A Comparison between SARS-CoV-2 and Gram-Negative Bacteria-Induced Hyperinflammation and Sepsis
Sepsis is a life-threatening condition caused by the body’s overwhelming response to an infection, such as pneumonia or urinary tract infection. It occurs when the immune system releases cytokines into the bloodstream, triggering widespread inflammation. If not treated, it can lead to organ failure...
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MDPI AG
2023-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/20/15169 |
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| author | Klaus Brandenburg Raquel Ferrer-Espada Guillermo Martinez-de-Tejada Christian Nehls Satoshi Fukuoka Karl Mauss Günther Weindl Patrick Garidel |
| author_facet | Klaus Brandenburg Raquel Ferrer-Espada Guillermo Martinez-de-Tejada Christian Nehls Satoshi Fukuoka Karl Mauss Günther Weindl Patrick Garidel |
| author_sort | Klaus Brandenburg |
| collection | DOAJ |
| description | Sepsis is a life-threatening condition caused by the body’s overwhelming response to an infection, such as pneumonia or urinary tract infection. It occurs when the immune system releases cytokines into the bloodstream, triggering widespread inflammation. If not treated, it can lead to organ failure and death. Unfortunately, sepsis has a high mortality rate, with studies reporting rates ranging from 20% to over 50%, depending on the severity and promptness of treatment. According to the World Health Organization (WHO), the annual death toll in the world is about 11 million. One of the main toxins responsible for inflammation induction are lipopolysaccharides (LPS, endotoxin) from Gram-negative bacteria, which rank among the most potent immunostimulants found in nature. Antibiotics are consistently prescribed as a part of anti-sepsis-therapy. However, antibiotic therapy (i) is increasingly ineffective due to resistance development and (ii) most antibiotics are unable to bind and neutralize LPS, a prerequisite to inhibit the interaction of endotoxin with its cellular receptor complex, namely Toll-like receptor 4 (TLR4)/MD-2, responsible for the intracellular cascade leading to pro-inflammatory cytokine secretion. The pandemic virus SARS-CoV-2 has infected hundreds of millions of humans worldwide since its emergence in 2019. The COVID-19 (Coronavirus disease-19) caused by this virus is associated with high lethality, particularly for elderly and immunocompromised people. As of August 2023, nearly 7 million deaths were reported worldwide due to this disease. According to some reported studies, upregulation of TLR4 and the subsequent inflammatory signaling detected in COVID-19 patients “mimics bacterial sepsis”. Furthermore, the immune response to SARS-CoV-2 was described by others as “mirror image of sepsis”. Similarly, the cytokine profile in sera from severe COVID-19 patients was very similar to those suffering from the acute respiratory distress syndrome (ARDS) and sepsis. Finally, the severe COVID-19 infection is frequently accompanied by bacterial co-infections, as well as by the presence of significant LPS concentrations. In the present review, we will analyze similarities and differences between COVID-19 and sepsis at the pathophysiological, epidemiological, and molecular levels. |
| first_indexed | 2024-03-10T21:13:04Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T21:13:04Z |
| publishDate | 2023-10-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-bc2b1d7943cd4f28942adf9bb4b9d5662023-11-19T16:42:40ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-10-0124201516910.3390/ijms242015169A Comparison between SARS-CoV-2 and Gram-Negative Bacteria-Induced Hyperinflammation and SepsisKlaus Brandenburg0Raquel Ferrer-Espada1Guillermo Martinez-de-Tejada2Christian Nehls3Satoshi Fukuoka4Karl Mauss5Günther Weindl6Patrick Garidel7Brandenburg Antiinfektiva, c/o Forschungszentrum Borstel, Leibniz-Lungenzentrum, Parkallee 10, 23845 Borstel, GermanyDepartment of Microbiology, University of Navarra, IdiSNA (Navarra Institute for Health Research), Irunlarrea 1, E-31008 Pamplona, SpainDepartment of Microbiology, University of Navarra, IdiSNA (Navarra Institute for Health Research), Irunlarrea 1, E-31008 Pamplona, SpainForschungszentrum