Int J Biol Sci 2022; 18(2):459-472. doi:10.7150/ijbs.59272 This issue


Cytokine storm in COVID-19: from viral infection to immune responses, diagnosis and therapy

Yizhou Jiang1#, Limor Rubin, MD2#, Tangming Peng1, Linlin Liu1, Xingan Xing1, Philip Lazarovici, PhD3, Wenhua Zheng, MD, PhD1✉

1. Center of Reproduction, Development & Aging, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.
2. Allergy and Clinical Immunology Unit, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
3. School of Pharmacy Institute for Drug Research, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
#Co-first equal contributing authors

This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.
Jiang Y, Rubin L, Peng T, Liu L, Xing X, Lazarovici P, Zheng W. Cytokine storm in COVID-19: from viral infection to immune responses, diagnosis and therapy. Int J Biol Sci 2022; 18(2):459-472. doi:10.7150/ijbs.59272. Available from

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Graphic abstract

The COVID-19 outbreak is emerging as a significant public health challenge. Excessive production of proinflammatory cytokines, also known as cytokine storm, is a severe clinical syndrome known to develop as a complication of infectious or inflammatory diseases. Clinical evidence suggests that the occurrence of cytokine storm in severe acute respiratory syndrome secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is closely associated with the rapid deterioration and high mortality of severe cases. In this review, we aim to summarize the mechanism of SARS-CoV-2 infection and the subsequent immunological events related to excessive cytokine production and inflammatory responses associated with ACE2-AngII signaling. An overview of the diagnosis and an update on current therapeutic regimens and vaccinations is also provided.

Keywords: cytokine storm, COVID-19, SARS-CoV-2, immune response, cytokines, diagnosis, therapy, vaccination