COVID-19 Cytokine Storm

On January 25, 2020, Prof Bin Cao's team published a research paper titled "Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.". The paper revealed that the immune system of critical patients with COVID-19 (a disease caused by SARS-CoV-2 infection) exists a lethal cytokine storm. So what is the COVID-19 cytokine storm? Why does COVID-19 lead to cytokine storm? And how to treat the cytokine storm caused by COVID-19?

What is COVID-19 Cytokine Storm?

Before introducing COVID-19 cytokine storm, we must get the knowledge of cytokine storm. As describled in the article entilted "What You Have to Know about Cytokine Storm and Virus Infection", cytokine storm is the phenomenon that a variety of cytokines in the body fluids are rapidly and massively produced after the body is infected with microorganisms. This is actually a large number of viral infections triggering the "suicide attack" of the human immune system.

COVID-19 cytokine storm acturally refers to the cytokine storm caused by COVID-19. Some reports have revealed the direct cause of death from acute COVID-19 is that the novel coronavirus destroy the human immune mechanism and trigger excessive immunity causing cytokine storm. Moreover, cytokine storm damages lungs and multiple organs of the human body (heart, kidney, liver, etc.) , and eventually leading to multiple organ functions exhaustion.

Why Does COVID-19 Lead to Cytokine Storm?

The cause of COVID-19 is SARS-CoV-2 (formerly known as 2019-nCoV), one of coronavirus. The SARS-CoV-2 infected humans for the first time, and the human immune system didn't recognize the virus. Studies have shown that the SARS-CoV-2 enters cells through angiotensin-converting enzyme 2 (ACE2). For this reason, lung tissue has become the main invasion target of the SARS-CoV-2 with high expression of ACE2. After the virus entered the lung, the immune system sent a large number of immune cells to the lung tissue to kill the virus. This formed pneumonia, and the patient showed fever, cough, and difficulty breathing.

However, these immune cells cannot locate the virus accurately because they are not recognize it. They only attack indiscriminately and recruit more immune cells to kill the virus. Once a cytokine storm is formed, the immune system may not be able to kill the virus, but it will certainly kill a large number of normal cells in the lung, which will seriously damage the function of the lung. Patients will have respiratory failure until they die of hypoxia.

What are The Cytokines of Cytokine Storm Caused by COVID-19?

According to the publication of Prof Bin Cao's team, they found that severe patients have significantly higher levels of plasma pro-inflammatory factors (IL2, IL7, IL-10, GSCF, IP-10, MCP-1, MIP1A, TNF-α) than mild patients with COVID-19, and these inflammatory indicators indicate a cytokine storm in severe patients.

Acturally, since the outbreak of the SARS epidemic, the "cytokine storm" has aroused great attention. Furthermore, the alignment between SARS-CoV-2 and 2002 SARS CoV has about 70% sequence similarity and 40% sequence similarity with MERS CoV. And all of them are belong to coronavirus. Although the study of SARS-CoV-2 is not very large, we can refer to the study of 2002 SARS CoV and MERS CoV. Accumulating studies indicated that the cytokine storm caused by SARS is mainly related to IL-1β, IL-6, IL12A, IFN-γ, IP10 and MCP1, and the cytokine storm caused by MERS is mainly related to IFNγ, TNFα, IL15 and IL17A.

For the cytokine storm detction, mainly depends on the detection of elevated inflammatory factors in the blood. And different viruses do not trigger cytokine storms through exactly the same mechanism, so they will cause different cytokine changes.

Related ELISA Kits

In this section, we list several ELISA Kits of cytokine storm caused by coronavirus infection.

Target	Product Name	Code	Sample Types	Detection Range
IFNγ	Human IFN-γ ELISA KIT	CSB-E04577h	Cell Culture Supernates	0.312 ng/ml-20 ng/ml
IL10	Human IL-10 ELISA KIT	CSB-E04593h	serum, urine, cell culture supernates, ascitic fluid, cerebrospinal fluid (CSF), saliva	12.5 pg/mL-800 pg/mL
IL15	Human IL-15 ELISA KIT	CSB-E04603h	serum, plasma, tissue homogenates, cell culture supernates	3.12 pg/mL-200 pg/mL
IL17A	Human IL-17A/IL-17 ELISA KIT	CSB-E12819h	serum, urine, cell culture supernates, tissue homogenates	6.25 pg/mL-400 pg/mL
IL1B	Human IL-1β ELISA KIT	CSB-E08053h	serum, cell culture supernates, urine, cerebrospinal fluid (CSF)	125 pg/mL-8000 pg/mL
IL2	Human IL-2 ELISA KIT	CSB-E04626h	serum, plasma, tissue homogenates	3.12 pg/mL-200 pg/mL
IL6	Human IL-6 ELISA KIT	CSB-E04638h	serum, plasma, cell culture supernates, tissue homogenates, urine	7.8 pg/mL-500 pg/mL
IL7	Human IL-7 ELISA KIT	CSB-E14032h	serum, plasma, cell culture supernates, tissue homogenates, urine	0.78 pg/mL-50 pg/mL
IP10	Human IP-10 ELISA KIT	CSB-E08181h	serum, plasma, tissue homogenates	31.25 pg/mL-2000 pg/mL
MCP1	Human MCP-1/MCAF ELISA KIT	CSB-E04655h	serum, plasma, urine, saliva, cerebrospinal fluid (CSF), ascitic fluid, cell culture supernates, tissue homogenates	31.25 pg/mL-2000 pg/mL
MIP1A	Human MIP-1α ELISA KIT	CSB-E04662h	serum, plasma, tissue homogenates	3.12 pg/mL-200 pg/mL
TNFα	Human TNF-α ELISA KIT	CSB-E04740h	serum, plasma, cell culture supernates, tissue homogenates, cell lysates	7.8 pg/mL-500 pg/mL

How to Treat COVID-19 Cytokine Storm?

Currently, the treatments of COVID-19 cytokine storm primarily focus on the following four principles:

Anti-shock therapy (treatment of symptoms, life-saving first): infusion to ensure blood volume, application of vasoactive drugs, mechanical ventilation if necessary, protection of important organ functions;
Support and symptomatic treatment (restoration of physical strength): routine infusion, maintaining water, electrolyte and acid-base balance, nutrition support, etc .;
Inhibit excessive immune cell activation and cytokine production (curative, seek recovery): clinically, hormone therapy (adrenal corticosteroids, etc.) with appropriate doses and treatments is often used, and nonsteroidal anti-inflammatory drugs and free radical scavengers ( A lot of vitamin C, vitamin E) and so on.
Antibody-neutralizing cytokine storm (precise treatment): neutralizing monoclonal antibodies against elevated cytokines to prevent severe disease and death.