Blood microbial analyses reveal long-term effects of SARS-CoV-2 infection on patients who recovered from COVID-19

Objective: Few symptoms persist for a long time after patients recover from COVID-19, called "long COVID". We explored the potential microbial risk factors for COVID-19 for a deeper understanding and assistance in the follow-up treatment of these sequelae. Methods: Microbiome re-annotation was performed using whole blood RNA-Seq data collected from recovered COVID-19 patients and healthy controls at multiple time points. Subsequently, a series of downstream analyses were conducted to reveal the microbial characteristics of patients who recovered from SARS-CoV-2 infection. Results: The blood microbiome at 12 weeks post-infection was most evidently disturbed, including an increasing ratio of Bacillota/Bacteroidota and a higher microbial alpha diversity. In addition, a group of pathogenic microbes at 12 weeks post-infection were identified, including Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, which were positively associated with host genes involved in immune regulatory and olfactory transduction pathways. Several microbes, such as Streptococcus pneumoniae were associated with infiltrating immune cells, such as M2 macrophages. Conclusion: This study provides insights into the relationship between the blood microbiome and COVID-19 sequelae. Several pathogenic microbes were enriched in recovered COVID-19 patients and thus affected host genes participating in the immune and olfactory transduction pathways, which play critical roles in COVID-19 sequelae.