Calming the inflammatory storm in severe COVID-19 infections: Role of biologics- A narrative review

• Published in: Saudi pharmaceutical journal 2021-03, Vol.29 (3), p.213-222
• Main Authors: Banji, David, Alqahtani, Saad S., Banji, Otilia J.F., Machanchery, Shamna, Shoaib, Ambreen
• Format: Article
• Language: English
• Subjects: COVID-19; Cytokine storm; GM-CSF inhibitors; IL-6 inhibitors; JAK-STAT inhibitors; Review
• ISSN: 1319-0164; 2213-7475
• DOI: 10.1016/j.jsps.2021.01.005

The risk of Coronavirus infection continues, and the fear of resurgence indicates the lack of a successful therapeutic strategy. In severe COVID-19 infection, many immune cells and their products are involved, making management difficult. The abundant release of cytokines and chemokines in severe COVID-19 patients leads to profound hyper inflammation and the mobilization of immune cells, triggering the cytokine storm. The complications associated with the cytokine storm include severe respiratory distress, intravascular coagulation, multi-organ failure, and death. The enormous formation of interleukin (IL)-6 and hemopoietic factors such as granulocyte–macrophage colony-stimulating factor (GM-CSF) are implicated in the severity of the infection. Moreover, these inflammatory cytokines and factors signal through the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway causing the activation of cytokine-related genes. The neutralization of these proteins could be of therapeutic help in COVID-19 patients and could mitigate the risk of mortality. IL-6 antagonist, IL-6 receptor antagonists, GM-CSF receptor inhibitors, and JAK-STAT inhibitors are being investigated to prevent intense lung injury in COVID-19 patients and increase the chances of survival. The review focuses the role of IL-6, GM-CSF, and JAK-STAT inhibitors in regulating the immune response in severely affected COVID-19 patients.