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Novel Coronavirus Disease 2019 (COVID-19) and Cytokine Storms for More Effective Treatments from an Inflammatory Pathophysiology

by 1,2,3,4,*, 5, 1,6,7 and 3,8,9,10
1
Department of Pediatrics, Yokohama City University, Yokohama 236-0004, Japan
2
Fuji-Toranomon Children’s Center, Gotemba 412-0045, Japan
3
Japan Medical Research Foundation (JMRF), Tokyo 135-0063, Japan
4
Japan College of Fibromyalgia Investigation (JCFI), Tokyo 160-0022, Japan
5
Pediatric Rheumatology, Institute of Rheumatology, Tokyo Women’s Medical University, Tokyo 162-0054, Japan
6
Chairman of Stroke Center, Teikyo University School of Medicine Mizonokuchi Hospital, Kawasaki 192-0395, Japan
7
Japan Society of Neurovegetative Research (JSNR), Tokyo 170-0002, Japan
8
Global Health Innovation Policy Program (GHIPP), National Graduate Institute for Policy Studies (GRIPS), Tokyo 106-0032, Japan
9
American College of Rheumatology (ACR), Atlanta, GA 30319, USA
10
St. Marianna University, Kawasaki 216-8511, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: Sukhwinder Singh Sohal
J. Clin. Med. 2021, 10(4), 801; https://doi.org/10.3390/jcm10040801
Received: 7 January 2021 / Revised: 3 February 2021 / Accepted: 9 February 2021 / Published: 17 February 2021
(This article belongs to the Special Issue Pediatric and Adolescent Rheumatology: A Rapidly Developing Field)
The Novel Coronavirus Disease 2019 (COVID-19) has swept the world and caused a global pandemic. SARS-CoV-2 seems to have originated from bats as their reservoir hosts over time. Similar to SARS-CoV, this new virus also exerts its action on the human angiotensin-converting enzyme 2. This action causes infections in cells and establishes an infectious disease, COVID-19. Against this viral invasion, the human body starts to activate the innate immune system in producing and releasing proinflammatory cytokines such as IL-6, IL-1β, IL-8, TNF-α, and other chemokines, such as G-CSF, IP10 and MCPl, which all develop and increase the inflammatory response. In cases of COVID-19, excessive inflammatory responses occur, and exaggerated proinflammatory cytokines and chemokines are detected in the serum, resulting in cytokine release syndrome or cytokine storm. This causes coagulation abnormalities, excessive oxidation developments, mitochondrial permeability transition, vital organ damage, immune system failure and eventually progresses to disseminated intravascular coagulation and multiple organ failure. Additionally, the excessive inflammatory responses also cause mitochondrial dysfunction due to progressive and persistent stress. This damages cells and mitochondria, leaving products containing mitochondrial DNA and cell debris involved in the excessive chronic inflammation as damage-associated molecular patterns. Thus, the respiratory infection progressively leads to disseminated intravascular coagulation from acute respiratory distress syndrome, including vascular endothelial cell damage and coagulation-fibrinolysis system disorders. This condition causes central nervous system disorders, renal failure, liver failure and, finally, multiple organ failure. Regarding treatment for COVID-19, the following are progressive and multiple steps for mitigating the excessive inflammatory response and subsequent cytokine storm in patients. First, administering of favipiravir to suppress SARS-CoV-2 and nafamostat to inhibit ACE2 function should be considered. Second, anti-rheumatic drugs (monoclonal antibodies), which act on the leading cytokines (IL-1β, IL-6) and/or cytokine receptors such as tocilizumab, should be administered as well. Finally, melatonin may also have supportive effects for cytokine release syndrome, resulting in mitochondrial function improvement. This paper will further explore these subjects with reports mostly from China and Europe. View Full-Text
Keywords: novel coronavirus diseases (or COVID-19); cytokine storm; innate immunity; mitochondrial dysfunction novel coronavirus diseases (or COVID-19); cytokine storm; innate immunity; mitochondrial dysfunction
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MDPI and ACS Style

Yokota, S.; Miyamae, T.; Kuroiwa, Y.; Nishioka, K. Novel Coronavirus Disease 2019 (COVID-19) and Cytokine Storms for More Effective Treatments from an Inflammatory Pathophysiology. J. Clin. Med. 2021, 10, 801. https://doi.org/10.3390/jcm10040801

AMA Style

Yokota S, Miyamae T, Kuroiwa Y, Nishioka K. Novel Coronavirus Disease 2019 (COVID-19) and Cytokine Storms for More Effective Treatments from an Inflammatory Pathophysiology. Journal of Clinical Medicine. 2021; 10(4):801. https://doi.org/10.3390/jcm10040801

Chicago/Turabian Style

Yokota, Shumpei, Takako Miyamae, Yoshiyuki Kuroiwa, and Kusuki Nishioka. 2021. "Novel Coronavirus Disease 2019 (COVID-19) and Cytokine Storms for More Effective Treatments from an Inflammatory Pathophysiology" Journal of Clinical Medicine 10, no. 4: 801. https://doi.org/10.3390/jcm10040801

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