Controlling Cytokine Storm Is Vital in COVID-19

Abstract

Corona virus disease 2019 (COVID-19) has caused a global outbreak and severely posed threat to people’s health and social stability. Mounting evidence suggests that immunopathological changes, including diminished lymphocytes and elevated cytokines, are important drivers of disease progression and death in coronavirus infections. Cytokine storm not only limits further spread of virus in the body but also induces secondary tissue damage through the secretion of large amounts of active mediators and inflammatory factors. It has been determined that cytokine storm is a major cause of deaths in COVID-19; therefore, in order to reverse the deterioration of severe and critically ill patients from this disease, the cytokine storm has become a key therapeutic target. Although specific mechanisms of the occurrences of cytokine storms in COVID-19 have not been fully illuminated, hyper-activated innate immune responses, and dysregulation of ACE2 (angiotensin converting enzyme 2) expression and its downstream pathways might provide possibilities. Tailored immunoregulatory therapies have been applied to counteract cytokine storms, such as inhibition of cytokines, corticosteroids, blood purification therapy, and mesenchymal stem cell therapy. This review will summarize advances in the research of cytokine storms induced by COVID-19, as well as potential intervention strategies to control cytokine storms.

Neural epidermal growth factor-like 1 protein variant increases survival and modulates the inflammatory and immune responses in human ACE-2 transgenic mice infected with SARS-CoV-2

“…62 Cytokines/chemokines involved in neutrophil recruitment, migration and activation were also increased, such as IL-9, LIX, MIP-2, KC and G-CSF, suggesting an important role of neutrophils in SARS-CoV-2 viral clearance and cytokine balance. [63][64][65][66] Although there are numerous clinical reports on the increase or decrease of IL-6 in COVID-19, we observed an increased level in NV1-treated mice. There is no consensus on the levels and role of IL-6 as biomarker for disease progression but clinical trials using potent inhibitors of IL-6 show the increased propensity for secondary infections.…”

“…74 These biological effects are likely to promote survival and recovery from lung tissue damage. 65,75 Further testing of this hypothesis will be conducted in larger statistically powered study with a wider escalating dose range (lower doses than 1.25 mg/kg), histopathology of lung tissue to examine the severity of tissue injury and scarring, analysis of immune cell populations and examining early (after first administration of NV1) and late effects (at euthanasia) on the levels of the viral load and inflammatory molecules.…”

A novel glucocorticoid and androgen receptor modulator reduces viral entry and innate immune inflammatory responses in the Syrian Hamster model of SARS-CoV-2

“…In conclusion, these data demonstrate disease progression and pathology within the lungs of SARS-CoV-2-infected animals depends upon production of both ACE2 and TMPRSS2, which facilitate viral entry and replication, leading to recruitment of macrophages that initiate a severe innate immune response leading to broncho-interstitial pneuomonia and consolidation of the lung parenchyma. Expression of IL-6 is necessary for recruitment of immune cells to the site of infection, which leads to the ‘cytokine storm’ and decreased prognosis for patients [55, 56]. PT150 treatment interrupts this progression of disease, limiting viral entry, thereby reducing viral loads and decreasing the severity of the immune response to SARS-CoV-2 infection.…”

Tissue Integrity and COVID-19

“…The various methods to prevent or decrease cytokine storm in COVID-19 patients have been recently reviewed [34]. The application of interleukin-1 blockers, interleukin-6 inhibitors, and Janus kinase inhibitors in treatment of COVID-19 has been suggested with the aim to block hyperinflammation [35].…”