{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:35:09Z","timestamp":1760150109740,"version":"build-2065373602"},"reference-count":87,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T00:00:00Z","timestamp":1697241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"C.N. Phospholipid Research Center","award":["CNE-2022-104\/1-1"],"award-info":[{"award-number":["CNE-2022-104\/1-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sepsis is a life-threatening condition caused by the body\u2019s 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 \u201cmimics bacterial sepsis\u201d. Furthermore, the immune response to SARS-CoV-2 was described by others as \u201cmirror image of sepsis\u201d. 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.<\/jats:p>","DOI":"10.3390\/ijms242015169","type":"journal-article","created":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T14:38:42Z","timestamp":1697294322000},"page":"15169","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A Comparison between SARS-CoV-2 and Gram-Negative Bacteria-Induced Hyperinflammation and Sepsis"],"prefix":"10.3390","volume":"24","author":[{"given":"Klaus","family":"Brandenburg","sequence":"first","affiliation":[{"name":"Brandenburg Antiinfektiva, c\/o Forschungszentrum Borstel, Leibniz-Lungenzentrum, Parkallee 10, 23845 Borstel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raquel","family":"Ferrer-Espada","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Navarra, IdiSNA (Navarra Institute for Health Research), Irunlarrea 1, E-31008 Pamplona, Spain"},{"name":"Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3755-451X","authenticated-orcid":false,"given":"Guillermo","family":"Martinez-de-Tejada","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Navarra, IdiSNA (Navarra Institute for Health Research), Irunlarrea 1, E-31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9210-3271","authenticated-orcid":false,"given":"Christian","family":"Nehls","sequence":"additional","affiliation":[{"name":"Forschungszentrum Borstel, FG Biophysik, Parkallee 10, 23845 Borstel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Fukuoka","sequence":"additional","affiliation":[{"name":"National Institute of Advanced Industrial Science and Technology (AIST), Takamatsu 761-0395, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl","family":"Mauss","sequence":"additional","affiliation":[{"name":"Brandenburg Antiinfektiva, c\/o Forschungszentrum Borstel, Leibniz-Lungenzentrum, Parkallee 10, 23845 Borstel, Germany"},{"name":"Sylter Klinik Karl Mauss, Dr.-Nicolas-Strasse 3, 25980 Westerland (Sylt), Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4493-7597","authenticated-orcid":false,"given":"G\u00fcnther","family":"Weindl","sequence":"additional","affiliation":[{"name":"Pharmazeutisches Institut, Abteilung Pharmakologie und Toxikologie, Universit\u00e4t Bonn, Gerhard-Domagk-Str. 3, 53121 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Garidel","sequence":"additional","affiliation":[{"name":"Physikalische Chemie, Martin-Luther-Universit\u00e4t Halle-Wittenberg, 06108 Halle (Saale), Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41579-020-00459-7","article-title":"Characteristics of SARS-CoV-2 and COVID-19","volume":"19","author":"Hu","year":"2021","journal-title":"Nat. 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