ACE2/ACE2 and COVID-19

Angiotensin-converting enzyme 2 (ACE2) and COVID-19

Stage 1 - Early Infection
For most people, this involves an incubation period associated with mild and often non-specific symptoms, such as malaise, fever, and a dry cough. During this period, SARS-CoV-2 multiplies and establishes residence in the host, primarily focusing on the respiratory system.

Nose

Some patients lose their sense of smell.

Lungs

Respiratory symptoms include coughing, sore throat, difficulty breathing or shortness of breath.

Stage 2 - Pulmonary Phase
In the second stage of established pulmonary disease, viral multiplication and localized inflammation in the lung are the norm. Most patients with COVID-19 would need to be hospitalized for close observation and management. This stage can be sub-divided:-
- Stage IIa (without hypoxia)
  During this stage, patients develop a viral pneumonia, with cough, fever, and possibly hypoxia.
  
  Lungs
  
  Respiratory symptoms include coughing, sore throat, difficulty breathing or shortness of breath. Long-term effects may include lung damage and scarring.
- Stage IIb (with hypoxia)
  Patients will progress to requiring mechanical ventilation
Lungs

Respiratory symptoms include coughing, sore throat, difficulty breathing or shortness of breath. Long-term effects may include lung damage and scarring.

Stage 3 - Hyperinflammation Phase
A minority of COVID-19 patients will transition into the third and most severe stage of the illness, which manifests as an extrapulmonary systemic hyperinflammation syndrome.
In this stage, shock, vasoplegia, respiratory failure, and even cardiopulmonary collapse are discernable. Systemic organ involvement, even myocarditis, would manifest during this stage.

Heart and blood vessels

Infection can promote blood clots, heart attacks, and cardiac inflammation. Long-term effects may include scarring of the heart muscle. Heart failure may occur.

Liver
Up to half of hospitalized patients have enzyme levels that signal a struggling liver. An immune system in overdrive and drugs given to fight the virus may be causing the damage.

Kidneys
Kidney damage is common in severe cases and makes death more likely. The virus may attack the kidneys directly, or kidney failure may be part of whole-body events like plummeting blood pressure.

Intestines
Patient reports and biopsy data suggest the virus can infect the lower gastrointestinal tract, which is rich in ACE2 receptors. Some 20% or more of patients have diarrhea.

Eyes
Conjunctivitis, inflammation of the membrane that lines the front of the eye and inner eyelid, is more common in the sickest patients.

Brain
Some COVID-19 patients have strokes, seizures, confusion, and brain inflammation.

Franz Wiesbauer, MD MPH COVID-19 disease progression MED Mastery, 19 November 2020
This article is an excellent one to start with. It is clear and concise. The stages of COVID-19 disease progression is based on the paper by Siddiqi and Mehra. Other data is illustrated by diagrams.

sciencemag.org How does coronavirus kill? Clinicians trace a ferocious rampage through the body, from brain to toes
This article describes how the disease COVID-19 can progress to a fatal outcome, including the role of ACE2 receptors. There is also an interactive diagram to illustrate the symptoms that occur in different parts of the body. Although not explicitly stated, those correspond to organs where ACE2 expression is present.

The Conversation, What is the ACE2 receptor, how is it connected to coronavirus and why might it be key to treating COVID-19? 14 May 2020
This is an easy-to-read article by three scientists with expertise in pharmacology, molecular biology and biochemistry. They answer questions such as - What is the ACE2 receptor? Where in the body is it found? What is the normal role ACE2 plays in the body? Which organs are most severely damaged by SARS-CoV-2? And more.