Preprint Article Version 2 Preserved in Portico This version is not peer-reviewed

Therapeutic Approaches for COVID-19 Based on the Dynamics of Interferon-mediated Immune Responses

Version 1 : Received: 11 March 2020 / Approved: 12 March 2020 / Online: 12 March 2020 (09:11:00 CET)
Version 2 : Received: 22 March 2020 / Approved: 23 March 2020 / Online: 23 March 2020 (10:27:57 CET)

A peer-reviewed article of this Preprint also exists.

Pouria Mosaddeghi, Farbod Shahabinezhad, Zahra Dehghani, Mitra Farahmandnejad, Mohammad Javad Taghipour, Mohsen Moghadami, Navid Nezafat, Seyed Masoom Masoompour and Manica Negahdaripour*, “Therapeutic Approaches for COVID-19 Based on the Interferon-mediated Immune Responses”, Current Signal Transduction Therapy (2021) 16: 1. https://doi.org/10.2174/1574362416666210120104636 Pouria Mosaddeghi, Farbod Shahabinezhad, Zahra Dehghani, Mitra Farahmandnejad, Mohammad Javad Taghipour, Mohsen Moghadami, Navid Nezafat, Seyed Masoom Masoompour and Manica Negahdaripour*, “Therapeutic Approaches for COVID-19 Based on the Interferon-mediated Immune Responses”, Current Signal Transduction Therapy (2021) 16: 1. https://doi.org/10.2174/1574362416666210120104636

Journal reference: Current Signal Transduction Therapy 2021, 16
DOI: 10.2174/1574362416666210120104636

Abstract

As the outbreak of COVID-19 has accelerated, an urgent need for finding strategies to combat the virus is growing. Thus, gaining more knowledge on the pathogenicity mechanisms of SARS-CoV-2, the causing agent of COVID-19, and its interaction with the immune system is of utmost importance. Although this novel virus is not well known yet, its structural and genetic similarity with SARS-CoV as well as the comparable pattern of age-mortality relations suggest that the previous findings on SARS can be applicable for COVID-19. Therefore, a systems biology study was conducted to investigate the most important signaling pathways activated by the virus. The results were then validated through a literature review on COVID-19 and the other closely related viruses, SARS and MERS. Interferons have shown to play a crucial role in the defense against coronavirus diseases. CoV can impede the interferon induction in humans. Moreover, STAT1, a key protein in the interferon-mediated immune response, is antagonized by the virus. This could explain the increased response threshold of immune cells to IFNs during CoV infections. A vivid correlation between the innate immune response threshold and the fatality rates in COVID-19 can be found. Differences in the dynamics of the interferon-related innate immune responses in children, adults, and elderly may explain the reported fatality rates. The increased mortality rates in the elderly can be explained by the higher threshold of interferon-mediated immune responses. Earlier induction of interferons in children and their less developed immune system could contribute to their near to zero fatality rate. Administration of interferon-inducing agents, such as poly (ICLC), could reduce the mortality of SARS at the very early stages of the disease. Interferon-γ combination with an interferon-I might induce synergistic effects and maximize the benefits. However, in-depth research is needed to validate it and determine the optimum dosage and timing to prevent unwanted results. Such interventions can act as a double-edged sword and aid the imbalance of the immune reactions, which may occur at the later stages of the disease. With the advancement of the disease and the virus overload, the responses would shift toward immnopathogenic over-reactions and probably cytokine storm. Moderating the activity of the immune system and supportive care in such conditions might be the optimum approach.

Keywords

2019 novel coronavirus infection; corons; SARS-CoV; interferon; systems biology

Comments (2)

Comment 1
Received: 23 March 2020
Commenter: Manica Negahdaripour
Commenter's Conflict of Interests: Author
Comment: Few hints are added regarding the need for research on usage of interferon-gamma. Several references and minor changes in some sentences are made.
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Comment 2
Received: 25 February 2021
Commenter: Manica Negahdaripour (Click to see Publons profile: )
Commenter's Conflict of Interests: I am the corresponding author of this paper.
Comment: This article is now published as:
Pouria Mosaddeghi, Farbod Shahabinezhad, Zahra Dehghani, Mitra Farahmandnejad, Mohammad Javad Taghipour, Mohsen Moghadami, Navid Nezafat, Seyed Masoom Masoompour and Manica Negahdaripour*, “Therapeutic Approaches for COVID-19 Based on the Interferon-mediated Immune Responses”, Current Signal Transduction Therapy (2021) 16: 1. https://doi.org/10.2174/1574362416666210120104636
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