Cytokine Storm in COVID-19: Immunopathogenesis and Therapy
Abstract
:1. Introduction
2. Etiopathogenesis of the Cytokine Storm
3. Clinical Features of the Cytokine Storm
4. COVID-19 Related Cytokine Storm
5. Targeting the Cytokine Storm in COVID-19
5.1. Anti-Inflammatory/Immunosuppressive Agents
5.2. RAAS Targeting Drugs
5.3. Cytokine Inhibitors
5.4. Antioxidants
5.5. Blood Purification Therapies
5.6. Vaccine and Cytokine Storm
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Genetic/Idiopathic Diseases |
---|
Primary HLH Autoinflammatory diseases Idiopathic MCD |
Secondary HLH-associated diseases |
Autoimmune diseases Malignancies Intracellular pathogens |
Infective diseases |
Sepsis HHV-8 infection (secondary MCD) EBV infection Coronaviruses (SARS, MERS, COVID-19) |
Iatrogenic causes |
Blinatumomab CAR T cell therapy TGN1412 |
Drugs and Treatments | Mechanism of Action | Confirmed Benefit in Cytokine Storm? | References |
---|---|---|---|
Glucocorticoids | Immunosuppression and anti-inflammatory effects | ↓ mortality (patients on O2 therapy or MV) | [48,49,50,51] |
Colchicine | Neutrophils’ activation and migration inhibitor + interferes with the inflammasome | No benefit demonstrated | [53,54,55] |
ACEIs | Angiotensin-converting enzyme inhibitor | Still uncertain | [56,57,58,59,60,61] |
Sartans | Angiotensin receptor antagonist | ||
Aliskiren | Renin inhibitor | ||
Anakinra | IL1R antagonist | Still uncertain (seem to be effective) | [65,66,67,68] |
Anti-IL6 MABs (tocilizumab) | IL6 inhibitors | Still uncertain (seem to be effective in addition to cortisone) | [73,74,75,76,77] |
Anti-TNF MABs (adalimumab, infliximab) | TNF inhibitors | Still uncertain (further RCTs are ongoing) | [78] |
Anti-JAK MABs (baricitinib, tofacitinib) | JAK inhibitors | Still uncertain (seem to be effective, further RCTs are ongoing) | [79,80] |
Antioxidant agents (methylene blue) | ROS, RNOS, and cytokines production inhibitors (+ inhibit SARS-CoV-2 cellular infection?) | Still uncertain (further RCTs are ongoing) | [83] |
Blood purification therapies (TPE) | Cytokines’ removal | Still uncertain | [89,90,91,92,93,94] |
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Zanza, C.; Romenskaya, T.; Manetti, A.C.; Franceschi, F.; La Russa, R.; Bertozzi, G.; Maiese, A.; Savioli, G.; Volonnino, G.; Longhitano, Y. Cytokine Storm in COVID-19: Immunopathogenesis and Therapy. Medicina 2022, 58, 144. https://doi.org/10.3390/medicina58020144
Zanza C, Romenskaya T, Manetti AC, Franceschi F, La Russa R, Bertozzi G, Maiese A, Savioli G, Volonnino G, Longhitano Y. Cytokine Storm in COVID-19: Immunopathogenesis and Therapy. Medicina. 2022; 58(2):144. https://doi.org/10.3390/medicina58020144
Chicago/Turabian StyleZanza, Christian, Tatsiana Romenskaya, Alice Chiara Manetti, Francesco Franceschi, Raffaele La Russa, Giuseppe Bertozzi, Aniello Maiese, Gabriele Savioli, Gianpietro Volonnino, and Yaroslava Longhitano. 2022. "Cytokine Storm in COVID-19: Immunopathogenesis and Therapy" Medicina 58, no. 2: 144. https://doi.org/10.3390/medicina58020144