The COVID Episode: What Do We Know Now?

We’re a year into the pandemic and, as a nurse, I’m curious: what have we learned are the best practices for treating COVID in the hospital? I sat down with a returning guest, Dr. Cyrus Shariat, an intensivist, and asked him about COVID pathophysiology, management of respiratory failure, medications, and risk of thromboembolism. 

COVID-19 Pathophysiology

Stages of COVID-19

  • The first stage of the illness is marked by viral replication in which the patient has general flu-like symptoms and lasts 7-10 days.
  • The second stage of the illness can be thought of as the inflammatory response, and in severe cases, is a cytokine storm. Patients who we are seeing in the hospital are almost always in this second stage of COVID.

Vascular Implications

  • COVID can be thought of as a vascular illness whose inflammatory effects cause endothelial (the inner lining of blood vessels) dysfunction which can cause multi organ illness.
  • When you have dysfunction of the endothelium likelihood of forming clots increases, therefore COVID patients are at high risk for MIs, stroke, kidney dysfunction, and DVTs and PEs

Risk Factors

While we don’t know why some (a very small minority of) young, healthy patients become critically ill with COVID, we do know know that the following are risk factors for developing severe COVID:

  • Diabetes
  • Obesity
  • Hypertension
  • Chronic heart disease (CAD and CHF)
  • Chronic lung disease
  • Chronic kidney disease
  • Cancer
  • Old age
  • Male gender
  • Immune dysfunction
  • Liver disease

COVID-19 Management for moderate to severe cases

Management of Respiratory Failure

At the beginning of COVID, much of our management of respiratory failure was driven by a strong fear of aerosolization. We have since learned how to adequately protect hospital staff by using proper PPE and negative airflow rooms, allowing for the use of aerosolizing devices such as high flow nasal cannula and CPAP/BiPAP.

When to Intubate

“We learned a lot of COVID patients have what’s what’s been described as happy hypoxemia or silent hypoxemia, where they’re hypoxic, they’re otherwise doing fine. And it could be watched with some high flow. And they could stay at levels that we were previously uncomfortable with.”

“A lot of these patients are able to actually tolerate low grade hypoxemia. And for weeks, without having any sort of an organ damage.”

“We’ve learned not to intubate solely based on a low oxygen and tachypnea, we’ve seen that these patients who are tachypneic, even though the number that sounds scary (RR: 30-35), a number that would have gotten your intubated a year ago COVID or not COVID. And if you keep a close eye on them, and you give them things like high flow [nasal cannula] and CPAP, and you just watch them, as long as they don’t have respiratory distress, they could avoid getting intubated.”

High Flow Nasal Cannula

“High flow [nasal canula] is fantastic. You’re able to deliver oxygen at very high flows, you’re able to decrease work of breathing by blowing out a lot of the CO2. It’s heated, it’s humidified, so it doesn’t dry you out.”

“High flow has prevented a lot of our patients from from getting intubated. And it’s the really the first thing we try as a COVID patient is getting worse. There’s some notion that it could provide a little PEEP as well if the flow is high enough, but unlikely enough PEEP to recruit [lung tissue].”

CPAP/BiPAP

“CPAP and BiPAP are useful because they could help to recruit lung (…) improve oxygenation.”

“The combination of CPAP and high flow [nasal cannula] is useful. I would say that if someone’s on CPAP or BiPAP for several days and are unable to come off of it, that’s a sign that they’re probably going to require intubation because they are drying their secretions out or not really coughing things up or not getting nutrition.”

“Patients who already use CPAP at home for sleep apnea and have COVID should be continued on it.”

Proning

Hypoxemic respiratory failure due to COVID pneumonia can be thought of as ARDS.

Physiology of Proning

Most of the blood flow to our lungs goes to the dorsal aspect of our lungs, i.e. the part of our lungs closest our backs. This is an evolutionary vestige from when our ancestors walked on all fours. 

What happens during proning is that pressure from the abdominal cavity, edematous lung tissue, the heart, the chest wall that is usually on the dorsal aspect of the lungs is shifted to the ventral aspect, allowing for recruitment of the dorsal alveoli, which gets more blood flow.

