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Endotoxemia and circulating bacteriome in severe COVID-19 patients
Phatadon Sirivongrangson1,2,3, Win Kulvichit1,2,3, Sunchai Payungporn4,5
1Division of Nephrology, Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Bangkok, 10330, Thailand.
Insights
Bacterial DNA and toxins were found in most severe COVID-19 patients, suggesting bacterial products may contribute to disease severity. This challenges the notion that secondary bacterial infections are rare in COVID-19.
Area of Science:
- Infectious Diseases
- Microbiology
- Critical Care Medicine
Background:
- Severe COVID-19 exhibits clinical similarities to bacterial sepsis.
- Secondary bacterial infections are infrequent in COVID-19.
- Epithelial injury in COVID-19 may allow bacterial products to enter circulation, influencing disease.
Purpose of the Study:
- To investigate the presence and impact of bacterial products in severely ill COVID-19 patients.
- To analyze endotoxin activity, (1→3)-β-D-glucan levels, and circulating bacterial DNA.
Main Methods:
- Studied 19 severely ill COVID-19 patients.
- Collected blood samples on days 1, 3, and 7.
- Performed endotoxin activity assay (EAA), (1→3)-β-D-glucan (BG) assay, and 16S rRNA gene sequencing.
Main Results:
- 8/19 patients had high endotoxin activity (EAA).
- Serum BG levels were elevated in about half of patients, increasing over time.
- 18/19 patients tested positive for bacterial 16S rRNA gene, with Proteobacteria being dominant.
Conclusions:
- Bacterial DNA and toxins are prevalent in severe COVID-19 pneumonia.
- These findings highlight a potential role for bacterial products in COVID-19 pathogenesis.
- This suggests bacterial products may significantly contribute to disease development.
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.
