Cytokine storm

Cytokines are a normal part of the body's immune response to infection, but their sudden release in large quantities may cause multisystem organ failure and death.

[8][9] Low blood plasma levels of trigonelline (one of the metabolites of vitamin B3) have been suggested for the prognosis of SARS-CoV-2 death (which is thought to be due to the inflammatory phase and cytokine storm).

[14] It is believed that cytokine storms were responsible for the disproportionate number of healthy young adult deaths during the 1918 influenza pandemic, which killed an estimated 50 million people worldwide.

[20] In 2006, a study at Northwick Park Hospital in England resulted in all 6 of the volunteers given the drug theralizumab becoming critically ill, with multiple organ failure, high fever, and a systemic inflammatory response.

[24][25] A cytokine storm can cause the severe symptoms of acute respiratory distress syndrome (ARDS), which has a high mortality rate in COVID-19 patients.

[26] SARS-CoV-2 activates the immune system resulting in a release of a large number of cytokines, including IL-6, which can increase vascular permeability and cause a migration of fluid and blood cells into the alveoli leading to such consequent symptoms as dyspnea and respiratory failure.

A group of markers showed over-stimulation of the immune system, including ADA, BTC, CA12, CAPG, CD40, CDCP1, CXCL9, ENTPD2, Flt3L, IL-6, IL-8, LRP1, OSM, PD-L1, PTN, STX8, and VEGFA; furthermore, DPP6 and EDIL3 indicated damage to arterial and cardiovascular organs.

Possible predictors of severe and fatal cases may include lymphopenia, thrombocytopenia and high levels of ferritin, D-dimer, aspartate aminotransferase, lactate dehydrogenase, C-reactive protein, neutrophils, procalcitonin and creatinine as well as interleukin-6 (IL-6).

An animal study found that mice producing an early strong interferon response to SARS-CoV-2 were likely to live, but in other cases the disease progressed to a highly morbid overactive immune system.