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Cytokine Storm - The Main Reason For Enormous Deaths In COVID -19 Pandemic

Cytokine Storm And COVID 19

The pandemic has taught us lot of lessons that we should change ourselves for growth and well being of mankind. The reason behind increase in mortality rate of COVID 19 patients is cytokine storm (Cytokine storm syndrome CSS ).Cytokine storm is pathological condition in which body kills its own cells in order to save the cell. Primary intention of body is to protect the body but in several conditions Immune system is confused between self and foreign.
1. What is Cytokine storm

“cytokine storm syndrome” (CSS)] cytokine storm is a systemic inflammatory response to infections and drugs and leads to excessive activation of immune cells and the generation of pro-inflammatory cytokines. Defination according to National Cancer Institute ” A severe immune reaction in which the body releases too many cytokines into the blood too quickly.” Cytokines play an important role in normal immune responses, but having a large amount of them released in the body all at once can be harmful. A cytokine storm can occur as a result of an infection, autoimmune condition, or other disease. It may also occur after treatment with some types of immunotherapy. Signs and symptoms include high fever, inflammation (redness and swelling), and severe fatigue and nausea. Sometimes, a cytokine storm may be severe or life threatening and lead to multiple organ failure. Also called hypercytokinemia.
2. Cytokines and COVID 19 patients

The doctors reported that the patients in ICU ( Intensive care unit ) studies showed that severely ill patients tended to have a higher concentration of pro-inflammatory cytokines, especially interleukin (IL) 6, than moderately ill patients in COVID-19. In postmortem examination of patient died with COVID 19 demonstrated the existence of acute respiratory distress syndrome (ARDS) and T-cell overactivation This phenomenon is due to an increase in the number of T-helper (Th) 17 cells and the high cytotoxicity of the CD8+ T cells. The uncontrolled inflammatory responses were activated by SARS-CoV- 2. These uncontrolled immune responses can lead to apoptosis of epithelial cells and endothelial cells, and vascular leakage and, finally, result in ARDS, other severe syndromes, and even death. The increased levels of cytokines may lead to the poor prognosis of disease and sometimes also death of an patients .

3.Diagnosis and Recognition of CSS in COVID 19 Patients

There is no specified method to diagnose the CSS . some clinical and labortary examinations to be conducted.Basic principle for consideraton of CSS
• sudden or rapid progression with multiple organ involvement (such as liver, cardiac or renal injury);
• (ii) the significant decline of peripheral blood lymphocyte counts;
• (iii) the significant elevation of systematic inflammatory indicators (such as CRP, serum ferritin, erythrocyte sedimentation rate); and (iv
• the elevation of multiple cytokines, such as IL-1β, IL-2R, IL-6, IFN-γ, IP-10, MCP-1, TNF-α and MIP1a

4. Prognosis of CSS in COVID 19 Patients

If CSS not treated properly it may cause multiple organ dysfunction(MOD).Due to excessive infiltration of inflammatory cells like monocytes and neutrophil into lung tissue leads to lung injury. Cytokine induced apoptosis of lung epithelial cells also lead to ARDS. ARDS may further lead in life-threatening hypoxia, hypercapnia, acidosis and pulmonary hypertension, and require a fast and goal-oriented therapy without further lung damage.

 5.Potential Treatment in Cytokine Storm       Syndrome associated with COVID 19

A.Glucocorticoid : Glucocorticoids are powerful anti inflammatory agents and are effective choice for treatment..Coticosteroids often leads to improvement of radiographic outcome and oxygenation in SARS as a consequence of more effective control of immunopathological lung damage glucocorticoids should not be used in the early phases of disease unless there is a clear indication for their use .Methylprednisolone Prednisone Hydrocortisone and Dexamethasone are used
B.Blood purification Therapy  : The application of blood purification technology is helpful to the removal of cytokines and may be beneficial to improve the clinical outcome of critically ill patients. Commonly used extracorporeal blood purification treatments in CSS include plasma exchange, blood/plasma filtration, adsorption, perfusion and continuous renal replacement therapy (CRRT)

C. IL-1 Inhibiting agents : Dysfunction of the innate immune system involving IL-1 is important to CSS pathogenesis. Anakinra is a recombinant, nonglycosylated form of human IL-1Ra, which can block the biologic activity of both IL-1α and IL-1β by competitively inhibiting their binding to IL-1R

D. IL-6 inhibiting agents : Tocilizumab, a recombinant human IL-6 monoclonal antibody, specifically binds to soluble and membrane-bound IL-6 receptors (IL-6R), thus blocking IL-6 signalling and its mediated inflammatory response, which has been demonstrated to show outstanding efficacy in the rescue of CSS accompanied by T-cell engaged therapy.

E. Janus Kinase (JAK) Inhibitor : Several cytokines signal through the JAK/STAT pathway, which is now recognized as a major target to inhibit the effect of a wide array of cytokines. baricitinib is proposed to have the ability to reduce both the viral entry and the inflammation, which is suggested as a possible candidate for the treatment of COVID-19. ,ruxolitinib (a JAK1/2 inhibitor) contributed to a numerically faster clinical improvement in patients with severe COVID-19.

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