Home About us Editorial board Ahead of print Browse Articles Search Submit article Instructions Subscribe Contacts Login 
  • Users Online: 664
  • Home
  • Print this page
  • Email this page

Previous article Browse articles Next article 
J Res Med Sci 2021,  26:129

COVID-19 cellular pathogenesis in brief

Department of Food Science and Nutrition, Nara Women's University, Kita-Uoya Nishimachi, Nara, Japan

Date of Submission29-Apr-2020
Date of Decision27-Jul-2020
Date of Acceptance02-Sep-2020
Date of Web Publication22-Dec-2021

Correspondence Address:
Satoru Matsuda
Department of Food Science and Nutrition, Nara Women's University, Kita-Uoya Nishimachi, Nara 630-8506
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jrms.JRMS_471_20

Rights and Permissions

How to cite this article:
Ikeda Y, Tsuji A, Murakami M, Matsuda S. COVID-19 cellular pathogenesis in brief. J Res Med Sci 2021;26:129

How to cite this URL:
Ikeda Y, Tsuji A, Murakami M, Matsuda S. COVID-19 cellular pathogenesis in brief. J Res Med Sci [serial online] 2021 [cited 2023 Mar 28];26:129. Available from: https://www.jmsjournal.net/text.asp?2021/26/1/129/333283

Dear Editor,

The most frequently used test for the diagnosis of COVID-19 is now reverse-transcriptase polymerase chain reaction (RT-PCR) executed by using nasopharyngeal swab specimens. The sensitivity of the severe acute respiratory syndrome (SARS)-CoV-2 RT-PCR tests has been described around 70%. The test could usually detect the virus 2 or 3 days before the onset of infectious symptoms. It should be toughly noted that the RT-PCR positivity does not mean an evidence of active and/or infectious virus. Vice versa, a negative result of the RT-PCR test does not exclude the SARS-CoV-2 infection.

In case the infection would be true, the SARS-CoV-2 virus simply enters the cells by attaching to the angiotensin-converting enzyme-2 (ACE2), which is expressed on pneumocytes of the lower airways. While ACE converts angiotensin I (Ang I) to Ang II, ACE2 uses Ang II as a substrate and produces Ang (1–7). The Ang II is a vasoconstrictor that causes oxidative stress, producing increased reactive oxygen species. Therefore, elevated Ang II level causes higher blood pressure, insulin resistance, proteinuria, and so on. In addition, ACE is surely correlated with asthma, chronic obstructive pulmonary disease, and acute respiratory distress syndrome. Furthermore, overactivation of ACE aggravates amyloid-β-induced apoptosis and/or neurodegeneration in Alzheimer's disease. On the other hand, the ACE2 is highly expressed in smokers and/or in patients with an underlying disease. As described below, several data have indicated the protective roles of the ACE2 pathway. Surface spike glycoprotein on the surface of SARS-CoV-2 binds to the ACE2 [Figure 1], which has been proven to be protective in pulmonary and cardiovascular diseases and so on.[1] The Ang (1–7) exerts its effects through the Mas receptor in various tissues, including kidneys, heart, brain, and vasculature, which even protects against aneurysm rupture via the Mas receptor.[2] Amazingly, upregulation of internal ACE2 could attenuate the exacerbation of nephropathy and hypertension in diabetic mice.[3] In addition, stimulation of ACE2/Ang (1–7)/Mas ameliorates Alzheimer's disease.[4] It has been reported that the ACE2/Ang (1–7)/Mas activates AKT signaling to ameliorate oxidative stress, inflammation, and hepatic steatosis.[5] In general, the PI3K/AKT activation opposes the AT1-induced apoptosis.
Figure 1: Schematic illustration implying that angiotensin-converting enzyme-2/angiotensin (1–7)/Mas axis protects host tissues via the PI3K/AKT/NRF2/HO1 signaling from various diseases without COVID-19. When COVID-19 infection abolishes the angiotensin-converting enzyme-2 axis, special dieting could substitute the protection by activating the PI3K/AKT signaling

Click here to view

The PI3K/AKT pathway is thought to correlate with host protection and disease prognosis. If the SARS-CoV-2 virus destroys the ACE2/Ang (1–7)/Mas/PI3K/AKT signaling pathway, a host protection system, it would be of significance to define appropriate strategies to achieve benefits to activate the PI3K/AKT pathway. As the efficiency of pharmacological and/or vaccinal treatments against COVID-19 has been imperfect at present, dietary choices could indicate a certain role in the host protection system via the PI3K/AKT activation. For example, dietary supplementation of fish oil attenuates lipopolysaccharideinduced inflammation as shown in previous studies. Lifestyle factors such as special diets could play certain roles against the severity of COVID-19.[6]

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Dhawale VS, Amara VR, Karpe PA, Malek V, Patel D, Tikoo K. Activation of angiotensin-converting enzyme 2 (ACE2) attenuates allergic airway inflammation in rat asthma model. Toxicol Appl Pharmacol 2016;306:17-26.  Back to cited text no. 1
Shimada K, Furukawa H, Wada K, Wei Y, Tada Y, Kuwabara A, et al. Angiotensin-(1-7) protects against the development of aneurysmal subarachnoid hemorrhage in mice. J Cereb Blood Flow Metab 2015;35:1163-8.  Back to cited text no. 2
Zhao S, Ghosh A, Lo CS, Chenier I, Scholey JW, Filep JG, et al. Nrf2 deficiency upregulates intrarenal angiotensin-converting enzyme-2 and angiotensin 1-7 receptor expression and attenuates hypertension and nephropathy in diabetic mice. Endocrinology 2018;159:836-52.  Back to cited text no. 3
Kamel AS, Abdelkader NF, Abd El-Rahman SS, Emara M, Zaki HF, Khattab MM. Stimulation of ACE2/ANG (1-7)/mas axis by diminazene ameliorates Alzheimer's disease in the D-galactose-ovariectomized rat model: Role of PI3K/Akt pathway. Mol Neurobiol 2018;55:8188-202.  Back to cited text no. 4
Cao X, Yang F, Shi T, Yuan M, Xin Z, Xie R, et al. Angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas axis activates Akt signaling to ameliorate hepatic steatosis. Sci Rep 2016;6:21592.  Back to cited text no. 5
Matsuda S, Ikeda Y, Murakami M, Tsuji A. Save children from mortal shock of COVID-19. J Adv Med Med Res 2020;32:23-5.  Back to cited text no. 6


  [Figure 1]


Previous article  Next article
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
Article Figures

 Article Access Statistics
    PDF Downloaded141    
    Comments [Add]    

Recommend this journal