Borstel, FG Biophysik, Parkallee 10, 23845 Borstel, GermanyNational Institute of Advanced Industrial Science and Technology (AIST), Takamatsu 761-0395, JapanBrandenburg Antiinfektiva, c/o Forschungszentrum Borstel, Leibniz-Lungenzentrum, Parkallee 10, 23845 Borstel, GermanyPharmazeutisches Institut, Abteilung Pharmakologie und Toxikologie, Universität Bonn, Gerhard-Domagk-Str. 3, 53121 Bonn, GermanyPhysikalische Chemie, Martin-Luther-Universität Halle-Wittenberg, 06108 Halle (Saale), GermanySepsis is a life-threatening condition caused by the body’s overwhelming response to an infection, such as pneumonia or urinary tract infection. It occurs when the immune system releases cytokines into the bloodstream, triggering widespread inflammation. If not treated, it can lead to organ failure and death. Unfortunately, sepsis has a high mortality rate, with studies reporting rates ranging from 20% to over 50%, depending on the severity and promptness of treatment. According to the World Health Organization (WHO), the annual death toll in the world is about 11 million. One of the main toxins responsible for inflammation induction are lipopolysaccharides (LPS, endotoxin) from Gram-negative bacteria, which rank among the most potent immunostimulants found in nature. Antibiotics are consistently prescribed as a part of anti-sepsis-therapy. However, antibiotic therapy (i) is increasingly ineffective due to resistance development and (ii) most antibiotics are unable to bind and neutralize LPS, a prerequisite to inhibit the interaction of endotoxin with its cellular receptor complex, namely Toll-like receptor 4 (TLR4)/MD-2, responsible for the intracellular cascade leading to pro-inflammatory cytokine secretion. The pandemic virus SARS-CoV-2 has infected hundreds of millions of humans worldwide since its emergence in 2019. The COVID-19 (Coronavirus disease-19) caused by this virus is associated with high lethality, particularly for elderly and immunocompromised people. As of August 2023, nearly 7 million deaths were reported worldwide due to this disease. According to some reported studies, upregulation of TLR4 and the subsequent inflammatory signaling detected in COVID-19 patients “mimics bacterial sepsis”. Furthermore, the immune response to SARS-CoV-2 was described by others as “mirror image of sepsis”. Similarly, the cytokine profile in sera from severe COVID-19 patients was very similar to those suffering from the acute respiratory distress syndrome (ARDS) and sepsis. Finally, the severe COVID-19 infection is frequently accompanied by bacterial co-infections, as well as by the presence of significant LPS concentrations. In the present review, we will analyze similarities and differences between COVID-19 and sepsis at the pathophysiological, epidemiological, and molecular levels.https://www.mdpi.com/1422-0067/24/20/15169sepsislipopolysaccharideGram-negative bacteriaCOVID-19 pandemichyperinflammationTLR4 |
| spellingShingle | Klaus Brandenburg Raquel Ferrer-Espada Guillermo Martinez-de-Tejada Christian Nehls Satoshi Fukuoka Karl Mauss Günther Weindl Patrick Garidel A Comparison between SARS-CoV-2 and Gram-Negative Bacteria-Induced Hyperinflammation and Sepsis International Journal of Molecular Sciences sepsis lipopolysaccharide Gram-negative bacteria COVID-19 pandemic hyperinflammation TLR4 |
| title | A Comparison between SARS-CoV-2 and Gram-Negative Bacteria-Induced Hyperinflammation and Sepsis |
| title_full | A Comparison between SARS-CoV-2 and Gram-Negative Bacteria-Induced Hyperinflammation and Sepsis |
| title_fullStr | A Comparison between SARS-CoV-2 and Gram-Negative Bacteria-Induced Hyperinflammation and Sepsis |
| title_full_unstemmed | A Comparison between SARS-CoV-2 and Gram-Negative Bacteria-Induced Hyperinflammation and Sepsis |
| title_short | A Comparison between SARS-CoV-2 and Gram-Negative Bacteria-Induced Hyperinflammation and Sepsis |
| title_sort | comparison between sars cov 2 and gram negative bacteria induced hyperinflammation and sepsis |
| topic | sepsis lipopolysaccharide Gram-negative bacteria COVID-19 pandemic hyperinflammation TLR4 |
| url | https://www.mdpi.com/1422-0067/24/20/15169 |
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