Acute Respiratory Distress Syndrome (ARDS) in COVID-19 Patients

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COVID-19 usually begins as an upper respiratory tract infection; however, for some patients, the SARS-CoV-2 virus enters the lower respiratory tract and causes direct injury to the lungs by filling the alveoli (air sacs) with excess fluid. As decrease in oxygenation occurs in the blood, breathing becomes distressed and organs become oxygen-deficient. The lungs attempt to heal, but the resulting inflammatory response often ends up damaging the lungs further.

This severe inflammatory disease of the lungs is called the acute respiratory distress syndrome (ARDS). ARDS is a condition most commonly associated with illnesses such as sepsis and bacterial pneumonia—and now with COVID-19. When a patient presents with symptoms associated with ARDS—shortness of breath, chest pain, rapid heart rate and reduced blood oxygen levels—they are transported to the intensive care unit (ICU) to be monitored and possibly treated with artificial or mechanical ventilation.

In this Q&A, Lorenzo Berra, MD, anesthesiologist in the Department of Anesthesia, Critical Care and Pain Medicine and medical director for respiratory care, and Charles Corey Hardin, MD, PhD, physician in the Division of Pulmonary and Critical Care Medicine, explain the link between ARDS and COVID-19.

Q: Does ARDS onset through COVID-19 present different treatment challenges vs. typical ARDS onset?

Hardin: The ARDS that we are currently seeing caused by COVID-19 is not different than ARDS caused by seasonal influenza or bacterial pneumonia. With ARDS, there is always a spectrum of severity—low, medium and high—but this is a viral infection leading to a syndrome with which we at Mass General are very familiar. The good news about that is we have 50 years of experience in treating this disease, so everything we’ve learned thus far about ARDS, through all of our usual approaches, work very well in the setting of COVID-19.

Q: What is the standard practice of care for ARDS?

Berra: The treatment for ARDS is gentle and supportive, which is why there are specialized respiratory therapists working together with infectious disease specialists. Particularly in the acute phase, the type of treatment we administer in the ICU is lung-protective ventilation, which also involves monitoring the patients’ blood and airway pressure, fluid intake and breathing difficulty. As the lungs always need to oxygenate venous blood, it’s a fine balance of making sure the injured lungs are resting without excessive stretch while providing artificial ventilation to assist lung inflation to help the patient recover.

Hardin: The other things that helps oxygenation is prone ventilation, when the patient is lying on their stomach, and other adjunctive therapies such as inhaled nitric oxide.

Q: What are the signs, symptoms and clinical markers associated with ARDS onset?

Hardin: There is not presently a quantitative biomarker. It’s been a significant interest over the last 10 years to find more identifiable biomarkers that would mark prognosis, but those efforts are still in an early stage. So, presently, we use clinical assessment and pay a lot of attention to measures of the efficiency of blood oxygenation.

There’s a ratio called P/F, which is the ratio of the partial pressure of oxygen, or the oxygen that gets into the blood, to the fraction of inspired oxygen, or the amount of oxygen we are putting in via mechanical ventilation. We can also use clinical assessment in terms of imaging and patient trajectory.

The key to treatment, as Dr. Berra says, is resting the lung. Just like you would put a cast on a broken leg, we aim to provide support to the lung to limit mechanical strain. If a patient is working very hard to breathe in a setting of lung inflammation, that triggers us to come in and use mechanical ventilation as a lung-protective strategy.

Q: Are there any clinical trials for ARDS?

Berra: We are actively enrolling patients into trials for different antiviral strategies. That is a big part of our efforts because we do not have specific or proven drugs for COVID-19 ARDS.

The respiratory care, pulmonary and critical care teams have put together an early stage trial to see if breathing a high concentration of nitric oxide gas—a likely COVID-19 virucide when administered to the patient twice a day along with oxygen—helps arrest the disease in COVID-19 positive patients before it progresses to ARDS.

Nitric oxide is an FDA-approved standard treatment of ARDS—particularly in neonatal pediatrics—to improve oxygenation since it augments ventilation perfusion matching, i.e., it increases blood flow in the areas of the lung that are well-ventilated. About a million patients have been treated with inhaled nitric oxide over the past 30 years.

The first study of nitric oxide use in patients with ARDS was conducted by Warren Zapol, MD, former Mass General anesthetist-in-chief and my mentor. In 2004, during the severe acute respiratory syndrome (SARS) outbreak, it was shown that higher levels of the gas than we generally use in pediatrics have antiviral activity against the coronavirus responsible for SARS, as ventilated patients on inhaled nitric oxide recovered faster. In vitro studies confirmed that nitric oxide is viricidal to SARS virus.

Another study we will commence is for health care providers in which we administer a high dose of inhaled nitric oxide at both the beginning and end of their shifts, to learn if it prevents viral invasion and reduces the chance of a positive diagnosis of COVID-19.

Hardin: It would be particularly fortuitous if it also had an antiviral effect, as it’s already a treatment we are inclined to use for patients with pronounced oxygenation difficulties.

Q: There has been a lot of talk about early intubation as a preventative measure for ARDS onset through COVID-19. What is the therapeutic benefit of it and are there other measures to consider?

Berra: The best measures that we have to prevent worsening of the lung condition are: (1) focusing on the patient’s lung protection through early intubation; and (2) ensuring that when a patient is presented to the health care system, COVID disease is recognized early so that we can switch our focus to lung protection as soon as possible.

Hardin: There are two aspects to the benefits of early intubation. One has to do with the idea that if a patient is working hard to breathe, they can worsen their lung injury. So, intubating those patients earlier can prevent further damage. The other issue is one of predicting the future a bit. When we do perform an intubation, we want to do it in a controlled way with staff fully donned in personal protective equipment and in a negative pressure room. When we see a patient who might be heading toward intubation, we do try to intervene in a controlled way earlier in the process.

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