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SARS-CoV-2 Cytokine Storm

In most patients developing severe COVID-19, inflammatory processes do not subside. Instead, a cytokine storm emerges, a hyper-inflammatory response involving the dysregulated activation of a large number of immune and inflammatory cells.

IL-6 levels continue to increase and the levels of IL- 2, IL-7, IL-10, TNF-α, G-CSF, CXCL10, CCL2, and CCL3 are also substantially higher in COVID-19 patients. CD4+ and CD8+ T cell numbers are anti-proportional to the levels of TNF-alpha, IL-6, and IL-10 in COVID-19 patients. Expression of the exhaustion markers PD-1 and HAVCR2 are also increased in these cells.

On the other hand, in severe cases of COVID-19 numbers of CD14+CD16+ inflammatory monocytes are increased in peripheral blood. CD14+CD16+ monocytes have also been linked to Kawasaki Disease, a rare acute inflammatory disease of the arteries in young children that has been observed in conjunction with COVID-19 recently. These CD14+CD16+ monocytes are also CD11b+ , CD14+ , CD16+ , CD68+ , CD80+ , CD163+ , CD206+ and secrete IL-6, IL-10 and TNF-alpha, thus further contributing to inflammation.

All these factors contribute to the development of a cytokine release syndrome or cytokine storm, an excessive inflammatory reaction in which cytokines are rapidly produced in large amount in response to an infection. Cytokine storm is considered an important contributor to acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS).

NLRP3 inflammasome dysregulation in COVID-19

Evidence suggests an increased susceptibility to a severe course of COVID-19 due to life style related low-grade inflammation or genetics. These factors can lead to enhanced exposure to damage associated molecular patterns (DAMPs) and further NLRP3 inflammasome activation. One of the DAMPs downstream of NLRP3 inflammasome activation is HMGB1. It is typically found in elevated serum concentrations during inflammatory events and acts as a central mediator of an excessive inflammatory response in case of viral infections. HMGB1 has been proposed to be one of the main contributors to the cytokine storm through a positive feedback loop involving induction of IL-17 production by Th17 cells and the subsequent neutrophil infiltration, leading to further NLRP3 inflammasome activation.

The SARS-CoV-2 N protein triggers activation of the lectin pathway of the complement system through interaction with mannose binding lectin (MBL)-associated serine protease (MASP)2. Released soluble N protein dimers interact with MASP-2, further accelerating MASP-2 activation and activation of the complements system. The positive feedback through cell lysis and release of N-protein leads to further increase of pro-inflammatory cytokines and aggravation of the cytokine storm.

In addition to the damaging effect on the alveolar structure, inflammatory cytokines IL-1 and TNF induce increases expression of HA-synthase-2 (HAS2) in CD31+ endothelium, EpCAM+ lung alveolar epithelial cells, and fibroblasts. HAS2 catalyzes polymerization of hyaluronan, a component of the extracellular matrix that can absorb water up to a 1000 times its weight. Accumulation of this liquid jelly in the damaged lungs further limits the gas exchange in the lung, leading to low oxygen saturation of the blood.

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Cytokine Storm related Antibodies:

Product
Reactivity
Clonality
Application
Validations
Cat. No.
Quantity
Datasheet
Reactivity Human
Clonality Monoclonal
Application ELISA, IHC, ICC
Validations
  • (2)
  • (6)
Cat. No. ABIN969215
Quantity 100 μL
Datasheet Datasheet
Reactivity Human
Clonality Monoclonal
Application WB, IHC, ELISA, ICC, FACS
Validations
  • (2)
  • (7)
Cat. No. ABIN969505
Quantity 100 μL
Datasheet Datasheet
Reactivity Human
Clonality Polyclonal
Application WB, IF
Validations
  • (1)
  • (7)
Cat. No. ABIN3021617
Quantity 100 μL
Datasheet Datasheet
Reactivity Human
Clonality
Application ELISA
Validations
  • (8)
  • (5)
Cat. No. ABIN6730906
Quantity 96 tests
Datasheet Datasheet
Reactivity Human
Clonality Polyclonal
Application WB, IHC, IP, IF
Validations
  • (2)
  • (5)
Cat. No. ABIN3021171
Quantity 100 μL
Datasheet Datasheet
Reactivity Cow, Human
Clonality Monoclonal
Application WB, FACS, IP
Validations
  • (8)
  • (3)
Cat. No. ABIN94149
Quantity 0.1 mg
Datasheet Datasheet
Reactivity Human
Clonality Polyclonal
Application WB, ELISA, IHC, Neut
Validations
  • (1)
  • (2)
Cat. No. ABIN5596796
Quantity 100 μL
Datasheet Datasheet
Reactivity Human
Clonality Monoclonal
Application WB, ELISA, IHC, FACS, Neut, RIA
Validations
  • (3)
Cat. No. ABIN964743
Quantity 100 μg
Datasheet Datasheet
Reactivity Mouse
Clonality Polyclonal
Application WB, ELISA, IP, FACS, RIA, Neut
Validations
  • (3)
  • (2)
Cat. No. ABIN964783
Quantity 500 μg
Datasheet Datasheet
Reactivity Human
Clonality Monoclonal
Application ELISA
Validations
  • (2)
  • (1)
Cat. No. ABIN1724632
Quantity 100 μL
Datasheet Datasheet

