One of the biggest hurdles in dealing with a pandemic caused by a completely new virus is grappling with the sheer amount of unknown information.

In the case of the novel coronavirus, SARS-CoV2, this was particularly difficult because the presentation of each patient seemed so vastly different from the previous case.

Furthermore, many patients seemed to improve clinically before deteriorating, requiring an admission to the intensive care unit for weeks at a time. The pernicious behavior of the virus made pandemic response that much more difficult, and the unpredictable nature of the disease consumed and strained health care resources.

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Physicians who were treating COVID-19 patients took note and communicated to others by phone call, conference, or social media, but there was no central repository for their experiences, which ensured that the virus spread much faster than information.

Now, approximately four months since the first reported case in America, we are beginning to understand why.

Dr. Thomas Yadegar, a critical care physician for 20 years and now director of the intensive care unit at Providence Cedars-Sinai Tarzana Medical Center in Tarzana, California, has been on the front lines of the pandemic response.

The first time one of his patients deteriorated, he was completely stumped for the first time in his two decades in the ICU.

Many of his patients were in acute respiratory distress. But many other patients were experiencing abnormal coagulation, inflammatory heart disease, and some were even experiencing neurological deficits and weakened muscles.

“I have 20 years of critical care experience, and I can’t explain what just happened to my patient,” Yadegar said.

One evening after an exhausting shift, he sat down and pored over patient charts for all those cases, searching for a common thread. Finally, after one of the worst headaches of his life, he found it.

It was inflammation.

Early in the pandemic, Yadegar’s unit used treatment guidelines that came from doctors around the world, which recommended avoiding anti-inflammatory treatment and recommended early and aggressive use of ventilators to prevent patients from declining further.

But those guidelines were aimed at treating a severe viral respiratory disease by using a ventilator to assist with oxygenating the blood while the body uses its inflammatory pathways to mount a response to the virus.

Those guidelines did not address the treatment for when other organ systems began to fail.

In fact, using a ventilator is a highly invasive procedure, and the repeated and forced inspiration of air irritates the lungs, which feeds back into the inflammatory cycle. Many patients, once on a ventilator, never recover.

The only way to explain the highly complex disease course that seems to change from one patient to the next is that the virus is causing an autoimmune response, in which the body’s natural defense mechanisms go haywire and begin destroying the body they’re trying to protect.

The disease course is so unpredictable because every person’s immune system is unique to that person.

This phenomenon is not unheard of, and a common virus, Epstein-Barr virus, is known for potentially initiating the body’s inflammatory pathways to attack the nervous system and causing Guillain-Barre syndrome.

The main difference with SARS-CoV2 is that it’s much more efficient at doing this—and often in a catastrophic manner.

Yadegar and the ICU he manages have adjusted their protocols. Now, patients who test positive in his hospital for SARS-CoV2 are not sent home immediately, but tested for inflammatory markers.

Those with elevated inflammatory markers are kept in the hospital with a close eye on their oxygen saturation levels. If the patient begins to desaturate, the medical team evaluates the patient before starting a course of steroids and an IL-6 inhibitor.

IL-6 (interleukin-6) is a powerful mediator for the inflammatory pathway, so an IL-6 inhibitor would prevent a significant amount of inflammation from happening. Steroids have strong anti-inflammatory effects and also suppress the immune system more broadly.

The two of those do not treat the virus, but the potentially deadly autoimmune response it can cause.

But Yadegar cautioned that “you have to treat each patient within their own protocol.” Doctors must always treat the patients in front of them and cannot simply rely on these types of drugs for all critically ill COVID-19 patients.

That’s because using an IL-6 inhibitor with steroids would effectively strip the body of its immune response. If there’s a concomitant infection, which is extremely common in the hospital setting and even more so if a patient is on a ventilator, then using this combination of drugs will, almost certainly, kill the patient.

Still, Yadegar and his team have had remarkable success. They have not put a patient on a ventilator in at least two weeks, and the mortality rate in their ICU has been in the single digits, whereas nationally the mortality rate of critically ill patients has been between 40% and 70%.

There’s one thing we have known from the start about the COVID-19 virus, which is that it’s a tricky and pernicious one.

One of the important things that Yadegar has learned is that patients admitted to the ICU are often not coming in due to the direct effect of the virus, but rather from the out-of-control autoimmune process.

Information like that can only be had from front-line clinicians, and we should do our best to ensure they are heard.

The Centers for Disease Control and Prevention periodically hosts a Clinical Outreach and Communication Activity, in which clinicians are able to discuss their findings and experiences.

The CDC should be using those frequently to update information about COVID-19 and its multiple disease manifestations and to make the information easily and publicly accessible.

Furthermore, the CDC should be actively seeking this information from the front lines of COVID-19 hot spots, where the most relevant data will be found.

With steps like these, clinicians can be assured of clear lines of communication that may help drive down mortality rates in the future and ease the process of reopening the country.