COVID-19 Interest Group

July 1, 2020

 CIG Bulletin #16

Peeling Back the Layers of a New Disease

A perspective of an old retired cardiologist who has never seen a case of Covid-19

By Pate Thomson MD

There is much to learn from Peeling Back the Layers of the Covid -19 story.  What does it mean to say we have a new disease that becomes a pandemic with more than 10,000,000 world-wide cases and more than 500,000 deaths?  It means that there will be a lot to learn about it and great urgency to do so. This is particularly so for our health care providers.

Covid -19 is not the flu! It is an infection producing a very complex “disease” that can act like several diseases. Our front-line health care workers, who have been thrown into the fray are struggling to understand it.  In the US more than 400 have died in the line of duty, themselves victims of this infection. Traveling in sub-visible droplets, some laden with thousands of viral particles, the virus attacks respiratory cells in the upper airways, gains entrance to the cell, replicates, induces cellular, tissue and organ dysfunction and an immune response. Many feel ill with an ailment that is much like the flu, with the familiar cough, headache, fever, lassitude, and aching muscles.  At this stage treatment includes rest, fluids and Tylenol, a syndrome and course familiar to most everyone.  5-7 days later something else may happen. Shortness of breath becomes a major symptom; oxygen levels fall as first signs of the “new disease” and it is quite different from the earlier syndrome. The new disease is propagated by the immune system which may transform from its essential role as a protector to one that produces a very destructive inflammatory reaction. It is this cytokine driven inflammation that threatens all organs.

Another deadly process may develop.  It is a hypercoagulable state, triggered somehow, perhaps by the endothelium lining the vessels, and results in micro-thrombosis in tissue capillaries and macro-thrombosis in arteries and veins. These larger blood clots may produce heart attacks and strokes and blood clots in the lungs, any one of which can produce permanently disabling illness or death. Full understanding of the consequence of the capillary thrombosis is just beginning to be looked at more closely but we know that the news will not be good.

Clinically, damage to the lungs plays the central role and there is no other organ more profoundly affected. Is it the virus or the immune system doing the damage?  Is it the same problem in all patients?  It turns out that in the latter case, the answer may be no.

The physiologic picture of each case, the x ray and the level of distress may appear very different in one patient than it does in the next and more options exist in how each patient may be approached therapeutically.  Some, desperately ill, with low oxygen levels, require intubation and placement on a mechanical ventilator. This is not so for a significant number of patients as it is  now better recognized that lower oxygen levels can be tolerated and oxygen can be delivered in less invasive ways.  Insight Into the mechanics of how each patient is breathing, aided by understanding the individual’s physiology opens doors to simpler, and better tolerated ways to treat.  It is not the case that “one treatment fits all”.

Peeling back the layers offers new insights that may translate to current progress being made:  

      1. Understanding how the virus is transmitted offers a way to avoid it by social distancing, avoiding crowds, using masks, and observing good hand hygiene.

2. Recognizing the first week of flu like symptoms as a stage offers an opportunity to explore outpatient interventions that may favorably turn the tide in fending off the more critical illness that can follow.  Antiviral drugs, anti-inflammatory drugs, convalescent serum, or monoclonal antibodies may come to the rescue. This is yet to be shown.
3. Knowing the individuals pulmonary physiology should help chose measures other than intubation and machine ventilation and a may provide a more nuanced approaches to each patient.
4. The out of control inflammatory response occurs at least a few days after onset of symptoms. Dexamethasone, which dampens the immune response, reduces mortality significantly when given to  patients with lung involvement who are being treated with oxygen or intubated and on a ventilator. Applying dexamethasone earlier may be harmful.  Knowledge of the timing of the natural course of the infection is key to selecting the optimum time to administer this drug.  There will likely be a role for antiviral agents here as well and the drug Remdesivir has been shown to shorten hospitalization in patients that are in this phase.

5. Recognizing the risk of the hyper-coagulatable state has led to routine prophylactic use of heparin in the hospital setting. Multiple studies have shown improved outcomes with this approach.

There will surely be more to come.

The world waits for the vaccine chapter to unfold and phase 3 vaccine studies are now beginning.

With some trepidation we also await the long-term outcomes of those who have been seriously ill and recover. This chapter has not yet been told.

So, CIG members, please do keep vigilant and keep peeling these secrets away. It is the only way to expose the naked truth.