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Keeping Yale's COVID-19 Treatment Guidelines Up to Date

March 26, 2021
by Sonya Collins

What happens when an unknown disease enters the hospital? Doctors spend years in training to recognize and treat diseases based on volumes of available evidence about them. But what do they do when there are nearly no existing data about the disease that is killing the patient right in front of them? When patients with COVID-19 began pouring into intensive care units (ICUs) around the country, critical care providers faced these vexing questions.

“When the pandemic started, it was like a black hole. Nobody knew what would work,” says Maricar Malinis, MD, Medical Director, Transplant and Oncology Infectious Diseases, Section of Infectious Diseases. “But when you have a sick patient that you need to take care of and there’s no roadmap, you use the best science you have available to you.”

For the past year, Malinis and her colleagues across various disciplines have studied and carefully considered each new piece of evidence about treatment strategies for COVID-19 and translated it into standardized guidelines for Yale School of Medicine (YSM) and Yale New Haven Health System (YNHH) clinicians at patient bedsides. At times, the YSM/YNHH Ad Hoc COVID-19 Treatment Team’s recommendations have aligned with those of other institutions around the country and the world. At other times, the team has held fast against trends that were not borne out by the data. Today, in its 22nd iteration, YNHH’s clinical guidance for treating patients hospitalized with COVID-19 includes medications and dosages, the rationale for them, and other care recommended for patients both on and off oxygen.

Initial uncertainty

When its first COVID-19 patients arrived, the ICU at Yale New Haven Hospital faced two possible crises -- an influx of more patients than it could handle and clinicians with limited knowledge of how to care for them.

“It was unclear how to treat these patients because it was such a new virus. There was concern that people would just do their own thing based on what they’d heard or read,” says Charles Dela Cruz, MD, PhD, associate professor of medicine (pulmonary, critical care and sleep medicine) and of microbial pathogenesis. Dela Cruz is part of the Ad Hoc Team, which also includes Malinis; Christina Price, MD, assistant professor of medicine (immunology) and of pediatrics (immunology), Clinical Chief of Allergy and Immunology, Rheumatology, Allergy, & Immunology; Dayna McManus, PharmD, BCPS, senior clinical pharmacist, and Jeffrey Topal, MD, associate clinical professor of medicine (infectious diseases).

When the pandemic was new, the group met at least twice a week, but often daily, and sometimes several times in a day, to evaluate new information and incorporate it into standard treatment protocols for patients hospitalized with COVID-19.

Before clinical trial data became available, the team evaluated information from less traditional sources. It combed the medical records of Yale’s own patients and also considered anecdotes that their colleagues at other institutions shared through direct conversations or on social media.

Once trial results began to emerge, those findings took priority over information from any other source.

“The minute something was published, we dropped everything, read it, and met to discuss whether this was something we wanted to adopt,” McManus says. “We met evenings, weekends, whatever it took to make sure we were doing the best for our patients.”

With new data suddenly coming in so quickly and often arriving at opposing conclusions, keeping up with it, Dela Cruz says, “was like chasing a runaway train.”

Eventually, health and medical societies began to release recommendations that the Yale team also incorporated into its guidance.

The team also consulted with hospitalists and ICU doctors to learn from their experiences. “It’s very helpful for the clinicians who take care of these patients day in and day out to tell us what they think works,” Malinis says. “That way we are able to come up with a guidance that is almost a consensus among the treating providers and supported by the literature.”

Data-driven Care

The team’s confidence in certain medications rose and fell over time, depending on the latest clinical data.

Tocilizumab, for example, an immunosuppressant that is currently part of the guidance for patients on oxygen, has been both on and off the list of recommended medications. The team added it to the protocol based on early indications that it might help quell the so-called cytokine storm that arises in some patients.

“We were watching people rapidly decline,” Price says. “We had to address that unbridled inflammatory response.”

But later, when trials revealed mixed results, the team bumped the drug—until January 2021 when additional trials began to tip the scales toward a survival benefit for patients who receive the IL-6 inhibitor. Now, many organizations, including the National Institutes of Health, have followed suit and added tocilizumab to standard-of-care guidelines for certain patients hospitalized for COVID-19.

On the other side of the coin, the team resisted immense pressure to try drugs that had no solid evidence supporting their use. They didn’t succumb to the national hype of the hydroxychloroquine and azithromycin combination. “Some institutions recommended it based on a very small data set, but we never did,” McManus says. “We didn’t feel that the data suggested a benefit, and we were concerned about the safety of combining these drugs because of risk of arrhythmias.”

From the start, the guidelines have given providers more confidence to treat patients. One important benefit is that it has standardized care, so that caregivers who might see patients later in the course of treatment have a solid sense of the care the patients have already received.

“It levels the playing field,” Dela Cruz says. “You could have ten doctors with ten different views on how to treat, and this standardizes the practice. We know that [whoever] comes into our health system is getting similar treatment and care.”

New Challenges Ahead

Now, more than a year after the first COVID-19 case in the US, health care providers at Yale are more sure-footed. But they don’t have everything figured out. Nobody does. New and different manifestations of the disease continue to surface. For example, immunosuppressed patients tend to carry the virus for months and they appear to suffer from repeated symptom flares.

Clinicians must now learn how to treat patients with these new variations of symptoms just as they’ve learned to treat the more general population of COVID patients over the last year.

“We don’t yet have clear data and guidance on how to approach these particular patients,” McManus says. “These nuanced patients, and the challenges that they bring, are our new normal.”

Submitted by Robert Forman on March 26, 2021