Office of Dr. Mangat and Dr. Kaur 

Lessons to our students

In Clinical Medicine it is important to have good studies, but the major innovations have arisen from "standing on the shoulder of Giants". Sir Isaac Newton stood on Galileo shoulders to develop the laws of motion. Francis Crick and James Watson looked at the X ray diffraction gratings of Maurice Wilkins at Kings College London and  Linus Pauling alpha helix . Watson and Crick stood on the shoulders of these giants to make models of the double helix which fitted in with all the data known then.

 Using the Watson and Crick approach and standing on the shoulders of the Wuhan Giants  I note the following:

Covid 19 has varied presentations.  The respiratory presentation follows a predictable 2-11 day course after exposure. Flu like symptoms present on day 5 on average progressing to increased shortness of breath and a silent hypoxia manifest by a drop in oxygen saturation. This often leads to a viral pneumonia.  On day 10 there is a cytokine storm as the ACE 2 receptors become overloaded leading to respiratory and Multi organ failure. Recent studies confirm a clinical picture similar to High Altitude Pulmonary Edema that responds to acetazolamide, nifedipine and phosphodiesterases.

The activation of ACE 2 receptors in the arterial , venous and  cardiac endothelium  causes further inflammation resulting in thrombi notably worse in obese patients but treatable with dipyridamole. ACE 2 receptors exist in the GI tract notably the esophageal epithelium and the enterocytes of the ileum and Colon hence on activation the clinical picture of abdominal discomfort, nausea and diarrhea. Ace 2 receptors are also in the nervous system, activation causes  headaches, impaired taste, smell, ataxia , seizures and dizziness. 

Covid 19 is a Coronavirus that  lives in the nasopharynx in the first few days of infection, like other coronaviruses it knocks out lung CD 4 cells as it progresses down into the trachea and lungs. The first line of defense are piping hot drinks, salt gargles and nasal saline washes to decrease the viral load in the nasopharynx . There exists a narrow window of opportunity is to find the achilles tendon of this virus and counter attack. Once in the lungs it enters the alveoli via ACE 2 receptors resulting in a cytokine storm. The activation of the ACE 2 in the lungs results in a fluid build up and a culture medium for atypical bugs due to the lungs CD4 defense mechanism being inactivated. On day 2-3 after onset of infection patients present with a viral conjunctivitis with hallmark follicles presenting as mild pink eye which is resolved by drinking piping hot tea or soup that steams up spectacles. This follicular conjunctivitis may be explained by turbulent  and respiratory pathogen emissions. The article suggest we have to be more cognizant of health personnel taking care of ventilators.

Protease inhibitors such as Lopinavir/Ritonovir with oseltamvir  was used in China after day 10, India has used chloroquine and hydoxychloroquine to block the ACE 2 receptors and prevent the hemolysis ( similar to its mode af action in Malaria). In China they have correlated the cytokine storm with the elevation of IL6 and treated with Tocilizumab (undergoing phase 3 trials in US) along with steroids. South Korea has shown the inhaled steroid ciclesonide has been effective in preventing viral replication.Most patient will not present till day 5, limiting a very narrow window to knock out the virus using the antiviral cocktail of  lopinavir/ritonovir and oseltamavir along with hydroxychloroquine and an antibiotic for atypical bacteria. Additionally glycopyrralates now available in an MDI format will dry up secretions to lessen atypical bacteria taking root.

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