Illustration: Eniola Odetunde/Axios

Solutions for COVID-19 are being developed at the same time as knowledge about the disease evolves, a serious challenge for doctors treating patients and for researchers trying to create vaccines and treatments.

Why it matters: What was first thought of as a respiratory infection now appears much more complex, making efforts to tackle the disease more complicated.

"We’re laying the track as the train is moving and the train is coming very fast," says Mark Poznansky, director of the Vaccine & Immunotherapy Center at Massachusetts General Hospital. "That is an extraordinary place to be at the global level."

What's happening: When the world first encountered COVID-19 four months ago, it was deemed a respiratory infection that hammers the lungs. That's still the case but in recent weeks, clinicians have been reporting wide-ranging manifestations of the disease in some people.

  • Some of this could be that, with enough cases, there are outliers and anomalies. But that underscores that doctors and researchers are learning as they go.

Details: Renal failure, sepsis, damaged blood vessels, skin lesions, stroke, gastrointestinal problems and blood clots in the lungs and kidneys are being seen in some COVID-19 patients.

  • 20% of hospitalized patients in one study in Wuhan, China had heart damage.
  • 31% of people with the disease studied in a Danish ICU had blood clots.

"It comes across more as a systemic disease exhibited initially as a respiratory disease," says Poznansky. It's unclear whether the cause is the virus itself, the immune system's response to it, or the treatment received.

That has implications for developing vaccines. The goal is to prevent infection but not exacerbate the immune effects in response to the virus.

  • "Is [a vaccine] protective or not in a context where we don’t know what exactly defines a protective immune response to COVID-19?" asks Poznansky.
  • The evolving understanding underscores the need to have multiple vaccines in development. (The current count is 123, per the Milken Institute's tracker.)

What to watch: The changing percent of the disease will feature in regulatory discussions.

  • "This is the question companies will be discussing with regulators: which surrogate endpoints are acceptable as a proxy for going all the way to the worst possible outcomes in a patient?" says Phyllis Arthur, vice president of infectious diseases and diagnostics policy at biotech trade organization BIO.

The bottom line: Pandemics bring a potent mix of uncertainty and urgency to science that experts say requires both nimbleness and rigor to navigate.

  • "This is what a pandemic is like. It’s uncomfortable," says Arthur. "You need to move swiftly and do good, solid, evidence-based, risk-benefit ratio assessments and understand what you know and don’t know, and make evidence based policy decisions knowing you don’t have perfect information."

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