Endotoxemia and circulating bacteriome in severe COVID-19 patients

Abstract

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 immunology of SARS-CoV-2 infections and vaccines

“…In addition, we observed reduced frequencies of plasmacytoid DCs, and diminished production of IFNα by plasmacytoid DCs, and proinflammatory cytokines by myeloid DCs, in response to stimulation ex vivo, consistent with results by Zhou et al [ 43 ]. Lastly, increased bacterial products such as LPS and bacterial DNA in blood correlated with disease severity, consistent with the study by Srisawat and colleagues [ 47 ]. The concentration of LPS and bacterial DNA was strong correlated with the levels of proinflammatory cytokines such as IL-6, TNF, EN-RAGE, OSM and LIGHT, consistent with the study by Srisawat and colleagues [ 47 ], suggesting a potential role for such products in contributing to enhanced inflammatory cytokine production in severe disease [ 34 ].…”

Micronutrients, Non-Nutrients and Mediterranean Diet: A Potential Protective Role Against COVID-19 through Modulation of PAF Actions and Metabolism

“…Moreover, omega-3 can reduce PAF production in HUVEC endothelial cells [103]. In cases of endotoxemia, which is also observed in seriously ill COVID-19 patients [106], linolenic acid has been found to reduce PAF production in Sprague-Dawley rats [107]. In addition, a diet rich in fish oils (10%) has been found to reduce PAF and LTB4 [108].…”

Obesity and diabetes as comorbidities for COVID-19: Underlying mechanisms and the role of viral–bacterial interactions

“…A cross-sectional study of 30 patients with COVID-19, 24 patients with influenza A, and 30 matched healthy controls revealed a significantly higher abundance of opportunistic pathogens in gut microbiota of COVID-19 patients ( Gu and Chen, 2020 ). In a small prospective study on 19 patients with severe pulmonary forms of COVID-19, bacterial DNA and toxins were found in blood samples of almost all individuals, whereas over 40% of them had high, and over 89% had increased endotoxin levels measured with chemiluminescent-based endotoxin activity assay ( Sirivongrangson et al, 2020 ).…”