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SARS-CoV-2 uses the ACE-2 receptor to enter and infect host cells. Image credit:

Angiotensin-Converting Enzyme-2 (ACE-2): Covid-19 attacks the selected body organs for the same reason.

No doubt, Covid-19 is the most devastating global infectious disease since the 1918 Spanish flu. Initially thought of as a respiratory infection, Covid-19 causes multiorgan damage that culminates in substantial morbidity and mortality. Covid-19 damages all these organs for the same reason – their cells express the angiotensin-converting enzyme-2 (ACE-2) receptor within their membranes – a receptor that is the gateway for viral entry into the cells. In today’s article, we demystify the role ACE-2 plays in the propagation of Covid-19 and the complications the disease incurs onto the organs it affects.

Cells – the functional units of any living organism – make up tissues: tissues make up organs: organs become systems – systems make up the entire organism. The different cellular functions within various tissues and organs drive the systemic roles we envision that the human body executes. So, it’s imperative to understand that any cellular interaction within or without has an outward effect on how the body functions. SARS-CoV-2, through its spike protein, attaches onto the ACE-2 receptor on the cells and infects them. It then dysregulates several cellular mechanisms that lead to disease propagation, culminating in the outward effects that Covid-19 portrays among the susceptible individuals.

Various organs express the ACE-2 receptor: therefore, they are critical targets for Covid-19. They include the brain, lungs, heart, pancreas, kidneys, testis, intestines, and liver.

Only the bile duct epithelial cells (cholangiocytes) express the ACE-2 receptor. So, the liver damage that we observe among patients with Covid-19 is probably due to systemic inflammation and drug toxicity but not essentially a direct injury to the liver cells due to SARS-CoV-2.

Within the lungs, the type II alveolar epithelial cells (pneumocytes) express the ACE-2 receptor. The lung alveoli have two main types of cells – type I and type II pneumocytes. Type I pneumocytes form the gaseous exchange bed within the alveolus. Type II alveolar cells secrete surfactant – reducing surface tension within the alveolus to prevent its sudden collapse at the end of expiration. When SARS-CoV-2 attacks the type II cells, it attenuates their primary role – of secreting surfactant – leading potentiating the propensity of the affected alveolar sacs to collapse. Type I pneumocytes also maintain electrolyte and fluid balance within the alveoli and interact with the type II cells to secrete surfactants in response to stretch. So, any blockade in the interaction of these two cells creates a mismatch in the normal functioning of the lungs as a whole.

The enterocytes of the ileum: urothelial cells of the bladder; proximal tubule cells of the kidneys; the myocardial cells explicitly express the ACE2 receptor in their respective organs. It, therefore, is no coincidence that each of these organs may show derangements during Covid-19.

ACE2 is homologous to the angiotensin-converting enzyme, a widely abundant and crucial component of the renin-angiotensin-aldosterone system (RAAS) – a critical regulator of blood volume and systemic vascular resistance – the backbone of blood pressure and electrolyte balance within the body.  ACE-2 counteracts the effects of the RAAS.

It inactivates the most bioactive protein within the RAAS – angiotensin II by converting it to angiotensin-(1-7). Angiotensin II causes systemic vasoconstriction, cellular proliferation, hypertrophy, inflammation, oxidative stress, and fibrosis. Angiotensin-(1-7) causes the opposite effects: it drives vasodilatation, vascular protection, prevents fibrosis, cell proliferation, and inflammation.

The anchorage of SARS-CoV-2 onto the ACE-2 receptor renders it unavailable to counteract the effects of angiotensin II from the RAAS. It drives unparalleled system-wide inflammation, oxidative stress, and vasoconstriction. Through the kinin-Kallikrein system (KKS), ACE-2 interacts with molecules in this pathway to maintain the internal milieu of coagulation, inflammation, and pain. The absence of ACE-2 due to its SARS-CoV-2 occupancy leads to unparalleled production of protein molecules within the KKS that potentiate blood clotting. It worsens systemic inflammation and the frail immune response due to Covid-19.

The brain may swell due to cerebral oedema and neuron degeneration. Focal necrosis and vasculitis of the small veins occur within the kidneys. The movement of macrophage-laden SARS-C0V-2 cells distorts the endothelial integrity within the vascular beds. It causes increased permeability, microcirculation disturbance, and unregulated coagulation activation. The myocardial fibres may atrophy with infiltration of inflammatory molecules. Extensive damage due to Covid-19 occurs within the lungs – there’s extensive pulmonary oedema, hyaline membrane and microthrombi formation, followed by cellular fibro-myxoid exudates and inflammatory infiltrate resulting in the pulmonary architectural organisation and fibrosis – the hallmark of acute respiratory distress syndrome (ARDS).

Within the pancreas, SARS-CoV-2 hits the islets of Langerhans – the cells responsible for glucose metabolism. The inflammation that results culminates in reduced secretion of insulin.  Non-coincidentally, several patients with Covid-19 present with high blood sugars that require vast amounts of insulin to counteract.

Direct viral damage within the liver occurs in the cholangiocytes- the only cells that express ACE-2 on their surfaces. We demonstrate this by observing a substantial increase in the enzyme that these cells explicitly secrete – the Gamma-glutamyl transferase (GGT). The mild-to-moderate increase in the main liver enzymes, as noted earlier, is probably due to systemic inflammation and drug toxicity.

Covid-19 may cause male infertility due to the abundance of ACE-2 expressing cells within the testis. Scientists believe that the virus may directly attack the testicular cells and destroys them. It deprives them of their ability to manufacture gametocytes. It increases the probability of suffering infertility among susceptible male patients.

It’s prudent to understand the mechanisms of organ damage due to Covid-19: it will help you prevent the disease with reasons. Covid-19 attacks the selected organs because their cells express the angiotensin-converting enzyme-2 receptors on their surfaces that the virus primarily uses to enter and infect the host cells. Different therapeutic endeavours aim to hit the virus at various sites along the pathways through which it drives organ damage. However, the most prudent and cost-effective way to combat the infection is through prevention by adhering to safe operating procedures and mass vaccination.


Dr A. M. Ssekandi is a medical officer, researcher, content creator, author, and founder of He does private practice with a public touch. He is a certified digital marketer. He has earned certificates in Understanding Clinical Research and Writing in Sciences from the University of Cape Town and Stanford University respectively. He also has a certificate of Good Clinical Practice from

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