Transcriptomic Signatures and Immunomodulatory Treatments for COVID-19 Patients

33 Pages Posted: 26 Jun 2020

See all articles by Guobing Li

Guobing Li

University of Michigan

Xiaolu Zhao

University of Michigan

Qi Liu

Harvard University - Harvard Medical School

Shasha Ruan

Wuhan University

Yali Dou

University of Michigan at Ann Arbor - Department of Pathology

Fengbiao Mao

University of Michigan

Date Written: June 23, 2020

Abstract

Since December 2019, the novel coronavirus SARS-CoV-2 has infected over 9.0 million and led to death of over 472,000 people, damaging the world’s social and economic fabrics. Effective drugs are urgently needed to decrease the high mortality rate of COVID-19 patients. Unfortunately, effective antiviral drugs or vaccines are currently unavailable. Herein, we systematically evaluated the effect of SARS-CoV-2 on gene expression of both lung tissue and blood from COVID-19 patients using transcriptome profiling. Differential gene expression analysis revealed potential core mechanism of COVID-19-induced pneumonia in which IFN-α, IFN-β, IFN-γ, TNF and IL6 triggered cytokine storm mediated by neutrophil, macrophage, B and DC cells. Weighted gene correlation network analysis identified two gene modules that are highly correlated with clinical traits of COVID-19 patients, and confirmed that over-activation of immune system-mediated cytokine release syndrome is the underlying pathogenic mechanism for acute phase of COVID-19 infection. It suggested that anti-inflammatory therapies may be promising regimens for COVID-19 patients. Furthermore, drug repurposing analysis of thousands of drugs revealed that TNFα inhibitor etanercept and γ-aminobutyric acid-B receptor (GABABR) agonist baclofen showed most significant reversal power to COVID-19 gene signature, so we are highly optimistic about their clinical use for COVID-19 treatment. In addition, our results suggested that adalimumab, tocilizumab, rituximab and glucocorticoids may also have beneficial effects in restoring normal transcriptome, but not chloroquine, hydroxychloroquine or interferons. Controlled clinical trials of these candidate drugs are needed in search of effective COVID-19 treatment in current crisis.

Note: Funding: No specific grant from any funding agency for this study.

Conflict of Interest: The authors report no conflicts of interest in this work.

Keywords: COVID-19; SARS-CoV-2; Transcriptomic signatures; Immunomodulatory treatments

Suggested Citation

Li, Guobing and Zhao, Xiaolu and Liu, Qi and Ruan, Shasha and Dou, Yali and Mao, Fengbiao, Transcriptomic Signatures and Immunomodulatory Treatments for COVID-19 Patients (June 23, 2020). Available at SSRN: https://ssrn.com/abstract=3620818 or http://dx.doi.org/10.2139/ssrn.3620818

Guobing Li

University of Michigan ( email )

Xiaolu Zhao

University of Michigan ( email )

Qi Liu

Harvard University - Harvard Medical School ( email )

25 Shattuck St
Boston, MA 02115
United States

Shasha Ruan

Wuhan University ( email )

Wuhan
China

Yali Dou

University of Michigan at Ann Arbor - Department of Pathology

Ann Arbor, MI 48109,
United States

Fengbiao Mao (Contact Author)

University of Michigan ( email )

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