What We’ve Learned About Treating COVID

September 10, 2020 – This spring, healthcare providers in hospitals across the country scrambled to treat people severely affected by a virus they had just heard about. Usually, by the time a critically ill person arrives at the hospital, doctors either already know or can quickly find established guidelines, based on years of research, for treating the condition. But in the spring of 2020, nothing was established about COVID-19.

“It was a dramatic situation. We had a lot of sick, in a very short period of time, and it was overwhelming to take care of them. There was an almost irrational exuberance in trying any treatment we could think of, ”says David Kaufman, MD, director of critical medical care at New York University Langone Health in New York.

Although doctors have sometimes rushed to try anything, this trial and error over the past 6 months has helped to accumulate scientific evidence of what works and what does not in the treatment of COVID-19. .

“The ability of the medical community to come together quickly to complete these large critical care studies in a very short period of time with reliable, high quality results is incredible,” says Kaufman. “It’s like being in a war economy when all the auto and refrigerator factories convert to make tanks and airplanes.”

The case of steroids

At the start of the pandemic, doctors did not have medicine to give to critically ill COVID-19 patients admitted to their emergency and intensive care rooms. Today, corticosteroids are this drug. Last week, in the wake of several scientific studies that supported this decision, the World Health Organization (WHO) released its official recommendation that people with severe COVID-19 be given steroids to improve their chances of survival.

“Low-dose steroids for 10 days or until the patient is released, whichever comes first, can actually help alleviate symptoms, can avoid switching to a ventilator, and can reduce the risk of death,” explains Javier Lorenzo, MD, a critical care anesthetist at Stanford Hospital and Clinics in Stanford, California.

This is because steroids act like anti-inflammatory drugs. The worst cases of COVID-19 are marked by extreme inflammation that does not slow down. A little inflammation at the start of a viral infection helps fight it. But in severe cases of COVID-19, the inflammation gets out of hand and can eventually lead to organ failure and death.

“Steroids may not be good for people who have only had the infection for a few days because they can actually limit the body’s ability to fight infection,” Kaufman says. “But in people who are seriously ill from overinflammation, steroids help stop it.”

More and more evidence for Remdesivir

In May, the FDA cleared hospitals to give remdesivir to adults and children with severe COVID-19. At the end of August, the agency extended this authorization to anyone hospitalized with the virus.

In a study of 1,063 hospitalized adults with COVID-19, those who received remdesivir recovered in about 11 days, compared to about 15 for those who received a placebo.

“These data are not as strong as for steroids,” says Lorenzo, “but we do know that patients who receive remdesivir may experience faster resolution of symptoms, shorter hospital stays, and less likely to need a respirator. “

Controversy over convalescent plasma

Also at the end of August, the FDA granted healthcare providers emergency use authorization for convalescent plasma in the treatment of COVID-19.

Plasma is the part of the blood that carries antibodies against viruses. In this case, the treatment uses plasma donated by COVID-19 survivors. The idea is that COVID-19 survivors have antibodies that fight the virus. Using plasma, doctors can pass these anti-virus antibodies to other people who are fighting the disease.

The concept dates back at least to the Spanish flu pandemic of 1918. But it’s unclear how useful it is in COVID-19. There has not been a large randomized controlled clinical trial to compare the effects of convalescent plasma to placebo. Some trials are currently recruiting volunteers.

“The evidence for convalescent plasma is really weak,” says Lorenzo. “All plasma is not created equal. Not all plasma have high titers [high concentration of antibodies]and not all antibodies neutralize the virus. We use it, but it’s still not clear whether it’s effective or not. “

Intubate or not

Some intensive care physicians may delay intubating patients and put them on a mechanical ventilator for a little longer than at the start of the pandemic. Intubation requires strong sedation and intensive care. At the start of the pandemic, when doctors saw patients progressing in their need for oxygen, many erred on the side of caution and put patients on ventilators as soon as possible.

Back then, before doctors knew about the benefits of steroids and remdesivir, it was believed that the patient would degenerate and eventually need a ventilator no matter what.

