Fusobacteria accounted for 98% of sequences detected by 16S rRNA sequence analysis. Her 16S rRNA analysis of amplicon sequence variants (ASV) showed that the nasal microbial profile was highly individualized. Moraxellaceae and Corynebacteraceae ASVs showed higher prevalence in SARS-CoV-2-positive samples, whereas Pasteurellaceae and Streptococciaceae ASVs were less abundant.

Previous studies have yielded contrasting results on changes in the nasal and oral microbiome after COVID-19. For example, a recent study, based on 16S rRNA sequencing, but not COVID-19, showed that individual differences caused microbiome variation in the nose and mouth region. Another study showed a clear decrease in nasopharyngeal microbiome diversity in COVID-19 patients. Overall, there are insufficient data that SARS-CoV-2 infection affects the overall diversity of the nasal and oral microbiomes.

Conclusion

In summary, researchers detected one or more viruses or bacteria in 62% of the clinical samples examined in the current study. Streptococcus pyogenes When Streptococcus pneumoniae It has been identified as the most commonly co-infected bacterial species in COVID-19 patients. Researchers were unable to associate clinical manifestations of COVID-19 with co-infection due to lack of clinical data. However, no significant difference was observed in the number of microbial pathogens detected from SARS-CoV-2 positive and negative samples.

To determine which populations of the nasal microbiome may be associated with COVID-19 progression and severity, a more longitudinal study including cohorts with well-characterized clinical data Research is urgently needed.