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What is a Cytokine Storm?

A “cytokine storm” (CSS, cytokine storm syndrome or cytokine release syndrome) is when the body reacts to a situation, and releases a massive amount of inappropriate cytokines into the bloodstream too quickly during an immune response (NCI, n.d.). This overproduction of inappropriate cytokines (and release thereof) can then stimulate even more inappropriate cytokines to be released (positive feedback loop)—hence the “storm” (hypercytokinemia) descriptor. While the release of cytokines is a normal immunological response, higher (or much higher) than normal amounts of cytokines can promote severe adverse reactions (including but not limited to multiple organ failure). Cytokine storms are a characteristic of Systemic Inflammatory Response Syndrome (SIRS).

When the body’s immune response goes haywire and starts attacking itself in an “overreaction”, it can cause leaky blood vessels, fluid build-up in the lungs (from leaky vessels), blood clots forming (further impeding blood flow), a steep drop in blood pressure, and multiple organ failure as seen in some of the COVID-19 cases (Dance, 2020). Symptoms may include (but not limited to) fever, headache, impaired nervous system, seizures, and coma (Dance, 2020).

In COVID-19 patients, the onset of CSS can present quickly. It is a very fine line to walk. While respiratory failure from acute respiratory distress syndrome (ARDS) remains the primary cause of COVID-19 deaths, the second leading cause of deaths seems to be due to secondary (or acquired) haemophagocytic lymphohistiocytosis (sHLH) with ensuing hypercytokinemia and multiorgan failure from the inappropriate persistence of histiocytes and cytotoxic T-lymphocytes (CTL) (Mehta et al., 2020; Sandler et al., 2019).

Severe COVID-19 cases presented with sHLH have a profile of: “increased interleukin (IL)-2, IL-7, granulocyte-colony stimulating factor, interferon-γ inducible protein 10, monocyte chemoattractant protein 1, macrophage inflammatory protein 1-α, and tumor necrosis factor-α” (Mehta et al., 2020).

There is no single test/diagnostic that can detect CSS. Doctors have noted elevated levels of ferritin and C-reactive protein (CRP) in a study of 150 confirmed COVID-19 cases: “mean 1297·6 nanograms/ml in non-survivors vs 614·0 ng/ml in survivors; p<0·001) and IL-6 (p<0·0001)” (Mehta et al., 2020).

It is posited that this hyperinflammatory state/response may be an additional outcome of the COVID-19 disease.

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