The five reasons why COVID-19 causes death.

Yesterday, in the Journal of Cardiothoracic and Vascular Anesthesia, there was a Letter to the Editor by a group of physicians in Italy were where they described the five reasons why people die of COVID-19. I found it quite interesting that this article was published in that particular journal. Given that the audience to my content is medical professionals who mostly work in the ICU, the five reasons will not come as a surprise to us because we take care of these patients every day. Their take is that COVID-19 causes death due to five reasons:

  • Organ reserve
  • The viral infection itself
  • The disproportionate inflammatory response
  • Microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome (MicroCLOTS)
  • Complications of preexistent comorbidities or ongoing therapies

The first reason to explain includes the organ reserve of a patient. What they mean by this is as a person ages and has more comorbidities it makes the threshold for them falling off the hypothetical cliff from a physiological perspective far easier. Without giving up any personal information of any patients that I’ve taken care of, I recently took care of a gentleman with end-stage COPD on a baseline 6 L of nasal cannula who caught COVID-19. It was very easy to tip him over with a worsening of his acute on chronic hypoxemic respiratory failure. Fortunately for him, he did well with supportive care remaining on high-flow nasal cannula although he did have a quite lengthy hospital stay. When I saw his CT scan that was performed in the emergency department on admission I thought that the guy had no chance of surviving whatsoever. His lungs were absolutely trashed at baseline and then the ground glass capacities opacities from the COVID-19 inflammation left him with a little wiggle room to oxygenate. We’ve all seen patients who have underlying co-morbidities that unfortunately have left them with little gas in the tank to fight off the illness.

The second reason that the authors explained as a cause of death was the viral infection infection itself. I’m not so sure about this one. The reason for this is because I personally do not think that people die from the acute viral infection. What I mean by the acute viral infection is when our patients are still at their house with non-complicating manifestations such as when they lose their sense of smell, have a sore throat, runny nose, lose their sense of taste, have chills, fatigue, malaise, fever, diarrhea, nausea, vomiting, abdominal pain, myalgias, etc. After numerous discussions of the clinical manifestations that led to the patients presenting to the emergency department and later on the intensive care unit where they meet me, they were mostly feeling quite crummy to reasonable until approximately one week into their clinical course they started having worsening cough and shortness of breath. This then translates into the third cause of death in these patients which is the disproportionate inflammatory response to the virus itself.

This disproportionate inflammatory phase that we see in that we see manifest itself in our COVID patients is what frightens me the most. When a patient presents to the emergency department and the baseline labs on them show a C-reactive protein that exceeds double digits and a ferritin level that exceeds 1000 I know that the inflammatory response has possibly run itself too far. At that point, we need to work fast to help mitigate this information to save the life of this patient. This is where we have noted the benefits of using corticosteroids and in some cases tocilizumab or other monoclonal antibodies to mitigate this hyper inflammatory response. This is by no means a medical recommendation but I subscribe to the notion where we need to provide certain patients with higher doses of corticosteroids than just the 6 mg of dexamethasone that was initially recommended by the RECOVERY trial. I currently favor using 125 mg of Solu-Medrol twice daily for three days and then continuing with the dexamethasone for the subsequent seven days to complete a 10 day course. As we have all unfortunately experienced, despite our best efforts to mitigate this inflammation, some patients just do not survive this inflammatory phase and they succumb to this unfortunate situation.

The fourth cause of death is the coagulopathy that we see in COVID-19. This paper taught me a cool term called MicroCLOTS which stands for Microvascular COVID-19 Long vessels Obstructive Thromboinflammatory Syndrome. This is the first time I had heard of this. The authors of this paper describe to the syndrome consisting of in situ pulmonary clot formation and also includes classical thromboembolism. I know that there is still a debate as to whether these patients need full-dose anticoagulation to mitigate this as there is no high-quality prospective randomized controlled trial looking at full-dose anticoagulation to my knowledge. Despite the lack of high-quality evidence I am currently and I coagulating my critically ill COVID patients after weighing the risks and benefits.

The last noted reason why these authors think that Covid patients die is secondary to complications of pre-existing comorbidities and ongoing therapies. Unfortunately, we have had very little success at saving the lives of patients who have body mass indices that are extremely high. Given that there habitus is a relative contraindication for ECMO and they proved to be quite challenging to oxygenate and ventilate once they are on mechanical ventilation. Not to mention that they are extremely challenging to put in prone position once they are sedated and intubated. They are unable to assist in their own turning. It’s unfortunately a topic, that in my opinion, it’s not sufficiently discussed. This would be an opportunity to capitalize on the statistics of obesity and death in COVID patients as a way to educate the general population as to the risks that are associated with obesity not only for underlying heart disease, diabetes, and other commonly discussed illnesses but, in addition to that the fact that obesity increases the risk of death from COVID-19. I guess that is not really a complication of pre-existing comorbidities in the opinion of some but I guess I could justify it being here.

In addition to this, since we are treating our patients with corticosteroids and other immuno modulating products, this makes our patients more susceptible to secondary infections. This includes Pseudomonas, Staph aureus, and fungal infections such as candidemia. This makes it extremely tricky to care for our patients who are baseline already has an elevated white blood cell count due to the steroids and our febrile from their underlying inflammatory process. In addition, it goes without saying but these patients do not get extubated in 24 to 48 hours. They tend to linger for multiple days and weeks and sometimes even months. Every day that passes increases their likelihood of developing a secondary infection. I could personally go on and on about complications that we have seen due to these comorbidities and the therapies that have been received. But I will spare you.

To conclude this post I would like to tip my hat to the authors of this paper and I definitely recommend that you read it for yourself. It’s actually quite short at about two pages in total. I guess this post is, in text form, actually longer than their original letter to the editor. Oh well. I hope you got something out of this post and I’m interested in hearing your feedback. I have plenty of other COVID-19 content HERE.


Marilena Marmiere, Filippo D’Amico, Alberto Zangrillo, Giovanni Landoni. The five reasons why people die of COVID-19. Journal of Cardiothoracic and Vascular Anesthesia (2021). doi:
Link to Article

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