Cytokine storm in COVID-19 patients that do poorly?

David Posnett — Tue, 07 Apr 2020 03:34:09 +0000

I have been reading some reports about cytokine storms in patients with COVID-19 that fare poorly and end up on ventilators in the ICU.

Here is one such study which was submitted for publication on March 6th:

Exuberant elevation of IP-10, MCP-3 and IL-1ra during SARS-CoV-2 infection is associated with disease severity and fatal outcome

Yang Yang, Chenguang Shen, Jinxiu Li, , , Fuxiang Wang, , Yanjie Li, Li Xing, Ling Peng, Jinli Wei, Mengli Cao, Haixia Zheng, , Rongrong Zou, , Zhixiang Xu, , Mingxia Zhang, Zheng Zhang, Lei Liu, Yingxia Liu

doi: https://doi.org/10.1101/2020.03.02.20029975

Here are the key findings and cautions:

They analyzed levels of 48 cytokines (!) in COVID-19 patients and healthy controls.

Key Findings:
• Many cytokines were elevated with COVID-19
(IFNy, IL-1Ra, IL-2Ra, IL-6, IL-10, IL-18, HGF, MCP-3, MIG, M-CSF, G-CSF, MIG-1a, and IP-10).
IP-10, IL-1Ra, and MCP-3 (esp. together) were associated with disease severity and fatal outcome.
• IP-10 was correlated to patient viral load (r=0.3006, p=0.0075).
• IP-10, IL-1Ra, and MCP-3 were correlated to loss of lung function (PaO2/FaO2 (arterial/atmospheric O2) and Murray Score (lung injury) with MCP-3 being the most correlated (r=0.4104 p<0.0001 and r=0.5107 p<0.0001 respectively).
• Viral load (Lower Ct Value from qRT-PCR) was associated with upregulated IP-10 only (not IL-1Ra or MCP-3) and was mildly correlated with decreased lung function: PaO2/FaO2 (arterial/atmospheric O2) and Murray Score (lung injury).
• Lymphopenia (decreased CD4 and CD8 T cells) and increased neutrophil correlated w/ severe patients.

Caution: Collection time of clinical data and lab results was not reported directly making it very difficult to determine if cytokines were predictive of patient outcome or reflective of patient compensatory immune response. Small numbers for cytokine analysis (N=2 fatal and N=5 severe/critical, and N=7 moderate or discharged). @sinaiimmunologyreviewproject

What is IP-10? Also known as CXCL10: it is a chemoattractant for various types of white blood cells and promotes inflammation.

What is IL-1Ra? The interleukin-1 receptor antagonist (IL-1Ra) blocks the IL-1 receptor and is a natural inhibitor of the pro-inflammatory effect of IL1 (which causes fever for example). A slightly modified version of IL-1Ra, called anakinra, is used in the treatment of rheumatoid arthritis, an autoimmune disease in which IL-1 plays a key role

What is MCP-3? Also known as CCL7. It is a chemokine that attracts monocytes, a type of white blood cell.

It is beginning to look like a familiar scenario. Too much of an immune response is not a good thing. Cytokine storms have famously contributed to the lethality of influenza such as the Spanish flu of 1918.

It is important, because there are a number of drugs that can block specific cytokines. For example, anti-IP-10 is a possible therapeutic (Eldelumab).

It may be premature, but it is the best available data to explain why some with COVID-19 have a minor disease and others have life threatening disease.

ICU patients – R&R – Reachout and Rebuild

Cytokine storm in COVID-19 patients that do poorly?