Role of epinephrine in attenuating cytokine storm, decreasing ferritin, and inhibiting ferroptosis in SARS-CoV-2

Abstract

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for coronavirus disease 2019. It presents one of the most threatening pandemics in the history of humanity. The mortality and morbidity represent an unprecedented challenge to the modern medical era. SARS-CoV-2 results in acute respiratory distress syndrome, high concentrations of proinflammatory mediators, cytokine storm (CS) due to massive release of cytokines, hypercoagulation, and hemoglobin disintegration. Dysregulation of iron homeostasis, iron overload as indicated by high ferritin level, and ferroptosis are major factors in the pathogenesis of the disease. We report a case of SARS-CoV-2 in which the use of epinephrine (Epi) resulted in an unexpected attenuation of CS, decreasing ferritin level and inhibiting ferroptosis.

Case presentation

A 64-year-old male patient with a history of multiple medical comorbidities had been diagnosed with SARS-CoV-2. Further evaluation showed marked increase in inflammatory markers, severe hyperferritinemia, and lymphopenia in laboratory blood tests. The characteristic score of CS was strongly positive, and in addition to regular treatment, the patient received Epi due to development of acute generalized skin rash, severe itching, and edema of lips and tongue. Epi may have successfully terminated not only the acute cutaneous condition, but also have attenuated CS, decreased ferritin level, and other inflammatory markers in addition to complete patient’s recovery.

Conclusion

Epinephrine may attenuate CS and inhibit ferroptosis which is an iron-dependent, non-apoptotic mode of cell death. Epi interacts with ferric and/or ferrous iron and built a stable complex that impedes activation of beta-adrenergic receptors. Epi may cause marked decrease of ferritin and other inflammatory markers. Epi may be used to decrease iron overload which is associated with many medical diseases like type 2 diabetes mellitus and cardiometabolic diseases such as coronary heart disease and cerebrovascular disease. As a new clinical indication extensive studies are required for further assessment and possible therapeutic uses.