• Shruti GOCHHWAL

What Is “Cytokine Storm” And What It Has To Do With Covid-19?

What Are Cytokines?

Cytokines are proteins generated during an immune response. Cytokines can be pro-inflammatory or anti-inflammatory. Cytokines are produced by several immune cells including the innate macrophages, dendritic cells, natural killer cells, and the adaptive T and B lymphocytes.

If the production of cytokines is too high, the condition is called “cytokine storm”. This session discusses whether there is any real “cytokine storm” in the pathogenesis of Covid-19 and whether anti-cytokine treatments are effective to treat Covid-19.

Covid-19

Covid-19

Coronavirus, Credits: pixabay


Covid-19 infects the respiratory tract resulting in pneumonia in most of the cases and acute respiratory distress syndrome (ARDS) in about 15 % of the cases.

It is believed that mortality is linked with the presence of “cytokine storm” induced by the virus.

The excess production of pro-inflammatory cytokines can lead to ARDS and cause widespread tissue damage, resulting in multi-organ failure and death.

Not only in Covid-19, but a “cytokine storm” has also been reported in severe viral infections like influenza H1N1 virus, and the two coronaviruses highly related to COVID-19; “SARS-CoV” and “MERS-CoV”.

“Cytokine Targeted therapy” is the recent approach being tried to improve survival rates and reduce mortality in Covid-19. However, few reports are stating that there is no involvement of “cytokine storm” in Covid-19 pathogenesis.

Laboratory Parameters In Covid-19

A recent study identified that in severe cases of Covid-19, a higher neutrophil to lymphocyte ratio (NLR) was observed. NLR is a parameter to determine the overall inflammatory status of the patients.

The other laboratory findings include an increase in the C-reactive protein and ESR, and the levels of procalcitonin levels remained normal.

Platelet counts are either normal or mildly decreased.

An elevation in the liver enzyme levels (AST and ALT) are identified in complicated cases.

Cytokines in The Pathogenesis Of Covid-19?

Cytokines

Inflammation, Credits: pixabay


Covid-19 infection is thought to be accompanied by a destructive inflammatory response with the release of a large amount of pro-inflammatory cytokines, causing a “cytokine storm”.

The host immune response results in a hyperactive condition involving an excessive inflammatory reaction.

Numerous studies analyzed the cytokine profile in Covid-19 patients and identified that cytokine storm correlated directly with lung injury, multi-organ failure, and unfavorable prognosis of severe COVID-19.

The immune system is structurally organized to respond to pathogens and elicit an anti-viral immune response. Anti-viral immune response requires the activation of the inflammatory pathways of the immune system.

Cytokines are a crucial part of the inflammatory responses.  There are pattern recognition receptors in the body that recognize the invading virus. This leads to the activation of several signaling pathways, resulting in the recruitment of leukocytes and plasma proteins to the site of infection where they perform various effector functions that serve to combat the triggering infection.

The important inflammatory cytokines involved in innate immune responses are IL-1, TNF- α, and IL-6. The “cytokine storm” happens where there is a sudden increase in the circulating levels of these pro-inflammatory cytokines.

This increase in cytokines results in the influx of various immune cells such as macrophages, neutrophils, and T cells from the circulation into the site of infection with destructive effects on human tissue resulting from the destabilization of endothelial cell to cell interactions, damage to vascular barrier, capillary damage, diffuse alveolar damage, multiorgan failure, and ultimately death. Lung injury is one consequence of the cytokine storm that can progress into acute lung injury or its more severe form ARDS.

The early recognition of “cytokine storm” can help in planning a prompt treatment and better treatment outcome can be expected. Several cytokine drugs used to treat rheumatoid arthritis and psoriasis are being experimented to treat Covid-19.

Cytokine Targeted therapies in Covid-19

Drugs for COVID

Scientist involved in research, Credits: pxfuel


An Anti-IL6 drug called tocilizumab is used to manage the cytokine storm accompanying COVID-19.

The US Food and Drug Administration (FDA) has approved Roche’s Phase III clinical trial of the use of tocilizumab in hospitalized patients with severe COVID-19 pneumonia. The trial is planned to include 330 patients with severe COVID-19 pneumonia. The results are quite promising.

Itolizumab (anti-CD6 IgG1 monoclonal antibody) is a drug used for psoriasis developed by Biocon. The Drug Controller General of India has approved this drug for restricted emergency use for Covid-19 treatment.

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