“So if we did it early, rather than waiting until it was an emergency, when we could take our time putting on the personal protective equipment, we would also reduce the risk of exposure to. our healthcare workers, ”explains Lorenzo.

Doctors also feared that oxygen delivered through a tube in the nose – a step under a mechanical ventilator – could push the virus into the air and increase the risk of exposure for healthcare workers as well.

“But we now know that in some patients, if we give the steroids and remdesivir a little longer, and allow them to worsen a little further with the high flow nasal flow [oxygen], we could just squeak and not have to put them on a ventilator, ”Lorenzo says.

At the Stanford ISUs, Lorenzo says, they now believe their staff are protected. “The risk of the virus aerosolizing is real. But we now know that our health care provider’s infection rate is low. So if we maintain our comprehensive PPE guidelines, the risk of transmission is low and we may be able to prevent the patient from switching to a ventilator. “

New research shows this can be a safe risk to take. A recent study found that there was no difference in survival rates between COVID-19 patients who went directly on a ventilator and those who were put on nasal oxygen first.

Tends to recover faster

Some patients on ventilators may recover faster by spending some time each day lying face down or face down on the floor. It doesn’t work for everyone. But for those who benefit, the idea is that the face-down position can distribute oxygen more evenly throughout the lungs. Long before COVID-19, intensive care providers returned sedated patients with ventilators to their stomachs in order to get more oxygen into their lungs.

But since the pandemic, some ICUs have been trying it on patients who are awake and may be about to need a ventilator. There are many ongoing clinical trials looking at the benefits for patients who are not yet on a ventilator but who have difficulty obtaining oxygen.

“For some patients, the oxygen level rises, but it’s not universal,” Kaufman says. “And shortly after you stop lying on your stomach, the oxygen goes back down.”

Unprecedented collaboration

In the path of finding what works, health care providers have thrown away many things that have also been shown to be ineffective.

“A lot of people were talking about hydroxychloroquine,” Lorenzo says. “But we now know, unequivocally, that we shouldn’t be using it. It does not work. And it can probably cause more harm than good. “

They learned what works and what doesn’t work faster through unprecedented collaboration with their colleagues and frontline healthcare workers around the world.

Under “normal” circumstances, researchers keep data tightly until it is published. “Now, some of these trials may publish unpublished data if they feel the benefit is real and substantial,” Lorenzo says.

Social media groups aimed at intensive care physicians, he says, are also more active than ever.

Kaufman is part of an email chain with pulmonologists and intensive care physicians around the world. Many are in Europe and have gained intensive experience with COVID-19 months before doctors in the United States. “To be connected with some of the world’s masters in mechanical ventilation who are in some of the hardest-hit cities in the world is an incredible privilege. It’s like sitting at the foot of Sophocles, learning from the old masters, ”he says.

But despite everything they’ve learned, much remains unknown. Doctors still don’t understand why some patients go through the virus after a week of mild symptoms while others switch to a ventilator within the same amount of time. “We still don’t know how patients progress with this disease,” Lorenzo says.

But after a frenzied spring in which many healthcare providers tried everything that could work, Lorenzo says, “We have learned from this pandemic that we cannot relax our scientific rigor. We have to go through the same peer-reviewed clinical trial process that we normally do, otherwise we can harm patients.

Sources

David Kaufman, MD, director, Critical Medical Care, New York University Langone Health, New York.

Javier Lorenzo, MD, Stanford Hospital and Clinics, Stanford, California.

WHO: “Corticosteroids for COVID-19”.

Press release, FDA.

New England Journal of Medicine: “Remdesivir for the treatment of Covid-19 – Preliminary report.”

Annals of Internal Medicine: “Meta-analysis: Convalescent blood products for Spanish influenza pneumonia: a future treatment against H5N1?”

Press release, University of Michigan Health.

Intensive care medicine: “Timing of intubation and mortality in critically ill 2019 coronavirus disease patients.”

Press release, Columbia University.


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