Background When severe, COVID-19 shares many clinical features with bacterial sepsis. Yet, secondary bacterial infection is uncommon. However, as epithelium is injured and barrier function is lost, bacterial products entering the circulation might contribute to the pathophysiology of COVID-19. Methods We studied 19 adults, severely ill patients with COVID-19 infection, who were admitted to King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between 13th March and 17th April 2020. Blood samples on days 1, 3, and 7 of enrollment were analyzed for endotoxin activity assay (EAA), (1 → 3)-β-d-glucan (BG), and 16S rRNA gene sequencing to determine the circulating bacteriome. Results Of the 19 patients, 13 were in intensive care and 10 patients received mechanical ventilation. We found 8 patients with high EAA (≥ 0.6) and about half of the patients had high serum BG levels which tended to be higher in later in the illness. Although only 1 patient had a positive blood culture, 18 of 19 patients were positive for 16S rRNA gene amplification. Proteobacteria was the most abundant phylum. The diversity of bacterial genera was decreased overtime. Conclusions Bacterial DNA and toxins were discovered in virtually all severely ill COVID-19 pneumonia patients. This raises a previously unrecognized concern for significant contribution of bacterial products in the pathogenesis of this disease.

Background: When severe, COVID-19 shares many clinical features with bacterial sepsis. Yet, secondary bacterial infection is uncommon. However, as epithelium are injured and barrier function is lost, bacterial products entering the circulation might contribute to the pathophysiology of COVID-19. Methods: We studied 19 adults, severely ill patients with COVID-19 infection, who were admitted to King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between 13th March and 17th April 2020. Blood samples on day 1, 3, and 7 of enrollment were analyzed for endotoxin activity assay (EAA), Beta-D-Glucan (BG), and 16S rRNA gene sequencing to determine the circulating bacteriome. Findings: Of the 19 patients, 14 were in intensive care and 10 patients received mechanical ventilation. We found 8 patients with high EAA (≥ 0.6) and about half of the patients had high serum BG levels which tended to be higher in later in the illness. Although only 1 patient had a positive blood culture, 18 of 19 patients were positive for 16S rRNA gene amplification. Proteobacteria was the most abundant phylum. The diversity of bacterial genera was decreased overtime. Interpretation: Bacterial DNA and toxins were discovered in virtual all severely ill COVID-19 pneumonia patients. This raises a previously unrecognized concern for significant contribution of bacterial products in the pathogenesis of this disease.

The upper respiratory tract is inhabited by diverse range of commensal microbiota which plays a role in protecting the mucosal surface from pathogens. Alterations of the bacterial community from respiratory viral infections could increase the susceptibility to secondary infections and disease severities. We compared the upper respiratory bacterial profiles among Thai patients with influenza or COVID-19 by using 16S rDNA high-throughput sequencing based on MiSeq platform. The Chao1 richness was not significantly different among groups, whereas the Shannon diversity of Flu A and Flu B groups were significantly lower than Non-Flu & COVID-19 group. The beta diversity revealed that the microbial communities of influenza (Flu A and Flu B), COVID-19, and Non-Flu & COVID-19 were significantly different; however, the comparison of the community structure was similar between Flu A and Flu B groups. The bacterial classification revealed that Enterobacteriaceae was predominant in influenza patients, while Staphylococcus and Pseudomonas were significantly enriched in the COVID-19 patients. These implied that respiratory viral infections might be related to alteration of upper respiratory bacterial community and susceptibility to secondary bacterial infections. Moreover, the bacteria that observed in Non-Flu & COVID-19 patients had high abundance of Streptococcus, Prevotella, Veillonella, and Fusobacterium. This study provides the basic knowledge for further investigation of the relationship between upper respiratory microbiota and respiratory disease which might be useful for better understanding the mechanism of viral infectious diseases.

Because studies on all fecal organisms (bacteria, fungi, and viruses) in sepsis are rare and bacteriophages during sepsis might have adapted against gut bacteria with possible pathogenicity, cecal ligation and puncture (CLP; a sepsis mouse model) was evaluated. In fecal bacteriome, sepsis increased Bacteroides and Proteobacteria but decreased Firmicutes, while fecal virome demonstrated increased Podoviridae when compared with sham feces. There was no difference in the fungal microbiome (predominant Ascomycota in both sham and CLP mice) and the abundance of all organisms between sepsis and control groups. Interestingly, the transfers of feces from CLP mice worsened sepsis severity when compared with sham fecal transplantation, as evaluated by mortality, renal injury (serum creatinine and histology), liver damage (liver enzyme and histology), spleen apoptosis, serum cytokines, endotoxemia, and bacteremia. In contrast, the transfers of fecal viral particles from sepsis mice, but not from sham mice, attenuated inflammation in CLP sepsis possibly through the decrease in several fecal pathogenic bacteria (such as Proteobacteria, Gammaproteobacteria, and Prevotellaceae) as evaluated by fecal microbiome analysis. Perhaps the isolation of favorable bacteriophages in sepsis feces and increased abundance ex vivo before oral treatment in a high concentration are beneficial.

Cordyceps militaris is an industrially important fungus, which is often used in Asia as traditional medicine. There has been a published genome-scale metabolic model (GSMM) of C. militaris useful for predicting its growth behaviors; however, lipid metabolism, which plays a vital role in cellular functions, remains incomplete in the GSMM of C. militaris. A comprehensive study on C. militaris was thus performed by enhancing GSMM through integrative analysis of metabolic footprint and transcriptome data. Through the enhanced GSMM of C. militaris (called iPC1469), it contained 1469 genes, 1904 metabolic reactions and 1229 metabolites. After model evaluation, in silico growth simulation results agreed well with the experimental data of the fungal growths on different carbon sources. Beyond the model-driven integrative data analysis, interestingly, we found key metabolic responses in alteration of lipid metabolism in C. militaris upon different carbon sources. The sphingoid bases (e.g., sphinganine, sphingosine, and phytosphingosine) and ceramide were statistically significant accumulated in the xylose culture when compared with other cultures; this study suggests that the sphingolipid biosynthetic capability in C. militaris was dependent on the carbon source assimilated for cell growth; this finding provides a comprehensive basis for the sphingolipid biosynthesis in C. militaris that can help to further redesign its metabolic control for medicinal and functional food applications.