Sept. 10, 2020 — This past spring, health care providers at hospitals around the country scrambled to treat people who were critically ill with a virus theyâd only just heard of themselves. Usually, when a severely ill person arrives at the hospital, doctors already know or can quickly find established guidelines, based on years of research, for treating the sickness. But in the spring of 2020, nothing was established about COVID-19.
âIt was a dramatic situation. We had a lot of sick people, in a very short period of time, and it was overwhelming to take care of them. There was an almost irrational exuberance to try any treatment that we could think of,â says David Kaufman, MD, director of medical intensive care at New York University Langone Health in New York City.
While doctors may have at times rushed to try anything, that trial and error over the last 6 months has helped accumulate the scientific evidence of what works and what doesnât in the treatment of COVID-19.
âThe ability of the medical community to pull together quickly to get these large critical care studies done in a very short period of time with reliable, high-quality results is amazing,â Kaufman says. âItâs like being in a wartime economy when all automobile and refrigerator factories convert to make tanks and planes.â
At the start of the pandemic, doctors didnât have a go-to medication they could give to critically sick COVID-19 patients admitted to their ERs and ICUs. Today, corticosteroids are that medication. Last week, on the heels of several scientific studies that supported the move, the World Health Organization (WHO) released its official recommendation that people with severe COVID-19 receive steroids to improve their chances of survival.
âLow-dose steroids for 10 days or until the patient is discharged, whichever one comes first, can actually help with symptoms, can avoid escalating to a ventilator, and can lower the risk of death,â says Javier Lorenzo, MD, a critical care anesthesiologist at Stanford Hospital and Clinics in Stanford, CA.
Thatâs because steroids act as anti-inflammatories. The worst cases of COVID-19 are marked by extreme inflammation that doesnât let up. A little inflammation at the beginning of a viral infection helps fight it off. But in serious cases of COVID-19, the inflammation gets out of control and can eventually lead to organ failure and death.
âSteroids may not be good for people who have only had the infection for a few days because they may actually limit the bodyâs ability to fight infection,â Kaufman says. âBut in people who are critically ill because of over-inflammation, steroids help put a lid on it.â
In May, the FDA authorized hospitals to give remdesivir to adults and children with severe COVID-19. In late August, the agency expanded that authorization to anyone hospitalized with the virus.
In a study of 1,063 adults in the hospital with COVID-19, the ones who got remdesivir recovered in about 11 days compared to about 15 for those who got a placebo.
âThis data is not quite as robust as it is for steroids,â Lorenzo says, âbut we know that patients who get remdesivir can experience faster resolution of symptoms, shorter duration of hospitalization, and be less likely to need a ventilator.â
Also in late August, the FDA granted health care 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 survivors of COVID-19. The idea is that COVID-19 survivors have antibodies that fight the virus. Through plasma, doctors can pass those virus-fighting antibodies onto others struggling to fight the illness.
The concept dates back to at least the 1918 Spanish flu pandemic. But itâs unclear just how helpful it is in COVID-19. There hasnât been a large, randomized, controlled clinical trial to compare the effects of convalescent plasma to placebo. Some trials are currently enrolling volunteers.
âThe evidence for convalescent plasma is really weak,â Lorenzo says. âNot all plasma is equal. Not all plasma has high titers [high concentration of antibodies], and not all antibodies neutralize the virus. Weâre using it, but itâs still not clear whether itâs effective or not.â
Some critical care doctors may be holding off on intubating patients and putting them on a mechanical ventilator a little longer than they did earlier in the pandemic. Intubation requires heavy sedation and care in the ICU. Early in the pandemic, when doctors saw that patients were progressing in their need for oxygen, many erred on the side of caution and put patients on a ventilator sooner rather than later.
At the time, before doctors knew the benefits of steroids and remdesivir, the thought was that the patient would escalate and eventually need the ventilator no matter what.
âSo if we did it early, rather than waiting until it was an emergency, when we could take our time donning the personal protective equipment, we would also reduce the risk of exposure to our health care workers,â Lorenzo says.
Doctors were also concerned that oxygen delivered through a tube in the nose â a step below a mechanical ventilator — could push the virus out into the air and increase exposure risk for health care workers, too.
âBut we now know that in some patients, if we give the steroids and remdesivir a little bit more time, and allow them to escalate a little further along with high-flow nasal [oxygen], we might just squeak by and not have to put them on a ventilator,â Lorenzo says.
In Stanfordâs ICU, Lorenzo says, they are now confident their staff are protected. âThe risk of aerosolization of the virus is real. But we now know that our health care provider infection rate is low. So if we maintain our full PPE guidelines, then the risk of transmission is low, and we might be able to prevent the patient from escalating to a ventilator.â
New research shows this may be a safe risk to take. A recent study found that there was no difference in survival rates among COVID-19 patients who went directly on a ventilator and those who were put on nasal oxygen first.
Some patients on ventilators may recover faster by spending some time each day lying prone, or face down. It doesnât work for everyone. But for those who benefit, the idea is that the face-down position may distribute oxygen more evenly throughout the lungs. Long before COVID-19, critical care providers flipped sedated patients on ventilators onto their stomachs in order to get more oxygen into their lungs.
But since the pandemic, some ICUs are trying it on patients who are awake and perhaps on the way to needing a ventilator. Numerous clinical trials in progress are examining the benefits for patients who are not yet on a ventilator but struggling to get oxygen.
âFor some patients, the oxygen level goes up, but itâs not universal,â Kaufman says. âAnd soon after you stop lying on your stomach, the oxygen goes back down.â
On the road to finding what works, health care providers have thrown out many things that proved not to work, too.
âA lot of people were talking about hydroxychloroquine,â Lorenzo says. âBut we now know, unequivocally, that we shouldnât be using it. It doesnât work. And it probably can cause more harm than good.â
Theyâve learned what works and what doesnât more quickly through unprecedented collaboration with their co-workers and frontline health care workers around the globe.
Under ânormalâ circumstances, researchers tightly guard data until it is published. âNow, some of these trials may release unpublished data if they feel that the benefit is real and substantial,â Lorenzo says.
Kaufman is part of an email chain with pulmonologists and critical care doctors from all over the world. Many are in Europe and got intensive experience with COVID-19 months ahead of doctors in the U.S. âTo be connected with some of the worldwide masters in mechanical ventilation who are at some of the hardest hit cities in the world is an amazing privilege. Itâs like sitting at the foot of Sophocles, learning from the ancient masters,â he says.
But for all theyâve learned, much is still unknown. Doctors still donât understand why some patients get through the virus after a week of mild symptoms while others escalate to a ventilator in the same amount of time. âWe still donât know how patients progress in this disease,â Lorenzo says.
But after a frenzied springtime in which many health care providers tried anything that might work, Lorenzo says, âWe have learned from this pandemic that we canât relax our scientific rigor. We have to abide by the same process of peer-reviewed clinical trials that we normally do or we can harm patients.â
New England Journal of Medicine: âRemdesivir for the Treatment of Covid-19 â Preliminary Report.â
Annals of Internal Medicine: âMeta-Analysis: Convalescent Blood Products for Spanish Influenza Pneumonia: A Future H5N1 Treatment?â
Critical Care Medicine: âTiming of Intubation andÂ MortalityÂ Among Critically IllÂ Coronavirus Disease 2019Â Patients.â
News – What Weâve Learned About Treating COVID