Cytokine storm in COVID-19: Potential therapeutics for immunomodulation

Abstract

Hyperinflammatory response in COVID-19 infection Cytokines are a broad group of small proteins that are released by cells to control cell functionalities like proliferation and differentiation. 14 Despite these functions, another significant role of cytokines is to regulate immune and inflammatory responses. 14 In COVID-19 infection, the uncoated viral RNA genome is released into the cytoplasm to allow two polyproteins to translate, followed by transcription of the sub-genomic RNAs and viral genome replication. 15 This results in the progression of CRSinduced ARDS due to the upregulation of proinflammatory cytokines. This massive cytokine release is analogous to secondary hemophagocytic lymphohistiocytosis (sHLH), which is characterized by persistent activation of natural killer (NK) cells and cytotoxic T cells. 16-18 In most severe Review Article The outbreak of new coronavirus disease-2019 or COVID-19 infection has become a global health emergency at the beginning of this year. Currently, no specific vaccines and therapeutic medications are available to treat this disease. Even though several vaccine candidates are under investigation, it will take some time to make them available for the mass population. Hyperinflammation due to excessive cytokine release in COVID-19 infected patients with other inflammatory diseases makes lethal effects, including multiorgan failure and even death. The increasing gain of insight about the pathophysiology of this novel coronavirus enables experts to consider some commonly available anti-inflammatory drugs as potential immunomodulatory candidates for the cytokine release syndrome (CRS) treatment in COVID-19 infection. This review was conducted to discuss all the possible signalling pathways involved in COVID-19 related hyperinflammation. It also emphasized on the efficacy of both synthetic and natural therapeutic drugs for immunomodulation in the COVID-19 related CRS treatment.

Nanocurcumin improves Treg cell responses in patients with mild and severe SARS-CoV2

“…as anti-inflammatory agents, as well as other immunomodulatory drugs, including monoclonal antibodies, interferon beta, Janus Kinase Inhibitors, corticosteroids (dexamethasone, methylprednisolone, etc. ), and nonsteroidal anti-inflammatory drugs (NSAIDs), highlights the importance of suppressing inflammatory responses and enhancing anti-inflammatory responses of Tregs in the course of COVID-19 infection [ 38 , 39 ]. There are several natural substances known to have antiviral and anti-inflammatory effects against coronaviruses and other virus types, including lycorine, flavones, quinones, fatty acids, terpenes, alkaloids, and tannins.…”

Changes in oxidative markers in COVID-19 patients

“…These interactions between oxidative stress and inflammatory cytokines can lead to several organ failures in COVID-19 patients who proceed to worsening the condition. “Cytokine storm” in covid-19 patients is well established ( 27 , 28 ). Cytokine storm has prominent role in development of acute respiratory distress syndrome and various organ dysfunctions ( 13 ).…”

Polymer-based nano-therapies to combat COVID-19 related respiratory injury: progress, prospects, and challenges

“…[ 46 ] Moreover, a wide range of conventional anti-inflammatory drugs have been proposed to treat ARDS because these drugs work by regulating inflammatory signalling targets (Losartan: Angiotensin II receptor blocker, Tocilizumab, Siltuximab: Interleukin-6 or IL-6 inhibitor, Baricitinib: Janus kinase or JAK-1/2 inhibitor, Anakinra: IL-1 inhibitor, Polyphenolic compounds: Kinase inhibitors, and so on) within the inflammatory systems in the body. [ 8 , 47–49 ] Despite the potentiality of these proposed treatments, developing these therapeutics is lagging behind the need for them due to extensive research and clinical trials to prove their efficacy and safety. [ 50 ] Recently, Russel et al investigated the efficacy of corticosteroid treatment for COVID-19 related lung injury.…”