Cytokine Storm And COVID 19
The pandemic has taught us lot of lessons that we should change ourselves foe 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
➢ 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
➢ 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)
➢ 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
➢ 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.
➢ 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..
References :
https://www.cancer.gov/publications/dictionaries/cancer-
terms/def/cytokine-storm
https://onlinelibrary.wiley.com/doi/full/10.1111/joim.13144
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365923/
https://www.covid19treatmentguidelines.nih.gov/immunomodulators/
corticosteroids/
https://www.hindawi.com/journals/mi/2020/8198963/
https://www.news-medical.net/amp/health/What-is-Cytokine-
Storm.aspx
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