Cytokine Storm related ELISA Kits:

Product
Method Type
Sample Type
Detection Method
Validations
Cat. No.
Quantity
Datasheet
Method Type Sandwich ELISA
Sample Type Plasma, Serum
Detection Method Colorimetric
(Pre-coated)
Validations
  • (53)
  • (6)
Cat. No. ABIN6574155
Quantity 96 tests
Datasheet Datasheet
Method Type Sandwich ELISA
Sample Type Cell Culture Supernatant, Cell Lysate, Plasma, Serum, Tissue Homogenate
Detection Method Colorimetric
(Pre-coated)
Validations
  • (31)
  • (5)
Cat. No. ABIN6574165
Quantity 96 tests
Datasheet Datasheet
Method Type Sandwich ELISA
Sample Type Cell Culture Supernatant, Cell Lysate, Plasma, Serum, Tissue Homogenate
Detection Method Colorimetric
(Pre-coated)
Validations
  • (16)
  • (5)
Cat. No. ABIN6574129
Quantity 96 tests
Datasheet Datasheet
Method Type Sandwich ELISA
Sample Type Cell Culture Supernatant, Cell Lysate, Plasma, Serum, Tissue Homogenate
Detection Method Colorimetric
(Pre-coated)
Validations
  • (4)
  • (5)
Cat. No. ABIN6730879
Quantity 96 tests
Datasheet Datasheet
Method Type Sandwich ELISA
Sample Type Cell Culture Supernatant, Cell Lysate, Plasma, Serum, Tissue Homogenate
Detection Method Colorimetric
(Pre-coated)
Validations
  • (8)
  • (5)
Cat. No. ABIN6730906
Quantity 96 tests
Datasheet Datasheet
Method Type Sandwich ELISA
Sample Type Cell Culture Supernatant, Cell Lysate, Tissue Homogenate
Detection Method Colorimetric
(Pre-coated)
Validations
  • (3)
  • (5)
Cat. No. ABIN6574284
Quantity 96 tests
Datasheet Datasheet
Method Type Sandwich ELISA
Sample Type Cell Culture Supernatant, Cell Lysate, Plasma, Serum, Tissue Homogenate
Detection Method Colorimetric
(Pre-coated)
Validations
  • (4)
  • (4)
Cat. No. ABIN6730878
Quantity 96 tests
Datasheet Datasheet
Method Type
Sample Type
Detection Method Sterile plate
Validations
Cat. No. ABIN1447108
Quantity 96 tests
Datasheet Datasheet
Method Type
Sample Type
Detection Method Sterile plate
Validations
Cat. No. ABIN1446656
Quantity 96 tests
Datasheet Datasheet

Other COVID-19 DAMPs

The host's immune response to a SARS-CoV-2 infection is also determined by DAMPs other than HMGB1. These can be host-derived endogenous molecules that are released upon cell-death, injury-modified extracellular matrix components, or DAMP-inducible secreted proteins that downstream serve as DAMPs themselves. Besides HMGB1, DAMPs indicative of COVID-19 are CIRBP, S100A8/A9, and SP-A.

