The immunopathogenesis of a cytokine storm : the key mechanisms underlying severe COVID-19

Hiti, Luka (author), Markovič, Tijana (author), Lainščak, Mitja (author), Farkaš-Lainščak, Jerneja (author), Pal, Emil (author), Mlinarič-Raščan, Irena (author)

A cytokine storm is marked by excessive pro-inflammatory cytokine release, and has emerged as a key factor in severe COVID-19 cases – making it a critical therapeutic target. However, its pathophysiology was poorly understood, which hindered effective treatment. SARS-CoV-2 initially disrupts angiotensin signalling, promoting inflammation through ACE-2 downregulation. Some patients’ immune systems then fail to shift from innate to adaptive immunity, suppressing interferon responses and leading to excessive pyroptosis and neutrophil activation. This amplifies tissue damage and inflammation, creating a pro-inflammatory loop. The result is the disruption of Th1/Th2 and Th17/Treg balances, lymphocyte exhaustion, and extensive blood clotting. Cytokine storm treatments include glucocorticoids to suppress the immune system, monoclonal antibodies to neutralize specific cytokines, and JAK inhibitors to block cytokine receptor signalling. However, the most effective treatment options for mitigating SARS-CoV-2 infection remain vaccines as a preventive measure and antiviral drugs for the early stages of infection. This article synthesizes insights into immune dysregulation in COVID-19, offering a framework to better understand cytokine storms and to improve monitoring, biomarker discovery, and treatment strategies for COVID-19 and other conditions involving cytokine storms.

• Language: English
• Keywords: COVID-19, severe disease, cytokine storm, inflammation, immune system, treatment
• Work type: Article
• Typology: 1.02 - Review Article
• Organization: FFA - Faculty of Pharmacy; MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: Str. 1-17
• Numbering: Vol. 82
• PID: 20.500.12556/RUL-167824
• UDC: 614
• ISSN on article: 1879-0305
• DOI: 10.1016/j.cytogfr.2024.12.003
• COBISS.SI-ID: 222549507
• Publication date in RUL: 13.03.2025

Record is a part of a journal

• Title: Cytokine & growth factor reviews
• Shortened title: Cytokine growth factor rev.
• Publisher: Elsevier
• ISSN: 1879-0305
• COBISS.SI-ID: 175319555

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: covid-19, imunski sistem