{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:33:25Z","timestamp":1790660005670,"version":"4.1.0"},"reference-count":35,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T00:00:00Z","timestamp":1719446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>In late December 2019, SARS-CoV-2 was identified as the cause of a new pneumonia (COVID-19), leading to a global pandemic declared by the WHO on 11 March 2020, with significant human, economic, and social costs. Although most COVID-19 cases are asymptomatic or mild, 14% progress to severe disease, and 5% develop critical illness with complications such as interstitial pneumonia, acute respiratory distress syndrome (ARDS), and multiple organ dysfunction syndrome (MODS). SARS-CoV-2 primarily targets the respiratory system but can affect multiple organs due to the widespread presence of angiotensin-converting enzyme 2 (ACE2) receptors, which the virus uses to enter cells. This broad distribution of ACE2 receptors means that SARS-CoV-2 infection can lead to cardiovascular, gastrointestinal, renal, hepatic, central nervous system, and ocular damage. The virus triggers the innate and adaptive immune systems, resulting in a massive cytokine release, known as a \u201ccytokine storm\u201d, which is linked to tissue damage and poor outcomes in severe lung disease. Interleukin-6 (IL-6) is particularly important in this cytokine release, with elevated levels serving as a marker of severe COVID-19. IL-6 is a multifunctional cytokine with both anti-inflammatory and pro-inflammatory properties, acting through two main pathways: classical signalling and trans-signalling. Classical signalling involves IL-6 binding to its membrane-bound receptor IL-6R and then to the gp130 protein, while trans-signalling occurs when IL-6 binds to the soluble form of IL-6R (sIL-6R) and then to membrane-bound gp130 on cells that do not express IL-6R. The soluble form of gp130 (sgp130) can inhibit IL-6 trans-signalling by binding to sIL-6R, thereby preventing it from interacting with membrane-bound gp130. Given the central role of IL-6 in COVID-19 inflammation and its association with severe disease, we aimed to analyse the behaviour of IL-6 and its soluble receptor complex during different waves of the pandemic. This analysis could help determine whether IL-6 levels can serve as prognostic markers of disease severity.<\/jats:p>","DOI":"10.3390\/life14070814","type":"journal-article","created":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T13:26:43Z","timestamp":1719494803000},"page":"814","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Behaviour of IL-6 and Its Soluble Receptor Complex during Different Waves of the COVID-19 Pandemic"],"prefix":"10.3390","volume":"14","author":[{"given":"Gaetano","family":"Di Spigna","sequence":"first","affiliation":[{"name":"Department of Translational Medical Sciences, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Covelli","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7652-970X","authenticated-orcid":false,"given":"Maria","family":"Vargas","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Di Caprio","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5646-2795","authenticated-orcid":false,"given":"Valentina","family":"Rubino","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5032-1668","authenticated-orcid":false,"given":"Carmine","family":"Iacovazzo","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1925-9912","authenticated-orcid":false,"given":"Filomena","family":"Napolitano","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Servillo","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5382-8106","authenticated-orcid":false,"given":"Loredana","family":"Postiglione","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1056\/NEJMoa2001017","article-title":"A novel coronavirus from patients with pneumonia in China, 2019","volume":"382","author":"Zhu","year":"2020","journal-title":"N. 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