SARS-CoV-2 DAMPs antibodies:

Product
Reactivity
Clonality
Application
Validations
Cat. No.
Quantity
Datasheet
Reactivity Human
Clonality Polyclonal
Application WB, IHC, IF, IHC (p), ICC, IHC (wm), IHC (ff)
Validations
  • (4)
  • (12)
Cat. No. ABIN2854997
Quantity 100 μL
Datasheet Datasheet
Reactivity Human
Clonality Polyclonal
Application WB, IHC (p)
Validations
  • (1)
  • (3)
Cat. No. ABIN653083
Quantity 400 μL
Datasheet Datasheet

Clonality Monoclonal
Application IHC, IF, FACS, StM
Validations
  • (2)
Cat. No. ABIN6940546
Quantity 100 μg
Datasheet Datasheet

SARS-CoV-2 DAMPs ELISA Kits:

Product
Method Type
Sample Type
Detection Method
Validations
Cat. No.
Quantity
Datasheet
Method Type Sandwich ELISA
Sample Type Plasma, Serum
Detection Method Colorimetric
(Pre-coated)
Validations
  • (53)
  • (6)
Cat. No. ABIN6574155
Quantity 96 tests
Datasheet Datasheet
Method Type Sandwich ELISA
Sample Type Cell Culture Supernatant, Cell Lysate, Plasma, Serum, Tissue Homogenate
Detection Method Colorimetric
(Pre-coated)
Validations
  • (6)
  • (6)
Cat. No. ABIN6574287
Quantity 96 tests
Datasheet Datasheet
Method Type Sandwich ELISA
Sample Type Cell Culture Supernatant, Cell Lysate, Plasma, Serum, Tissue Homogenate
Detection Method Colorimetric
(Pre-coated)
Validations
  • (4)
  • (5)
Cat. No. ABIN6730867
Quantity 96 tests
Datasheet Datasheet
Method Type Sandwich ELISA

Detection Method Colorimetric
(Pre-coated)
Validations
  • (10)
  • (1)
Cat. No. ABIN6959778
Quantity 96 tests
Datasheet Datasheet
Method Type Sandwich ELISA
Sample Type Cell Lysate, Tissue Homogenate
Detection Method Colorimetric
(Pre-coated)
Validations
  • (1)
Cat. No. ABIN6954897
Quantity 96 tests
Datasheet Datasheet

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References

Blanco-Melo, Nilsson-Payant, Liu, Uhl, Hoagland, Møller, Jordan, Oishi, Panis, Sachs, Wang, Schwartz, Lim, Albrecht, tenOever: "Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19." in: Cell, Vol. 181, Issue 5, pp. 1036-1045.e9, (2020) (PubMed).

Lin, Fu, Yin, Li, Liu, Zhang, Xing, Wang, Xue, Xiong, Zhang, Zhao, Xu, Zhang, Wang, Nian, Wang, Wu: "ORF8 contributes to cytokine storm during SARS-CoV-2 infection by activating IL-17 pathway." in: iScience, Vol. 24, Issue 4, pp. 102293, (2021) (PubMed).

Tay, Poh, Rénia, MacAry, Ng: "The trinity of COVID-19: immunity, inflammation and intervention." in: Nature reviews. Immunology, Vol. 20, Issue 6, pp. 363-374, (2020) (PubMed).

van den Berg, Te Velde: "Severe COVID-19: NLRP3 Inflammasome Dysregulated." in: Frontiers in immunology, Vol. 11, pp. 1580, (2020) (PubMed).

Ziegler-Heitbrock: "The CD14+ CD16+ blood monocytes: their role in infection and inflammation." in: Journal of leukocyte biology, Vol. 81, Issue 3, pp. 584-92, (2007) (PubMed).

  • Gao, T. et al. Highly pathogenic coronavirus N protein aggravates lung injury by MASP-2- mediated complement over-activation. medRxiv (2020). doi:10.1101/2020.03.29.20041962
  • Fan, X. et al. Changes of Damage Associated Molecular Patterns in COVID-19 Patients. Infectious Diseaeses & Immunity (2021). doi:10.1097/01.id9.0000733572.40970.6c
  • Zhang, D. et al. COVID-19 infection induces readily detectable morphological and inflammation-related phenotypic changes in peripheral blood monocytes, the severity of which correlate with patient outcome. medRxiv (2020). doi:10.1101/2020.03.24.20042655
Stefan Pellenz
Dr. Stefan Pellenz, PhD
Product Manager at antibodies-online.com

Goal-oriented, time line driven scientist, proficiently trained in different academic institutions in Germany, France and the USA. Experienced in the life sciences e-commerce environment with a focus on product development and customer relation management.

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