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Welcome back to Axios' special report about the science of pandemics. This week we look at zoonotic diseases, antibody treatments, how researchers are trying to keep up with a changing understanding of COVID-19, and more.

  • I’m moderating a virtual event about the future of artificial intelligence, hosted by the British Embassy on Thursday, May 14, at 12pm ET. We'll talk about AI in this pandemic and more. RSVP here to attend.
  • Please send us your feedback. You can reach me at alison@axios.com or hit reply to this email. Eileen is at eileen@axios.com, and Bryan is at bryan.walsh@axios.com.

This week's newsletter is 1,830 words, about a 7-minute read.

1 big thing: The viral spillovers that created the coronavirus are only growing

Illustration: Sarah Grillo/Axios

The novel coronavirus is the latest in a long list of pathogens that have jumped from animals to human beings, triggering pandemics that have killed hundreds of millions, Axios' Bryan Walsh writes.

Why it matters: COVID-19 underscores the desperate need to better understand and control the intersection of animal and human health. Preventing future pandemics will come down in part to better policing the border zones between animal health and human health.

The 21st century has already experienced four major spillovers: SARS (horseshoe bats via civet cats), H1N1 flu (pig), MERS (bats via camel), and COVID-19 (bats via an intermediate).

  • Scientists agree the rate of such events appears to be increasing, raising the risk for future pandemics.

The big picture: Nearly 1.7 million as yet undiscovered viruses are believed to exist in wildlife. Thomas Gillespie, a disease ecologist at Emory University, notes that we still lack data for almost 90% of zoonotic viruses in wild mammal species.

  • Despite the clear biological connections between animals and humans, animal health receives perhaps $1 for every $50 that goes to human health, estimates Gregory Gray, an epidemiologist at Duke University.
  • Experts are urging more funding to characterize those pathogens and track wet market workers and others who are likely to be the first people infected in a spillover.
  • The government funding for PREDICT, a program that was meant to do just that, was initially not going to be extended by the Trump administration last year, but an extension was granted last month. The U.S. Agency for International Development is also launching a similar program called STOP Spillover.
"If we could get hold of emerging viruses before they fully adapt to humans, it would help us better understand it and develop better treatments. That might help us avoid the next viral crossover."
— Peter Ben Embarek, WHO zoonoses expert

What's happening: Many experts are urging wet markets, where live animals and humans may be in close contact, be closed.

  • China announced in February what it called a "permanent ban" on wildlife trade and consumption, but some experts worry that could drive the markets underground.
  • "A better idea is to move them out of cities to more rural areas," says Duke's Gray.

How it works: The most widely accepted theory of the origins of COVID-19 is a textbook example of how "zoonotic spillovers" occur.

  • From a bat — which often features as the reservoir species for zoonoses, in part because there are simply so many of them — the novel coronavirus probably jumped to an intermediate species more likely to come in contact with humans.
  • Based on genetic analyses of the novel coronavirus, it likely took only a single spillover event from an infected animal to a human being to kick off a pandemic that has already killed more than 260,000 people around the world.

The bottom line: Humans and animals share this planet, and increasingly they share deadly pathogens as well. If we don't fully recognize that shared threat, COVID-19 won't be the last zoonotic pandemic.

Go deeper.

2. Antibodies offer hope for a quick coronavirus fix

Illustration: Aïda Amer/Axios

Researchers are racing to develop treatments based on antibodies to block or neutralize the coronavirus in patients, with the hopes these could be ready for possible emergency use by the fall, Axios' Eileen Drage O'Reilly writes.

Why it matters: Many experts feel antibodies from recovered patients and synthesized antibody drugs could be important bridge treatments for COVID-19 during the months or years until a successful vaccine is available.

Details: Antibody therapies can be synthesized or derived from human plasma or animals that have been infected.

  • The idea is to bolster a person’s immune system to stave off infection as a short-term prophylactic or to help an ill individual fight the disease off faster, in an effort that’s been used since the 1800s, with mixed results.
  • While using any blood product can raise concerns about other infections, antibody therapies can also sometimes backfire and make conditions worse.

Plasma from recovered COVID-19 patients has "investigational" status from the Food and Drug Administration and is being used in various clinical trials, in acute care facilities, and in individuals with serious infections who receive the plasma from their physicians.

  • "We believe this is a good biological shot on goal, but ... we have to be rigorous" in data collection, says Michael Joyner of the Mayo Clinic, which is serving as the lead institution for the FDA's program.

