Hyperferritinaemia could be causing severe COVID-19

A leading expert in the research, treatment and prevention of autoimmune diseases has suggested that severe COVID-19 symptoms may be linked to hyperferritinaemia.

According to Professor Yehuda Shoenfeld, hyperferritinaemia, or hyperferritinaemic syndrome, is a condition in which high levels of a major intracellular iron storage protein, called ferritin, activates macrophages to secrete cytokines. In severe cases, these secretions cause a cytokine storm.

Shoenfeld, professor at St Petersburg State University, Russia, said that the symptoms of COVID-19 are similar to that of hyperferritinaemia: “In 50 percent of cases, patients with exceptionally high ferritin levels die.”

Ferritin is essential at normal levels as it binds free iron ions, reducing their cytotoxicity and increasing their solubility so the body can expend them in cellular processes, such as oxygen metabolism. However, when ferritin becomes dysregulated it can cause disease: low levels of ferritin can result in iron deficient anaemia and high levels. If genetic, it can cause neurological disorders and vision problems. Hyperferritinaemic syndrome is also an indicator of bacterial or viral infection.

“When activated, macrophages begin to secrete cytokines. These are a category of signalling molecules that mediate and regulate immunity. At low concentrations, they are safe for the body and help to protect it against viruses and bacteria. At high levels, the so called ‘cytokine storm’ develops, which can be lethal for half of the patients, especially for the elderly,” explained Shoenfeld. “Thus, hyperferritinemia has been associated with increased illness severity and adverse outcomes. Our task is to find a way to combat it.”

He also identified a further indicator of macrophage activation associated with a high probability of complications, CD163. In the Laboratory of the Mosaic of Autoimmunity at St Petersburg University scientists are searching for a way to reduce circulating ferritin levels and studying antibodies that could inhibit the synthesis of CD163 and other macrophage signalling.

Additionally, Shoenfeld and his colleagues are working on a vaccine against COVID-19, using viral surface proteins as the main component.

The research was published in Autoimmunity Reviews.