Transcriptionally active nasopharyngeal commensals and opportunistic microbial dynamics define mild symptoms in the COVID 19 vaccination breakthroughs

Abstract

The development of COVID 19 vaccines as an effort to mitigate the outbreak, has saved millions of lives globally. However, vaccination breakthroughs have continuously challenged the vaccines’ effectiveness and provided incentives to explore facets holding potential to alter vaccination-induced immunity and protection from subsequent infection, especially VOCs (Variants Of Concern). We explored the functional dynamics of nasopharyngeal transcriptionally active microbes (TAMs) between vaccination breakthroughs and unvaccinated SARS-CoV-2 infected individuals. Microbial taxonomic communities were differentially altered with skewed enrichment of bacterial class/genera of Firmicutes and Gammaproteobacteria with grossly reduced phylum Bacteroidetes in vaccination breakthrough individuals. The Bacillus genus was abundant in Firmicutes in vaccination breakthrough whereas Prevotella among Bacteroides dominated the unvaccinated. Also, Pseudomonas and Salmonella of Gammaproteobacteria were overrepresented in vaccination breakthrough, whilst unvaccinated showed presence of several genera, Achromobacter, Bordetella, Burkholderia, Neisseria, Hemophilus, Salmonella and Pseudomonas, belonging to Proteobacteria. At species level, the microbiota of vaccination breakthrough exhibited relatively higher abundance of unique commensals, in comparison to potential opportunistic microbes enrichment in unvaccinated patients’ microbiota. Functional metabolic pathways like amino acid biosynthesis, sulphate assimilation, fatty acid and beta oxidation, associated with generation of SCFAs (short chain fatty acids), were enriched in vaccination breakthroughs. Majorly, metabolic pathways of LCFAs biosynthesis (long chain fatty acids; oleate, dodecenoate, palmitoleate, gondoate) were found associated with the unvaccinated. Our research highlights that vaccination decreases the microbial diversity in terms of depleting opportunistic pathogens and increasing the preponderance of commensals with respect to unvaccinated patients. Metabolic pathway analysis substantiates the shift in diversity to functionally modulate immune response generation, which may be related to mild clinical manifestations and faster recovery times during vaccination breakthroughs.

Mendelian randomization study revealed a gut microbiota-neuromuscular junction axis in myasthenia gravis

“…Class Gammaproteobacteria belongs to phylum proteobacteria, the abundance and functional characterization of which have been mixed across studies. Devi et al identified significant difference at the class level of the phylum Proteobacteria in the COVID 19 vaccination breakthroughs, where Alphaproteobacteria and Betaproteobacteria were found transcendent in the unvaccinated patients while Gammaproteobacteria was found enriched in the vaccinated patients 40 . Evidence exists to support this finding which suggests that an increase of Gammaproteobacteria produces beneficial effects for favorable immune responses post vaccination 41 .…”

Association of gut microbiota with COVID‐19 susceptibility and severity: A two‐sample Mendelian randomization study

“…Pseudomonas and Salmonella (also a member of the class Gammaproteobacteria ) were overrepresented in the COVID‐19 vaccination breakthrough. Gammaproteobacteria have been reported to be beneficial for a favorable immune response postvaccination 39 . The order Selenomonadales belongs to the class Negativicutes .…”

“…Gammaproteobacteria have been reported to be beneficial for a favorable immune response postvaccination. 39 The order Selenomonadales belongs to the class Negativicutes. Patients with human immunodeficiency virus (HIV) had a higher abundance of Negativicutes.…”

Longitudinal study across SARS-CoV-2 variants identifies transcriptionally active microbes (TAMs) associated with Delta severity

“…Our prior studies have lit up the dynamics of commensal and opportunistic TAMs at various phases of disease severity and the quicker turnaround rate of patients who had received vaccinations. 13 , 17 To the best of our knowledge, this is the first study to characterize the TAMs composition and host-microbe dynamics across different variants of SARS-CoV-2, namely Pre-VOC, Delta, and Omicron, as well as the clinical outcomes of each group, recovery, and mortality.…”

“…In yet another study by our group, the importance of commensal species including Streptococcus salivarius , Streptococcus dysgalactiae , and Pseudomonas alcaliphila were found in the milder presentation of the SARS-CoV-2 infected patients who received two doses of COVID-19 vaccine compared to unvaccinated & infected patients. 13 Many studies have demonstrated the superiority of commensal microbial composition over opportunistic pathogens in the early recovery of COVID-19 patients. 14 , 15 , 16 These findings suggest the importance of understanding the dynamics of TAMs in longitudinal studies with respect to the COVID-19 patients who were exposed to the virus during several waves, and if so, how this could be coupled to the severity of the disease and the patients' clinical outcomes.…”