Monoclonal antibody drugs are also being developed to target specific proteins or functions of the SARS-CoV-2 virus to neutralize and/or block it. There are at least 50 candidates in development, including by Regeneron and Eli Lilly.

  • "The good thing about a monoclonal is you can give it to sick patients immediately, and it should have an immediate effect. And you can also give it as a sort of temporary vaccine, because antibodies can stay in the bloodstream for weeks and sometimes even months," says drug discovery scientist Derek Lowe.

One of the problems with this coronavirus is that scientists don't yet know which part of SARS-CoV-2 is best to target.

  • Many efforts are focused on the spike protein on the surface of the virus, which it uses to bind to human cells and gain access.
  • Meanwhile, an early-stage study out this week suggests llama antibodies could inform the development of drugs to neutralize SAVS-CoV-2.

Go deeper.

3. The moving coronavirus target

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 this 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 a side effect of treatment.

That has implications for developing vaccines.

  • "Is [a vaccine] protective or not in a context where we don’t know what exactly defines a protective immune response to COVID-19?" says 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 evolving understanding 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.

4. Worthy of your time

Why does COVID-19 wallop some places and spare others? (Hannah Beech et al. — NYT)

  • It is far from the full picture but four factors are emerging: "demographics, culture, environment and the speed of government responses."
  • And luck.

The problem with stories about dangerous coronavirus mutations (Ed Yong — The Atlantic)

COVID-19 is not all good for wildlife (Brian Owens — Hakai)

  • The pandemic is affecting conservation projects — and their funding.

Coping with the pandemic's hidden mental health toll (Kim Hart — Axios)

  • "Mayors and local public health officials have launched initiatives to support their communities' most vulnerable residents — and are openly talking about their own struggles."
5. 1 viral thing

Illustration: Aïda Amer/Axios

The question of whether to deliberately infect volunteers with SARS-CoV-2 in order to test vaccines for COVID-19 is being hotly debated by scientists, ethicists and lawmakers.

The big picture: Controlled human infection studies have been used for centuries to evaluate vaccine doses and candidates for influenza, norovirus and other diseases. But COVID-19, with its severity, novelty and unknowns, presents thorny questions for this scientific tool.

How it works: Vaccine studies typically involve immunizing people with a vaccine (and others with a placebo), waiting for them to be exposed to the virus and seeing if the vaccine protects them.

  • In challenge studies, people are deliberately exposed to a virus in a controlled environment.

What's happening: No COVID-19 challenge trial is planned yet, but more than 14,000 people have said they'd participate in one, and scientists, ethicists, lawmakers and others are weighing in on how they might be done.

  • The World Health Organization yesterday released guidance for possible studies, emphasizing independent review of any trials.

"They're controversial, and right now there is so much we don't know," says ethicist Seema Shah of Lurie Children's Hospital of Chicago, an author of a new paper in the journal Science that outlines an ethical framework for using the studies for COVID-19. "But it is worth the investment in laying the groundwork to do such a study."

Proponents say the studies could speed up data collection about the effectiveness of a vaccine — especially if social distancing or a waning outbreak limit peoples' exposure to the virus — and therefore its availability.

  • Shah and her co-authors write that such studies could also help to better understand the course of the disease by being able to monitor the viral load and peak infection in a group of people known to be exposed.
  • And they could help determine correlates of protection — essentially markers of an immune response to a vaccine that could then be used to assess and accelerate other candidates.

Yes, but: There is currently no treatment to stop COVID-19 from progressing to a severe disease, making a challenge trial risky right now, says Myron Levine, associate dean for global health, vaccinology and infectious diseases at the University of Maryland School of Medicine.

  • And in the time it takes to grow the virus in the lab and design a challenge study, Levine says there could be several candidate vaccines that could be tested with rapid randomized control studies, citing what was done in West Africa to study a vaccine for Ebola.
  • The data, he says, would also represent the target population for a vaccine, which includes older adults, compared to challenge trials that propose enrolling young people.
"Personally, in the absence of a way to turn this off, I don’t think we should go ahead because I don’t think the risk and what we learn bring us faster to where we want to be."
— Myron Levine

The bottom line: Challenge trials can play a role in understanding disease, but there are open questions about when and how they should be used for COVID-19.

Editor's note: The last story has been updated to clarify that Myron Levine is with the University of Maryland School of Medicine.

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