The cytokine storm of COVID-19: a spotlight on prevention and protection

Abstract

Introduction:The cytokine release syndrome (CRS) of COVID-19 is associated with the development of critical illness requiring multi-organ support. Further research is required to halt progression of multiorgan injury induced by hyper-inflammation. Areas covered: PubMed/MEDLINE TM databases were accessed between May 9 th -June 9 th , 2020, to review the latest perspectives on the treatment and pathogenesis of CRS. Expert opinion: Over-activity of chemotaxis triggers a macrophage activation syndrome (MAS) resulting in the release of pro-inflammatory cytokines. IL-6 and TNF-α are at the forefront of hyperinflammation. The inflammatory cascade induces endothelial activation and capillary leak, leading to circulatory collapse and shock. As endothelial dysfunction persists, there is activation of the clotting cascade and microvascular obstruction. Continued endothelial activation results in multi-organ failure, regardless of pulmonary tissue damage. We propose that targeting the endothelium may interrupt this cycle. Immuno-modulating therapies have been suggested, however, further data is necessary to confirm that they do not jeopardize adaptive immunity. Inhibition of IL-6 and the Janus Kinase, signal transducer and activator of transcription proteins pathway (JAK/STAT), are favorable targets. Remote ischemic conditioning (RIC) reduces the inflammation of sepsis in animal models and should be considered as a low risk intervention, in combination with cardiovascular protection.

A review on possible mechanistic insights of Nitazoxanide for repurposing in COVID-19

“…COVID-19 causes a complicated clash between host antiviral innate immunity and continuous upsurge of inflammatory markers, the latter being responsible for a fatal condition called "Cytokine storm" ( Coperchini et al, 2020 ; Samudrala et al, 2020 ). High systemic levels of interleukins, interferons, interferon inducible protein, tumour necrosis factor, growth factors, colony-stimulating factors, macrophage inflammatory protein, monocyte chemoattractant protein, chemokines are a hallmark of the SARS-CoV-2 cytokine storm ( Costela-Ruiz et al, 2020 ; Henderson et al, 2020 ; Pearce et al, 2020 ; Samudrala et al, 2020 ). Nitazoxanide causes activation of innate immune responses and induction of host-directed antiviral mechanisms, thereby exhibiting great promise against the SARS-CoV-2 cytokine storm ( Fig.…”

Investigation of COVID-19 comorbidities reveals genes and pathways coincident with the SARS-CoV-2 viral disease

“…All of these presentations have common elements of abnormality of inflammatory responses and manifestations of vascular defects such as thrombosis, which may be causally related 5,6,7,8,9 .…”

Glucocorticoids save lives in COVID-19 patients

“…IL-6 is one of the important cytokines released by inflammatory cells, especially macrophage, and is increased in COVID-19 patients at severe-to-critical stages. Therefore, the level of IL-6 is most frequently measured during the period of hospitalization, especially in severe cases of COVID-19 patients by rescuing medical team [5,6]. The inhibition of glucocorticoids to production of IL-6 certainly serves as a good predictive value for suppressing cytokine storm for COVID-19 patients at severe-to-critical stages.…”

“…Glucocorticoid are steroids that occur naturally in our body, and are known for their effectiveness at reducing inflammation and suppressing the immune system 4 . It is believed that one of the causes for multi-organ failure and lethality of COVID-19 patients is cytokine storm, which occurs when an immune system, is overactivated by virus infection 5 , 6 . Therefore, how to inhibit the cytokine storm has become a focus for the treatment of COVID-19 patients at severe or critical stages.…”