"When this ends …."

"Research of the future will …"

"After this experience …"

These phrases are starting to show up in news stories, online conversations, and quotes from medical and research leaders. This pivot to the future is a reasonable twist, considering the enormity of the COVID-19 pandemic.

This pandemic may change the way we live and work. But, says Gregory Poland, M.D., director of Mayo Clinic's Vaccine Research Group, "Right now we still see people crowded in bars and restaurants, partying. Right now, we can't get people to stay home. In addition, we have to get institutions and governments to see vaccine and infectious diseases research as critical to their mission."

So, he says, now is the time to educate people in the here and now. That is what the future will actually depend on.

"Everything we're seeing right now in terms of numbers of COVID-19 cases is the result of what happened 14 to 28 days ago. There is a lag period between transmission and symptoms." This and the lack of knowledge makes the future still too fuzzy for anyone to accurately predict what will happen next and when, says Dr. Poland, using the concept of a digital image made up of data points called pixels. Digital pictures look fuzzy if there are too few pixels for the size of the image.

"In terms of this outbreak, we have about 10%–20% of the pixels and only 11 weeks of experience with this virus," says Dr. Poland. That's not nearly enough to see the whole picture.

"Each piece of research adds a pixel to the canvas, but it takes time," says Dr. Poland. "Whether we're talking about developing knowledge or a vaccine, the process is designed to be slow, evidence-based and reflective to help the most and harm the least."

While the collaboration across nations in research is a shining jewel in how this pandemic has unfolded, according to Dr. Poland, it makes it hard for media and the lay public to distinguish between a finding that is solid and one that could be built on a shaky foundation.

"What if use of a medication in the short term adds harm, but in the long term, it helps prevent disability? Or what if a drug that treats one disease is repurposed and we start giving it in huge numbers required for COVID-19 treatment? You've robbed Peter to pay Paul and taken the drug from where it is known to help to a person who it may or may not help. Is that wise?"

Despite forward-looking statements, the science still needs to be solid. Nonrandomized controlled trials identify what potentially has value, but all they do, says Dr. Poland, is pose possible questions that need to be answered in clinical trials.  The best way to find solid answers, he adds, is to eliminate as many barriers to clinical trials as is feasible and, most importantly, stay the course.

"We could have had a vaccine for SARS (severe acute respiratory syndrome), but none of the vaccine candidates came through phase 1 trials because the cases stopped," he says. "(At the time of this interview,) we have in the U.S.A. 150 people who have died from SARS-CoV-2 (the virus that causes COVID-19), but in the same amount of time, 30,000 Americans died of influenza." This makes an important point, he says, that the situation we find ourselves in is not new.

Dr. Poland, who has worked with RNA respiratory viruses for 33 years, points out that he's lived through pandemics and viral spillovers throughout his life.

"I lived through the 1958 (H2N2 influenza) and 1968 (H3N2) pandemics, HIV (identified in the 1980s), the 2002 SARS, H1N1 in 2009, MERS in 2012 ― with the point being that this always has and always will continue. This is our new norm."

In his lifetime, the number of people who flew internationally has grown from a few thousand to 1.4 billion a year. This means what was once improbable in terms of disease transmission is now entirely possible. "Consider someone in the United States being infected by contact with a person who breathed in a virus from a person who got it from contact with an infected mammal who was infected by a bat on another continent," says Dr. Poland. "That is a series of statistically improbable situations, but it happened. And while it took 67 days for the first 100,000 cases to occur, it's only taken 11 days for the next 100,000, and four days for the third group of 100,000 cases."

In addition to global interconnectivity, the economy has shifted in large part to a "just-in-time" model, and health care has shifted to manage staffing shortages and cut costs. But infectious disease hasn't changed. "Even in bad flu years, hospitals can be overrun," he says, adding that to solve the problem that pandemics put at the doorstep of humanity, people need to work together and work smarter.

"Right now, the picture is poorly pixilated. In January, the image was like a 5-by-7-foot image with a dot on it, but people were asking for predictions. And they generally found someone to say something," he says. "But today, depending on the topic, we have maybe a 70% image when it comes to genetics, and we may soon be at maybe 30% to 50% pixilation overall. But we won't be able to make accurate predictions until we get to 80% or 90% of the pixels in the picture."

In the more than 1,200 media requests that Dr. Poland has responded to over the past few months, he's stuck to an important principle.

"I believe in radical transparent honesty, including where I don't know," he says.

So what's going to happen with SARS-CoV-2 and how it will affect research, medical care and the world?

"I don't know. Right now, we want to keep people safe, keep our institutions viable, and put into practice the ideal we all signed up for: The needs of the patient come first."

For now, that needs to be the focus.

- Sara Tiner, March 24, 2020

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