History of Proning

“There are two interventions that have been shown to reduce mortality. The first was discovered about two decades ago. And that was the notion of using low tidal volume to avoid high pressures in the lungs. And to reduce damage to the lungs from the ventilator induced lung injury. That changed our practice. We stopped worrying about making the ABG look perfect. And we focused more on avoiding what we call barotrauma by using low tidal volumes as standard of practice.

“The second thing that showed to improve mortality and hypoxemic respiratory failure or ARDS is proning. There was a large European study done in which they took patients with severe ARDS, manually prone them early on in their course [of illness] — they proned them about 16 to 18 hours a day […] And this this had a significant reduction in mortality.

“So these are these are the two things [low tidal volumes and proning] that reduce mortality, and should be done in patients with ARDS whether it’s from COVID or not from COVID.”

Self Proning

“Does [proning] save lives in non intubated patients? The answer is we don’t know yet. We know it improves oxygenation. My intuition is that it will save lives once we have more data.”

“If something is safe and inexpensive, or in the case of proning an awake patient — free — I actually don’t think you need strong data because it’s probably not going to do harm. So I am comfortable [with it and will] continue self proning in the patient who is cooperative and awake because it’s free and it appears safe.”

Further Reading

PROSEVA Trial on mortality benefit from proning in severe ARDS

Medications for Hospitalized COVID-19

Steroids

“There is one medication with robust data of improved outcomes and mortality in COVID-19 and that’s steroids, that’s Decadron […] to briefly sum it up: if you’re sick enough that you are requiring oxygen, which in many cases means you’re already past the viral replication stage, you’re in the immune inflammatory state and giving steroids improves mortality. And it’s been replicated in multiple studies.

The proposed mechanism is by blunting the immune dysregulation, the cytokine storm. Steroids are an anti inflammatory and short course of steroids is generally safe. Steroids save lives in COVID […] I think every every institution now, once a COVID patient is on oxygen, they will give that patient steroids, question of dose and how long to give it are yet to be answered. So hopefully, we’ll know more.”

Remdesivir

“Remdesivir is an interesting drug. It’s an antiviral drug. And early studies in vitro showed that it decreases viral replication. And, you know, decreasing viral replication is not necessarily something that I’m going to get excited about. I want to improve patient outcomes: decrease respiratory failure, decrease mortality.

So they did the first big study last year, and there was actually no change in mortality, no change in respiratory failure. What they noted is that the COVID patients who got Remdesivir recovered a little faster.

“There were multiple other studies done on Remdesivir with with unimpressive results. The notion is that this is an anti viral medication, you’re giving it to patients that are in the ICU. By that time, they may be out of the viral replication phase, they may be just in the hyper immune phase. And I think that’s why it’s not too effective in ICU patients. If you look at the subset of the sickest patients, intubated patients, high flow patients, if you look at that subset of patients, and some of these studies from this severe was not effective at all.”

Tocilizumab

“Tocilizumab is an IL-6 inhibitor that decreases inflammation by targeting this cytokine. [A large study done late in the pandemic] shows the combination of steroids and tocilizumab may improve mortality.”

“Some of our patients who are now are on steroids, who are quite sick, I’m talking to my ID colleagues and we would be checking inflammatory markers and we would come up with a decision about whether we would inject with Tocilizumab because that may help.”

Venous Thromboembolism and DVT prophylaxis in COVID-19

“The inflammation pathway is closely linked to the coagulation pathway […] In COVID, patients have endothelial dysfunction and they also have this hyper inflammatory state when they’re sick and they’re going to be hypercoagulable. In addition to that, they they’ve studied COVID patients and they have some heparin resistance, so they they’re more likely to clot despite prophylactic heparin. So, multiple studies show they’re more likely to get DVTs, strokes, and MIs.”

Important Lessons That We Have Learned from COVID-19

  • Use caution with adopting an intervention into place without rigorous data (i.e.) in vitro data, biological plausibility, small pilot studies.  Case in point – hydroxychloroquine and convalescent plasma.
  • A lot of risk factors for COVID that predispose you to getting severely ill and dying from this virus are lifestyle related medical conditions. “We have an unhealthy population and the pandemic is unmasking that. We’re seeing a lot of people with lifestyle related diseases that are getting extremely sick. So I think part of the public health message, even now, and when we’re done with the pandemic, should be that we need a wake up call. And we need to figure out ways to be healthier as a population.”

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